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Conserved domains on  [gi|1878423636|gb|KAF5908435|]
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arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2-like [Clarias magur]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
BAR super family cl12013
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
34-248 1.04e-130

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


The actual alignment was detected with superfamily member cd07642:

Pssm-ID: 472257  Cd Length: 215  Bit Score: 394.40  E-value: 1.04e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVNRDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:cd07642      1 RNTVVAIEEALDVDRTVLYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSNCVCRDDPDLGSAFLKFSVFTKELTALFK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKGDLKKSFDKACKDYDTKVNKIEKEKREHAKQHGMIRTEISGGEIAEEMEKERRA 193
Cdd:cd07642     81 NLVQNMNNIITFPLDSLLKGDLKGVKGDLKKPFDKAWKDYETKVTKIEKEKKEHAKMHGMIRTEISGAEIAEEMEKERRF 160
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  194 FQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKL 248
Cdd:cd07642    161 FQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
419-537 4.60e-73

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


:

Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 236.73  E-value: 4.60e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  419 LSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFN 498
Cdd:cd08834      1 LTKSIIAEVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFN 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1878423636  499 DIMEANLSGEeiPKPTPSSDMQSRKDFITAKYTEKRFAQ 537
Cdd:cd08834     81 EIMEANLPPG--YKPTPNSDMEERKDFIRAKYVEKKFVV 117
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
297-403 2.13e-58

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270071  Cd Length: 108  Bit Score: 195.66  E-value: 2.13e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  297 QLQGNKAHGTERSGMLSKRSEG-LRKVWQKRKCSVKSGYLTISHGTANTPPAKLNLLTCQVKCNPEEKKSFDLISHDRTY 375
Cdd:cd13251      1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                           90       100
                   ....*....|....*....|....*...
gi 1878423636  376 HFQAEDEAECQIWVSVLQNSKEEALNDA 403
Cdd:cd13251     81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
SH3 super family cl17036
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
979-1034 2.64e-34

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


The actual alignment was detected with superfamily member cd11966:

Pssm-ID: 473055  Cd Length: 56  Bit Score: 125.07  E-value: 2.64e-34
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSRKGAFPVSFVHF 1034
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFVHF 56
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
584-677 2.16e-14

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 74.99  E-value: 2.16e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  584 QGETALHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKR 663
Cdd:COG0666    152 DGNTPLHLAAA---NGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAE 228
                           90
                   ....*....|....
gi 1878423636  664 LKNTQCEELLTQAQ 677
Cdd:COG0666    229 NGNLEIVKLLLEAG 242
PTZ00322 super family cl31426
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
621-737 3.90e-03

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional


The actual alignment was detected with superfamily member PTZ00322:

Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 41.04  E-value: 3.90e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  621 GNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKRLKNTQCEELLTQaqsgkfnvhvhveYEWCLHNEDLDE 700
Cdd:PTZ00322   115 GRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSR-------------HSQCHFELGANA 181
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1878423636  701 SDDEMEDKPIPQkrEERPVSCYLPGNAGSMQPSMAAL 737
Cdd:PTZ00322   182 KPDSFTGKPPSL--EDSPISSHHPDFSAVPQPMMGSL 216
 
Name Accession Description Interval E-value
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-248 1.04e-130

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP2 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2) is also known as DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. ASAP2 mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153326  Cd Length: 215  Bit Score: 394.40  E-value: 1.04e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVNRDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:cd07642      1 RNTVVAIEEALDVDRTVLYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSNCVCRDDPDLGSAFLKFSVFTKELTALFK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKGDLKKSFDKACKDYDTKVNKIEKEKREHAKQHGMIRTEISGGEIAEEMEKERRA 193
Cdd:cd07642     81 NLVQNMNNIITFPLDSLLKGDLKGVKGDLKKPFDKAWKDYETKVTKIEKEKKEHAKMHGMIRTEISGAEIAEEMEKERRF 160
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  194 FQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKL 248
Cdd:cd07642    161 FQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
419-537 4.60e-73

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 236.73  E-value: 4.60e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  419 LSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFN 498
Cdd:cd08834      1 LTKSIIAEVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFN 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1878423636  499 DIMEANLSGEeiPKPTPSSDMQSRKDFITAKYTEKRFAQ 537
Cdd:cd08834     81 EIMEANLPPG--YKPTPNSDMEERKDFIRAKYVEKKFVV 117
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
297-403 2.13e-58

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 195.66  E-value: 2.13e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  297 QLQGNKAHGTERSGMLSKRSEG-LRKVWQKRKCSVKSGYLTISHGTANTPPAKLNLLTCQVKCNPEEKKSFDLISHDRTY 375
Cdd:cd13251      1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                           90       100
                   ....*....|....*....|....*...
gi 1878423636  376 HFQAEDEAECQIWVSVLQNSKEEALNDA 403
Cdd:cd13251     81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
421-538 1.09e-46

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 162.78  E-value: 1.09e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  421 KAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDI 500
Cdd:pfam01412    1 KRVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEF 80
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1878423636  501 MEANLSGEeiPKPTPSSDMQSRKDFITAKYTEKRFAQR 538
Cdd:pfam01412   81 WEANLPPS--YKPPPSSDREKRESFIRAKYVEKKFAKP 116
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
426-543 8.54e-37

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 134.39  E-value: 8.54e-37
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   426 EVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANL 505
Cdd:smart00105    3 LLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESNL 82
                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 1878423636   506 SGEEIpKPTPSSDMQSRKDFITAKYTEKRFAQRRRSDA 543
Cdd:smart00105   83 DDFSL-KPPDDDDQQKYESFIAAKYEEKLFVPPESAEE 119
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
979-1034 2.64e-34

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212899  Cd Length: 56  Bit Score: 125.07  E-value: 2.64e-34
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSRKGAFPVSFVHF 1034
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFVHF 56
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
413-535 1.28e-31

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 126.43  E-value: 1.28e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  413 NNIVQELSKAIvnevKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNV 492
Cdd:COG5347      4 KSEDRKLLKLL----KSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVG 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1878423636  493 GNAGFNDIMEANLSGEEIPKPTPSSDMQSRKDFITAKYTEKRF 535
Cdd:COG5347     80 GNSNANRFYEKNLLDQLLLPIKAKYDSSVAKKYIRKKYELKKF 122
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
34-266 5.95e-27

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 110.34  E-value: 5.95e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVnrDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:pfam16746   14 RSLLEEHEAELDELEKKLKKLLKLCKRMIEAGKEYSAAQRLFANSLLDFKFEFI--GDEETDESLKKFSQLLQEMENFHT 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDTKVNK---IEKEKREHAKQhgmirteisggEIAEEMEKE 190
Cdd:pfam16746   92 ILLDQAQRTIIKPLENFRKEDLKEVK-ELKKKFDKASEKLDAALEKnaqLSKKKKPSELE-----------EADNELAAT 159
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  191 RRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKLSTDLAGVKQVQEGEKKQL 266
Cdd:pfam16746  160 RKCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGYELFKDLEPFMKDLQAQLQQTREDTREEKEEL 235
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
584-677 2.16e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 74.99  E-value: 2.16e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  584 QGETALHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKR 663
Cdd:COG0666    152 DGNTPLHLAAA---NGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAE 228
                           90
                   ....*....|....
gi 1878423636  664 LKNTQCEELLTQAQ 677
Cdd:COG0666    229 NGNLEIVKLLLEAG 242
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
306-393 2.76e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 69.50  E-value: 2.76e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   306 TERSGMLSKRSEGLRKVWQKRKCSVKSGYLTI----SHGTANTPPAKLNLLTCQVKCNPE-----EKKSFDLISHDR-TY 375
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYykskKDKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIKTSDRkTL 80
                            90
                    ....*....|....*...
gi 1878423636   376 HFQAEDEAECQIWVSVLQ 393
Cdd:smart00233   81 LLQAESEEEREKWVEALR 98
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
976-1032 3.54e-13

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 64.87  E-value: 3.54e-13
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1878423636   976 KPKRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIegDSSRKGAFPVSFV 1032
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRL--GRGKEGLFPSNYV 55
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
422-494 1.47e-12

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 70.65  E-value: 1.47e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  422 AIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGN 494
Cdd:PLN03114    11 SVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGN 83
PH pfam00169
PH domain; PH stands for pleckstrin homology.
306-397 1.35e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.11  E-value: 1.35e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  306 TERSGMLSKRSEGLRKVWQKRKCSVKSGYLTI----SHGTANTPPAKLNLLTCQVKC-----NPEEKKSFDLISHD---- 372
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYykddKSGKSKEPKGSISLSGCEVVEvvasdSPKRKFCFELRTGErtgk 80
                           90       100
                   ....*....|....*....|....*
gi 1878423636  373 RTYHFQAEDEAECQIWVSVLQNSKE 397
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
Ank_2 pfam12796
Ankyrin repeats (3 copies);
589-673 2.21e-10

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 58.20  E-value: 2.21e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  589 LHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLrSKASVSITNEaGETPLDLAKRLKNTQ 668
Cdd:pfam12796    1 LHLAAK---NGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLL-EHADVNLKDN-GRTALHYAARSGHLE 75

                   ....*
gi 1878423636  669 CEELL 673
Cdd:pfam12796   76 IVKLL 80
SH3_9 pfam14604
Variant SH3 domain;
982-1032 7.54e-09

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 52.23  E-value: 7.54e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTG---RTGLVPANYV 48
BAR smart00721
BAR domain;
26-245 9.32e-07

BAR domain;


Pssm-ID: 214787 [Multi-domain]  Cd Length: 239  Bit Score: 51.23  E-value: 9.32e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636    26 FTTRMGHCRNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENE--------EQYIQALEKFGEACvnrdnpevaaa 97
Cdd:smart00721   36 FDTTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGGDdgeglgadSSYGKALDKLGEAL----------- 104
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636    98 flkfavftKELTALFKNLLQNMNNIITfPLDSLLKGDLKGVKGDLKKsFDKACKDYDTKVNKIEKEKREHAKQhgmIRTE 177
Cdd:smart00721  105 --------KKLLQVEESLSQVKRTFIL-PLLNFLLGEFKEIKKARKK-LERKLLDYDSARHKLKKAKKSKEKK---KDEK 171
                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1878423636   178 ISGGEiaEEMEKERRAF---QLQMCEYLIKVNEIKIRKGVDLVQNLIKyfhAQCNFFQDGLKVVENLKPTM 245
Cdd:smart00721  172 LAKAE--EELRKAKQEFeesNAQLVEELPQLVASRVDFFVNCLQALIE---AQLNFHRESYKLLQQLQQQL 237
PHA03095 PHA03095
ankyrin-like protein; Provisional
585-689 2.23e-06

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 51.56  E-value: 2.23e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  585 GETALHLAVRIAdrNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDN--SECLKLLLRSKASVSITNEAGETPLDLAk 662
Cdd:PHA03095    83 GFTPLHLYLYNA--TTLDVIKLLIKAGADVNAKDKVGRTPLHVYLSGFNinPKVIRLLLRKGADVNALDLYGMTPLAVL- 159
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1878423636  663 rLKNTQCE----ELLTQAQSGKFNV--------HVHVEY 689
Cdd:PHA03095   160 -LKSRNANvellRLLIDAGADVYAVddrfrsllHHHLQS 197
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
620-649 1.63e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 36.80  E-value: 1.63e-03
                            10        20        30
                    ....*....|....*....|....*....|
gi 1878423636   620 KGNTAVHYCCVTDNSECLKLLLRSKASVSI 649
Cdd:smart00248    1 DGRTPLHLAAENGNLEVVKLLLDKGADINA 30
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
621-737 3.90e-03

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 41.04  E-value: 3.90e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  621 GNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKRLKNTQCEELLTQaqsgkfnvhvhveYEWCLHNEDLDE 700
Cdd:PTZ00322   115 GRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSR-------------HSQCHFELGANA 181
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1878423636  701 SDDEMEDKPIPQkrEERPVSCYLPGNAGSMQPSMAAL 737
Cdd:PTZ00322   182 KPDSFTGKPPSL--EDSPISSHHPDFSAVPQPMMGSL 216
 
Name Accession Description Interval E-value
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-248 1.04e-130

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP2 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2) is also known as DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. ASAP2 mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153326  Cd Length: 215  Bit Score: 394.40  E-value: 1.04e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVNRDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:cd07642      1 RNTVVAIEEALDVDRTVLYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSNCVCRDDPDLGSAFLKFSVFTKELTALFK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKGDLKKSFDKACKDYDTKVNKIEKEKREHAKQHGMIRTEISGGEIAEEMEKERRA 193
Cdd:cd07642     81 NLVQNMNNIITFPLDSLLKGDLKGVKGDLKKPFDKAWKDYETKVTKIEKEKKEHAKMHGMIRTEISGAEIAEEMEKERRF 160
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  194 FQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKL 248
Cdd:cd07642    161 FQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
BAR_ASAPs cd07604
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-248 4.36e-120

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ASAPs (ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) with similarity to ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins) in that they contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and ankyrin (ANK) repeats. However, ASAPs contain an additional C-terminal SH3 domain. ASAPs function in regulating cell growth, migration, and invasion. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3. ASAP1 and ASAP2 shows GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but is able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153288  Cd Length: 215  Bit Score: 366.35  E-value: 4.36e-120
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVNRDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:cd07604      1 RNTVGALEESLEGDRVGLQKLKKAVKAIHNSGLAHVENELQFAEALEKLGSKALSREEEDLGAAFLKFSVFTKELAALFK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKGDLKKSFDKACKDYDTKVNKIEKEKREHAKQHGMIRTEISGGEIAEEMEKERRA 193
Cdd:cd07604     81 NLMQNLNNIIMFPLDSLLKGDLKGSKGDLKKPFDKAWKDYETKASKIEKEKKQLAKEAGMIRTEITGAEIAEEMEKERRM 160
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  194 FQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKL 248
Cdd:cd07604    161 FQLQMCEYLIKVNEIKTKKGVDLLQHLVEYYHAQNSYFQDGLKVIEHFRPYIEKL 215
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-248 1.04e-99

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1) is also known as DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. ASAP1 is an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6 However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153325  Cd Length: 215  Bit Score: 312.76  E-value: 1.04e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVNRDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:cd07641      1 RNTVNVLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQALDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKGDLKKSFDKACKDYDTKVNKIEKEKREHAKQHGMIRTEISGGEIAEEMEKERRA 193
Cdd:cd07641     81 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 160
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  194 FQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKL 248
Cdd:cd07641    161 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 215
BAR_ASAP3 cd07640
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-248 2.23e-90

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP3 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3) is also known as ACAP4 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 4), DDEFL1 (Development and Differentiation Enhancing Factor-Like 1), or centaurin beta-6. It is an Arf6-specific GTPase activating protein (GAP) and is co-localized with Arf6 in ruffling membranes upon EGF stimulation. ASAP3 is implicated in the pathogenesis of hepatocellular carcinoma and plays a role in regulating cell migration and invasion. ASAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153324  Cd Length: 213  Bit Score: 287.66  E-value: 2.23e-90
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVNRDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:cd07640      1 RSTAAALEESLEGDQASLQRIKKIVKAIHNSGLNHVENEEQYTEALENLGNSHLSQNNHELSTGFLNLAVFTREVTALFK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKGDLKKSFDKACKDYDTKVNKIEKEKREHAKQHGMIRTEISggEIAEEMEKERRA 193
Cdd:cd07640     81 NLVQNLNNIVSFPLDSLLKGQLRDGRLESKKQMEKAWKDYEAKIGKLEKERREKQKQHGLIRLDMT--DTAEDMQRERRN 158
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  194 FQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKL 248
Cdd:cd07640    159 FQLHMCEYLLKAQESQMKQGPDFLQSLIKFFHAQHNFFQDGWKAAQNLGPFIEKL 213
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
419-537 4.60e-73

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 236.73  E-value: 4.60e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  419 LSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFN 498
Cdd:cd08834      1 LTKSIIAEVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFN 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1878423636  499 DIMEANLSGEeiPKPTPSSDMQSRKDFITAKYTEKRFAQ 537
Cdd:cd08834     81 EIMEANLPPG--YKPTPNSDMEERKDFIRAKYVEKKFVV 117
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
419-539 1.14e-72

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.


Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 236.03  E-value: 1.14e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  419 LSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFN 498
Cdd:cd08849      1 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1878423636  499 DIMEANLSGEEIPKPTPSSDMQSRKDFITAKYTEKRFAQRR 539
Cdd:cd08849     81 EIMEACLPAEDVVKPNPGSDMNARKDYITAKYIERRYARKK 121
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
419-542 3.42e-66

ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP1 and ASAP2, ASAP3 do not have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350087 [Multi-domain]  Cd Length: 124  Bit Score: 218.18  E-value: 3.42e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  419 LSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFN 498
Cdd:cd17900      1 LTKLLIAEVKSRPGNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDLLSTSELLLAVSMGNTRFN 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1878423636  499 DIMEANLSGEEIPKPTPSSDMQSRKDFITAKYTEKRFAQRRRSD 542
Cdd:cd17900     81 EVMEATLPAHGGPKPSAESDMGTRKDYIMAKYVEHRFVRKRCTP 124
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
419-538 8.69e-65

ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350073 [Multi-domain]  Cd Length: 122  Bit Score: 214.13  E-value: 8.69e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  419 LSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFN 498
Cdd:cd08848      1 LTKAIIDDVQRLPGNEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFN 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1878423636  499 DIMEANLSGEEiPKPTPSSDMQSRKDFITAKYTEKRFAQR 538
Cdd:cd08848     81 DIMEGNLPSPS-PKPSPSSDMTARKEYITAKYVEHRFSRK 119
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
297-403 2.13e-58

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 195.66  E-value: 2.13e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  297 QLQGNKAHGTERSGMLSKRSEG-LRKVWQKRKCSVKSGYLTISHGTANTPPAKLNLLTCQVKCNPEEKKSFDLISHDRTY 375
Cdd:cd13251      1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                           90       100
                   ....*....|....*....|....*...
gi 1878423636  376 HFQAEDEAECQIWVSVLQNSKEEALNDA 403
Cdd:cd13251     81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
421-538 1.09e-46

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 162.78  E-value: 1.09e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  421 KAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDI 500
Cdd:pfam01412    1 KRVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEF 80
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1878423636  501 MEANLSGEeiPKPTPSSDMQSRKDFITAKYTEKRFAQR 538
Cdd:pfam01412   81 WEANLPPS--YKPPPSSDREKRESFIRAKYVEKKFAKP 116
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
424-530 3.53e-46

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


Pssm-ID: 350058 [Multi-domain]  Cd Length: 106  Bit Score: 160.74  E-value: 3.53e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  424 VNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEA 503
Cdd:cd08204      1 LEELLKLPGNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDSWTPEQVELMKAIGNARANAYYEA 80
                           90       100
                   ....*....|....*....|....*..
gi 1878423636  504 NLSgEEIPKPTPSSDMQSRKDFITAKY 530
Cdd:cd08204     81 NLP-PGFKKPTPDSSDEEREQFIRAKY 106
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
423-536 6.69e-41

ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP domain is an essential part of ACAP proteins that play important role in endocytosis, actin remodeling and receptor tyrosine kinase-dependent cell movement. ACAP subfamily of ArfGAPs are composed of coiled coils (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. In addition, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350064 [Multi-domain]  Cd Length: 116  Bit Score: 146.25  E-value: 6.69e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  423 IVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLgTSELL-LARNVGNAGFNDIM 501
Cdd:cd08835      3 ALEQVLSVPGNAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSW-EPELLkVMLELGNDVVNRIY 81
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1878423636  502 EANLSGEEIPKPTPSSDMQSRKDFITAKYTEKRFA 536
Cdd:cd08835     82 EANVPDDGSVKPTPDSSRQEREAWIRAKYVEKKFV 116
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
422-535 3.03e-37

ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. It has been shown that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) also have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages.


Pssm-ID: 350075 [Multi-domain]  Cd Length: 116  Bit Score: 135.84  E-value: 3.03e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  422 AIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIM 501
Cdd:cd08850      2 SILQRVQSIAGNDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIY 81
                           90       100       110
                   ....*....|....*....|....*....|....
gi 1878423636  502 EANLSGEEIPKPTPSSDMQSRKDFITAKYTEKRF 535
Cdd:cd08850     82 EAQCEELGLKKPTASSSRQDKEAWIKAKYVEKKF 115
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
426-543 8.54e-37

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 134.39  E-value: 8.54e-37
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   426 EVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANL 505
Cdd:smart00105    3 LLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESNL 82
                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 1878423636   506 SGEEIpKPTPSSDMQSRKDFITAKYTEKRFAQRRRSDA 543
Cdd:smart00105   83 DDFSL-KPPDDDDQQKYESFIAAKYEEKLFVPPESAEE 119
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
424-538 5.32e-35

ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350077 [Multi-domain]  Cd Length: 120  Bit Score: 129.31  E-value: 5.32e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  424 VNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEA 503
Cdd:cd08852      4 VAQVQSVDGNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDSWEPELVKLMCELGNVIINQIYEA 83
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1878423636  504 NLSGEEIPKPTPSSDMQSRKDFITAKYTEKRFAQR 538
Cdd:cd08852     84 RIEAMAIKKPGPSSSRQEKEAWIRAKYVEKKFITK 118
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
979-1034 2.64e-34

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212899  Cd Length: 56  Bit Score: 125.07  E-value: 2.64e-34
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSRKGAFPVSFVHF 1034
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFVHF 56
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
422-530 1.36e-33

ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350065 [Multi-domain]  Cd Length: 108  Bit Score: 125.10  E-value: 1.36e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  422 AIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIM 501
Cdd:cd08836      1 AALQAIRNVRGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVW 80
                           90       100
                   ....*....|....*....|....*....
gi 1878423636  502 EANLSGEEipKPTPSSDMQSRKDFITAKY 530
Cdd:cd08836     81 EGNTQGRT--KPTPDSSREEKERWIRAKY 107
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
427-535 1.32e-32

ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350076 [Multi-domain]  Cd Length: 116  Bit Score: 122.40  E-value: 1.32e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  427 VKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANLS 506
Cdd:cd08851      7 VQCIPGNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYEARVE 86
                           90       100
                   ....*....|....*....|....*....
gi 1878423636  507 GEEIPKPTPSSDMQSRKDFITAKYTEKRF 535
Cdd:cd08851     87 KMGAKKPQPGGQRQEKEAYIRAKYVERKF 115
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
427-530 1.05e-31

ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350079 [Multi-domain]  Cd Length: 109  Bit Score: 119.73  E-value: 1.05e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  427 VKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANLS 506
Cdd:cd08854      7 IRNAKGNSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSIWESCTQ 86
                           90       100
                   ....*....|....*....|....
gi 1878423636  507 GEEipKPTPSSDMQSRKDFITAKY 530
Cdd:cd08854     87 GRT--KPAPDSSREERESWIRAKY 108
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
413-535 1.28e-31

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 126.43  E-value: 1.28e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  413 NNIVQELSKAIvnevKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNV 492
Cdd:COG5347      4 KSEDRKLLKLL----KSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVG 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1878423636  493 GNAGFNDIMEANLSGEEIPKPTPSSDMQSRKDFITAKYTEKRF 535
Cdd:COG5347     80 GNSNANRFYEKNLLDQLLLPIKAKYDSSVAKKYIRKKYELKKF 122
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
979-1031 3.57e-30

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 113.18  E-value: 3.57e-30
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSRKGAFPVSF 1031
Cdd:cd11821      1 RVRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDPSRRGVFPVSF 53
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
420-552 1.37e-27

Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350059 [Multi-domain]  Cd Length: 115  Bit Score: 107.97  E-value: 1.37e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  420 SKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFND 499
Cdd:cd08830      1 ARAVLRELQKLPGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDSWSEKQLKKMELGGNAKLRE 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  500 IMEANlsgeEIPKPTPssdmqsrkdfITAKYTEKrFAQRRRSdatvKLRSLYD 552
Cdd:cd08830     81 FFESY----GISPDLP----------IREKYNSK-AAELYRE----KLAAEAE 114
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
424-530 1.42e-27

ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion.


Pssm-ID: 350080 [Multi-domain]  Cd Length: 110  Bit Score: 107.83  E-value: 1.42e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  424 VNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEA 503
Cdd:cd08855      5 IQSIRNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSVWEG 84
                           90       100
                   ....*....|....*....|....*..
gi 1878423636  504 NLSGEEipKPTPSSDMQSRKDFITAKY 530
Cdd:cd08855     85 ALDGYS--KPGPDSTREEKERWIRAKY 109
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
429-530 2.92e-27

Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 106.59  E-value: 2.92e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  429 RMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANLSgE 508
Cdd:cd08839      6 REEDNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDSWTPEQVQSMQEMGNARANAYYEANLP-D 84
                           90       100
                   ....*....|....*....|..
gi 1878423636  509 EIPKPTPSSDMQSrkdFITAKY 530
Cdd:cd08839     85 GFRRPQTDSALEN---FIRDKY 103
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
34-266 5.95e-27

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 110.34  E-value: 5.95e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVnrDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:pfam16746   14 RSLLEEHEAELDELEKKLKKLLKLCKRMIEAGKEYSAAQRLFANSLLDFKFEFI--GDEETDESLKKFSQLLQEMENFHT 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDTKVNK---IEKEKREHAKQhgmirteisggEIAEEMEKE 190
Cdd:pfam16746   92 ILLDQAQRTIIKPLENFRKEDLKEVK-ELKKKFDKASEKLDAALEKnaqLSKKKKPSELE-----------EADNELAAT 159
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  191 RRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTMEKLSTDLAGVKQVQEGEKKQL 266
Cdd:pfam16746  160 RKCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGYELFKDLEPFMKDLQAQLQQTREDTREEKEEL 235
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
417-530 9.79e-27

ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350061 [Multi-domain]  Cd Length: 113  Bit Score: 105.42  E-value: 9.79e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  417 QELSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAG 496
Cdd:cd08832      1 AERNKKRLLELLKLPGNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEK 80
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1878423636  497 FNDIMEANLsgeeiP----KPTPSSDMQSRKDFITAKY 530
Cdd:cd08832     81 AKAKYEAHV-----PafyrRPTPTDPQVLREQWIRAKY 113
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
979-1035 1.88e-26

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212898 [Multi-domain]  Cd Length: 57  Bit Score: 102.78  E-value: 1.88e-26
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSRKGAFPVSFVHFI 1035
Cdd:cd11965      1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 57
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
420-550 2.68e-26

ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350084 [Multi-domain]  Cd Length: 115  Bit Score: 104.52  E-value: 2.68e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  420 SKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFND 499
Cdd:cd08959      1 TRAVFKKLRSKPENKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDKWTEEQLRKMKVGGNANARE 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  500 IMEANLSGEEIPkptpssdmqsrkdfITAKYTEKRFAQRRRsdatvKLRSL 550
Cdd:cd08959     81 FFKQHGIYDSMD--------------IKEKYNSRAAALYRD-----KLAAL 112
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
422-535 3.60e-26

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics.


Pssm-ID: 350066 [Multi-domain]  Cd Length: 116  Bit Score: 104.00  E-value: 3.60e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  422 AIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDV-LGTSELL-LARNVGNAGFND 499
Cdd:cd08837      2 EVAEKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTkVWTEELVeLFLKLGNDRANR 81
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1878423636  500 IMEANL-SGEEIpkpTPSSDMQSRKDFITAKYTEKRF 535
Cdd:cd08837     82 FWAANLpPSEAL---HPDADSEQRREFITAKYREGKY 115
BAR cd07307
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
44-243 5.63e-26

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


Pssm-ID: 153271 [Multi-domain]  Cd Length: 194  Bit Score: 106.37  E-value: 5.63e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   44 LDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACVNRDNPEVAAAFLKFAVFTKELTALFKNLLQNMNNII 123
Cdd:cd07307      2 LDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPDLSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKV 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  124 TFPLDSLLKGDLKGVKgDLKKSFDKACKDYDTKVNKIEKEKREHAKQHGMIRTEisggeiaEEMEKERRAFQLQMCEYLI 203
Cdd:cd07307     82 IEPLKEYLKKDLKEIK-KRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEAE-------EELQEAKEKYEELREELIE 153
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1878423636  204 KVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKP 243
Cdd:cd07307    154 DLNKLEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLLP 193
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
431-530 1.57e-25

The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 101.99  E-value: 1.57e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  431 SGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANL---SG 507
Cdd:cd08833      6 SNARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSLldpSQ 85
                           90       100
                   ....*....|....*....|....
gi 1878423636  508 EEIPKPTPSSDMQSRK-DFITAKY 530
Cdd:cd08833     86 SGKRKPIPPDPVHPTKeEFIKAKY 109
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
420-499 4.12e-25

Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350060 [Multi-domain]  Cd Length: 116  Bit Score: 101.08  E-value: 4.12e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  420 SKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFND 499
Cdd:cd08831      2 RDAIFKKLRSKPENKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDSWTPEQLRRMKVGGNAKARE 81
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
427-530 5.85e-24

ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350078 [Multi-domain]  Cd Length: 109  Bit Score: 97.39  E-value: 5.85e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  427 VKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANLS 506
Cdd:cd08853      7 IRNMRGNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSIWEGSSQ 86
                           90       100
                   ....*....|....*....|....
gi 1878423636  507 GEEipKPTPSSDMQSRKDFITAKY 530
Cdd:cd08853     87 GQT--KPSSDSTREEKERWIRAKY 108
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
433-534 1.29e-19

Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350083 [Multi-domain]  Cd Length: 107  Bit Score: 85.04  E-value: 1.29e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  433 NDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANLsgeeiPK 512
Cdd:cd08859     10 NKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAFL-----PE 84
                           90       100
                   ....*....|....*....|....
gi 1878423636  513 P--TPSSDmQSRKDFITAKYTEKR 534
Cdd:cd08859     85 NfrRPQTD-QAVEGFIRDKYEKKK 107
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
417-530 2.44e-19

ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350069 [Multi-domain]  Cd Length: 112  Bit Score: 84.29  E-value: 2.44e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  417 QELSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGvHYSRIQSLTLDVLGTSELLLARNVGnag 496
Cdd:cd08843      1 GKERRRAVLELLQRPGNARCADCGAPDPDWASYTLGVFICLSCSGIHRNIP-QVSKVKSVRLDAWEEAQVEFMASHG--- 76
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1878423636  497 fNDIMEANLSGEEIP---KPTPSSDMQSRKDFITAKY 530
Cdd:cd08843     77 -NDAARARFESKVPSfyyRPTPSDCQLLREQWIRAKY 112
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
433-535 7.48e-19

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 83.42  E-value: 7.48e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  433 NDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTS----ELLLArnVGNAGFNDIMEANLSGE 508
Cdd:cd08856     18 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSneliELFIV--VGNKPANLFWAANLFSE 95
                           90       100
                   ....*....|....*....|....*..
gi 1878423636  509 EIPKPTpsSDMQSRKDFITAKYTEKRF 535
Cdd:cd08856     96 EDLHMD--SDVEQRTPFITQKYKEGKF 120
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
423-535 2.23e-18

ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350067 [Multi-domain]  Cd Length: 113  Bit Score: 81.47  E-value: 2.23e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  423 IVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGvHysRIQSLTLDVLGTSELLLARNVGNAGFNDIME 502
Cdd:cd08838      3 ILRELLKLPENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN-H--RVKSISMSTFTPEEVEFLQAGGNEVARKIWL 79
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1878423636  503 ANLSGEEIPKPTPsSDMQSRKDFITAKYTEKRF 535
Cdd:cd08838     80 AKWDPRTDPEPDS-GDDQKIREFIRLKYVDKRW 111
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
429-535 2.70e-18

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP1 localizes to the plasma membrane, the Golgi complex, and endosomal compartments. It displays PI(3,4,5)P3-dependent ArfGAP activity that regulates Arf-, RhoA-, and Cdc42-dependent cellular events. For example, ARAP1 inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome.


Pssm-ID: 350088 [Multi-domain]  Cd Length: 116  Bit Score: 81.40  E-value: 2.70e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  429 RMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLD-VLGTSELL-LARNVGNAGFNDIMEANLS 506
Cdd:cd17901      9 SVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDrKVWTEELIeLFLLLGNGKANQFWAANVP 88
                           90       100
                   ....*....|....*....|....*....
gi 1878423636  507 GEEipKPTPSSDMQSRKDFITAKYTEKRF 535
Cdd:cd17901     89 PSE--ALCPSSSSEERRHFITAKYKEGKY 115
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
428-530 2.99e-18

GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350072 [Multi-domain]  Cd Length: 111  Bit Score: 81.22  E-value: 2.99e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  428 KRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANL-- 505
Cdd:cd08847      3 KRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSLld 82
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1878423636  506 -----SGEEipKPTPSSDMQSRK-DFITAKY 530
Cdd:cd08847     83 pasimSGKR--KANPQDKVHPNKaEFIRAKY 111
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
433-535 5.93e-17

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP3 possesses a unique dual-specificity GAP activity for Arf6 and RhoA regulated by PI(3,4,5)P3 and a small GTPase Rap1-GTP. The RhoGAP activity of ARAP3 is enhanced by direct binding of Rap1-GTP to the Ras-association (RA) domain. ARAP3 is involved in regulation of cell shape and adhesion.


Pssm-ID: 350089 [Multi-domain]  Cd Length: 116  Bit Score: 77.64  E-value: 5.93e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  433 NDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDV-LGTSELL-LARNVGNAGFNDIMEANL-SGEE 509
Cdd:cd17902     13 NRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTsVWSNEIVqLFIVLGNDRANRFWAARLpASEA 92
                           90       100
                   ....*....|....*....|....*.
gi 1878423636  510 IpkpTPSSDMQSRKDFITAKYTEKRF 535
Cdd:cd17902     93 L---HPDATPEQRREFISRKYREGRF 115
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
422-479 8.74e-16

Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350085 [Multi-domain]  Cd Length: 120  Bit Score: 74.72  E-value: 8.74e-16
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  422 AIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLD 479
Cdd:cd09028      8 AIFKRLRSVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELD 65
BAR_ACAPs cd07603
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
52-245 1.25e-15

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) containing an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. Vertebrates contain at least three members, ACAP1, ACAP2, and ACAP3. ACAP1 and ACAP2 are Arf6-specific GAPs, involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration, by mediating Arf6 signaling. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153287  Cd Length: 200  Bit Score: 76.57  E-value: 1.25e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   52 SKMKKSVKAINS---SGQTHVENEEQYIQALEKFGEACvnRDNPEVAAAFLKFAVFTKELTALFKNLLQNMNNIITFPLD 128
Cdd:cd07603     16 TRLEKLLKLCNGmvdSGKTYVNANSLFVNSLNDLSDYF--RDDSLVQNCLNKFIQALQEMNNFHTILLDQAQRTVSTQLQ 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  129 SLLKGDLKGVKgDLKKSFDKACKDYDTKVNKIEKEKREhaKQHGMirteisggeiaEEMEK----ERRAFQLQMCEYLIK 204
Cdd:cd07603     94 NFVKEDIKKVK-ESKKHFEKISDDLDNALVKNAQAPRS--KPQEA-----------EEATNiltaTRSCFRHTALDYVLQ 159
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1878423636  205 VNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTM 245
Cdd:cd07603    160 INVLQAKKRHEILSTLLSYMHAQFTFFHQGYDLLEDLEPYM 200
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
421-479 5.17e-15

Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350086 [Multi-domain]  Cd Length: 120  Bit Score: 72.40  E-value: 5.17e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1878423636  421 KAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLD 479
Cdd:cd09029      7 QTLFKRLRAIPTNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELD 65
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
584-677 2.16e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 74.99  E-value: 2.16e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  584 QGETALHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKR 663
Cdd:COG0666    152 DGNTPLHLAAA---NGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAE 228
                           90
                   ....*....|....
gi 1878423636  664 LKNTQCEELLTQAQ 677
Cdd:COG0666    229 NGNLEIVKLLLEAG 242
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
306-393 2.76e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 69.50  E-value: 2.76e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   306 TERSGMLSKRSEGLRKVWQKRKCSVKSGYLTI----SHGTANTPPAKLNLLTCQVKCNPE-----EKKSFDLISHDR-TY 375
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYykskKDKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIKTSDRkTL 80
                            90
                    ....*....|....*...
gi 1878423636   376 HFQAEDEAECQIWVSVLQ 393
Cdd:smart00233   81 LLQAESEEEREKWVEALR 98
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
550-673 6.26e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 73.45  E-value: 6.26e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  550 LYDAVRSRDIFSLLQVYADGVDLTETFpmanehEQGETALHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCC 629
Cdd:COG0666     91 LHAAARNGDLEIVKLLLEAGADVNARD------KDGETPLHLAAY---NGNLEIVKLLLEAGADVNAQDNDGNTPLHLAA 161
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1878423636  630 VTDNSECLKLLLRSKASVSITNEAGETPLDLAKRLKNTQCEELL 673
Cdd:COG0666    162 ANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLL 205
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
421-530 8.07e-14

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 68.64  E-value: 8.07e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  421 KAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGvHYSRIQSLTLDVLGTSELLLARNVGNAGFNDI 500
Cdd:cd08844      5 KKRLLELLKLPGNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLP-DISRVKSIRLDFWEDELVEFMKENGNLKAKAK 83
                           90       100       110
                   ....*....|....*....|....*....|....
gi 1878423636  501 MEAnlsgeEIP----KPTPSSDMQSRKDFITAKY 530
Cdd:cd08844     84 FEA-----FVPpfyyRPQANDCDVLKEQWIRAKY 112
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
308-401 9.22e-14

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 68.01  E-value: 9.22e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  308 RSGMLSKRSEGLRKVWQKRKCSVKSGYLTISHGTANTPPAKL--NLLTCQVK-CNPEEKK-SFDLISHDRTYHFQAEDEA 383
Cdd:cd13250      1 KEGYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDKKDEPTVMveDLRLCTVKpTEDSDRRfCFEVISPTKSYMLQAESEE 80
                           90
                   ....*....|....*...
gi 1878423636  384 ECQIWVSVLQNSKEEALN 401
Cdd:cd13250     81 DRQAWIQAIQSAIASALN 98
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
976-1032 3.54e-13

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 64.87  E-value: 3.54e-13
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1878423636   976 KPKRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIegDSSRKGAFPVSFV 1032
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRL--GRGKEGLFPSNYV 55
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
979-1031 4.15e-13

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 64.41  E-value: 4.15e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdsSRKGAFPVSF 1031
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNG--GREGLFPANY 51
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
422-494 1.47e-12

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 70.65  E-value: 1.47e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  422 AIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGN 494
Cdd:PLN03114    11 SVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGN 83
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
434-530 1.75e-12

GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350071 [Multi-domain]  Cd Length: 111  Bit Score: 64.74  E-value: 1.75e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  434 DVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYSRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANL-------S 506
Cdd:cd08846      9 EVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSLldpaqvqS 88
                           90       100
                   ....*....|....*....|....*
gi 1878423636  507 GEEipKPTPSSDMQ-SRKDFITAKY 530
Cdd:cd08846     89 GRR--KANPQDKVHpTKSEFIRAKY 111
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
308-392 5.80e-12

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 62.56  E-value: 5.80e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  308 RSGMLSKRSEGLRKVWQKRKCSVKSGYLTIS---HGTANTPPAKLNL---LTCQVKCNPEEKKSFDLI-SHDRTYHFQAE 380
Cdd:cd00821      1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYkskKDSSYKPKGSIPLsgiLEVEEVSPKERPHCFELVtPDGRTYYLQAD 80
                           90
                   ....*....|..
gi 1878423636  381 DEAECQIWVSVL 392
Cdd:cd00821     81 SEEERQEWLKAL 92
BAR_GAP10-like cd07634
The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are ...
73-243 1.14e-11

The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This group is composed of uncharacterized proteins called Rho GTPase activating protein (GAP) 10-like. GAP10-like may be a GAP with activity towards RhoA and Cdc42. Similar to GRAF and GRAF2, it contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of the related proteins GRAF and OPHN1, directly interact with their Rho GAP domains and inhibit theiractivity. The autoinhibited proteins are capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153318 [Multi-domain]  Cd Length: 207  Bit Score: 65.05  E-value: 1.14e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   73 EQYIQALEKFGEACV----NRDNPEVAAAFLKFAVFTKELTALFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDK 148
Cdd:cd07634     40 QKFSQSLQDFQFECIgdaeTDDEISIAQSLKEFARLLIAVEEERRRLIQNANDVLIAPLEKFRKEQIGAAK-DGKKKFDK 118
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  149 ACKDYdtkVNKIEKEKREHAKqhgmiRTEISGGEIAEEMEKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQC 228
Cdd:cd07634    119 ESEKY---YSILEKHLNLSAK-----KKESHLQRADTQIDREHQNFYEASLEYVFKIQEVQEKKKFEFVEPLLAFLQGLF 190
                          170
                   ....*....|....*
gi 1878423636  229 NFFQDGLKVVENLKP 243
Cdd:cd07634    191 TFYHEGYELAQEFAP 205
PH pfam00169
PH domain; PH stands for pleckstrin homology.
306-397 1.35e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.11  E-value: 1.35e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  306 TERSGMLSKRSEGLRKVWQKRKCSVKSGYLTI----SHGTANTPPAKLNLLTCQVKC-----NPEEKKSFDLISHD---- 372
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYykddKSGKSKEPKGSISLSGCEVVEvvasdSPKRKFCFELRTGErtgk 80
                           90       100
                   ....*....|....*....|....*
gi 1878423636  373 RTYHFQAEDEAECQIWVSVLQNSKE 397
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
Ank_2 pfam12796
Ankyrin repeats (3 copies);
589-673 2.21e-10

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 58.20  E-value: 2.21e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  589 LHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLrSKASVSITNEaGETPLDLAKRLKNTQ 668
Cdd:pfam12796    1 LHLAAK---NGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLL-EHADVNLKDN-GRTALHYAARSGHLE 75

                   ....*
gi 1878423636  669 CEELL 673
Cdd:pfam12796   76 IVKLL 80
BAR_APPL cd07601
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
89-257 2.58e-10

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains, and are localized to cytoplasmic membranes. Vertebrates contain two APPL proteins, APPL1 and APPL2. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153285  Cd Length: 215  Bit Score: 61.46  E-value: 2.58e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   89 RDNPEVAAAFLKFAVFTKELTALFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDTKVNKIEK--EKRE 166
Cdd:cd07601     58 RDDEILVSTLKQFSKVVDELSTMHSTLSSQLADTVLHPISQFMESDLAEIM-TLKELFKAASNDHDGVLSKYSRlsKKRE 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  167 HAKQHGmirteisggEIAEEMEKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGlkvVENLKPTME 246
Cdd:cd07601    137 NTKVKI---------EVNDEVYACRKKQHQTAMNYYCALNLLQYKKTTALLEPMIGYLQAQIAFFKMG---PEMFTRQTE 204
                          170
                   ....*....|.
gi 1878423636  247 KLSTDLAGVKQ 257
Cdd:cd07601    205 EFLSDINTSVQ 215
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
583-673 2.95e-10

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 62.66  E-value: 2.95e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  583 EQGETALHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAK 662
Cdd:COG0666     85 DGGNTLLHAAAR---NGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAA 161
                           90
                   ....*....|.
gi 1878423636  663 RLKNTQCEELL 673
Cdd:COG0666    162 ANGNLEIVKLL 172
BAR_ACAP3 cd07637
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
34-245 3.88e-10

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3), also called centaurin beta-5, is presumed to be an Arf GTPase activating protein (GAP) based on its similarity to the Arf6-specific GAPs ACAP1 and ACAP2. The specific function of ACAP3 is still unknown. ACAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153321  Cd Length: 200  Bit Score: 60.40  E-value: 3.88e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACvnRDNPEVAAAFLKFAVFTKELTALFK 113
Cdd:cd07637      1 RATIDEVETDVVEIEAKLDKLVKLCSGMIEAGKAYATTNKLFVSGIRDLSQQC--KKDEMISECLDKFGDSLQEMVNYHM 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDtkvnkIEKEKREHAKQHGMIRTEisggEIAEEMEKERRA 193
Cdd:cd07637     79 ILFDQAQRSVRQQLHSFVKEDVRKFK-ETKKQFDKVREDLE-----IALVKNAQAPRHKPHEVE----EATSTLTITRKC 148
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  194 FQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTM 245
Cdd:cd07637    149 FRHLALDYVLQINVLQAKKKFEILDSMLSFMHAQYTFFQQGYSLLHELDPYM 200
BAR_APPL1 cd07631
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
90-257 1.02e-09

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. APPL1 interacts with diverse receptors (e.g. NGF receptor TrkA, FSHR, adiponectin receptors) and signaling proteins (e.g. Akt, PI3K), and may function as an adaptor linked to many distinct signaling pathways. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153315  Cd Length: 215  Bit Score: 59.72  E-value: 1.02e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   90 DNPEVAAAFLKFAVFTKELTALFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDTKVNKIEK--EKREH 167
Cdd:cd07631     59 DDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEIL-TLKEVFQIASNDHDAAINRYSRlsKRREN 137
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  168 AKqhgmirteiSGGEIAEEMEKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGlkvVENLKPTMEK 247
Cdd:cd07631    138 EK---------VKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMG---SENLNEQLEE 205
                          170
                   ....*....|
gi 1878423636  248 LSTDLAGVKQ 257
Cdd:cd07631    206 FLTNIGTSVQ 215
Ank_2 pfam12796
Ankyrin repeats (3 copies);
550-651 1.03e-09

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 56.28  E-value: 1.03e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  550 LYDAVRSRDIFSLLQVYADGVDLTETFPmaneheQGETALHLAVRiadRNSLHIVDFLVQNsGNLDKQTvKGNTAVHYCC 629
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDK------NGRTALHLAAK---NGHLEIVKLLLEH-ADVNLKD-NGRTALHYAA 69
                           90       100
                   ....*....|....*....|..
gi 1878423636  630 VTDNSECLKLLLRSKASVSITN 651
Cdd:pfam12796   70 RSGHLEIVKLLLEKGADINVKD 91
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
979-1032 1.25e-09

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 54.73  E-value: 1.25e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFV 1032
Cdd:cd11840      1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQT---GLFPSNYV 51
BAR_APPL2 cd07632
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
93-238 1.58e-09

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. Both APPL proteins interact with the transcriptional repressor Reptin, acting as activators of beta-catenin/TCF-mediated trancription. APPL2 is essential for cell proliferation. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153316  Cd Length: 215  Bit Score: 59.27  E-value: 1.58e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   93 EVAAAFLKFAVFTKELTALFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDTKVNKIEK--EKREHAKQ 170
Cdd:cd07632     62 EVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVS-TLKDLFGIASNEHDLSMAKYSRlpKKRENEKV 140
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  171 HGmirteisggEIAEEMEKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVV 238
Cdd:cd07632    141 KA---------EVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFFKKGAELF 199
PLN03131 PLN03131
hypothetical protein; Provisional
417-555 2.21e-09

hypothetical protein; Provisional


Pssm-ID: 178677 [Multi-domain]  Cd Length: 705  Bit Score: 61.33  E-value: 2.21e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  417 QELSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMgVHysRIQSLTLDVLGTSELLLARNVGNAG 496
Cdd:PLN03131     7 EERNEKIIRGLMKLPPNRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF-TH--RVKSVSMSKFTSQDVEALQNGGNQR 83
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  497 FNDIM--EANLSGEEIPKptpSSDMQSRKDFITAKYTEKRFAQRRRSDAT----VKLRSLYDAVR 555
Cdd:PLN03131    84 AREIYlkDWDQQRQRLPD---NSKVDKIREFIKDIYVDKKYAGGKTHDKPprdlQRIRSHEDETR 145
SH3_Bbc1 cd11887
Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces ...
977-1032 6.18e-09

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212820 [Multi-domain]  Cd Length: 60  Bit Score: 53.12  E-value: 6.18e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  977 PKRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGH-IEGDSSRK-GAFPVSFV 1032
Cdd:cd11887      1 PFKVKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEyVDSNGNTKeGIFPKNFV 58
SH3_9 pfam14604
Variant SH3 domain;
982-1032 7.54e-09

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 52.23  E-value: 7.54e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTG---RTGLVPANYV 48
BAR_GRAF2 cd07635
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR ...
42-241 1.18e-08

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase 2 (GRAF2), also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA which regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle and also interacts with PKNbeta, which is a target of Rho. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153319  Cd Length: 207  Bit Score: 56.54  E-value: 1.18e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   42 EALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEA-----------CVNRDNPEVAAAFLKFAVFTKELTA 110
Cdd:cd07635      2 ERIRAHEAELERTNRFIKELLKDGKNLIAATKSLSAAQRKFAHSlrdfkfefigdAETDDERCIDASLQEFSNFLKNLEE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  111 LFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDY----DTKVNKIEKEKREHAKqhgmirteisggEIAEE 186
Cdd:cd07635     82 QREIMALNVTETLIKPLERFRKEQLGAVK-EEKKKFDKETEKNysllEKHLNLSAKKKEPQLQ------------EADVQ 148
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  187 MEKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENL 241
Cdd:cd07635    149 VEQNRQHFYELSLEYVCKLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDF 203
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
979-1032 1.32e-08

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 51.97  E-value: 1.32e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEE--DKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11875      1 KARVLFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELNG---KRGVFPDNFV 53
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
979-1034 1.64e-08

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212815 [Multi-domain]  Cd Length: 54  Bit Score: 51.53  E-value: 1.64e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIvDGEEDKE--WWVGHIEGdssRKGAFPVSFVHF 1034
Cdd:cd11882      1 RARALYACKAEDESELSFEPGQIIT-NVQPSDEpgWLEGTLNG---RTGLIPENYVEF 54
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
978-1032 4.55e-08

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212709 [Multi-domain]  Cd Length: 57  Bit Score: 50.39  E-value: 4.55e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEG-EVIIVDGEEDKEWWVGHIEgDSSRKGAFPVSFV 1032
Cdd:cd11775      1 KRGKVLYDFDAQSDDELTVKEGdVVYILDDKKSKDWWMVENV-STGKEGVVPASYI 55
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
584-673 4.55e-08

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 55.73  E-value: 4.55e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  584 QGETALHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKR 663
Cdd:COG0666    185 DGETPLHLAAE---NGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTALLLAAA 261
                           90
                   ....*....|
gi 1878423636  664 LKNTQCEELL 673
Cdd:COG0666    262 AGAALIVKLL 271
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
982-1032 4.72e-08

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212925  Cd Length: 52  Bit Score: 50.39  E-value: 4.72e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDgEEDKEWWVGHIEgdsSRKGAFPVSFV 1032
Cdd:cd11992      4 ALYPYSSSEPGDLTFNEGEEILVT-QKDGEWWTGSIE---DRTGIFPSNYV 50
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
979-1032 5.15e-08

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 50.01  E-value: 5.15e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11826      1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNG---VTGLFPGNYV 51
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
979-1031 6.28e-08

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212724 [Multi-domain]  Cd Length: 64  Bit Score: 50.40  E-value: 6.28e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIV---DGEEDKE--WWVGHIEGDsSRKGAFPVSF 1031
Cdd:cd11790      4 KVRATHDYTAEDTDELTFEKGDVILVipfDDPEEQDegWLMGVKEST-GCRGVFPENF 60
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
979-1032 6.33e-08

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 50.11  E-value: 6.33e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11827      1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRG---KEGLFPGNYV 51
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
979-1032 6.40e-08

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 49.93  E-value: 6.40e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11805      1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRG---RVGIFPANYV 51
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
978-1032 6.65e-08

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 49.77  E-value: 6.65e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWvghiEGDSSRK-GAFPVSFV 1032
Cdd:cd11820      1 RKVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWW----KGSNHRGeGLFPANFV 52
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
417-546 7.17e-08

putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional


Pssm-ID: 178666  Cd Length: 648  Bit Score: 56.39  E-value: 7.17e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  417 QELSKAIVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGvhySRIQSLTLDVLGTSELLLARNVGNAG 496
Cdd:PLN03119     7 EERNEKIIRGLMKLPPNRRCINCNSLGPQYVCTTFWTFVCMACSGIHREFT---HRVKSVSMSKFTSKEVEVLQNGGNQR 83
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1878423636  497 FNDIMEANLSGEEIPKPTpSSDMQSRKDFITAKYTEKRFAQRRRSDATVK 546
Cdd:PLN03119    84 AREIYLKNWDHQRQRLPE-NSNAERVREFIKNVYVQKKYAGANDADKPSK 132
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
980-1032 8.11e-08

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212894 [Multi-domain]  Cd Length: 53  Bit Score: 49.83  E-value: 8.11e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHG---SRGLFPSNYV 51
BAR_OPHN1 cd07633
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid ...
42-226 8.20e-08

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Oligophrenin-1 (OPHN1) is a GTPase activating protein (GAP) with activity towards RhoA, Rac, and Cdc42, that is expressed in developing spinal cord and in adult brain areas with high plasticity. It plays a role in regulating the actin cystoskeleton as well as morphology changes in axons and dendrites, and may also function in modulating neuronal connectivity. Mutations in the OPHN1 gene causes X-linked mental retardation associated with cerebellar hypoplasia, lateral ventricle enlargement and epilepsy. OPHN1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153317 [Multi-domain]  Cd Length: 207  Bit Score: 53.85  E-value: 8.20e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   42 EALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEA-----------CVNRDNPEVAAAFLKFAVFTKELTA 110
Cdd:cd07633      2 ERLKCYEQELERTNKFIKDVIKDGNALISAIKEYSSAVQKFSQTlqsfqfdfigdTLTDDEINIAESFKEFAELLQEVEE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  111 LFKNLLQNMNNIITFPLDSLLKGDLkGVKGDLKKSFDKACKDYDTKVNK---IEKEKREHAKQhgmirteisggEIAEEM 187
Cdd:cd07633     82 ERMMMVQNASDLLIKPLENFRKEQI-GFTKERKKKFEKDSEKFYSLLDRhvnLSSKKKESQLQ-----------EADLQV 149
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1878423636  188 EKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHA 226
Cdd:cd07633    150 DKERQNFYESSLEYVYQIQEVQESKKFDVVEPVLAFLHS 188
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
980-1033 9.66e-08

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 49.23  E-value: 9.66e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFVH 1033
Cdd:cd11877      2 VRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNG---KTGWFPSNYVK 52
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
981-1029 9.82e-08

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 49.12  E-value: 9.82e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDssRKGAFPV 1029
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGG--KEGLIPS 47
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
980-1032 1.10e-07

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 49.22  E-value: 1.10e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGG---KTGLIPSNYV 51
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
979-1032 1.34e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 49.21  E-value: 1.34e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFV 1032
Cdd:cd11996      2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVT---GLFPSNYV 52
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
979-1032 1.90e-07

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212730  Cd Length: 51  Bit Score: 48.51  E-value: 1.90e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11796      1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNG---RRGIFPEGFV 51
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
979-1032 1.97e-07

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 48.48  E-value: 1.97e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11874      1 RCKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNG---KVGVFPSNFV 51
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
979-1032 2.08e-07

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212770 [Multi-domain]  Cd Length: 55  Bit Score: 48.51  E-value: 2.08e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKE--WWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11836      1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEpgWLAGELKG---KTGWFPANYV 53
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
978-1032 2.63e-07

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 48.48  E-value: 2.63e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWvghiEGDSSRK-GAFPVSFV 1032
Cdd:cd11963      2 RKVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWW----KGENHRGvGLFPSNFV 53
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
980-1028 2.72e-07

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 48.16  E-value: 2.72e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIV----DGEEDKEWWVGHIEGdssRKGAFP 1028
Cdd:cd11762      2 VRALYDYEAQSDEELSFPEGAIIRIlrkdDNGVDDGWWEGEFNG---RVGVFP 51
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
979-1032 3.59e-07

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 47.72  E-value: 3.59e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11823      1 RCKALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNG---KKGIFPATYV 51
BAR_GRAF cd07636
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; ...
34-241 4.09e-07

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase (GRAF), also called Rho GTPase activating protein 26 (ARHGAP26), is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153320 [Multi-domain]  Cd Length: 207  Bit Score: 51.98  E-value: 4.09e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALEKFGEACV----NRDNPEVAAAFLKFAVFTKELT 109
Cdd:cd07636      1 RERLKSHEAELDKTNKFIKELIKDGKSLIAALKNLSSAKRKFADSLNEFKFQCIgdaeTDDEICIARSLQEFAAVLRNLE 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  110 ALFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYdtkVNKIEKEKREHAKqhgmiRTEISGGEIAEEMEK 189
Cdd:cd07636     81 DERTRMIENASEVLITPLEKFRKEQIGAAK-EAKKKYDKETEKY---CAVLEKHLNLSSK-----KKESQLHEADSQVDL 151
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  190 ERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENL 241
Cdd:cd07636    152 VRQHFYEVSLEYVFKVQEVQERKMFEFVEPLLAFLQGLFTFYHHGYELAKDF 203
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
980-1032 4.38e-07

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 47.76  E-value: 4.38e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEgdsSRKGAFPVSFV 1032
Cdd:cd11828      2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIR---DEEGWFPASFV 51
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
307-401 5.11e-07

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270098  Cd Length: 105  Bit Score: 49.18  E-value: 5.11e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  307 ERSG---MLSKRSEGLRKVWQKRKCSVKS---GYLTIS-HGTANTPPAKLNLLTCQVKCNPEE--KKSFDL-ISHDRTYH 376
Cdd:cd13280      1 EKSGwlyMKTSVGKPNRTIWVRRWCFVKNgvfGMLSLSpSKTYVEETDKFGVLLCSVRYAPEEdrRFCFEVkIFKDISII 80
                           90       100
                   ....*....|....*....|....*
gi 1878423636  377 FQAEDEAECQIWVSVLQNSKEEALN 401
Cdd:cd13280     81 LQAETLKELKSWLTVFENAKRYALQ 105
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
981-1032 5.16e-07

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 47.25  E-value: 5.16e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFV 1032
Cdd:cd11803      4 RALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQS---GFFPVNYV 52
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
979-1032 5.52e-07

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 47.21  E-value: 5.52e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGG---RVGLVPSTAV 51
BAR_ACAP2 cd07638
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
34-245 7.16e-07

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2), also called centaurin beta-2, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153322  Cd Length: 200  Bit Score: 50.77  E-value: 7.16e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   34 RNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENEEQYIQALekfgeacvnRDnpeVAAAFLKFAVFTKELTAlFK 113
Cdd:cd07638      1 RAALEDVEGDVAELELKLDKLVKLCIGMIDAGKAFCQANKQFMNGI---------RD---LAQYSSKDAVIETSLTK-FS 67
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  114 NLLQNMNNI-----------ITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDTKVNKIEKEKREhaKQHgmirtEISggE 182
Cdd:cd07638     68 DTLQEMINYhtilfdqaqrsIKAQLQTFVKEDLRKFK-DAKKQFDKVSEEKENALVKNAQVQRN--KQH-----EVE--E 137
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  183 IAEEMEKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTM 245
Cdd:cd07638    138 ATNILTATRKCFRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLTFFHQGYDLFSELGPYM 200
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
979-1032 8.13e-07

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 46.63  E-value: 8.13e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11816      1 RCVARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNG---KIGIFPLNFV 51
SH3_SH3RF2_1 cd11929
First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
979-1032 8.61e-07

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212862  Cd Length: 54  Bit Score: 46.86  E-value: 8.61e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFV 1032
Cdd:cd11929      2 RAKALCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVS---GIFPASSV 52
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
979-1032 8.86e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 46.87  E-value: 8.86e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11995      2 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNG---QVGLFPSNYV 52
BAR smart00721
BAR domain;
26-245 9.32e-07

BAR domain;


Pssm-ID: 214787 [Multi-domain]  Cd Length: 239  Bit Score: 51.23  E-value: 9.32e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636    26 FTTRMGHCRNTVSGLEEALDADRSVLSKMKKSVKAINSSGQTHVENE--------EQYIQALEKFGEACvnrdnpevaaa 97
Cdd:smart00721   36 FDTTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGGDdgeglgadSSYGKALDKLGEAL----------- 104
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636    98 flkfavftKELTALFKNLLQNMNNIITfPLDSLLKGDLKGVKGDLKKsFDKACKDYDTKVNKIEKEKREHAKQhgmIRTE 177
Cdd:smart00721  105 --------KKLLQVEESLSQVKRTFIL-PLLNFLLGEFKEIKKARKK-LERKLLDYDSARHKLKKAKKSKEKK---KDEK 171
                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1878423636   178 ISGGEiaEEMEKERRAF---QLQMCEYLIKVNEIKIRKGVDLVQNLIKyfhAQCNFFQDGLKVVENLKPTM 245
Cdd:smart00721  172 LAKAE--EELRKAKQEFeesNAQLVEELPQLVASRVDFFVNCLQALIE---AQLNFHRESYKLLQQLQQQL 237
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
431-535 1.17e-06

ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350090 [Multi-domain]  Cd Length: 116  Bit Score: 48.45  E-value: 1.17e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  431 SGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYsRIQSLTLDVLGTSELLLARNVGNAGFNDIMEANLSGEEI 510
Cdd:cd17903     12 AANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPH-RVKSISMTTFTEPEVLFLQARGNEVCRKIWLGLFDARTS 90
                           90       100
                   ....*....|....*....|....*
gi 1878423636  511 PKPTpSSDMQSRKDFITAKYTEKRF 535
Cdd:cd17903     91 LIPD-SRDPQKVKEFLQEKYEKKRW 114
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
980-1032 1.44e-06

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 45.95  E-value: 1.44e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12046      2 VVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKG---KIGIFPSAFV 51
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
979-1033 1.87e-06

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212716 [Multi-domain]  Cd Length: 53  Bit Score: 45.80  E-value: 1.87e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFVH 1033
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGG---RQGIFPVSYVQ 52
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
307-398 1.88e-06

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 47.00  E-value: 1.88e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  307 ERSGMLSKRS-EGLRKVWQKRkcSVKSGYLTISHGTANTPPAKLNL--LTCQVKCNPEEKKSFDLISHDRTYHFQAEDEA 383
Cdd:cd13253      1 IKSGYLDKQGgQGNNKGFQKR--WVVFDGLSLRYFDSEKDAYSKRIipLSAISTVRAVGDNKFELVTTNRTFVFRAESDD 78
                           90
                   ....*....|....*
gi 1878423636  384 ECQIWVSVLQNSKEE 398
Cdd:cd13253     79 ERNLWCSTLQAAISE 93
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
979-1032 1.97e-06

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 45.77  E-value: 1.97e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGhiEGDSSRKGAFPVSFV 1032
Cdd:cd11819      1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLG--VNAKGQKGLFPANYV 52
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
308-393 2.18e-06

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 47.62  E-value: 2.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  308 RSGMLSKRSeGLRKVWQKRKCSVKSGYLTIsHGTANTP--PA---KLNLLT--CQVKCNPEEKKSFDLISHDRTYHFQAE 380
Cdd:cd13215     23 KSGYLSKRS-KRTLRYTRYWFVLKGDTLSW-YNSSTDLyfPAgtiDLRYATsiELSKSNGEATTSFKIVTNSRTYKFKAD 100
                           90
                   ....*....|...
gi 1878423636  381 DEAECQIWVSVLQ 393
Cdd:cd13215    101 SETSADEWVKALK 113
PHA03095 PHA03095
ankyrin-like protein; Provisional
585-689 2.23e-06

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 51.56  E-value: 2.23e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  585 GETALHLAVRIAdrNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDN--SECLKLLLRSKASVSITNEAGETPLDLAk 662
Cdd:PHA03095    83 GFTPLHLYLYNA--TTLDVIKLLIKAGADVNAKDKVGRTPLHVYLSGFNinPKVIRLLLRKGADVNALDLYGMTPLAVL- 159
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1878423636  663 rLKNTQCE----ELLTQAQSGKFNV--------HVHVEY 689
Cdd:PHA03095   160 -LKSRNANvellRLLIDAGADVYAVddrfrsllHHHLQS 197
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
980-1032 2.26e-06

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 45.59  E-value: 2.26e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11950      2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHG---KLGLFPANYV 51
SH3_SNX18 cd11897
Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal ...
979-1032 2.74e-06

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212830 [Multi-domain]  Cd Length: 55  Bit Score: 45.37  E-value: 2.74e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWvghIEGDSSR--KGAFPVSFV 1032
Cdd:cd11897      1 RARALYDFRSENPGEISLREHEVLSLCSEQDIEGW---LEGVNSRgdRGLFPASYV 53
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
978-1032 2.85e-06

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 45.32  E-value: 2.85e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFV 1032
Cdd:cd11964      1 RKVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGT---GLFPSNFV 52
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
980-1033 3.03e-06

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 45.18  E-value: 3.03e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFVH 1033
Cdd:cd11951      2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISG---RVGFFPRNYVH 52
BAR_RhoGAP_OPHN1-like cd07602
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR ...
90-245 3.31e-06

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of Rho and Rac GTPase activating proteins (GAPs) with similarity to oligophrenin1 (OPHN1). Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. Some members contain a C-terminal SH3 domain. Vertebrates harbor at least three Rho GAPs in this subfamily including OPHN1, GTPase Regulator Associated with Focal adhesion kinase (GRAF), GRAF2, and an uncharacterized protein called GAP10-like. OPHN1, GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. In addition, OPHN1 is active towards Rac. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of OPHN1 and GRAF directly interact with their Rho GAP domains and inhibit their activity. The autoinhibited proteins are able to bind membranes and tubulate liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domains can occur simultaneously.


Pssm-ID: 153286  Cd Length: 207  Bit Score: 49.24  E-value: 3.31e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   90 DNPEVAAAFLKFAVFTKELTALFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKA----CKDYDTKVNKIEKEKR 165
Cdd:cd07602     61 DEIEIAESLKEFGRLIETVEDERDRMLENAEEQLIEPLEKFRKEQIGGAK-EEKKKFDKEtekfCSSLEKHLNLSTKKKE 139
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  166 EHAKqhgmirteisggEIAEEMEKERRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKPTM 245
Cdd:cd07602    140 NQLQ------------EADAQLDMERRNFHQASLEYVFKLQEVQERKKFEFVETLLSFMYGWLTFYHQGHEVAKDFKPYL 207
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
982-1032 3.69e-06

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212772 [Multi-domain]  Cd Length: 52  Bit Score: 45.10  E-value: 3.69e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDgEEDKEWWVGHIeGDssRKGAFPVSFV 1032
Cdd:cd11838      4 ALYPYESNEPGDLTFNAGDVILVT-KKDGEWWTGTI-GD--RTGIFPSNYV 50
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
308-395 4.99e-06

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 46.31  E-value: 4.99e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  308 RSGMLSKRSEGL----RKVWQKR----KCSVKSGYLTISHGtaNTPPAKLNLLTCQVKC-NPEEKKSFDLISHDRTYHFQ 378
Cdd:cd13296      1 KSGWLTKKGGGSstlsRRNWKSRwfvlRDTVLKYYENDQEG--EKLLGTIDIRSAKEIVdNDPKENRLSITTEERTYHLV 78
                           90
                   ....*....|....*..
gi 1878423636  379 AEDEAECQIWVSVLQNS 395
Cdd:cd13296     79 AESPEDASQWVNVLTRV 95
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
981-1035 5.56e-06

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 44.50  E-value: 5.56e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEE--DKEWWVGHIEGdssRKGAFPVSFVHFI 1035
Cdd:cd12057      3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNG---RRGVFPDNFVKLL 56
PHA03100 PHA03100
ankyrin repeat protein; Provisional
585-667 5.80e-06

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 50.05  E-value: 5.80e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  585 GETALHLAVRiADRNSLHIVDFLVQNSGNLDKQT----------------VKGNTAVHYCCVTDNSECLKLLLRSKASVS 648
Cdd:PHA03100   141 GENLLHLYLE-SNKIDLKILKLLIDKGVDINAKNrvnyllsygvpinikdVYGFTPLHYAVYNNNPEFVKYLLDLGANPN 219
                           90
                   ....*....|....*....
gi 1878423636  649 ITNEAGETPLDLAKRLKNT 667
Cdd:PHA03100   220 LVNKYGDTPLHIAILNNNK 238
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
308-394 5.81e-06

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 45.75  E-value: 5.81e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  308 RSGMLSKRSeGLRKVWQKRKCSVKSGYLTI---SHGTANTPPAKLNLLT-CQVKCNpEEKKSFDLISHDRTYHFQAEDEA 383
Cdd:cd13282      1 KAGYLTKLG-GKVKTWKRRWFVLKNGELFYyksPNDVIRKPQGQIALDGsCEIARA-EGAQTFEIVTEKRTYYLTADSEN 78
                           90
                   ....*....|.
gi 1878423636  384 ECQIWVSVLQN 394
Cdd:cd13282     79 DLDEWIRVIQN 89
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
990-1032 6.59e-06

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 44.38  E-value: 6.59e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1878423636  990 NPDELTFTEGEVIIVDGE--EDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12142     12 APDELALKKGDVIEVISKetEDEGWWEGELNG---RRGFFPDNFV 53
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
988-1032 6.87e-06

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 44.11  E-value: 6.87e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1878423636  988 ADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12052     10 AQHEDELTITVGDIITKIKKDDGGWWEGEIKG---RRGLFPDNFV 51
Ank_4 pfam13637
Ankyrin repeats (many copies);
587-641 7.62e-06

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 44.19  E-value: 7.62e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  587 TALHLAvriADRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLL 641
Cdd:pfam13637    3 TALHAA---AASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLLL 54
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
423-535 8.86e-06

ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG1 is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG1 plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG1 promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350082 [Multi-domain]  Cd Length: 116  Bit Score: 45.80  E-value: 8.86e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  423 IVNEVKRMSGNDVCCDCGAPNPTWLSTNLGILICIECSGIHREMGVHYsRIQSLTLDVLGTSELLLARNVGNAGFNDIME 502
Cdd:cd08857      4 MLREMTSLPHNRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPPH-RVKSISMTTFTQQEIEFLQKHGNEVCKQIWL 82
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1878423636  503 ANLSGEEIPKPTpSSDMQSRKDFITAKYTEKRF 535
Cdd:cd08857     83 GLFDDRSSAIPD-FRDPQKVKEFLQEKYEKKRW 114
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
980-1032 1.16e-05

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 43.52  E-value: 1.16e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12061      2 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNG---RTGWFPSNYV 51
PHA03100 PHA03100
ankyrin repeat protein; Provisional
572-652 1.16e-05

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 48.89  E-value: 1.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  572 LTETFPMANEHEQGETALHLAVriaDRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITN 651
Cdd:PHA03100   179 LSYGVPINIKDVYGFTPLHYAV---YNNNPEFVKYLLDLGANPNLVNKYGDTPLHIAILNNNKEIFKLLLNNGPSIKTII 255

                   .
gi 1878423636  652 E 652
Cdd:PHA03100   256 E 256
PHA03095 PHA03095
ankyrin-like protein; Provisional
552-658 1.34e-05

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 48.87  E-value: 1.34e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  552 DAVRSRDIFSLLQVYADGVDLT-ETFPM-----ANEHEQGE---TALHLAVRIADRNSLHIVDFLVQNSGNLDKQTVKGN 622
Cdd:PHA03095     5 ESVDIIMEAALYDYLLNASNVTvEEVRRllaagADVNFRGEygkTPLHLYLHYSSEKVKDIVRLLLEAGADVNAPERCGF 84
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1878423636  623 TAVHYCCVTDNSE-CLKLLLRSKASVSITNEAGETPL 658
Cdd:PHA03095    85 TPLHLYLYNATTLdVIKLLIKAGADVNAKDKVGRTPL 121
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
979-1032 1.40e-05

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 43.47  E-value: 1.40e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWvghIEGDSSR--KGAFPVSFV 1032
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDGW---LEGRNSRgeVGLFPSSYV 53
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
978-1032 1.45e-05

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 43.42  E-value: 1.45e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFV 1032
Cdd:cd12054      1 RQCKVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKS---GLFPSNFV 52
SH3_Noxa1_C cd12047
C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox ...
979-1032 1.54e-05

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212980  Cd Length: 53  Bit Score: 43.27  E-value: 1.54e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12047      1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDG---RIGIFPKCFA 51
SH3_Stac_1 cd11833
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) ...
982-1033 1.71e-05

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212767 [Multi-domain]  Cd Length: 53  Bit Score: 43.26  E-value: 1.71e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEgdsSRKGAFPVSFVH 1033
Cdd:cd11833      4 ALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIE---DRVGFFPANFVQ 52
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
980-1031 1.95e-05

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 42.85  E-value: 1.95e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSF 1031
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNG---REGIFPRAF 50
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
981-1032 1.96e-05

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 43.08  E-value: 1.96e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11920      4 RAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHG---RVGIFPISYV 52
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
540-673 2.09e-05

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 47.64  E-value: 2.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  540 RSDATVKLRSLYDAVRSRDIFSLLQVYADGVDLTETFPMANEHEQGETALHLAVRIADrnsLHIVDFLVQNSGNLDKQTV 619
Cdd:COG0666      9 LLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGD---LLVALLLLAAGADINAKDD 85
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  620 KGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKRLKNTQCEELL 673
Cdd:COG0666     86 GGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLL 139
SH3_PACSIN_like cd11999
Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C ...
979-1032 2.18e-05

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212932 [Multi-domain]  Cd Length: 56  Bit Score: 43.00  E-value: 2.18e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEgDSSRKGAFPVSFV 1032
Cdd:cd11999      3 RVRAVYDYTGQEPDELSFKAGEELLKVEDEDEQGWCKGVT-DGGAVGLYPANYV 55
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
979-1032 2.53e-05

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988 [Multi-domain]  Cd Length: 53  Bit Score: 42.68  E-value: 2.53e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12055      1 RCQVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNG---KTGMFPSNFI 51
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
981-1032 2.53e-05

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 42.73  E-value: 2.53e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFV 1032
Cdd:cd11786      3 KALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQ---GFFPASYV 51
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
979-1032 2.55e-05

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 42.74  E-value: 2.55e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDgEEDKEWWVGHIEGDSSrkGAFPVSFV 1032
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVL-EQQEMWWFGELEGGEE--GWFPKSYV 51
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
980-1032 2.68e-05

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 42.70  E-value: 2.68e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdsSRKGAFPVSFV 1032
Cdd:cd11825      2 VKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGG--KKQKWFPANYV 52
SH3_PACSIN3 cd11997
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); ...
979-1032 2.72e-05

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212930 [Multi-domain]  Cd Length: 56  Bit Score: 42.64  E-value: 2.72e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWV-GHIEgdSSRKGAFPVSFV 1032
Cdd:cd11997      3 RVRALYDYTGQEADELSFKAGEELLKIGEEDEQGWCkGRLL--SGRIGLYPANYV 55
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
979-1013 2.80e-05

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212741 [Multi-domain]  Cd Length: 57  Bit Score: 42.75  E-value: 2.80e-05
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIV---DGEEDKEWW 1013
Cdd:cd11807      2 VVYALFDYEAENGDELSFREGDELTVlrkGDDDETEWW 39
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
980-1032 2.86e-05

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 42.68  E-value: 2.86e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12060      4 VKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNG---KTGWFPSNYV 53
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
978-1032 3.37e-05

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212713 [Multi-domain]  Cd Length: 57  Bit Score: 42.31  E-value: 3.37e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKE-WWVGHIEGdSSRKGAFPVSFV 1032
Cdd:cd11779      1 PRVKALYPHAAGGETQLSFEEGDVITLLGPEPRDgWHYGENER-SGRRGWFPIAYT 55
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
981-1032 3.77e-05

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 41.94  E-value: 3.77e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNG---RVGIFPASYV 51
SH3_Sorbs2_2 cd11923
Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
982-1035 4.99e-05

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212856 [Multi-domain]  Cd Length: 57  Bit Score: 41.83  E-value: 4.99e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdSSRKGAFPVSFVHFI 1035
Cdd:cd11923      5 AKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPG-TNRQGIFPVSYVEVI 57
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
308-398 5.53e-05

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 43.56  E-value: 5.53e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  308 RSGMLSKRSEGlRKVWQKRKCSVKSGYLTISHGTANTPPAKLNLLTCQVKCNPEEKK----SFDLISHDRTYHFQAEDEA 383
Cdd:cd13255      8 KAGYLEKKGER-RKTWKKRWFVLRPTKLAYYKNDKEYRLLRLIDLTDIHTCTEVQLKkhdnTFGIVTPARTFYVQADSKA 86
                           90
                   ....*....|....*
gi 1878423636  384 ECQIWVSVLQNSKEE 398
Cdd:cd13255     87 EMESWISAINLARQA 101
SH3_SKAP2 cd12045
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called ...
981-1019 5.76e-05

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212978  Cd Length: 53  Bit Score: 41.81  E-value: 5.76e-05
                           10        20        30        40
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gi 1878423636  981 KAIYKCVADNPDELTFTEGEVI-IVDGEEDK-EWWVGHIEG 1019
Cdd:cd12045      3 QGLWDCTGDQPDELSFKRGDTIyILSKEYNRfGWWVGEMKG 43
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
979-1032 7.83e-05

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 41.26  E-value: 7.83e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDK--EWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSqnDWWTGRIGG---REGIFPANYV 53
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
980-1032 8.30e-05

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 41.10  E-value: 8.30e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNG---KRGMFPDNFV 51
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
981-1032 8.77e-05

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 41.35  E-value: 8.77e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEE--DKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12056      5 KALFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELNG---KEGVFPDNFV 55
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
979-1032 1.00e-04

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 40.81  E-value: 1.00e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWvgHIEGDSSRKGAFPVSFV 1032
Cdd:cd11758      2 YVRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWW--NARNSEGKTGMIPVPYV 53
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
979-1032 1.13e-04

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 40.57  E-value: 1.13e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEgdSSRKGAFPVSFV 1032
Cdd:cd11812      1 TVVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLV--NGQQGYFPANYV 52
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
309-392 1.43e-04

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 42.23  E-value: 1.43e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  309 SGMLSKRSEGlRKVWQK-----RKCSVkSGYltishgtANTPPAKL-------NLLTCQVKCNPEEKKSFDLISHDRTYH 376
Cdd:cd13298      9 SGYLLKRSRK-TKNWKKrwvvlRPCQL-SYY-------KDEKEYKLrrvinlsELLAVAPLKDKKRKNVFGIYTPSKNLH 79
                           90
                   ....*....|....*.
gi 1878423636  377 FQAEDEAECQIWVSVL 392
Cdd:cd13298     80 FRATSEKDANEWVEAL 95
SH3_p67phox-like_C cd11870
C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; ...
979-1032 1.49e-04

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212803 [Multi-domain]  Cd Length: 53  Bit Score: 40.59  E-value: 1.49e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11870      1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDG---RVGIFPKCFV 51
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
979-1032 1.56e-04

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212777 [Multi-domain]  Cd Length: 53  Bit Score: 40.48  E-value: 1.56e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWV-GHIEGdssRKGAFPVSFV 1032
Cdd:cd11843      1 PVRALYDYEGQESDELSFKAGDILTKLEEEDEQGWCkGRLDG---RVGLYPANYV 52
SH3_Sorbs1_2 cd11922
Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ...
988-1036 1.56e-04

Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212855 [Multi-domain]  Cd Length: 58  Bit Score: 40.74  E-value: 1.56e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1878423636  988 ADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdSSRKGAFPVSFVHFIT 1036
Cdd:cd11922     11 GDTQVEMSFRKGERITLLRQVDENWYEGRIPG-TSRQGIFPITYVDVIK 58
SH3_DOCK_AB cd11872
Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are ...
982-1033 1.63e-04

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212805 [Multi-domain]  Cd Length: 56  Bit Score: 40.26  E-value: 1.63e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDgEEDKEWWVGHIEGDSSRKGAFPVSFVH 1033
Cdd:cd11872      4 AIYNFQGDGEHQLSLQVGDTVQIL-EECEGWYRGFSLRNKSLKGIFPKSYVH 54
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
978-1036 1.73e-04

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 40.38  E-value: 1.73e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFVHFIT 1036
Cdd:cd11972      3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVT---GLFPGNYVESIM 58
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
981-1032 2.29e-04

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212907  Cd Length: 54  Bit Score: 40.05  E-value: 2.29e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEgdsSRKGAFPVSFV 1032
Cdd:cd11974      4 EALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNE---DREAWFPASFV 52
Ank_5 pfam13857
Ankyrin repeats (many copies);
607-661 2.52e-04

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 40.02  E-value: 2.52e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  607 LVQN-SGNLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLA 661
Cdd:pfam13857    1 LLEHgPIDLNRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
SH3_CAS cd11844
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ...
981-1028 3.07e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212778  Cd Length: 56  Bit Score: 39.64  E-value: 3.07e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIV---DGEEDKEWWVGHIEGdssRKGAFP 1028
Cdd:cd11844      3 RALYDNVAESPDELAFRRGDILTVleqNTAGLEGWWLCSLRG---RQGIAP 50
PHA03095 PHA03095
ankyrin-like protein; Provisional
539-667 3.21e-04

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 44.63  E-value: 3.21e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  539 RRSDATVK-LRSLYDA---VRSRDIF--SLLQVYAD---------------GVDLTETFPMANeheqgeTALHLAVRIAD 597
Cdd:PHA03095   161 KSRNANVElLRLLIDAgadVYAVDDRfrSLLHHHLQsfkprarivreliraGCDPAATDMLGN------TPLHSMATGSS 234
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  598 RNSLHIVDFLVQNSGnLDKQTVKGNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKRLKNT 667
Cdd:PHA03095   235 CKRSLVLPLLIAGIS-INARNRYGQTPLHYAAVFNNPRACRRLIALGADINAVSSDGNTPLSLMVRNNNG 303
SH3_PACSIN1-2 cd11998
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) ...
979-1032 3.43e-04

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212931 [Multi-domain]  Cd Length: 56  Bit Score: 39.55  E-value: 3.43e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWV-GHIegDSSRKGAFPVSFV 1032
Cdd:cd11998      2 RVRALYDYDGQEQDELSFKAGDELTKLEDEDEQGWCkGRL--DSGQVGLYPANYV 54
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
979-1032 3.50e-04

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 39.30  E-value: 3.50e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHieGDSSRKGAFPVSFV 1032
Cdd:cd11960      1 RARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGT--GPDGTYGLFPANYV 52
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
979-1031 3.82e-04

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212752 [Multi-domain]  Cd Length: 50  Bit Score: 39.39  E-value: 3.82e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSF 1031
Cdd:cd11818      1 KARALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRG---KSGIFPKNF 50
SH3_Lasp1_C cd11934
C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic ...
978-1035 3.91e-04

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212867 [Multi-domain]  Cd Length: 59  Bit Score: 39.60  E-value: 3.91e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEgDSSRKGAFPVSFVHFI 1035
Cdd:cd11934      3 KRYRAVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGTVE-RTGDTGMLPANYVEAI 59
SH3_Bem1p_2 cd11879
Second Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this ...
988-1034 4.65e-04

Second Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212812 [Multi-domain]  Cd Length: 56  Bit Score: 39.24  E-value: 4.65e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1878423636  988 ADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSRKGAFPVSFVHF 1034
Cdd:cd11879     10 AERPDELDAKAGDAIIICAHSNYEWFVAKPIGRLGGPGLIPVSFVEI 56
BAR_SFC_plant cd07606
The Bin/Amphiphysin/Rvs (BAR) domain of the plant protein SCARFACE (SFC); BAR domains are ...
32-243 4.65e-04

The Bin/Amphiphysin/Rvs (BAR) domain of the plant protein SCARFACE (SFC); BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. The plant protein SCARFACE (SFC), also called VAscular Network 3 (VAN3), is a plant ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein), an Arf GTPase Activating Protein (GAP) that plays a role in the trafficking of auxin efflux regulators from the plasma membrane to the endosome. It is required for the normal vein patterning in leaves. SCF contains an N-terminal BAR domain, followed by a Pleckstrin Homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153290  Cd Length: 202  Bit Score: 42.48  E-value: 4.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   32 HCRNTVSGLEEALDADrsvlskmkksvkaINSSGqthveneeqyiqALEKFGEAcvnrDNPEVAAAFL-----KFAVFTK 106
Cdd:cd07606     23 GCRKYRDALGEAYDGD-------------SAFAE------------SLEEFGGG----HDDPISVAVGgpvmtKFTSALR 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  107 ELTALFKNLLQNMNNIITFPLDSLLKGDLKGVKgDLKKSFDKACKDYDtkvnkiekekREHAKQhgMIRTEISGGEIAEE 186
Cdd:cd07606     74 EIGSYKEVLRSQVEHMLNDRLAQFADTDLQEVK-DARRRFDKASLDYE----------QARSKF--LSLTKDAKPEILAA 140
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  187 MEKE----RRAFQLQMCEYLIKVNEIKIRKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKP 243
Cdd:cd07606    141 AEEDlgttRSAFETARFDLMNRLHAADARKRVEFLERLSGSMDAHLAFFKSGYELLRQLEP 201
SH3_Vinexin_2 cd11924
Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 ...
982-1033 5.50e-04

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212857  Cd Length: 56  Bit Score: 38.79  E-value: 5.50e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdSSRKGAFPVSFVH 1033
Cdd:cd11924      5 AQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITG-TGRQGIFPASYVQ 55
SH3_SH3RF1_1 cd11927
First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ...
981-1033 5.71e-04

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212860  Cd Length: 54  Bit Score: 38.78  E-value: 5.71e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFVH 1033
Cdd:cd11927      4 KALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNG---IHGFFPTNFVQ 53
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
981-1033 6.95e-04

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212861  Cd Length: 54  Bit Score: 38.75  E-value: 6.95e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDssrKGAFPVSFVH 1033
Cdd:cd11928      4 KALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGC---HGFLPASYIQ 53
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
982-1033 7.03e-04

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 38.53  E-value: 7.03e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDssrKGAFPVSFVH 1033
Cdd:cd11806      4 AIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGC---CGYIPASHLH 52
SH3_Intersectin1_4 cd11993
Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
976-1036 7.21e-04

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212926  Cd Length: 65  Bit Score: 38.95  E-value: 7.21e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1878423636  976 KPKRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIE--GDSSRKGAFPVSFVHFIT 1036
Cdd:cd11993      2 KPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQarGKKRQIGWFPANYVKLLS 64
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
981-1019 7.90e-04

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212977  Cd Length: 53  Bit Score: 38.30  E-value: 7.90e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKE--WWVGHIEG 1019
Cdd:cd12044      3 QGLWDCFGDNPDELSFQRGDLIYILSKEYNMygWWVGELNG 43
Ank_4 pfam13637
Ankyrin repeats (many copies);
621-661 8.71e-04

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 38.41  E-value: 8.71e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1878423636  621 GNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLA 661
Cdd:pfam13637    1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFA 41
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
982-1019 9.47e-04

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212800  Cd Length: 53  Bit Score: 38.18  E-value: 9.47e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1878423636  982 AIYKCVADNPDELTFTEGEVI-IVDGEEDKE-WWVGHIEG 1019
Cdd:cd11866      4 GLWDCSGNEPDELSFKRGDLIyIISKEYDSFgWWVGELNG 43
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
308-397 9.68e-04

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269939  Cd Length: 103  Bit Score: 39.50  E-value: 9.68e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  308 RSGMLSKRSEGlRKVWQKRKCSVKSGYLTIsHGTANTPPAK--LNLLTCQVKCNPEEKK------SFDLISHDRTYHFQA 379
Cdd:cd01233      8 KRGYLLFLEDA-TDGWVRRWVVLRRPYLHI-YSSEKDGDERgvINLSTARVEYSPDQEAllgrpnVFAVYTPTNSYLLQA 85
                           90
                   ....*....|....*...
gi 1878423636  380 EDEAECQIWVSVLQNSKE 397
Cdd:cd01233     86 RSEKEMQDWLYAIDPLLA 103
SH3_Stac3_1 cd11986
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 ...
982-1032 9.75e-04

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212919 [Multi-domain]  Cd Length: 53  Bit Score: 38.35  E-value: 9.75e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIegdSSRKGAFPVSFV 1032
Cdd:cd11986      4 ALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKI---GEKTGYFPMNFI 51
PHA02874 PHA02874
ankyrin repeat protein; Provisional
550-678 9.97e-04

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 42.64  E-value: 9.97e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  550 LYDAVRSRDIFSLLQVYADGVDLTEtfpmanEHEQGETALHLAVRiadRNSLHIVDFLVQNSGNLDKQTVKGNTAVHYCC 629
Cdd:PHA02874   128 LHYAIKKGDLESIKMLFEYGADVNI------EDDNGCYPIHIAIK---HNFFDIIKLLLEKGAYANVKDNNGESPLHNAA 198
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1878423636  630 VTDNSECLKLLLRSKASVSITNEAGETPLDLAKrLKNTQCEELLTQAQS 678
Cdd:PHA02874   199 EYGDYACIKLLIDHGNHIMNKCKNGFTPLHNAI-IHNRSAIELLINNAS 246
SH3_RasGAP cd11788
Src Homology 3 domain of Ras GTPase-Activating Protein 1; RasGAP, also called Ras p21 protein ...
977-1014 1.07e-03

Src Homology 3 domain of Ras GTPase-Activating Protein 1; RasGAP, also called Ras p21 protein activator, RASA1, or p120RasGAP, is part of the GAP1 family of GTPase-activating proteins. It is a 120kD cytosolic protein containing an SH3 domain flanked by two SH2 domains at the N-terminal end, a pleckstrin homology (PH) domain, a calcium dependent phospholipid binding domain (CaLB/C2), and a C-terminal catalytic GAP domain. It stimulates the GTPase activity of normal RAS p21. It acts as a positive effector of Ras in tumor cells. It also functions as a regulator downstream of tyrosine receptors such as those of PDGF, EGF, ephrin, and insulin, among others. The SH3 domain of RasGAP is unable to bind proline-rich sequences but have been shown to interact with protein partners such as the G3BP protein, Aurora kinases, and the Calpain small subunit 1. The RasGAP SH3 domain is necessary for the downstream signaling of Ras and it also influences Rho-mediated cytoskeletal reorganization. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212722  Cd Length: 59  Bit Score: 38.13  E-value: 1.07e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1878423636  977 PKRVKAI--YKCVADNpDELTFTEGEVIIVDGEEDKEW-WV 1014
Cdd:cd11788      1 RRRVRAIlpYNKVPDT-DELSFQKGDIFVVHNELEDGWlWV 40
BAR_ArfGAP_fungi cd07608
The Bin/Amphiphysin/Rvs (BAR) domain of uncharacterized fungal Arf GAP proteins; BAR domains ...
36-243 1.17e-03

The Bin/Amphiphysin/Rvs (BAR) domain of uncharacterized fungal Arf GAP proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. This group is composed of uncharacterized fungal proteins containing an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and an Arf GTPase Activating Protein (GAP) domain. These proteins may play roles in Arf-mediated functions involving membrane dynamics. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153292  Cd Length: 192  Bit Score: 41.19  E-value: 1.17e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636   36 TVSGLEEALDADRSVLSKMKK-SVKAINSSGQThVENeeQYIQALEKFGEAcvnRDNPEVAAAFlkFAVFTKELTALFKN 114
Cdd:cd07608      2 TLSNLERKTRLLRSYLKRLIKrIVKLIEAQDQL-VDL--EFNELLSEAKFK---NDFNVALDSY--FDPFLLNLAFFLRD 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  115 LLQNMNNIITFPLDSLLKGDLKGVKGDLKKSFDKACKDYDTKVNKI----EKEKREHAKQhgmirteisggeiaeemEKE 190
Cdd:cd07608     74 VCQDLQLKKIEPLLKIYSINDIKELSDKKKDFEEESKDYYSWLSKYlsneSDKKRPDSKL-----------------LAK 136
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  191 RRAFQLQMCEYLIKVNEIKI-RKGVDLVQNLIKYFHAQCNFFQDGLKVVENLKP 243
Cdd:cd07608    137 RKTFELSRFDYLNYLQDLHGgRKEQELLSILTKFINQQYDSIALTSNKIDALRP 190
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
979-1035 1.33e-03

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212904 [Multi-domain]  Cd Length: 59  Bit Score: 38.08  E-value: 1.33e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSsrkGAFPVSFVHFI 1035
Cdd:cd11971      1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVT---GLFPGNYVESI 54
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
303-393 1.45e-03

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 38.84  E-value: 1.45e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  303 AHGTeRSGMLSKRSeGLRKVWQKRKCSVKSGYLT-ISHGTANTPPAKLNLLTC---QVKCNPEEKKSFDLISHDRTYHFQ 378
Cdd:cd10573      1 SLGS-KEGYLTKLG-GIVKNWKTRWFVLRRNELKyFKTRGDTKPIRVLDLRECssvQRDYSQGKVNCFCLVFPERTFYMY 78
                           90
                   ....*....|....*
gi 1878423636  379 AEDEAECQIWVSVLQ 393
Cdd:cd10573     79 ANTEEEADEWVKLLK 93
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
306-399 1.53e-03

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241446  Cd Length: 103  Bit Score: 39.21  E-value: 1.53e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  306 TERSGMLSKRSEgLRKVWQKRKCSVKSGYLTI-----SHGTAntPPAKLNLLTCQVKCNPEEKKSFDLISHDRT---YHF 377
Cdd:cd13292      2 PTMKGYLKKWTN-YAKGYKTRWFVLEDGVLSYyrhqdDEGSA--CRGSINMKNARLVSDPSEKLRFEVSSKTSGspkWYL 78
                           90       100
                   ....*....|....*....|..
gi 1878423636  378 QAEDEAECQIWVSVLQNSKEEA 399
Cdd:cd13292     79 KANHPVEAARWIQALQKAIEWA 100
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
979-1032 1.57e-03

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212822  Cd Length: 53  Bit Score: 37.48  E-value: 1.57e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSrKGAFPVSFV 1032
Cdd:cd11889      1 KVKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLRRNGA-EGIFPSNFV 53
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
620-649 1.63e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 36.80  E-value: 1.63e-03
                            10        20        30
                    ....*....|....*....|....*....|
gi 1878423636   620 KGNTAVHYCCVTDNSECLKLLLRSKASVSI 649
Cdd:smart00248    1 DGRTPLHLAAENGNLEVVKLLLDKGADINA 30
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
980-1032 1.74e-03

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212827  Cd Length: 56  Bit Score: 37.61  E-value: 1.74e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIV---DGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11894      2 VKALYDYEGQTDDELSFPEGAIIRIlnkENQDDDGFWEGEFNG---RIGVFPSVLV 54
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
980-1022 1.74e-03

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 37.40  E-value: 1.74e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSS 1022
Cdd:cd11773      2 YKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKVKLKVNSS 44
SH3_Intersectin2_4 cd11994
Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
986-1032 1.87e-03

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212927  Cd Length: 59  Bit Score: 37.60  E-value: 1.87e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1878423636  986 CVADNPDELTFTEGEVIIVDGEEDKEWWVGHIE--GDSSRKGAFPVSFV 1032
Cdd:cd11994      8 YVASGVEQLSLSPGQLILILKKNSSGWWLGELQarGKKRQKGWFPASHV 56
SH3_FCHSD_1 cd11761
First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
977-1034 1.91e-03

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212695 [Multi-domain]  Cd Length: 57  Bit Score: 37.34  E-value: 1.91e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  977 PKRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVgHIEGDSSRKGAFPVSFVHF 1034
Cdd:cd11761      1 PVTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWV-KARNKSGEVGYVPENYLQF 57
SH3_BCAR1 cd12001
Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, ...
981-1028 1.95e-03

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212934  Cd Length: 68  Bit Score: 37.71  E-value: 1.95e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDgEEDKE----WWVGHIEGdssRKGAFP 1028
Cdd:cd12001      6 KALYDNVAESPDELSFRKGDIMTVL-ERDTQgldgWWLCSLHG---RQGIVP 53
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
982-1032 2.11e-03

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212924  Cd Length: 52  Bit Score: 37.27  E-value: 2.11e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDgEEDKEWWVGHIegdSSRKGAFPVSFV 1032
Cdd:cd11991      4 AMYTYESNEQGDLTFQQGDVILVT-KKDGDWWTGTV---GDKTGVFPSNYV 50
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
980-1031 2.29e-03

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 37.26  E-value: 2.29e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSR--KGAFPVSF 1031
Cdd:cd11883      2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKvkRGWFPSNY 55
SH3_ARHGEF9 cd11975
Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also ...
981-1034 2.49e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212908  Cd Length: 62  Bit Score: 37.38  E-value: 2.49e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDssrKGAFPVSFVHF 1034
Cdd:cd11975      8 EAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDE---EGWFPASFVRL 58
SH3_Vinexin_1 cd11921
First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3) ...
978-1035 2.62e-03

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212854  Cd Length: 55  Bit Score: 37.21  E-value: 2.62e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFVHFI 1035
Cdd:cd11921      1 KAARLKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHG---RVGIFPANYVEVL 55
SH3_Nebulin_C cd11933
C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 ...
978-1035 2.74e-03

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212866 [Multi-domain]  Cd Length: 58  Bit Score: 36.91  E-value: 2.74e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1878423636  978 KRVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEgDSSRKGAFPVSFVHFI 1035
Cdd:cd11933      2 KSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQ-RTGKTGMLPANYVEAI 58
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
982-1032 2.91e-03

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212881 [Multi-domain]  Cd Length: 54  Bit Score: 36.72  E-value: 2.91e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1878423636  982 AIYKCVADNPDELTFTEGEVI-IVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11948      4 ALYSFQATESDELPFQKGDILkILNMEDDQNWYKAELQG---REGYIPKNYI 52
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
979-1032 3.16e-03

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212714 [Multi-domain]  Cd Length: 55  Bit Score: 36.90  E-value: 3.16e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGhIEGDSSRKGAFPVSFV 1032
Cdd:cd11780      1 RYRALYSYTPQNEDELELREGDIVYVMEKCDDGWFVG-TSERTGLFGTFPGNYV 53
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
980-1013 3.52e-03

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212885 [Multi-domain]  Cd Length: 56  Bit Score: 36.83  E-value: 3.52e-03
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIV---DGEEDKEWW 1013
Cdd:cd11952      3 VYALWDYSAEFPDELSFKEGDMVTVlrkDGEGTDWWW 39
PHA02874 PHA02874
ankyrin repeat protein; Provisional
572-707 3.63e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 41.10  E-value: 3.63e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  572 LTETFPMANEHEQGETALHLAVrIADRNslhIVDFLVQNSgNLDKQTVKGNTAVHYC----CVTDnseCLKLLLRSKASV 647
Cdd:PHA02874   210 IDHGNHIMNKCKNGFTPLHNAI-IHNRS---AIELLINNA-SINDQDIDGSTPLHHAinppCDID---IIDILLYHKADI 281
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  648 SITNEAGETPLDLAKRL--KNTQCEELLTQA----QSGKFNVHVHVEYEWCLHNEDLD----ESDDEMED 707
Cdd:PHA02874   282 SIKDNKGENPIDTAFKYinKDPVIKDIIANAvlikEADKLKDSDFLEHIEIKDNKEFSdfikECNEEIED 351
SH3_ASEF cd11973
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ...
981-1034 3.74e-03

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212906 [Multi-domain]  Cd Length: 73  Bit Score: 37.30  E-value: 3.74e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIegdSSRKGAFPVSFVHF 1034
Cdd:cd11973     21 EALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRV---LDSEGWFPASFVRL 71
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
621-737 3.90e-03

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 41.04  E-value: 3.90e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1878423636  621 GNTAVHYCCVTDNSECLKLLLRSKASVSITNEAGETPLDLAKRLKNTQCEELLTQaqsgkfnvhvhveYEWCLHNEDLDE 700
Cdd:PTZ00322   115 GRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSR-------------HSQCHFELGANA 181
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1878423636  701 SDDEMEDKPIPQkrEERPVSCYLPGNAGSMQPSMAAL 737
Cdd:PTZ00322   182 KPDSFTGKPPSL--EDSPISSHHPDFSAVPQPMMGSL 216
SH3_Intersectin1_2 cd11989
Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
979-1032 4.24e-03

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212922 [Multi-domain]  Cd Length: 52  Bit Score: 36.23  E-value: 4.24e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKeWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11989      1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG---QKGWFPKSYV 50
Ank pfam00023
Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the ...
584-618 4.35e-03

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO(3) anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. The ANK repeats are found to form a contiguous spiral stack such that ion transporters like the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.


Pssm-ID: 459634 [Multi-domain]  Cd Length: 34  Bit Score: 35.73  E-value: 4.35e-03
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1878423636  584 QGETALHLAVRIadRNSLHIVDFLVQNSGNLDKQT 618
Cdd:pfam00023    1 DGNTPLHLAAGR--RGNLEIVKLLLSKGADVNARD 33
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
980-1034 4.62e-03

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212727 [Multi-domain]  Cd Length: 55  Bit Score: 36.16  E-value: 4.62e-03
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gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGDSSRkGAFPVSFVHF 1034
Cdd:cd11793      2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLRDGER-GWFPSSYTEE 55
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
981-1032 4.73e-03

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 36.16  E-value: 4.73e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1878423636  981 KAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIE--GDSSRKGAFPVSFV 1032
Cdd:cd11839      3 QVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQarGKKRQIGWFPANYV 56
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
979-1032 5.48e-03

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212747  Cd Length: 53  Bit Score: 35.94  E-value: 5.48e-03
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gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd11813      1 RAKALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNG---LRGWFPAKFV 51
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
982-1032 6.90e-03

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 35.96  E-value: 6.90e-03
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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1878423636  982 AIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVGHIEGdssRKGAFPVSFV 1032
Cdd:cd12073      5 ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHG---HRGLFPANYV 52
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
979-1027 7.81e-03

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212723 [Multi-domain]  Cd Length: 55  Bit Score: 35.76  E-value: 7.81e-03
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gi 1878423636  979 RVKAIYKCVADNPDELTFTEGEVIIvDGEEDKEWWVghiEGDSSRKGAF 1027
Cdd:cd11789      1 RYRAMYDYAAADDDEVSFQEGDVII-NVEIIDDGWM---EGTVQRTGQS 45
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
980-1015 8.79e-03

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212902  Cd Length: 55  Bit Score: 35.58  E-value: 8.79e-03
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gi 1878423636  980 VKAIYKCVADNPDELTFTEGEVIIVDGEEDKEWWVG 1015
Cdd:cd11969      2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKG 37
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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