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Conserved domains on  [gi|153791377|ref|NP_077286|]
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pleckstrin homology domain-containing family F member 1 [Homo sapiens]

Protein Classification

PLEKHF1 family PH domain-containing protein; PH domain-containing protein( domain architecture ID 10100639)

PLEKHF1 family PH (pleckstrin homology) domain-containing protein similar to PH region of pleckstrin homology domain-containing family F member 1 (PLEKHF1) that may induce apoptosis through the lysosomal-mitochondrial pathway| PH (pleckstrin homology) domain-containing protein similar to Caenorhabditis elegans protein C15H7.4

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
7-129 1.59e-78

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 233.30  E-value: 1.59e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377   7 NTEINSQRIAAVESCFGASGQPLALPGRVLLGEGVLTKECRKKAKPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVT 86
Cdd:cd01218    1 NSEANRRRIAAVESCFGGSGQPLVKPGRVLVGEGVLTKVCRKKPKPRQFFLFNDILVYGSIVINKKKYNKQRIIPLEDVK 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 153791377  87 LELLPETLQAKNRWMIKTAKKSFVVSAASATERQEWISHIEEC 129
Cdd:cd01218   81 IEDLEDTGELKNGWQIISPKKSFVVYAATATEKSEWMDHINKC 123
FYVE_PKHF1 cd15754
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar ...
148-211 1.05e-41

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar proteins; Phafin-1, also termed lysosome-associated apoptosis-inducing protein containing PH (pleckstrin homology) and FYVE domains (LAPF), or pleckstrin homology domain-containing family F member 1 (PKHF1), or PH domain-containing family F member 1, or apoptosis-inducing protein, or PH and FYVE domain-containing protein 1, or zinc finger FYVE domain-containing protein 15, is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway.


:

Pssm-ID: 277293 [Multi-domain]  Cd Length: 64  Bit Score: 137.78  E-value: 1.05e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377 148 PWIPDKATDICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCYREL 211
Cdd:cd15754    1 PWIPDKATDICMRCTQTNFSLLTRRHHCRKCGFVVCHECSRQRFLIPRLSPKPVRVCSLCYRKL 64
 
Name Accession Description Interval E-value
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
7-129 1.59e-78

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 233.30  E-value: 1.59e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377   7 NTEINSQRIAAVESCFGASGQPLALPGRVLLGEGVLTKECRKKAKPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVT 86
Cdd:cd01218    1 NSEANRRRIAAVESCFGGSGQPLVKPGRVLVGEGVLTKVCRKKPKPRQFFLFNDILVYGSIVINKKKYNKQRIIPLEDVK 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 153791377  87 LELLPETLQAKNRWMIKTAKKSFVVSAASATERQEWISHIEEC 129
Cdd:cd01218   81 IEDLEDTGELKNGWQIISPKKSFVVYAATATEKSEWMDHINKC 123
FYVE_PKHF1 cd15754
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar ...
148-211 1.05e-41

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar proteins; Phafin-1, also termed lysosome-associated apoptosis-inducing protein containing PH (pleckstrin homology) and FYVE domains (LAPF), or pleckstrin homology domain-containing family F member 1 (PKHF1), or PH domain-containing family F member 1, or apoptosis-inducing protein, or PH and FYVE domain-containing protein 1, or zinc finger FYVE domain-containing protein 15, is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway.


Pssm-ID: 277293 [Multi-domain]  Cd Length: 64  Bit Score: 137.78  E-value: 1.05e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377 148 PWIPDKATDICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCYREL 211
Cdd:cd15754    1 PWIPDKATDICMRCTQTNFSLLTRRHHCRKCGFVVCHECSRQRFLIPRLSPKPVRVCSLCYRKL 64
FYVE pfam01363
FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: ...
147-211 3.90e-22

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.


Pssm-ID: 426221 [Multi-domain]  Cd Length: 68  Bit Score: 87.05  E-value: 3.90e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 153791377  147 APWIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLP--RLSPKPVRVCSLCYREL 211
Cdd:pfam01363   1 PVWVPDSSATVCMIC-SKPFTFFRRRHHCRNCGRVFCSACSSKKISLLpeLGSNKPVRVCDACYDTL 66
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
146-208 5.04e-19

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 79.01  E-value: 5.04e-19
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377   146 AAPWIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSP-KPVRVCSLCY 208
Cdd:smart00064   1 RPHWIPDEEVSNCMGC-GKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGIeRPVRVCDDCY 63
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
39-131 7.49e-13

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: 63.34  E-value: 7.49e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377    39 EGVLTK---ECRKKAKPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVTLELLPETLQAKNRWMIK---TAKKSFVVS 112
Cdd:smart00233   4 EGWLYKksgGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEiktSDRKTLLLQ 83
                           90
                   ....*....|....*....
gi 153791377   113 AASATERQEWISHIEECVR 131
Cdd:smart00233  84 AESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
39-131 1.39e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 57.19  E-value: 1.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377   39 EGVLTKECRKKA---KPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVTLELLPETLQAKNRWMIK------TAKKSF 109
Cdd:pfam00169   4 EGWLLKKGGGKKkswKKRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFElrtgerTGKRTY 83
                          90       100
                  ....*....|....*....|..
gi 153791377  110 VVSAASATERQEWISHIEECVR 131
Cdd:pfam00169  84 LLQAESEEERKDWIKAIQSAIR 105
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
152-210 5.98e-03

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 38.14  E-value: 5.98e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377  152 DKATDICMRCTQTrFSAL-----TRRHHCRKCGFVVCAEC--SRQRFLLPRLSpKPVR--------VCSLCYRE 210
Cdd:PTZ00303  457 DESSDSCPSCGRA-FISLsrplgTRAHHCRSCGIRLCVFCitKRAHYSFAKLA-KPGSsdeaeerlVCDTCYKE 528
 
Name Accession Description Interval E-value
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
7-129 1.59e-78

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 233.30  E-value: 1.59e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377   7 NTEINSQRIAAVESCFGASGQPLALPGRVLLGEGVLTKECRKKAKPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVT 86
Cdd:cd01218    1 NSEANRRRIAAVESCFGGSGQPLVKPGRVLVGEGVLTKVCRKKPKPRQFFLFNDILVYGSIVINKKKYNKQRIIPLEDVK 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 153791377  87 LELLPETLQAKNRWMIKTAKKSFVVSAASATERQEWISHIEEC 129
Cdd:cd01218   81 IEDLEDTGELKNGWQIISPKKSFVVYAATATEKSEWMDHINKC 123
FYVE_PKHF1 cd15754
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar ...
148-211 1.05e-41

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar proteins; Phafin-1, also termed lysosome-associated apoptosis-inducing protein containing PH (pleckstrin homology) and FYVE domains (LAPF), or pleckstrin homology domain-containing family F member 1 (PKHF1), or PH domain-containing family F member 1, or apoptosis-inducing protein, or PH and FYVE domain-containing protein 1, or zinc finger FYVE domain-containing protein 15, is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway.


Pssm-ID: 277293 [Multi-domain]  Cd Length: 64  Bit Score: 137.78  E-value: 1.05e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377 148 PWIPDKATDICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCYREL 211
Cdd:cd15754    1 PWIPDKATDICMRCTQTNFSLLTRRHHCRKCGFVVCHECSRQRFLIPRLSPKPVRVCSLCYRKL 64
FYVE_PKHF cd15717
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), ...
148-208 2.27e-34

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), and similar proteins; This family includes protein containing both PH and FYVE domains 1 (phafin-1) and 2 (phafin-2). Phafin-1 is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway. Phafin-2 is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.


Pssm-ID: 277257 [Multi-domain]  Cd Length: 61  Bit Score: 118.62  E-value: 2.27e-34
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 153791377 148 PWIPDKATDICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15717    1 VWVPDSEAPVCMHCKKTKFTAINRRHHCRKCGAVVCGACSSKKFLLPHQSSKPLRVCDTCY 61
FYVE_PKHF2 cd15755
FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar ...
149-211 1.96e-26

FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar proteins; Phafin-2, also termed endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains (EAPF), or pleckstrin homology domain-containing family F member 2 (PKHF2), or PH domain-containing family F member 2, or PH and FYVE domain-containing protein 2, or zinc finger FYVE domain-containing protein 18, is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.


Pssm-ID: 277294 [Multi-domain]  Cd Length: 64  Bit Score: 98.18  E-value: 1.96e-26
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791377 149 WIPDKATDICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCYREL 211
Cdd:cd15755    2 WVPDSEATVCMRCQKAKFTPVNRRHHCRKCGFVVCGPCSEKKFLLPSQSSKPVRVCDFCYDLL 64
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
32-137 7.33e-23

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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: 275424  Cd Length: 124  Bit Score: 90.79  E-value: 7.33e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  32 PGRVLLGEGVLTKECRKKAKPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVTLElLPETLQAKNRWMIKTAKKSFVV 111
Cdd:cd13389   10 PGRKLIKEGELMKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNNELPLSGMKVK-LPEDEEYSNEFQIISTKRSFTL 88
                         90       100
                 ....*....|....*....|....*...
gi 153791377 112 SAASATERQEWISHIEECVR--RQLRAT 137
Cdd:cd13389   89 IASSEEERDEWVKALSRAIEehTKKQRT 116
FYVE pfam01363
FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: ...
147-211 3.90e-22

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.


Pssm-ID: 426221 [Multi-domain]  Cd Length: 68  Bit Score: 87.05  E-value: 3.90e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 153791377  147 APWIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLP--RLSPKPVRVCSLCYREL 211
Cdd:pfam01363   1 PVWVPDSSATVCMIC-SKPFTFFRRRHHCRNCGRVFCSACSSKKISLLpeLGSNKPVRVCDACYDTL 66
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
146-208 5.04e-19

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 79.01  E-value: 5.04e-19
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377   146 AAPWIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSP-KPVRVCSLCY 208
Cdd:smart00064   1 RPHWIPDEEVSNCMGC-GKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGIeRPVRVCDDCY 63
FYVE_endofin cd15729
FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE ...
149-211 1.13e-18

FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE domain-containing protein 16 (ZFY16), or endosome-associated FYVE domain protein, is a FYVE domain-containing protein that is localized to EEA1-containing endosomes. It is regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Endofin is involved in Bone morphogenetic protein (BMP) signaling through interacting with Smad1 preferentially and enhancing Smad1 phosphorylation and nuclear localization upon BMP stimulation. It also functions as a scaffold protein that brings Smad4 to the proximity of the receptor complex in Transforming growth factor (TGF)-beta signaling. Moreover, endofin is a novel tyrosine phosphorylation target downstream of epidermal growth factor receptor (EGFR) in EGF-signaling. In addition, endofin plays a role in endosomal trafficking by recruiting cytosolic TOM1, an important molecule for membrane recruitment of clathrin, onto endosomal membranes.


Pssm-ID: 277268 [Multi-domain]  Cd Length: 68  Bit Score: 77.78  E-value: 1.13e-18
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCYREL 211
Cdd:cd15729    7 WVPDSEAPNCMQC-EVKFTFTKRRHHCRACGKVLCSACCSLKARLEYLDNKEARVCVPCYQTL 68
PH1_FGD6 cd15793
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin ...
32-130 4.34e-18

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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: 275436  Cd Length: 123  Bit Score: 78.15  E-value: 4.34e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  32 PGRVLLGEGVLTKECRKKAKPRIFFLFNDILVYGSIVlNKRKYRSQHIIPLEEVTLElLPETLQAKNRWMIKTAKKSFVV 111
Cdd:cd15793   10 PGRVFLKEGTLMKLSRKVMQPRMFFLFNDALLYTTPV-QSGMYKLNNMLSLAGMKVS-KPSQEAYQNELNIESVERSFIL 87
                         90
                 ....*....|....*....
gi 153791377 112 SAASATERQEWISHIEECV 130
Cdd:cd15793   88 SASSATERDEWLEAISRAI 106
FYVE_LST2 cd15731
FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; ...
149-208 4.66e-18

FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; Lst2, also termed zinc finger FYVE domain-containing protein 28, is a monoubiquitinylated phosphoprotein that functions as a negative regulator of epidermal growth factor receptor (EGFR) signaling. Unlike other FYVE domain-containing proteins, Lst2 displays primarily non-endosomal localization. Its endosomal localization is regulated by monoubiquitinylation. Lst2 physically binds Trim3, also known as BERP or RNF22, which is a coordinator of endosomal trafficking and interacts with Hrs and a complex that biases cargo recycling.


Pssm-ID: 277270 [Multi-domain]  Cd Length: 65  Bit Score: 76.23  E-value: 4.66e-18
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSP-KPVRVCSLCY 208
Cdd:cd15731    5 WVPDEACPQCMAC-SAPFTVLRRRHHCRNCGKIFCSRCSSNSVPLPRYGQmKPVRVCNHCF 64
FYVE_EEA1 cd15730
FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed ...
148-211 1.26e-17

FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed endosome-associated protein p162, or zinc finger FYVE domain-containing protein 2, is an essential component of the endosomal fusion machinery and required for the fusion and maturation of early endosomes in endocytosis. It forms a parallel coiled-coil homodimer in cells. EEA1 serves as the p97 ATPase substrate and the p97 ATPase may regulate the size of early endosomes by governing the oligomeric state of EEA1. It can interact with the GTP-bound form of Rab22a and be involved in endosomal membrane trafficking. EEA1 also functions as an obligate scaffold for angiotensin II-induced Akt activation in early endosomes. It can be phosphorylated by p38 mitogen-activated protein kinase (MAPK) and further regulate mu opioid receptor endocytosis. EEA1 consists of an N-terminal C2H2 Zn2+ finger, four long heptad repeats, and a C-terminal region containing a calmodulin binding (IQ) motif, a Rab5 interaction site, and a FYVE domain. This model corresponds to the FYVE domain that is responsible for binding phosphatidyl inositol-3-phosphate (PtdIns3P or PI3P) on the membrane.


Pssm-ID: 277269 [Multi-domain]  Cd Length: 63  Bit Score: 75.13  E-value: 1.26e-17
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377 148 PWIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRlSPKPVRVCSLCYREL 211
Cdd:cd15730    2 KWADDEEVQNCMAC-GKGFSVTVRKHHCRQCGNIFCNECSSKTATTPS-SKKPVRVCDACFDDL 63
FYVE_ZFY26 cd15724
FYVE domain found in FYVE domain-containing protein 26 (ZFY26 or ZFYVE26); ZFY26, also termed ...
149-208 1.91e-17

FYVE domain found in FYVE domain-containing protein 26 (ZFY26 or ZFYVE26); ZFY26, also termed FYVE domain-containing centrosomal protein (FYVE-CENT), or spastizin, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that localizes to the centrosome and midbody. ZFY26 and its interacting partners TTC19 and KIF13A are required for cytokinesis. It also interacts with Beclin 1, a subunit of class III phosphatidylinositol 3-kinase complex, and may have potential implications for carcinogenesis. In addition, it has been considered as the causal agent of a rare form of hereditary spastic paraplegia. ZFY26 contains a FYVE domain that is important for targeting of FYVE-CENT to the midbody.


Pssm-ID: 277263 [Multi-domain]  Cd Length: 61  Bit Score: 74.47  E-value: 1.91e-17
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377 149 WIPDKATDICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15724    1 WVPDEAVSVCMVCQVERFSMFNRRHHCRRCGRVVCSSCSTKKMLVEGYRENPVRVCDQCY 60
FYVE_ZF21 cd15727
FYVE domain found in zinc finger FYVE domain-containing protein 21 (ZF21) and similar proteins; ...
148-209 4.78e-17

FYVE domain found in zinc finger FYVE domain-containing protein 21 (ZF21) and similar proteins; ZF21 is phosphoinositide-binding protein that functions as a regulator of focal adhesions and cell movement through interaction with focal adhesion kinase. It can also bind to the cytoplasmic tail of membrane type 1 matrix metalloproteinase, a potent invasion-promoting protease, and play a key role in regulating multiple aspects of cancer cell migration and invasion. ZF21 contains a FYVE domain, which corresponds to this model.


Pssm-ID: 277266 [Multi-domain]  Cd Length: 64  Bit Score: 73.57  E-value: 4.78e-17
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791377 148 PWIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLS-PKPVRVCSLCYR 209
Cdd:cd15727    3 PWVPDKECPVCMSC-KKKFDFFKRRHHCRRCGKCFCSDCCSNKVPLPRMCfVDPVRVCNECAL 64
FYVE_RUFY1_like cd15721
FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; ...
149-208 2.89e-15

FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1 and RUFY2. RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. Both RUFY1 and RUFY2 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.


Pssm-ID: 277261 [Multi-domain]  Cd Length: 58  Bit Score: 68.56  E-value: 2.89e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377 149 WIPDKATDICMRCTQtRFSALTRRHHCRKCGFVVCAECSRQRFLLPRlSPKPVRVCSLCY 208
Cdd:cd15721    1 WADDKEVTHCQQCEK-EFSLSRRKHHCRNCGGIFCNSCSDNTMPLPS-SAKPVRVCDTCY 58
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
29-131 3.62e-15

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains 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: 269928  Cd Length: 109  Bit Score: 69.65  E-value: 3.62e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  29 LALPGRVLLGEGVLTKECRKKAKPRIFFLFNDILVYGSIVL---NKRKYRSQhiIPLEEVTLELLPETLQAKNRWMIKTA 105
Cdd:cd01220    1 LVQPGREFIREGCLQKLSKKGLQQRMFFLFSDVLLYTSRSPtpsLQFKVHGQ--LPLRGLMVEESEPEWGVAHCFTIYGG 78
                         90       100
                 ....*....|....*....|....*.
gi 153791377 106 KKSFVVSAASATERQEWISHIEECVR 131
Cdd:cd01220   79 NRALTVAASSEEEKERWLEDLQRAID 104
FYVE_WDFY3 cd15719
FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar ...
149-211 6.96e-15

FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar proteins; WDFY3, also termed autophagy-linked FYVE protein (Alfy), is a ubiquitously expressed phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein required for selective macroautophagic degradation of aggregated proteins. It regulates the protein degradation through the direct interaction with the autophagy protein Atg5. Moreover, WDFY3 acts as a scaffold that bridges its cargo to the macroautophagic machinery via the creation of a greater complex with Atg12, Atg16L, and LC3. It also functionally associates with sequestosome-1/p62 (SQSTM1) in osteoclasts. WDFY3 shuttles between the nucleus and cytoplasm. It predominantly localizes to the nucleus and nuclear membrane under basal conditions, but is recruited to cytoplasmic ubiquitin-positive protein aggregates under stress conditions. WDFY3 contains a PH-BEACH domain assemblage, five WD40 repeats and a PtdIns3P-binding FYVE domain.


Pssm-ID: 277259 [Multi-domain]  Cd Length: 65  Bit Score: 67.80  E-value: 6.96e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRL-SPKPVRVCSLCYREL 211
Cdd:cd15719    3 WVKDEGGDSCTGC-SVRFSLTERRHHCRNCGQLFCSKCSRFESEIRRLrISRPVRVCQACYNIL 65
FYVE_FGD1_2_4 cd15741
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia ...
149-208 1.09e-14

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.


Pssm-ID: 277280 [Multi-domain]  Cd Length: 65  Bit Score: 67.13  E-value: 1.09e-14
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 153791377 149 WIPDKATDICMRCTQTrFSALT-RRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15741    3 WVRDNEVTMCMRCKEP-FNALTrRRHHCRACGYVVCWKCSDYKATLEYDGNKLNRVCKHCY 62
FYVE_FGD6 cd15743
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar ...
149-208 1.22e-14

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar proteins; FGD6, also termed zinc finger FYVE domain-containing protein 24 is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) whose biological function remains unclear. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Moreover, the FYVE domain of FGD6 is a canonical FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site.


Pssm-ID: 277282 [Multi-domain]  Cd Length: 61  Bit Score: 67.08  E-value: 1.22e-14
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377 149 WIPDKATDICMRCTqTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15743    3 WIPDSRVTMCMICT-SEFTVTWRRHHCRACGKVVCGSCSSNKAPLEYLKNKSARVCDECF 61
FYVE_like_SF cd00065
FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger ...
158-208 1.85e-14

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.


Pssm-ID: 277249 [Multi-domain]  Cd Length: 52  Bit Score: 66.40  E-value: 1.85e-14
                         10        20        30        40        50
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gi 153791377 158 CMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRL-SPKPVRVCSLCY 208
Cdd:cd00065    2 CMLC-GKKFSLFRRRHHCRRCGRVFCSKCSSKKLPLPSFgSGKPVRVCDSCY 52
FYVE_Hrs cd15720
FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) ...
156-211 1.51e-13

FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins; Hrs, also termed protein pp110, is a tyrosine phosphorylated protein that plays an important role in the signaling pathway of HGF. It is localized to early endosomes and an essential component of the endosomal sorting and trafficking machinery. Hrs interacts with hypertonia-associated protein Trak1, a novel regulator of endosome-to-lysosome trafficking. It can also forms an Hrs/actinin-4/BERP/myosin V protein complex that is required for efficient transferrin receptor (TfR) recycling but not for epidermal growth factor receptor (EGFR) degradation. Moreover, Hrs, together with STAM proteins, STAM1 and STAM2, and EPs15, forms a multivalent ubiquitin-binding complex that sorts ubiquitinated proteins into the multivesicular body pathway, and plays a regulatory role in endocytosis/exocytosis. Furthermore, Hrs functions as an interactor of the neurofibromatosis 2 tumor suppressor protein schwannomin/merlin. It is also involved in the inhibition of citron kinase-mediated HIV-1 budding. Hrs contains a single ubiquitin-interacting motif (UIM) that is crucial for its function in receptor sorting, and a FYVE domain that harbors double Zn2+ binding sites.


Pssm-ID: 277260 [Multi-domain]  Cd Length: 61  Bit Score: 63.94  E-value: 1.51e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 153791377 156 DICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLS-PKPVRVCSLCYREL 211
Cdd:cd15720    6 DECHRC-RVQFGVFQRKHHCRACGQVFCGKCSSKSSTIPKFGiEKEVRVCDPCYEKL 61
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
39-131 7.49e-13

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: 63.34  E-value: 7.49e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377    39 EGVLTK---ECRKKAKPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVTLELLPETLQAKNRWMIK---TAKKSFVVS 112
Cdd:smart00233   4 EGWLYKksgGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEiktSDRKTLLLQ 83
                           90
                   ....*....|....*....
gi 153791377   113 AASATERQEWISHIEECVR 131
Cdd:smart00233  84 AESEEEREKWVEALRKAIA 102
FYVE_spVPS27p_like cd15735
FYVE domain found in Schizosaccharomyces pombe vacuolar protein sorting-associated protein 27 ...
155-208 3.23e-12

FYVE domain found in Schizosaccharomyces pombe vacuolar protein sorting-associated protein 27 (spVps27p) and similar proteins; spVps27p, also termed suppressor of ste12 deletion protein 4 (Sst4p), is a conserved homolog of budding Saccharomyces cerevisiae Vps27 and of mammalian Hrs. It functions as a downstream factor for phosphatidylinositol 3-kinase (PtdIns 3-kinase) in forespore membrane formation with normal morphology. It colocalizes and interacts with Hse1p, a homolog of Saccharomyces cerevisiae Hse1p and of mammalian STAM, to form a complex whose ubiquitin-interacting motifs (UIMs) are important for sporulation. spVps27p contains a VHS (Vps27p/Hrs/Stam) domain, a FYVE domain, and two UIMs.


Pssm-ID: 277274 [Multi-domain]  Cd Length: 59  Bit Score: 60.24  E-value: 3.23e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 153791377 155 TDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLS-PKPVRVCSLCY 208
Cdd:cd15735    6 SDVCMRC-RTAFTFTNRKHHCRNCGGVFCQQCSSKSLPLPHFGiNQPVRVCDGCY 59
FYVE_scVPS27p_like cd15760
FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 ...
148-208 4.16e-12

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and similar proteins; scVps27p, also termed Golgi retention defective protein 11, is the putative yeast counterpart of the mammalian protein Hrs and is involved in endosome maturation. It is a mono-ubiquitin-binding protein that interacts with ubiquitinated cargoes, such as Hse1p, and is required for protein sorting into the multivesicular body. Vps27p forms a complex with Hse1p. The complex binds ubiquitin and mediates endosomal protein sorting. At the endosome, Vps27p and a trimeric protein complex, ESCRT-1, bind ubiquitin and are important for multivesicular body (MVB) sorting. Vps27p contains an N-terminal VHS (Vps27/Hrs/STAM) domain, a FYVE domain that binds PtdIns3P, followed by two ubiquitin-interacting motifs (UIMs), and a C-terminal clathrin-binding motif.


Pssm-ID: 277299 [Multi-domain]  Cd Length: 59  Bit Score: 60.00  E-value: 4.16e-12
                         10        20        30        40        50        60
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gi 153791377 148 PWIPDKATDICmrctQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPK--PVRVCSLCY 208
Cdd:cd15760    1 HWKPDSRCDVC----RKKFGLFKRRHHCRNCGDSFCSEHSSRRIPLPHLGPLgvPQRVCDRCF 59
FYVE_RUFY1 cd15758
FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; ...
149-211 6.34e-12

FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.


Pssm-ID: 277297 [Multi-domain]  Cd Length: 71  Bit Score: 60.08  E-value: 6.34e-12
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLsPKPVRVCSLCYREL 211
Cdd:cd15758    6 WLKDDEATHCKQC-EKEFSISRRKHHCRNCGHIFCNTCSSNELALPSY-PKPVRVCDSCHTLL 66
FYVE_MTMR4 cd15733
FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also ...
149-208 7.34e-12

FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also termed FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2), or zinc finger FYVE domain-containing protein 11, is an dual specificity protein phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). It is localizes to early endosomes, as well as to Rab11- and Sec15-positive recycling endosomes, and regulates sorting from early endosomes. Moreover, MTMR4 is preferentially associated with and dephosphorylated the activated regulatory Smad proteins (R-Smads) in cytoplasm to keep transforming growth factor (TGF) beta signaling in homeostasis. It also functions as an essential negative modulator for the homeostasis of bone morphogenetic protein (BMP)/decapentaplegic (Dpp) signaling. In addition, MTMR4 acts as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4) and may play a role in the biological process of muscle breakdown. MTMR4 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain.


Pssm-ID: 277272 [Multi-domain]  Cd Length: 60  Bit Score: 59.37  E-value: 7.34e-12
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSP-KPVRVCSLCY 208
Cdd:cd15733    1 WVPDHAASHCFGC-DCEFWLAKRKHHCRNCGNVFCADCSNYKLPIPDEQLyDPVRVCNSCY 60
FYVE_FGD5 cd15742
FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 5 (FGD5) and similar ...
157-211 4.50e-11

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 5 (FGD5) and similar proteins; FGD5, also termed zinc finger FYVE domain-containing protein 23, is an endothelial cell (EC)-specific guanine nucleotide exchange factor (GEF) that regulates endothelial adhesion, survival, and angiogenesis by modulating phosphatidylinositol 3-kinase signaling. It functions as a novel genetic regulator of vascular pruning by activation of endothelial cell-targeted apoptosis. FGD5 is a homologue of FGD1 and contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. The FYVE domain of FGD5 resembles a FYVE-like domain that is different from the canonical FYVE domains, since it lacks one of the three conserved signature motifs (the WxxD motif) that are involved in phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding and exhibits altered lipid binding specificities.


Pssm-ID: 277281 [Multi-domain]  Cd Length: 67  Bit Score: 57.25  E-value: 4.50e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 153791377 157 ICMRCTqTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCYREL 211
Cdd:cd15742   11 MCMNCG-SDFTLTLRRHHCHACGKIVCRNCSRNKYPLKYLKDRPAKVCDGCFAEL 64
FYVE_ANFY1 cd15728
FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar ...
156-208 4.65e-11

FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar proteins; ANFY1, also termed ankyrin repeats hooked to a zinc finger motif (Ankhzn), is a novel cytoplasmic protein that belongs to a new group of double zinc finger proteins involved in vesicle or protein transport. It is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. ANFY1 contains an N-terminal coiled-coil region and a BTB/POZ domain, ankyrin repeats in the middle, and a C-terminal FYVE domain.


Pssm-ID: 277267 [Multi-domain]  Cd Length: 63  Bit Score: 57.05  E-value: 4.65e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 153791377 156 DICMRCTqTRFSALTRRHHCRKCGFVVCAECSRQrfLLPRLS---PKPVRVCSLCY 208
Cdd:cd15728    8 DYCYECG-VKFGITTRKHHCRHCGRLLCSKCSTK--EVPIIKfdlNKPVRVCDVCF 60
FYVE_ZFYV1 cd15734
FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar ...
149-208 1.05e-10

FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar proteins; ZFYV1, also termed double FYVE-containing protein 1 (DFCP1), or SR3, or tandem FYVE fingers-1, is a novel tandem FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. The subcellular distribution of exogenously-expressed ZFYV1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by wortmannin, a PI3-kinase inhibitor. In addition to C-terminal tandem FYVE domain, ZFYV1 contains an N-terminal putative C2H2 type zinc finger and a possible nucleotide binding P-loop.


Pssm-ID: 277273 [Multi-domain]  Cd Length: 61  Bit Score: 56.19  E-value: 1.05e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLS-PKPVRVCSLCY 208
Cdd:cd15734    2 WVPDSEIKECSVC-KRPFSPRLSKHHCRACGQGVCDDCSKNRRPVPSRGwDHPVRVCDPCA 61
PH1_FGD5 cd15792
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin ...
32-143 1.11e-10

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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: 275435  Cd Length: 123  Bit Score: 57.93  E-value: 1.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  32 PGRVLLGEGVLTKECRKKAKPRIFFLFNDILVYgSIVLNKRKYRSQHIIPLEEVTLElLPETLQAKNRWMIKTAKKSFVV 111
Cdd:cd15792   10 PGREFVKEGTLMKVSGKNRHPRHLFLMNDVLLY-TYPQKDGKYRLKNTLAVSGMKVS-RPVIEKAQNVLKIEVSEVCLTL 87
                         90       100       110
                 ....*....|....*....|....*....|..
gi 153791377 112 SAASATERQEWIShieeCVRRQLRATGRPPST 143
Cdd:cd15792   88 SASSCSERDEWYS----CLSRTIPDDYKAQNA 115
PH pfam00169
PH domain; PH stands for pleckstrin homology.
39-131 1.39e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 57.19  E-value: 1.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377   39 EGVLTKECRKKA---KPRIFFLFNDILVYGSIVLNKRKYRSQHIIPLEEVTLELLPETLQAKNRWMIK------TAKKSF 109
Cdd:pfam00169   4 EGWLLKKGGGKKkswKKRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFElrtgerTGKRTY 83
                          90       100
                  ....*....|....*....|..
gi 153791377  110 VVSAASATERQEWISHIEECVR 131
Cdd:pfam00169  84 LLQAESEEERKDWIKAIQSAIR 105
FYVE_WDFY1_like cd15718
FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and ...
155-208 1.67e-10

FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and similar proteins; This family includes WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2. WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. Both WDFY1 and WDFY2 contain a FYVE domain and multiple WD-40 repeats.


Pssm-ID: 277258 [Multi-domain]  Cd Length: 70  Bit Score: 55.79  E-value: 1.67e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 153791377 155 TDICMRCTQTRF----------SALTRRHHCRKCGFVVCAECSRQRFLLPRLS-PKPVRVCSLCY 208
Cdd:cd15718    6 SDNCQKCSRPFFwnfkqmwekkTLGVRQHHCRKCGKAVCDKCSSNRSTIPVMGfEFPVRVCNECY 70
FYVE_RUFY3 cd15744
FYVE-related domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar ...
157-208 2.52e-10

FYVE-related domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar proteins; RUFY3, also termed Rap2-interacting protein x (RIPx or RPIPx), or single axon-regulated protein (singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5. Moreover, the FYVE domain of RUFY3 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue).


Pssm-ID: 277283 [Multi-domain]  Cd Length: 52  Bit Score: 54.73  E-value: 2.52e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 153791377 157 ICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15744    1 SCSLCQEDFASLALPKHNCYNCGGTFCDACSSNELPLPSSIYEPARVCDVCY 52
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
39-126 4.54e-10

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: 55.24  E-value: 4.54e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  39 EGVLTKEC---RKKAKPRIFFLFNDILVYGSIVlNKRKYRSQHIIPLEEVTLELLPETLQAKNRWMIKTAK-KSFVVSAA 114
Cdd:cd00821    2 EGYLLKRGgggLKSWKKRWFVLFEGVLLYYKSK-KDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDgRTYYLQAD 80
                         90
                 ....*....|..
gi 153791377 115 SATERQEWISHI 126
Cdd:cd00821   81 SEEERQEWLKAL 92
FYVE_PIKfyve_Fab1 cd15725
FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, ...
149-209 7.84e-10

FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, also termed FYVE finger-containing phosphoinositide kinase, or 1-phosphatidylinositol 3-phosphate 5-kinase, or phosphatidylinositol 3-phosphate 5-kinase (PIP5K3), or phosphatidylinositol 3-phosphate 5-kinase type III (PIPkin-III or type III PIP kinase), is a phosphoinositide 5-kinase that forms a complex with its regulators, the scaffolding protein Vac14 and the lipid phosphatase Fig4. The complex is responsible for synthesizing phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] from phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). Then phosphatidylinositol-5-phosphate (PtdIns5P) is generated directly from PtdIns(3,5)P2. PtdIns(3,5)P2 and PtdIns5P regulate endosomal trafficking and responses to extracellular stimuli. At this point, PIKfyve is vital in early embryonic development. Moreover, PIKfyve forms a complex with ArPIKfyve (associated regulator of PIKfyve) and SAC3 at the endomembranes, which plays a role in receptor tyrosine kinase (RTK) degradation. The phosphorylation of PIKfyve by AKT can facilitate Epidermal growth factor receptor (EGFR) degradation. In addition, PIKfyve may participate in the regulation of the glutamate transporters EAAT2, EAAT3 and EAAT4, and the cystic fibrosis transmembrane conductance regulator (CFTR). It is also essential for systemic glucose homeostasis and insulin-regulated glucose uptake/GLUT4 translocation in skeletal muscle. It can be activated by protein kinase B (PKB/Akt) and further up-regulates human ether-a-go-go (hERG) channels. This family also includes the yeast and plant orthologs of human PIKfyve, Fab1. PIKfyve and its orthologs share a similar architecture. They contain an N-terminal FYVE domain, a middle region related to the CCT/TCP-1/Cpn60 chaperonins that are involved in productive folding of actin and tubulin, a second middle domain that contains a number of conserved cysteine residues (CCR) unique to this family, and a C-terminal lipid kinase domain related to PtdInsP kinases.


Pssm-ID: 277264 [Multi-domain]  Cd Length: 62  Bit Score: 53.87  E-value: 7.84e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 153791377 149 WIPDKATDICMRCTQtRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLS-PKPVRVCSLCYR 209
Cdd:cd15725    2 WMPDSSCKECYECSE-KFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFIGyPGDLRVCTYCCK 62
FYVE_MTMR3 cd15732
FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also ...
149-208 2.40e-09

FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also termed Myotubularin-related phosphatase 3, or FYVE domain-containing dual specificity protein phosphatase 1 (FYVE-DSP1), or zinc finger FYVE domain-containing protein 10, is a ubiquitously expressed phosphoinositide 3-phosphatase specific for phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and PIKfyve, which produces PtdIns(3,5)P2 from PtdIns3P. It regulates cell migration through modulating phosphatidylinositol 5-phosphate (PtdIns5P) levels. MTMR3 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain. Unlike conventional FYVE domains, the FYVE domain of MTMR3 neither confers endosomal localization nor binds to PtdIns3P. It is also not required for the enzyme activity of MTMR3. In contrast, the PH-G domain binds phosphoinositides.


Pssm-ID: 277271 [Multi-domain]  Cd Length: 61  Bit Score: 52.59  E-value: 2.40e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSP-KPVRVCSLCY 208
Cdd:cd15732    2 WVPDHLAASCYGC-EREFWLASRKHHCRNCGNVFCGSCCNQKLPVPSQQLfEPSRVCKSCF 61
FYVE2_Vac1p_like cd15737
FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed ...
148-207 2.60e-09

FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The family corresponds to the second FYVE domain that is responsible for the ability of Pep7p to efficiently interact with Vac1p and Vps45p.


Pssm-ID: 277276 [Multi-domain]  Cd Length: 83  Bit Score: 52.89  E-value: 2.60e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377 148 PWIPDKATDICMRCTQTrFSALTRRHHCRKCGFVVCA----ECSR------QRFLLPRLS-------------PKPVRVC 204
Cdd:cd15737    1 PWEDDSSVTHCPICLRS-FGLLLRKHHCRLCGKVVCDdrrtKCSTevpldlLSSALPDLPfvfkepqsdipddTKSVRVC 79

                 ...
gi 153791377 205 SLC 207
Cdd:cd15737   80 RDC 82
FYVE_RBNS5 cd15716
FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and ...
148-208 3.74e-09

FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and similar proteins; Rbsn-5, also termed zinc finger FYVE domain-containing protein 20, is a novel Rab5 effector that is complexed to the Sec1-like protein VPS45 and recruited in a phosphatidylinositol-3-kinase-dependent fashion to early endosomes. It also binds to Rab4 and EHD1/RME-1, two regulators of the recycling route, and is involved in cargo recycling to the plasma membrane. Moreover, Rbsn-5 regulates endocytosis at the apical side of the wing epithelium and plays a role of the apical endocytic trafficking of Fmi in the establishment of planar cell polarity (PCP).


Pssm-ID: 277256 [Multi-domain]  Cd Length: 61  Bit Score: 51.96  E-value: 3.74e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 153791377 148 PWIPDKATDICMRCTQtRFSALTRRHHCRKCGFVVCAECSrqRFLLPRLspkpvRVCSLCY 208
Cdd:cd15716    3 PWVNDSDVPFCPDCGK-KFNLARRRHHCRLCGSIMCNKCS--QFLPLHI-----RCCHHCK 55
FYVE_RUFY2 cd15759
FYVE domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; ...
149-211 4.72e-09

FYVE domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions.


Pssm-ID: 277298 [Multi-domain]  Cd Length: 71  Bit Score: 51.95  E-value: 4.72e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRlSPKPVRVCSLCYREL 211
Cdd:cd15759    4 WLKDKEATHCKLC-EKEFSLSKRKHHCRNCGEIFCNACSDNELPLPS-SPKPVRVCDSCHAML 64
PH_RalBD_exo84 cd01226
Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 ...
31-135 8.47e-09

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. 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: 269933  Cd Length: 115  Bit Score: 52.27  E-value: 8.47e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  31 LPGRVLLGEGVLTKECRKKAKP--RI-FFLFNDILVYGSIVLNKR---KYRSQHIIPLEEVTLELLPETLQAKNRWMIKT 104
Cdd:cd01226    3 VPGRYLLHEGDLLELDPDDYKPiqKVhLFLLNDVLLIASWLPNRRgpvRYKFQALYPLEDLAVVNVKDLGPVKNAFKLLT 82
                         90       100       110
                 ....*....|....*....|....*....|.
gi 153791377 105 AKKSFVVSAASATERQEWISHIEECVRRQLR 135
Cdd:cd01226   83 FPETRVFQCENAKIKKEWLEKFEQAKRAKLA 113
FYVE_MTMR_unchar cd15738
FYVE-related domain found in uncharacterized myotubularin-related proteins mainly from ...
164-208 5.03e-08

FYVE-related domain found in uncharacterized myotubularin-related proteins mainly from eumetazoa; This family includes a group of uncharacterized myotubularin-related proteins mainly found in eumetazoa. Although their biological functions remain unclear, they share similar domain architecture that consists of an N-terminal pleckstrin homology (PH) domain, a highly conserved region related to myotubularin proteins, a C-terminal FYVE domain. The model corresponds to the FYVE domain, which resembles the FYVE-related domain as it has an altered sequence in the basic ligand binding patch.


Pssm-ID: 277277 [Multi-domain]  Cd Length: 61  Bit Score: 48.86  E-value: 5.03e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 153791377 164 TRFSALTRRHHCRKCGFVVCAECSRQRFLLP-RLSPKPVRVCSLCY 208
Cdd:cd15738   16 TPFDHFSKKHHCWRCGNVFCTRCIDKQRALPgHLSQRPVPVCRACY 61
PH_alsin cd13269
Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual ...
55-135 5.85e-08

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. 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: 241423  Cd Length: 106  Bit Score: 49.70  E-value: 5.85e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  55 FFLFNDILVYGSIVlnkrkyrSQHIIPLEEVTLELLPETLQAKNRWMIKTAKKSFVVSAASATERQEWISHIEECVRRQL 134
Cdd:cd13269   32 FILFNDALVHAQFS-------THHIFPLATLWVEPIPDEDSGQNALKITTPEESFTLVASTPQEKAEWLRAINQAIDQAL 104

                 .
gi 153791377 135 R 135
Cdd:cd13269  105 N 105
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
36-136 6.37e-08

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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: 269931  Cd Length: 138  Bit Score: 50.72  E-value: 6.37e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  36 LLGEGVLTKECRKKAKPRIFFLFNDILVYG---SIVLNKRKYRSQhiIPLEEVTLELLPE--------TLqaKNRWMIKT 104
Cdd:cd01224   29 LIHSGELTKISAGRAQERTFFLFDHQLVYCkkdLLRRKNYIYKGR--IDTDNMEIEDLPDgkddesgvTV--KNAWKIYN 104
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 153791377 105 AKKS--FVVSAASATERQEWISHI-EEcvrRQLRA 136
Cdd:cd01224  105 ASKNkwYVLCAKSAEEKQRWLEAFaEE---REKVE 136
FYVE_WDFY1 cd15756
FYVE domain found in WD40 repeat and FYVE domain-containing protein 1 (WDFY1) and similar ...
155-211 8.26e-08

FYVE domain found in WD40 repeat and FYVE domain-containing protein 1 (WDFY1) and similar proteins; WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. In addition to FYVE domain, WDFY1 harbors multiple WD-40 repeats.


Pssm-ID: 277295 [Multi-domain]  Cd Length: 76  Bit Score: 48.53  E-value: 8.26e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 153791377 155 TDICMRCTQTRFSALT----------RRHHCRKCGFVVCAECSRQRFLLPRLSPK-PVRVCSLCYREL 211
Cdd:cd15756    6 SDSCQKCEQPFFWNIKqmwdtktlglRQHHCRKCGQAVCGKCSSKRSSYPIMGFEfQVRVCDSCFETI 73
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
39-126 1.20e-07

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). 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: 275410  Cd Length: 92  Bit Score: 48.64  E-value: 1.20e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  39 EGVLTKECRKK--AKPRIFFLFNDILVYG--SIVLNKRKYRSQHIIPL-----EEVTLELLPETLQaknrwmIKTAKKSF 109
Cdd:cd13328    2 EGQILKLSAKNgtPQPRYLFLFNDMLLYCvpKLSLVGQKFSVRNRLDVagmkvREPVNENYPHTFK------ISGKERSL 75
                         90
                 ....*....|....*..
gi 153791377 110 VVSAASATERQEWISHI 126
Cdd:cd13328   76 ELQASSAEEKDEWIQAI 92
FYVE_FYCO1 cd15726
FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar ...
149-208 5.40e-07

FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar proteins; FYCO1, also termed zinc finger FYVE domain-containing protein 7, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport. It acts as an effector of GTP-bound Rab7, a GTPase that recruits FYCO1 to autophagosomes and has been implicated in autophagosome-lysosomal fusion. FYCO1 also interacts with two microtubule motor proteins, kinesin (KIF) 5B and KIF23, and thus functions as a platform for assembly of vesicle fusion and trafficking factors. FYCO1 contains an N-terminal alpha-helical RUN domain followed by a long central coiled-coil region, a FYVE domain and a GOLD (Golgi dynamics) domain in C-terminus.


Pssm-ID: 277265 [Multi-domain]  Cd Length: 58  Bit Score: 45.63  E-value: 5.40e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377 149 WIPDKATDICMRCtQTRFSALTRRHHCRKCGFVVCAECSrQRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15726    1 WQDDTDVTHCLDC-KSEFSWMVRRHHCRLCGRIFCYACS-NFYVLTAHGGKKERCCKACF 58
FYVE_FGD3 cd15740
FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) and similar ...
152-208 1.51e-06

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) and similar proteins; FGD3, also termed zinc finger FYVE domain-containing protein 5, is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) that undergoes the ubiquitin ligase SCFFWD1/beta-TrCP-mediated proteasomal degradation. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Due to this difference, FGD3 may play different roles from that of FGD1 to regulate cell morphology or motility. The FYVE domain of FGD3 resembles a FYVE-like domain that is different from the canonical FYVE domains, since it lacks one of the three conserved signature motifs (the WxxD motif) that are involved in phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding and exhibits altered lipid binding specificities.


Pssm-ID: 277279 [Multi-domain]  Cd Length: 54  Bit Score: 44.61  E-value: 1.51e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 153791377 152 DKATDICMRCTQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSpkpvRVCSLCY 208
Cdd:cd15740    2 EKEKQTCKGCNESFNSITKRRHHCKQCGAVICGKCSEFKDLASRHN----RVCRDCF 54
FYVE_RUFY4 cd15745
FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar ...
157-208 5.66e-06

FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; RUFY4 belongs to the FUFY protein family which is characterized by the presence of an N-terminal RUN domain and a C-terminal FYVE domain. The FYVE domain of RUFY4 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue). The biological function of RUFY4 still remains unclear.


Pssm-ID: 277284 [Multi-domain]  Cd Length: 52  Bit Score: 42.87  E-value: 5.66e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 153791377 157 ICMRCtQTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRL-SPKPVRVCSLCY 208
Cdd:cd15745    1 ACAIC-AKAFSLFRRKYVCRLCGGVVCHSCSSEDLVLSVPdTCIYLRVCKTCY 52
FYVE_WDFY2 cd15757
FYVE domain found in WD40 repeat and FYVE domain-containing protein 2 (WDFY2); WDFY2, also ...
155-208 1.15e-05

FYVE domain found in WD40 repeat and FYVE domain-containing protein 2 (WDFY2); WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. WDFY2 contains WD40 motifs and a FYVE domain.


Pssm-ID: 277296 [Multi-domain]  Cd Length: 70  Bit Score: 42.36  E-value: 1.15e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 153791377 155 TDICMRCTQTRFSALT----------RRHHCRKCGFVVCAECSRQRFLLPRLSPK-PVRVCSLCY 208
Cdd:cd15757    6 SDSCQKCDQPFFWNFKqmwdskkiglRQHHCRKCGKAVCGKCSSKRSTIPLMGFEfEVRVCDSCH 70
PH_RARhoGAP cd13319
RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called ...
34-124 2.08e-05

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. 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: 270129  Cd Length: 97  Bit Score: 42.23  E-value: 2.08e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  34 RVLLGEGVLTKECRKKAKPRIFFLFNDILVYGSIvLNKRKYRSQHIIPLEEVTLELLPETLQAKNrwmiKTAKKSF---- 109
Cdd:cd13319    1 RTFLLEGPVQLTRGLQTQERHLFLFSDVLVVAKP-KSKNSFKLKHKIRLSELWLASCVDEVCEGS----KSADKSFvlgw 75
                         90       100
                 ....*....|....*....|
gi 153791377 110 -----VVSAASATERQEWIS 124
Cdd:cd13319   76 pttnfVATFSSQEEKDLWLS 95
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
70-133 3.20e-05

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: 41.99  E-value: 3.20e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377  70 NKRKYRSQHIIPLEEVTLEllpeTLQAKNRWMIKTAKKSFVVSAASATERQEWISHIEECVRRQ 133
Cdd:cd13253   35 SEKDAYSKRIIPLSAISTV----RAVGDNKFELVTTNRTFVFRAESDDERNLWCSTLQAAISEY 94
FYVE_scVPS27p_Vac1p_like cd15736
FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 ...
157-208 4.01e-05

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and FYVE-related domain 1 found in yeast protein VAC1 (Vac1p) and similar proteins; The family includes Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and protein VAC1 (Vac1p). scVps27p, also termed Golgi retention defective protein 11, is the putative yeast counterpart of the mammalian protein Hrs and is involved in endosome maturation. It is a mono-ubiquitin-binding protein that interacts with ubiquitinated cargoes, such as Hse1p, and is required for protein sorting into the multivesicular body. Vps27p forms a complex with Hse1p. The complex binds ubiquitin and mediates endosomal protein sorting. At the endosome, Vps27p and a trimeric protein complex, ESCRT-1, bind ubiquitin and are important for multivesicular body (MVB) sorting. Vps27p contains an N-terminal VHS (Vps27/Hrs/STAM) domain, a FYVE domain that binds PtdIns3P, followed by two ubiquitin-interacting motifs (UIMs), and a C-terminal clathrin-binding motif. Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The FYVE domain in both Vps27p and Vac1p harbors a zinc-binding site composed of seven Cysteines and one Histidine, which is different from that of other FYVE domain containing proteins.


Pssm-ID: 277275 [Multi-domain]  Cd Length: 56  Bit Score: 40.63  E-value: 4.01e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 153791377 157 ICMRCTQtRFSALTRRHHCRKCGFVVCAECSRQRFLLPR-----LSPKPVRVCSLCY 208
Cdd:cd15736    1 CCHTCSR-TFNLNIRAHHCRKCGKLFCRRHLPNMIPLNLsaydpRNGKWYRCCHSCF 56
FYVE_RABE_unchar cd15739
FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This ...
149-208 4.94e-05

FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This family includes a group of uncharacterized rab GTPase-binding effector proteins found in bilateria. Although their biological functions remain unclear, they all contain a FYVE domain that harbors a putative phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding site.


Pssm-ID: 277278 [Multi-domain]  Cd Length: 73  Bit Score: 40.79  E-value: 4.94e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377 149 WIPDKATDICMRCTQTrFSALTRRHHCRKCGFVVCAECSRqRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15739    4 WQHEDDVDQCPNCKTP-FSVGKRKHHCRHCGKIFCSDCLT-KTVPSGPNRRPARVCDVCH 61
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
47-135 1.22e-04

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 41.09  E-value: 1.22e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  47 RKKAKPRIFFLFNDILVYGSIVLNKR-------KYRSQhiIPLEEVTLEllPETLQAKNRWMIKT-----AKKSFVVSAA 114
Cdd:cd13241   33 LQKGKERRVFLFEQIIIFSEILGKKTqfsnpgyIYKNH--IKVNKMSLE--ENVDGDPLRFALKSrdpnnPSETFILQAA 108
                         90       100
                 ....*....|....*....|.
gi 153791377 115 SATERQEWISHIEECVRRQLR 135
Cdd:cd13241  109 SPEVRQEWVDTINQILDTQRD 129
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
39-133 2.41e-04

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 39.99  E-value: 2.41e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  39 EGVLTKE-CRKKA-KPRIFFLFNDILVYgsivlnkRKYRSQH----IIPLEEVTLELLP--------ETLQAKNRWMIKT 104
Cdd:cd01252    6 EGWLLKLgGRVKSwKRRWFILTDNCLYY-------FEYTTDKeprgIIPLENLSVREVEdkkkpfcfELYSPSNGQVIKA 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 153791377 105 AKK------------SFVVSAASATERQEWISHIEECVRRQ 133
Cdd:cd01252   79 CKTdsdgkvvegnhtVYRISAASEEERDEWIKSIKASISRD 119
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
48-133 4.93e-04

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: 38.43  E-value: 4.93e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  48 KKAKPRIFFLFNDILVYgsivlnkrkYRSQHII---PLEEVTLELLPETLQA--KNRWMIKTAKKSFVVSAASATERQEW 122
Cdd:cd13282   13 KTWKRRWFVLKNGELFY---------YKSPNDVirkPQGQIALDGSCEIARAegAQTFEIVTEKRTYYLTADSENDLDEW 83
                         90
                 ....*....|.
gi 153791377 123 ISHIEECVRRQ 133
Cdd:cd13282   84 IRVIQNVLRRQ 94
FYVE_ZFY19 cd15749
FYVE-related domain found in FYVE domain-containing protein 19 (ZFY19) and similar proteins; ...
158-208 6.70e-04

FYVE-related domain found in FYVE domain-containing protein 19 (ZFY19) and similar proteins; ZFY19, also termed mixed lineage leukemia (MLL) partner containing FYVE domain, is encoded by a novel gene, MLL partner containing FYVE domain (MPFYVE). The FYVE domain of ZFY19 resembles FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. The biological function of ZFY19 remains unclear.


Pssm-ID: 277288 [Multi-domain]  Cd Length: 51  Bit Score: 37.10  E-value: 6.70e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 153791377 158 CMRCTqTRFSALTRRHHCRKCGFVVCAECSRQRFLLPRLSPKPVRVCSLCY 208
Cdd:cd15749    2 CFGCA-AKFSLFKKECGCKNCGRSFCKGCLTFSAVVPRKGNQKQKVCKQCH 51
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
39-128 8.71e-04

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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: 270096  Cd Length: 111  Bit Score: 38.03  E-value: 8.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791377  39 EGVLTKEcRKKA-------KPRIFFLFNDILVYgsivLNKRKyrSQHI--IPLEEVTLELLPEtLQ-----AKNRWMIKT 104
Cdd:cd13277    6 EGYLLKR-RKKTlgstggwKLRYGVLDGNILEL----YESRG--GQLLesIKLRNAQIERQPN-LPddkygTRHGFLINE 77
                         90       100       110
                 ....*....|....*....|....*....|.
gi 153791377 105 AKKS-------FVVSAASATERQEWISHIEE 128
Cdd:cd13277   78 HKKSglssttkYYLCAETDKERDEWVSALSE 108
FYVE_SlaC2-c cd15753
FYVE-related domain found in Slp homolog lacking C2 domains c (SlaC2-c) and similar proteins; ...
158-187 1.03e-03

FYVE-related domain found in Slp homolog lacking C2 domains c (SlaC2-c) and similar proteins; SlaC2-c, also termed Rab effector MyRIP, or exophilin-8, or myosin-VIIa- and Rab-interacting protein, or synaptotagmin-like protein lacking C2 domains c, is a GTP-bound form of Rab27A-, myosin Va/VIIa-, and actin-binding protein mainly present on retinal melanosomes and secretory granules. It may play a role in insulin granule exocytosis. It is also involved in the control of isoproterenol (IPR)-induced amylase release from parotid acinar cells. SlaC2-c belongs to the Slp homolog lacking C2 domains (Slac2) family. It contains an N-terminal Slp homology domain (SHD), but lacks tandem C2 domains. The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of SlaC2-c are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. Moreover, Slac2-c has a middle myosin-binding domain and a C-terminal actin-binding domain.


Pssm-ID: 277292  Cd Length: 49  Bit Score: 36.23  E-value: 1.03e-03
                         10        20        30
                 ....*....|....*....|....*....|
gi 153791377 158 CMRCTQTRFSALTRRHHCRKCGFVVCAECS 187
Cdd:cd15753    2 CMRCCSPFTFLFNRKRQCRDCKFNVCKSCA 31
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
65-133 2.88e-03

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal 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: 270092  Cd Length: 110  Bit Score: 36.50  E-value: 2.88e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 153791377  65 GSIVLNKRkyrsqhiipleeVTLELLPETLQAKNRWMIKTAKKSFVVSAASATERQEWISHIEECVRRQ 133
Cdd:cd13273   49 GEIALDSN------------CCVESLPDREGKKCRFLVKTPDKTYELSASDHKTRQEWIAAIQTAIRLS 105
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
152-210 5.98e-03

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 38.14  E-value: 5.98e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 153791377  152 DKATDICMRCTQTrFSAL-----TRRHHCRKCGFVVCAEC--SRQRFLLPRLSpKPVR--------VCSLCYRE 210
Cdd:PTZ00303  457 DESSDSCPSCGRA-FISLsrplgTRAHHCRSCGIRLCVFCitKRAHYSFAKLA-KPGSsdeaeerlVCDTCYKE 528
 
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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