Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Insulin Receptor tyrosine kinase Substrate p53; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. IRSp53 (Insulin Receptor tyrosine kinase Substrate p53) is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. Its IMD domain binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799   5 RSEEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTYAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 84
Cdd:cd07646     1 RTEEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799  85 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKELQY 164
Cdd:cd07646    81 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQY 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1867163799 165 IDAISNKQGELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQACADPSKI 236
Cdd:cd07646   161 IEAISNKQGELENYVSDGYKTALTEERRRYCFLVEKQCAVAKNSIAYHSKGKELLTQKLPSWQQACSDPNKI 232

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Insulin Receptor tyrosine kinase Substrate p53; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. IRSp53 (Insulin Receptor tyrosine kinase Substrate p53) is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. Its IMD domain binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799   5 RSEEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTYAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 84
Cdd:cd07646     1 RTEEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799  85 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKELQY 164
Cdd:cd07646    81 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQY 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1867163799 165 IDAISNKQGELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQACADPSKI 236
Cdd:cd07646   161 IEAISNKQGELENYVSDGYKTALTEERRRYCFLVEKQCAVAKNSIAYHSKGKELLTQKLPSWQQACSDPNKI 232

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1867163799 377 MRVKAIFSHAAGDNSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMRGWFPFSYTRVL 435
Cdd:cd11915     1 TRVQAIFSHAAGDNSTLLSFKEGDYITLLVPEARDGWHYGECEKTKMRGWFPFSYTRVL 59

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1867163799 378 RVKAIFSHAaGDNSTLLSFKEGDLITLLvPEARDGWHYGESekTKMRGWFPFSYTRVL 435
Cdd:pfam07653   1 YGRVIFDYV-GTDKNGLTLKKGDVVKVL-GKDNDGWWEGET--GGRVGLVPSTAVEEI 54

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Insulin Receptor tyrosine kinase Substrate p53; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. IRSp53 (Insulin Receptor tyrosine kinase Substrate p53) is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. Its IMD domain binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799   5 RSEEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTYAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 84
Cdd:cd07646     1 RTEEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799  85 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKELQY 164
Cdd:cd07646    81 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQY 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1867163799 165 IDAISNKQGELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQACADPSKI 236
Cdd:cd07646   161 IEAISNKQGELENYVSDGYKTALTEERRRYCFLVEKQCAVAKNSIAYHSKGKELLTQKLPSWQQACSDPNKI 232

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), a dimerization module that binds and bends membranes; Inverse (I)-BAR (or IMD) is a member of the Bin/Amphiphysin/Rvs (BAR) domain family. It is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. IMD domains are found in Insulin Receptor tyrosine kinase Substrate p53 (IRSp53), Missing in Metastasis (MIM), and Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-like (BAIAP2L) proteins. These are multi-domain proteins that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. Most members contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus, exccept for MIM which does not carry an SH3 domain. Some members contain additional domains and motifs. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799   7 EEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTYAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHRQI 86
Cdd:cd07605     1 EELNRLTENIYKNIKEQFNPVLRNLIKAGKKYQKALQALSQAAKVFFDALAKIGELASQSRGSQELGEALKQIVDTHKSI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799  87 QNQLEEMLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSkNPQKYSDKELQYID 166
Cdd:cd07605    81 EASLEQVAKAFHGELILPLEKKLELDQKVINKFEKDYKKEYKQKREDLDKARSELKKLQKKSQKS-GTGKYQEKLDQALE 159

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1867163799 167 AISNKQGELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQAC 230
Cdd:cd07605   160 ELNDKQKELEAFVSQGLRDALLEERRRYCFLVDKHCSVAKHEIAYHAKAMTLLSTRLPLWQELC 223

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. This group is composed of uncharacterized proteins known as BAIAP2L2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2). They contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799   9 MHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTYAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHRQIQN 88
Cdd:cd07644     3 LYRSTISIYKSIMEQFNPALENLVYLGNNYLRAFHALSEAAEVYFSAIAKIGEQALQSLTSQSLGEILIQMSETQRKLSA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799  89 QLEEMLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKL-RKKSQGSKNPQKYsdkeLQYIDA 167
Cdd:cd07644    83 DLEVVFQTFHVDLLQHMDKNTKLDMQFIEDSRRVYELEYRHRAANLEKCMSELWRMeRQRDRNVREMKEN----VNRLRQ 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1867163799 168 isnkqgELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQ 228
Cdd:cd07644   159 ------SMQAFLKESQRAAELEEKRRYRFLAEKHYLLNNTFLQFQSRARGMLQTRVPSWKE 213

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1867163799 377 MRVKAIFSHAAGDnSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMRGWFPFSYTR 433
Cdd:cd11779     1 PRVKALYPHAAGG-ETQLSFEEGDVITLLGPEPRDGWHYGENERSGRRGWFPIAYTE 56

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1867163799 378 RVKAIFSHAAGDNSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMRGWFPFSYTRVL 435
Cdd:cd11914     2 RVRAIVSHPAGSNPTLLRFNRGDIITVLVPEARNGWLYGKLEGSSRQGWFPEAYVKAL 59

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1867163799 378 RVKAIFSHAAgDNSTLLSFKEGDLITLLvPEARDGWHYGESEKTKmRGWFPFSY 431
Cdd:cd00174     1 YARALYDYEA-QDDDELSFKKGDIITVL-EKDDDGWWEGELNGGR-EGLFPANY 51

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1867163799 378 RVKAIFSHAaGDNSTLLSFKEGDLITLLvPEARDGWHYGESekTKMRGWFPFSYTRVL 435
Cdd:pfam07653   1 YGRVIFDYV-GTDKNGLTLKKGDVVKVL-GKDNDGWWEGET--GGRVGLVPSTAVEEI 54

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1867163799 388 GDNSTLLSFKEGDLITLLvpEARDGWHYGESEKTKmRGWFPFSY 431
Cdd:cd11837    10 AKKENHLSFAKGDIITVL--EQQEMWWFGELEGGE-EGWFPKSY 50

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1867163799 378 RVKAIFSHAAGDNSTLlSFKEGDLItLLVPEARDGWHYGESEKTKMRGWFPFSYTRVL 435
Cdd:cd11934     4 RYRAVYDYNAADEDEV-SFQDGDTI-VNVQQIDDGWMYGTVERTGDTGMLPANYVEAI 59

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1867163799 378 RVKAIFSHAAGDnSTLLSFKEGDLItLLVP-----EARDGWHYGESEKTKMRGWFPFSYTRVL 435
Cdd:cd11790     4 KVRATHDYTAED-TDELTFEKGDVI-LVIPfddpeEQDEGWLMGVKESTGCRGVFPENFTERI 64

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799   5 RSEEMHRLTENVYKTIME--QFNPSLRNFIAMGKNYEKALAGVtyaakgyfdalvkMGELASESQGSKELGDVLFQMAEV 82
Cdd:pfam03114  34 RFDTTEKEIKKLQKDTKGylQPNPGARAKQTVLEQPEELLAES-------------MIEAGKDLGEDSSFGKALEDYGEA 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867163799  83 HRQIQNQLEEMLKSFHNELLTQLEQKVElDSRYLSAALKKYQteqrSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKEL 162
Cdd:pfam03114 101 LKRLAQLLEQLDDRVETNFLDPLRNLLK-EFKEIQKHRKKLE----RKRLDYDAAKTRVKKAKKKKSSKAKDESQAEEEL 175

                  ..
gi 1867163799 163 QY 164
Cdd:pfam03114 176 RK 177

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1867163799 378 RVKAIFSHAAGDNSTLlSFKEGDLITlLVPEARDGWHYGESEKTKMRGWFPFSY 431
Cdd:cd11789     1 RYRAMYDYAAADDDEV-SFQEGDVII-NVEIIDDGWMEGTVQRTGQSGMLPANY 52

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1867163799 379 VKAIFSHAAGDNStLLSFKEGDLITLLVPEAR---DGWHYGESEKTKmRGWFPFSY 431
Cdd:cd11883     2 VVALYDFTPKSKN-QLSFKAGDIIYVLNKDPSgwwDGVIISSSGKVK-RGWFPSNY 55

Src Homology 3 domain of Myosin VIIa and similar proteins; Myo7A is an uncoventional myosin that is involved in organelle transport. It is required for sensory function in both Drosophila and mammals. Mutations in the Myo7A gene cause both syndromic deaf-blindness [Usher syndrome I (USH1)] and nonsyndromic (DFNB2 and DFNA11) deafness in humans. It contains an N-terminal motor domain, light chain-binding IQ motifs, a coiled-coil region for heavy chain dimerization, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1867163799 386 AAGDNSTLLSFKEGDLITLLVPEA----RDGWHYGESEKTKMRGWFP 428
Cdd:cd11881    12 NPSDGSSFLSFAKGDLIILDQDTGeqvmNSGWCNGRNDRTGQRGDFP 58

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

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gi 1867163799 379 VKAIFSHAAGDNSTLlSFKEGDLITLLVPEARDGWhYGESEKTKmrGWFPFSYTRV 434
Cdd:cd11828     2 AEALWDHVTMDPEEL-GFKAGDVIEVLDMSDKDWW-WGSIRDEE--GWFPASFVRL 53

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

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gi 1867163799 378 RVKAIFSHAAgDNSTLLSFKEGDLITLLVPEARDGWHYGESEKtKMRGWFPFSY 431
Cdd:cd11763     1 KVRALYDFDS-QPSGELSLRAGEVLTITRQDVGDGWLEGRNSR-GEVGLFPSSY 52

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

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1867163799 377 MRVKAIFSHAaGDNSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMrGWFPFSY 431
Cdd:cd11999     2 VRVRAVYDYT-GQEPDELSFKAGEELLKVEDEDEQGWCKGVTDGGAV-GLYPANY 54

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

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gi 1867163799 386 AAGDNStlLSFKEGDLITLLvpEARDGWHYGESEKtkMRGWFPFSYTRV 434
Cdd:cd11989    10 AKKDNH--LNFNKNDVITVL--EQQDMWWFGEVQG--QKGWFPKSYVKL 52

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

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gi 1867163799  76 LFQMAEVHRQIQnQLEEMLKSfHNELLTQLEQKVE-LDSRY--LSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSK 152
Cdd:COG1579     9 LLDLQELDSELD-RLEHRLKE-LPAELAELEDELAaLEARLeaAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVR 86

                          90       100
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gi 1867163799 153 NPQKYSDKELQyIDAISNKQGELE 176
Cdd:COG1579    87 NNKEYEALQKE-IESLKRRISDLE 109

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

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gi 1867163799 390 NSTLLSFKEGDLITLLvPEARDGWHYGESEKTKMRGWFPFSYTRVL 435
Cdd:cd11917    17 NEDELELREGDVIDVM-EKCDDGWFVGTSRRTKFFGTFPGNYVKRL 61

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1867163799 394 LSFKEGDLITLLVPEArDGWHYGESEKTKMRGWFPFSYTR 433
Cdd:cd11938    16 LSLQQADVVLVLQTES-DGWYYGERLRDGERGWFPSSCAK 54

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1867163799 388 GDNSTLLSFKEGDLITLLVPEARDGWHYGESEKTKmRGWFPFSY 431
Cdd:cd11851    17 DDPEEELSFHAGDVVRVYGPMDEDGFYYGELEGGR-KGLVPSNF 59

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1867163799 380 KAIFSHAAGDNSTLlSFKEGDLITLLVPEARDGWHYGEsekTKMR-GWFPFSY 431
Cdd:cd11830     3 KARYDFCARDMREL-SLKEGDVVKIYNKKGQQGWWRGE---INGRiGWFPSTY 51

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1867163799 379 VKAIFSHAAGDNSTLLSFKEGDLITLLV---PEARD-GWHYGESEKTKMrGWFPFSYTRV 434
Cdd:cd11771     2 CRALYDFTPENPEMELSLKKGDIVAVLSktdPLGRDsEWWKGRTRDGRI-GWFPSNYVEV 60

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

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gi 1867163799 394 LSFKEGDLITlLVPEARDGWHYGESEKTKmrGWFPFSYTRVL 435
Cdd:cd11803    17 LGFKEGDIIT-LTNQIDENWYEGMVNGQS--GFFPVNYVEVL 55

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

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gi 1867163799 380 KAIFSHAAGDNSTLlSFKEGDLITLLVPEARDgWHYGESEKTKmrGWFPFSYTRV 434
Cdd:cd11975     8 EAVWDHVTMANREL-AFKAGDVIKVLDASNKD-WWWGQIDDEE--GWFPASFVRL 58