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 148702774   5 RSEEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 84
Cdd:cd07646    1 RTEEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774  85 QIQNQLEETLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKELQY 164
Cdd:cd07646   81 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQY 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 148702774 165 IDAISNKQGELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQACADPNKI 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 148702774   5 RSEEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 84
Cdd:cd07646    1 RTEEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774  85 QIQNQLEETLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKELQY 164
Cdd:cd07646   81 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQY 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 148702774 165 IDAISNKQGELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQACADPNKI 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 148702774 378 MRVKAIFSHAAGDNSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMRGWFPFSYTRVL 436
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 148702774  379 RVKAIFSHAaGDNSTLLSFKEGDLITLLvPEARDGWHYGESekTKMRGWFPFSYTRVL 436
Cdd:pfam07653   1 YGRVIFDYV-GTDKNGLTLKKGDVVKVL-GKDNDGWWEGET--GGRVGLVPSTAVEEI 54

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774     3 LSRSEEMHRLTENVYKTIME--QFNPSLRNFIAMGKNYEKALAGVtfaaKGYFDALVKMGELASESQGSKELGDVLFQMA 80
Cdd:smart00721  33 ERRFDTTEAEIEKLQKDTKLylQPNPAVRAKLASQKKLSKSLGEV----YEGGDDGEGLGADSSYGKALDKLGEALKKLL 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774    81 EVHRQIQNQLEETLKSFHNELLTQLEqkveldsrYLSAALKKYQteqrSKGDALDKCQAELKKLRKKSQGSKNpQKYSDK 160
Cdd:smart00721 109 QVEESLSQVKRTFILPLLNFLLGEFK--------EIKKARKKLE----RKLLDYDSARHKLKKAKKSKEKKKD-EKLAKA 175

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 148702774   161 ELQYIDAISN---KQGELENYVSDGYKTALTEERRRFCFLVEKQCavaknsaAYHSKGKELLAQKLPLWQQ 228
Cdd:smart00721 176 EEELRKAKQEfeeSNAQLVEELPQLVASRVDFFVNCLQALIEAQL-------NFHRESYKLLQQLQQQLDK 239

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 148702774   5 RSEEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 84
Cdd:cd07646    1 RTEEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774  85 QIQNQLEETLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKELQY 164
Cdd:cd07646   81 QIQNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQY 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 148702774 165 IDAISNKQGELENYVSDGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQACADPNKI 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 148702774   7 EEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHRQI 86
Cdd:cd07605    1 EELNRLTENIYKNIKEQFNPVLRNLIKAGKKYQKALQALSQAAKVFFDALAKIGELASQSRGSQELGEALKQIVDTHKSI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774  87 QNQLEETLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSkNPQKYSDKELQYID 166
Cdd:cd07605   81 EASLEQVAKAFHGELILPLEKKLELDQKVINKFEKDYKKEYKQKREDLDKARSELKKLQKKSQKS-GTGKYQEKLDQALE 159

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148702774 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 148702774   9 MHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHRQIQN 88
Cdd:cd07644    3 LYRSTISIYKSIMEQFNPALENLVYLGNNYLRAFHALSEAAEVYFSAIAKIGEQALQSLTSQSLGEILIQMSETQRKLSA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774  89 QLEETLKSFHNELLTQLEQKVELDSRYLSAALKKYQTEQRSKGDALDKCQAELKKL-RKKSQGSKNPQKYsdkeLQYIDA 167
Cdd:cd07644   83 DLEVVFQTFHVDLLQHMDKNTKLDMQFIEDSRRVYELEYRHRAANLEKCMSELWRMeRQRDRNVREMKEN----VNRLRQ 158

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 148702774 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 148702774 378 MRVKAIFSHAAGDnSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMRGWFPFSYTR 434
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 148702774 379 RVKAIFSHAAGDNSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMRGWFPFSYTRVL 436
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 148702774 379 RVKAIFSHAAgDNSTLLSFKEGDLITLLvPEARDGWHYGESEKTKmRGWFPFSY 432
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 148702774  379 RVKAIFSHAaGDNSTLLSFKEGDLITLLvPEARDGWHYGESekTKMRGWFPFSYTRVL 436
Cdd:pfam07653   1 YGRVIFDYV-GTDKNGLTLKKGDVVKVL-GKDNDGWWEGET--GGRVGLVPSTAVEEI 54

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR 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
                 ....*....|....*....|....*....|....*....
gi 148702774 395 LSFKEGDLITLL-VPEarDGWHygESEKTKMRGWFPFSY 432
Cdd:cd11829   17 LSFEAGELIRVLqAPD--GGWW--EGEKDGLRGWFPASY 51

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774  28 LRNFIAMGKNYEKALAGVTFAAKGYFDALVKMGELASESQgSKELGDVLFQMAEVHRQIQNQLEETLKSFHNELLTQLEQ 107
Cdd:cd07307    9 LKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPDLS-NTDLGEALEKFGKIQKELEEFRDQLEQKLENKVIEPLKE 87

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 148702774 108 kveldsrYLSAALKKYQT---EQRSKGDALDKCQAELKKLRKKsqgSKNPQKYSDKELQYIDAISN 170
Cdd:cd07307   88 -------YLKKDLKEIKKrrkKLDKARLDYDAAREKLKKLRKK---KKDSSKLAEAEEELQEAKEK 143

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 148702774 379 RVKAIFSHAAGDnSTLLSFKEGDLItLLVP-----EARDGWHYGESEKTKMRGWFPFSYTRVL 436
Cdd:cd11790    4 KVRATHDYTAED-TDELTFEKGDVI-LVIPfddpeEQDEGWLMGVKESTGCRGVFPENFTERI 64

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 148702774 381 KAIFSHAAgDNSTLLSFKEGDLITLLvPEARDGWHYGESEKTKMRGWFPFSYTRVL 436
Cdd:cd11916    5 QALYSYAP-QNDDELELRDGDIVDVM-EKCDDGWFVGTSRRTKQFGTFPGNYVKLL 58

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 148702774 395 LSFKEGDLITLLVPEArDGWHYGESEKTKMRGWFPFSYTR 434
Cdd:cd11793   16 LTLEEGDVVNVLRKMP-DGWYEGERLRDGERGWFPSSYTE 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 148702774 380 VKAIFSHAAGDNSTLlSFKEGDLItLLVPEARDGWHYGESEKTKMRGWFPFSY 432
Cdd:cd11933    4 FRAMYDYRAADDDEV-SFKDGDTI-VNVQTIDEGWMYGTVQRTGKTGMLPANY 54

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second 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 148702774 380 VKAIFSHAA-GDNStlLSFKEGDLITLLVPEARDGWHYGESEKTKmrGWFPFSY 432
Cdd:cd11778    2 VEALYDYEAqGDDE--ISIRVGDRIAVIRGDDGSGWTYGEINGVK--GLFPTSY 51

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 148702774    5 RSEEMHRLTENVYKTIME--QFNPSLRNFIAMGKNYEKALAGVtfaakgyfdalvkMGELASESQGSKELGDVLFQMAEV 82
Cdd:pfam03114  34 RFDTTEKEIKKLQKDTKGylQPNPGARAKQTVLEQPEELLAES-------------MIEAGKDLGEDSSFGKALEDYGEA 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774   83 HRQIQNQLEETLKSFHNELLTQLEQKVElDSRYLSAALKKYQteqrSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKEL 162
Cdd:pfam03114 101 LKRLAQLLEQLDDRVETNFLDPLRNLLK-EFKEIQKHRKKLE----RKRLDYDAAKTRVKKAKKKKSSKAKDESQAEEEL 175

                  ..
gi 148702774  163 QY 164
Cdd:pfam03114 176 RK 177

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 148702774 379 RVKAIFSHAAgDNSTLLSFKEGDLITLLVPEARDGWHYGESEKtKMRGWFPFSY 432
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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 148702774 378 MRVKAIFSHAaGDNSTLLSFKEGDLITLLVPEARDGWHYGESEKTKMrGWFPFSY 432
Cdd:cd11999    2 VRVRAVYDYT-GQEPDELSFKAGEELLKVEDEDEQGWCKGVTDGGAV-GLYPANY 54

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774  76 LFQMAEVHRQIQnQLEETLKSfHNELLTQLEQKVE-LDSRY--LSAALKKYQTEQRSKGDALDKCQAELKKLRKKSQGSK 152
Cdd:COG1579    9 LLDLQELDSELD-RLEHRLKE-LPAELAELEDELAaLEARLeaAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVR 86

                         90       100
                 ....*....|....*....|....
gi 148702774 153 NPQKYSDKELQyIDAISNKQGELE 176
Cdd:COG1579   87 NNKEYEALQKE-IESLKRRISDLE 109

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 148702774 389 GDNSTLLSFKEGDLITLLvPEARDGWHYGESEKTKMRGWFPFSYTRVL 436
Cdd:cd11922   11 GDTQVEMSFRKGERITLL-RQVDENWYEGRIPGTSRQGIFPITYVDVI 57

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three 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 148702774 381 KAIFSHAAGDNSTLlSFKEGDLITLLVPeARDGWHYGESEKTKMRGWFPFSY 432
Cdd:cd11935    4 RAMYDYSAQDEDEV-SFRDGDYIVNVQP-IDEGWMYGTVQRTGRTGMLPANY 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 148702774 377 RMRVKAIFSHAAGDNSTLLSFKEGDLITLLvPEARDGWHYGESEKTKMRG 426
Cdd:cd11788    1 RRRVRAILPYNKVPDTDELSFQKGDIFVVH-NELEDGWLWVTSLRTGESG 49

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. 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 148702774 380 VKAIFSHAAgDNSTLLSFKEGDLITL---LVPEARDGWHYGESEKTKMRGWFPFSYTR 434
Cdd:cd11791    2 LRVLYPYTP-QEEDELELVPGDYIYVspeELDSSSDGWVEGTSWLTGCSGLLPENYTE 58

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 148702774 381 KAIFSHAA---GDnstlLSFKEGDLItLLVPEARDGWHYGESEKTkmRGWFPFSYTRV 435
Cdd:cd11786    3 KALYNYEGkepGD----LSFKKGDII-LLRKRIDENWYHGECNGK--QGFFPASYVQV 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 148702774 379 RVKAIFsHAAGDNSTLLSFKEGDLITLLVPEARDGW-HYGESEKTKmRGWFPFSY 432
Cdd:cd11966    1 RVKALY-NCVADNPDELTFSEGEIIIVDGEEDKEWWiGHIDGEPTR-RGAFPVSF 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 148702774 379 RVKAIFSHAAgDNSTLLSFKEGDLITLLVPEARD-GWHYGESEKTkmRGWFP 429
Cdd:cd11875    1 KARVLFDYEA-ENEDELTLREGDIVTILSKDCEDkGWWKGELNGK--RGVFP 49

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774     3 LSRSEEMHRLTENVYKTIME--QFNPSLRNFIAMGKNYEKALAGVtfaaKGYFDALVKMGELASESQGSKELGDVLFQMA 80
Cdd:smart00721  33 ERRFDTTEAEIEKLQKDTKLylQPNPAVRAKLASQKKLSKSLGEV----YEGGDDGEGLGADSSYGKALDKLGEALKKLL 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148702774    81 EVHRQIQNQLEETLKSFHNELLTQLEqkveldsrYLSAALKKYQteqrSKGDALDKCQAELKKLRKKSQGSKNpQKYSDK 160
Cdd:smart00721 109 QVEESLSQVKRTFILPLLNFLLGEFK--------EIKKARKKLE----RKLLDYDSARHKLKKAKKSKEKKKD-EKLAKA 175

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 148702774   161 ELQYIDAISN---KQGELENYVSDGYKTALTEERRRFCFLVEKQCavaknsaAYHSKGKELLAQKLPLWQQ 228
Cdd:smart00721 176 EEELRKAKQEfeeSNAQLVEELPQLVASRVDFFVNCLQALIEAQL-------NFHRESYKLLQQLQQQLDK 239

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 148702774 381 KAIFSHAAGDNSTLlSFKEGDLITLLVPEARDgWHYGESEKTKmrGWFPFSYTRV 435
Cdd:cd11975    8 EAVWDHVTMANREL-AFKAGDVIKVLDASNKD-WWWGQIDDEE--GWFPASFVRL 58