The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSIN 3 or Syndapin III is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSIN 3 contains an N-terminal F-BAR domain and a C-terminal SH3 domain. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567  41 FWEAGNYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGTVEKGPQYGTLEKAWHAFFTAAERLSALH 120
Cdd:cd07681     1 FWEAGNYRRTVKRIEDGYRLCNDLVSCFQERAKIEKGYAQQLSDWARKWRGIVEKGPQYGTLEKAWHAFLTAAERLSEIH 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 121 LEVREKLQGQDSERVRAWQRGAFHRPVLGGFRESRAAEDGFRKAQKPWLKRLKEVEASKKSYHAARKDEKTAQTRESHAK 200
Cdd:cd07681    81 LELRENLVGEDSEKVRAWQKEAFHKQMIGGFRESKEAEEGFRKAQKPWVKKLKEVESSKKGYHAARKDERTAQTRETHAK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 201 ADSAVSQEQLRKLQERVERCAKEAEKTKAQYEQTLAELHRYTPRYMEDMEQAFETCQAAERQRLLFFKDMLLTLHQHLDL 280
Cdd:cd07681   161 ADSTVSQEQLRKLQDRVEKCTQEAEKAKEQYEKALEELNRYNPRYMEDMEQAFEICQEAERKRLCFFKEMLLDLHQHLDL 240

                         250
                  ....*....|....*...
gi 2217282567 281 SSSEKFHELHRDLHQGIE 298
Cdd:cd07681   241 SSSDSFHALYRDLHQTIS 258

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSIN 3 or Syndapin III is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSIN 3 contains an N-terminal F-BAR domain and a C-terminal SH3 domain. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567  41 FWEAGNYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGTVEKGPQYGTLEKAWHAFFTAAERLSALH 120
Cdd:cd07681     1 FWEAGNYRRTVKRIEDGYRLCNDLVSCFQERAKIEKGYAQQLSDWARKWRGIVEKGPQYGTLEKAWHAFLTAAERLSEIH 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 121 LEVREKLQGQDSERVRAWQRGAFHRPVLGGFRESRAAEDGFRKAQKPWLKRLKEVEASKKSYHAARKDEKTAQTRESHAK 200
Cdd:cd07681    81 LELRENLVGEDSEKVRAWQKEAFHKQMIGGFRESKEAEEGFRKAQKPWVKKLKEVESSKKGYHAARKDERTAQTRETHAK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 201 ADSAVSQEQLRKLQERVERCAKEAEKTKAQYEQTLAELHRYTPRYMEDMEQAFETCQAAERQRLLFFKDMLLTLHQHLDL 280
Cdd:cd07681   161 ADSTVSQEQLRKLQDRVEKCTQEAEKAKEQYEKALEELNRYNPRYMEDMEQAFEICQEAERKRLCFFKEMLLDLHQHLDL 240

                         250
                  ....*....|....*...
gi 2217282567 281 SSSEKFHELHRDLHQGIE 298
Cdd:cd07681   241 SSSDSFHALYRDLHQTIS 258

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217282567  390 GVRVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQSGRIGLYPANYVE 445
Cdd:smart00326   2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDD-GWWKGRLGRGKEGLFPSNYVE 56

Fes/CIP4, and EFC/F-BAR homology domain; Alignment extended from. Highly alpha-helical. The cytosolic endocytic adaptor proteins in fungi carry this domain at the N-terminus; several of these have been referred to as muniscin proteins. These N-terminal BAR, N-BAR, and EFC/F-BAR domains are found in proteins that regulate membrane trafficking events by inducing membrane tubulation. The domain dimerizes into a curved structure that binds to liposomes and either senses or induces the curvature of the membrane bilayer to cause biophysical changes to the shape of the bilayer; it also thereby recruits other trafficking factors, such as the GTPase dynamin. Most EFC/F-BAR domain-family members localize to actin-rich structures.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217282567  47 YRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGTVEKG-PQYGTLEKAWHAFFTAAERLSALHLE 122
Cdd:pfam00611   2 FKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKKKKKPeDDGGTLKKAWDELLTETEQLAKQHLK 78

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSIN 3 or Syndapin III is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSIN 3 contains an N-terminal F-BAR domain and a C-terminal SH3 domain. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567  41 FWEAGNYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGTVEKGPQYGTLEKAWHAFFTAAERLSALH 120
Cdd:cd07681     1 FWEAGNYRRTVKRIEDGYRLCNDLVSCFQERAKIEKGYAQQLSDWARKWRGIVEKGPQYGTLEKAWHAFLTAAERLSEIH 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 121 LEVREKLQGQDSERVRAWQRGAFHRPVLGGFRESRAAEDGFRKAQKPWLKRLKEVEASKKSYHAARKDEKTAQTRESHAK 200
Cdd:cd07681    81 LELRENLVGEDSEKVRAWQKEAFHKQMIGGFRESKEAEEGFRKAQKPWVKKLKEVESSKKGYHAARKDERTAQTRETHAK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 201 ADSAVSQEQLRKLQERVERCAKEAEKTKAQYEQTLAELHRYTPRYMEDMEQAFETCQAAERQRLLFFKDMLLTLHQHLDL 280
Cdd:cd07681   161 ADSTVSQEQLRKLQDRVEKCTQEAEKAKEQYEKALEELNRYNPRYMEDMEQAFEICQEAERKRLCFFKEMLLDLHQHLDL 240

                         250
                  ....*....|....*...
gi 2217282567 281 SSSEKFHELHRDLHQGIE 298
Cdd:cd07681   241 SSSDSFHALYRDLHQTIS 258

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 2 (PACSIN2); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSIN 2 contains an N-terminal F-BAR domain and a C-terminal SH3 domain. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567  41 FWEAGNYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGTVEKGPQYGTLEKAWHAFFTAAERLSALH 120
Cdd:cd07679     1 FWEVGNYKRTVKRIDDGHRLCNDLMNCLHERARIEKVYAQQLTEWAKRWRQLVEKGPQYGTVEKAWCALMSEAEKVSELH 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 121 LEVREKLQGQDSERVRAWQRGAFHRPVLGGFRESRAAEDGFRKAQKPWLKRLKEVEASKKSYHAARKDEKTAQTRESHAK 200
Cdd:cd07679    81 LEVKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVEAAKKAYHTACKEEKLATSREANSK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 201 ADSAVSQEQLRKLQERVERCAKEAEKTKAQYEQTLAELHRYTPRYMEDMEQAFETCQAAERQRLLFFKDMLLTLHQHLDL 280
Cdd:cd07679   161 ADPALNPEQLKKLQDKVEKCKQDVLKTKEKYEKSLKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDL 240

                         250
                  ....*....|....*...
gi 2217282567 281 SSSEKFHELHRDLHQGIE 298
Cdd:cd07679   241 SNVASYKNIYRELEQSIK 258

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217282567 390 GVRVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11997     1 GVRVRALYDYTGQEADELSFKAGEELLKIGEEDEQGWCKGRLLSGRIGLYPANYVE 56

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217282567 391 VRVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11998     1 VRVRALYDYDGQEQDELSFKAGDELTKLEDEDEQGWCKGRLDSGQVGLYPANYVE 55

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217282567  390 GVRVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQSGRIGLYPANYVE 445
Cdd:smart00326   2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDD-GWWKGRLGRGKEGLFPSNYVE 56

Fes/CIP4 homology domain; Alignment extended from original report. Highly alpha-helical. Also known as the RAEYL motif or the S. pombe Cdc15 N-terminal domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567   40 SFWEAG--NYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGTVEKGPQYGTLEKAWHAFFTAAERLS 117
Cdd:smart00055   2 GFWSELddGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKKLRAVRDTEPEYGSLSKAWEVLLSETDALA 81

                   ....*.
gi 2217282567  118 ALHLEV 123
Cdd:smart00055  82 KQHLEL 87

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 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDGWLEGRNSRGEVGLFPSSYVE 54

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11819     1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDE-GWWLGVNAKGQKGLFPANYVE 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217282567 393 VRALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLQsGRIGLYPANYVE 445
Cdd:cd11772     2 FRALYDYEAQHPDELSFEEG-DLLYISDKSDPNWWKATCG-GKTGLIPSNYVE 52

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 2217282567 390 GVRVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQ-SGRIGLYPANYVECV 447
Cdd:cd11933     1 GKSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDE-GWMYGTVQrTGKTGMLPANYVEAI 58

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
                  ....*....|....*....|....*....|....*....|....*...
gi 2217282567 394 RALYDYAGQEADELSFRAGEElLKMSEEDEQGWCQGQLQSGRIGLYPA 441
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDI-IIVLEKSEDGWWKGRNKGGKEGLIPS 47

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11960     1 RARALYDYQAADDTEISFDPGDIITDIEQIDE-GWWRGTGPDGTYGLFPANYVE 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQsGRIGLYPANYVE 445
Cdd:cd11882     1 RARALYACKAEDESELSFEPGQIITNVQPSDEPGWLEGTLN-GRTGLIPENYVE 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDeQGWCQGQLqSGRIGLYPANYVE 445
Cdd:cd11840     1 QVIALFPYTAQNEDELSFQKGDIINVLSKDD-PDWWRGEL-NGQTGLFPSNYVE 52

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217282567 389 TGVRVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQ-SGRIGLYPANYVECV 447
Cdd:cd11934     1 GGKRYRAVYDYNAADEDEVSFQDGDTIVNVQQIDD-GWMYGTVErTGDTGMLPANYVEAI 59

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.

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gi 2217282567 394 RALYDYAGQEADELSFRAGEELLKMSEEDEQgWCQGQLQsGRIGLYPANYVEC 446
Cdd:cd11786     3 KALYNYEGKEPGDLSFKKGDIILLRKRIDEN-WYHGECN-GKQGFFPASYVQV 53

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11896     1 KARALYSFQSENKEEINIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVE 54

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

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gi 2217282567 392 RVRALYDYAGQEADELSFRAGE--ELLKMSEEDeqgWCQGQLQsGRIGLYPANYVE 445
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDiiTVLDSSDPD---WWKGELR-GRVGIFPANYVQ 52

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.

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gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMS----EEDEQGWCQGQLQS-GRIGLYPANYVE 445
Cdd:cd11790     4 KVRATHDYTAEDTDELTFEKGDVILVIPfddpEEQDEGWLMGVKEStGCRGVFPENFTE 62

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). 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 2217282567 393 VRALYDYAGQEADELSFRAGEELLKMSEEDEQ-GWCQGQLqSGRIGLYPANYV 444
Cdd:cd11841     2 VTALYSFEGQQPCDLSFQAGDRITVLTRTDSQfDWWEGRL-RGRVGIFPANYV 53

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

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gi 2217282567 393 VRALYDYAGQEADELSFRAGE--ELLKMSEEdeqGWCQGQLQsGRIGLYPANYVE 445
Cdd:cd11950     2 VRALYDFEALEDDELGFNSGDviEVLDSSNP---SWWKGRLH-GKLGLFPANYVA 52

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

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gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11897     1 RARALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSRGDRGLFPASYVE 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.

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gi 2217282567 393 VRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLqSGRIGLYPANY 443
Cdd:cd11778     2 VEALYDYEAQGDDEISIRVGDRIAVIRGDDGSGWTYGEI-NGVKGLFPTSY 51

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

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gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQgWCQGQLQSGrIGLYPANYV 444
Cdd:cd11963     3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDAN-WWKGENHRG-VGLFPSNFV 53

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

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gi 2217282567 393 VRALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 445
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKG-DIITVTQVVEGGWWEGTL-NGKTGWFPSNYVK 52

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

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gi 2217282567 392 RVRALYDYAGQEADELSFRAGEELLKMSE-EDEQGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11767     1 VVVALYPFTGENDEELSFEKGERLEIIEKpEDDPDWWKARNALGTTGLVPRNYVE 55

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

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gi 2217282567 393 VRALYDYAGQEADELSFRAGEELLKMSEEDEQ---GWCQGQLqSGRIGLYPANYVE 445
Cdd:cd11762     2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNGvddGWWEGEF-NGRVGVFPSLVVE 56

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions 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 2217282567 394 RALYDYAGQEADELSFRAGEElLKMSEEDEQ----GWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11864     3 RAEYDFVAESEDELSFRAGDK-LRLAPKELQprvrGWLLATVDGQKIGLVPANYVK 57

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, 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 2217282567 395 ALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQsGRIGLYPANYVE 445
Cdd:cd11959     4 ALYDYQAADDDEISFDPDDIITNIEMIDE-GWWRGVCR-GKYGLFPANYVE 52

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 2217282567 392 RVRALYDY-------AGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 445
Cdd:cd11851     1 LMVALYDYnpetmspNDDPEEELSFHAGDVVRVYGPMDEDGFYYGELEGGRKGLVPSNFVQ 61

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

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gi 2217282567 393 VRALYDYAGQEADELSFRAGEELLKMSEEDEQgWCQGQLQsGRIGLYPANYVE 445
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFVDDD-WWLGECH-GSRGLFPSNYVE 52