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 1958787453  63 KVGNYKRTVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKGPQYGTVEKAWMAVMSEAERVSELHLE 142
Cdd:cd07679     3 EVGNYKRTVKRIDDGHRLCNDLMNCLHERARIEKVYAQQLTEWAKRWRQLVEKGPQYGTVEKAWCALMSEAEKVSELHLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 143 VKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVDAAKKAHHTACKEEKLAVSREANSKAD 222
Cdd:cd07679    83 VKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVEAAKKAYHTACKEEKLATSREANSKAD 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 223 PSLNPEQLKKLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSN 302
Cdd:cd07679   163 PALNPEQLKKLQDKVEKCKQDVLKTKEKYEKSLKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSN 242

                         250
                  ....*....|....*.
gi 1958787453 303 VASYKGIYRELEQSIK 318
Cdd:cd07679   243 VASYKNIYRELEQSIK 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 1958787453  63 KVGNYKRTVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKGPQYGTVEKAWMAVMSEAERVSELHLE 142
Cdd:cd07679     3 EVGNYKRTVKRIDDGHRLCNDLMNCLHERARIEKVYAQQLTEWAKRWRQLVEKGPQYGTVEKAWCALMSEAEKVSELHLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 143 VKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVDAAKKAHHTACKEEKLAVSREANSKAD 222
Cdd:cd07679    83 VKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVEAAKKAYHTACKEEKLATSREANSKAD 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 223 PSLNPEQLKKLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSN 302
Cdd:cd07679   163 PALNPEQLKKLQDKVEKCKQDVLKTKEKYEKSLKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSN 242

                         250
                  ....*....|....*.
gi 1958787453 303 VASYKGIYRELEQSIK 318
Cdd:cd07679   243 VASYKNIYRELEQSIK 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 1958787453  471 EVRVRALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLDSGQVGLYPANYVE 526
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 1958787453  67 YKRTVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKG-PQYGTVEKAWMAVMSEAERVSELHLE 142
Cdd:pfam00611   2 FKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKKKKKPeDDGGTLKKAWDELLTETEQLAKQHLK 78

Chromosome segregation protein NDC80, interacts with SMC proteins [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 121 TVEKAWMAVMSEAERVSELHLEVKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVDAAKK 200
Cdd:COG5185   351 SLTENLEAIKEEIENIVGEVELSKSSEELDSFKDTIESTKESLDEIPQNQRGYAQEILATLEDTLKAADRQIEELQRQIE 430

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 201 AhHTACKEEKLAVSREANS---KADPSLNPEQLKKLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCq 277
Cdd:COG5185   431 Q-ATSSNEEVSKLLNELISelnKVMREADEESQSRLEEAYDEINRSVRSKKEDLNEELTQIESRVSTLKATLEKLRAKL- 508

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1958787453 278 qfeEKRLRFFREVLLEVQKHLDLSNVASYKGIYRELEQSIKAADAVEDL 326
Cdd:COG5185   509 ---ERQLEGVRSKLDQVAESLKDFMRARGYAHILALENLIPASELIQAS 554

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 1958787453  63 KVGNYKRTVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKGPQYGTVEKAWMAVMSEAERVSELHLE 142
Cdd:cd07679     3 EVGNYKRTVKRIDDGHRLCNDLMNCLHERARIEKVYAQQLTEWAKRWRQLVEKGPQYGTVEKAWCALMSEAEKVSELHLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 143 VKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVDAAKKAHHTACKEEKLAVSREANSKAD 222
Cdd:cd07679    83 VKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVEAAKKAYHTACKEEKLATSREANSKAD 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 223 PSLNPEQLKKLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSN 302
Cdd:cd07679   163 PALNPEQLKKLQDKVEKCKQDVLKTKEKYEKSLKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSN 242

                         250
                  ....*....|....*.
gi 1958787453 303 VASYKGIYRELEQSIK 318
Cdd:cd07679   243 VASYKNIYRELEQSIK 258

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; 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. 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. 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 1958787453  63 KVGNYKRTVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKGPQYGTVEKAWMAVMSEAERVSELHLE 142
Cdd:cd07655     3 EVGNYKRTVKRIEDGHKLCDDLMKMVQERAEIEKAYAKKLKEWAKKWRDLIEKGPEYGTLETAWKGLLSEAERLSELHLS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 143 VKASLMNEDFEKIKNWQKEAFHKQMMGGFKETKEAEDGFRKAQKPWAKKLKEVDAAKKAHHTACKEEKLAVSREANSKAD 222
Cdd:cd07655    83 IRDKLLNDVVEEVKTWQKENYHKSMMGGFKETKEAEDGFAKAQKPWAKLLKKVEKAKKAYHAACKAEKSAQKQENNAKSD 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 223 PSLNPEQLKKLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSN 302
Cdd:cd07655   163 TSLSPDQVKKLQDKVEKCKQEVSKTKDKYEKALEDLNKYNPRYMEDMEQVFDKCQEFEEKRLDFFKEILLSYHRHLDLST 242

                         250
                  ....*....|....*
gi 1958787453 303 VASYKGIYRELEQSI 317
Cdd:cd07655   243 NPSFKAIYRDLQQTI 257

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 1958787453 472 VRVRALYDYEGQEHDELSFKAGDELTKIEDEDEQGWCKGRLDSGQVGLYPANYVEA 527
Cdd:cd11998     1 VRVRALYDYDGQEQDELSFKAGDELTKLEDEDEQGWCKGRLDSGQVGLYPANYVEP 56

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 1958787453 472 VRVRALYDYEGQEHDELSFKAGDELTKIEDEDEQGWCKGRLDSGQVGLYPANYVE 526
Cdd:cd11999     2 VRVRAVYDYTGQEPDELSFKAGEELLKVEDEDEQGWCKGVTDGGAVGLYPANYVE 56

The Extended FES-CIP4 Homology (FCH) or F-BAR (FCH and Bin/Amphiphysin/Rvs) domain, a dimerization module that binds and bends membranes; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. F-BAR domain containing proteins, also known as Pombe Cdc15 homology (PCH) family proteins, include Fes and Fer tyrosine kinases, PACSINs/Syndapins, FCHO, PSTPIP, CIP4-like proteins and srGAPs. Many members also contain an SH3 domain and play roles in endocytosis. 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. These tubules have diameters larger than those observed with N-BARs. The F-BAR domains of some members such as NOSTRIN and Rgd1 are important for the subcellular localization of the protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453  70 TVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKGPQ-----YGTVEKAWMAVMSEAERVSELHLEVK 144
Cdd:cd07610     1 GFELLEKRTELGLDLLKDLREFLKKRAAIEEEYAKNLQKLAKKFSKKPEsgktsLGTSWNSLREETESAATVHEELSEKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 145 ASLMNEDFEKIKNWQKEAfhkqmmgGFKETKEAEDGFRKAQKPWAKKLKEvdaakkahhtackeeklavsreanskadps 224
Cdd:cd07610    81 SQLIREPLEKVKEDKEQA-------RKKELAEGEKLKKKLQELWAKLAKK------------------------------ 123

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 225 lnpeqlkklqdkiekckqdvlktkdKYEKALKELDQTTPQYMENMeQVFEQCQQFEEKRLRFFREVLLEVQKHLDLSNVA 304
Cdd:cd07610   124 -------------------------ADEEYREQVEKLNPAQSEYE-EEKLNKIQAEQEREEERLEILKDNLKNYINAIKE 177

                         250
                  ....*....|....
gi 1958787453 305 SYKGIYRELEQSIK 318
Cdd:cd07610   178 IPQKIQQELEQSIN 191

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 1958787453   58 NHFSSK-VGNYKRTVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKGPQYGTVEKAWMAVMSEAERV 136
Cdd:smart00055   1 MGFWSElDDGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKKLRAVRDTEPEYGSLSKAWEVLLSETDAL 80

                   ....*..
gi 1958787453  137 SELHLEV 143
Cdd:smart00055  81 AKQHLEL 87

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Proline-Serine-Threonine Phosphatase-Interacting Proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Vetebrates contain two Proline-Serine-Threonine Phosphatase-Interacting Proteins (PSTPIPs), PSTPIP1 and PSTPIP2. PSTPIPs are mainly expressed in hematopoietic cells and are involved in the regulation of cell adhesion and motility. Mutations in PSTPIPs have been shown to cause autoinflammatory disorders. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain, while PSTPIP2 contains only the N-terminal F-BAR 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 1958787453  60 FSSKVGnYKRTVKRIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARrwrqLVEKGPQYGTVEKAWMAVMSEAERVSEL 139
Cdd:cd07647     1 FTSTTG-FDTLLQRLKEGKKMCKELEDFLKQRAKAEEDYGKALLKLSK----SAGPGDEIGTLKSSWDSLRKETENVANA 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 140 HLEVKASLmNEDFEKIknwqkEAFHKQMMggfKETKEAEDGFRKAQKPWAKKLKEVDAAKKAHHTACKEEKLAvsREANS 219
Cdd:cd07647    76 HIQLAQSL-REEAEKL-----EEFREKQK---EERKKTEDIMKRSQKNKKELYKKTMKAKKSYEQKCREKDKA--EQAYE 144

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958787453 220 KADPSLNPEQLKKLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCQQFEEKRLRFFREVL 291
Cdd:cd07647   145 KSSSGAQPKEAEKLKKKAAQCKTSAEEADSAYKSSIGCLEDARVEWESEHATACQVFQNMEEERIKFLRNAL 216

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 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLDSGQVGLYPANYVE 526
Cdd:cd11960     1 RARALYDYQAADDTEISFDPGDIITDIEQIDE-GWWRGTGPDGTYGLFPANYVE 53

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 1958787453 475 RALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLDSGQVGLYPA 522
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSED-GWWKGRNKGGKEGLIPS 47

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958787453 476 ALYDYEGQEHDELSFKAGDELTKIEDEDEQGWCKGRLDSGQVGLYPANYVEA 527
Cdd:cd11761     6 VLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQF 57

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 1958787453 474 VRALYDYEGQEHDELSFKAGDeLTKIEDEDEQGWCKGRLDsGQVGLYPANYVEA 527
Cdd:cd11772     2 FRALYDYEAQHPDELSFEEGD-LLYISDKSDPNWWKATCG-GKTGLIPSNYVEE 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLD-SGQVGLYPANYVEAI 528
Cdd:cd11934     4 RYRAVYDYNAADEDEVSFQDGDTIVNVQQIDD-GWMYGTVErTGDTGMLPANYVEAI 59

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 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIEDEDEQGWCKGRLdSGQVGLYPANYVE 526
Cdd:cd11882     1 RARALYACKAEDESELSFEPGQIITNVQPSDEPGWLEGTL-NGRTGLIPENYVE 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLDsGQVGLYPANYVE 526
Cdd:cd11826     1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDD-GWYEGVLN-GVTGLFPGNYVE 52

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958787453 476 ALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLDsGQVGLYPANYVE 526
Cdd:cd12073     5 ALYDYQGEGDDEISFDPQETITDIEMVDE-GWWKGTCH-GHRGLFPANYVE 53

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958787453 476 ALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLdSGQVGLYPANYVEA 527
Cdd:cd11959     4 ALYDYQAADDDEISFDPDDIITNIEMIDE-GWWRGVC-RGKYGLFPANYVEL 53

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 1958787453 474 VRALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLD-SGQVGLYPANYVEAI 528
Cdd:cd11933     4 FRAMYDYRAADDDEVSFKDGDTIVNVQTIDE-GWMYGTVQrTGKTGMLPANYVEAI 58

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIEDEDEQgWCKGRLDSGqVGLYPANYVEA 527
Cdd:cd11964     2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDPN-WWKGETPQG-TGLFPSNFVTA 54

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIEDEDEQgWCKGRLDSGQvGLYPANYVEA 527
Cdd:cd11820     2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPN-WWKGSNHRGE-GLFPANFVTA 54

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTkIEDEDEQGWCKGRLdSGQVGLYPANYVE 526
Cdd:cd11823     1 RCKALYSYTANREDELSLQPGDIIE-VHEKQDDGWWLGEL-NGKKGIFPATYVE 52

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Schizosaccharomyces pombe Cdc15, and similar proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. This subfamily is composed of Schizosaccharomyces pombe Cdc15 and Imp2, and similar proteins. These proteins contain an N-terminal F-BAR domain and a C-terminal SH3 domain. S. pombe Cdc15 and Imp2 play both distinct and overlapping roles in the maintenance and strengthening of the contractile ring at the division site, which is required in cell division. Cdc15 is a component of the actomyosin ring and is required in normal cytokinesis. Imp2 colocalizes with the medial ring during septation and is required for normal septation. 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 1958787453  73 RIDDGHRLCGDLMNCLHERARIEKAYAQQLTEWARrwrqLVEKGPQYGTVEKAWMAVMSEAERVSELHLEVKASLMNEDF 152
Cdd:cd07651    13 RIKDSLRTLEELRSFYKERASIEEEYAKRLEKLSR----KSLGGSEEGGLKNSLDTLRLETESMAKSHLKFAKQIRQDLE 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 153 EKIknwqkEAFHKQMMggfKETKEAEDGFRKAQKPWAKKLKEVDAAKKAHHTACKEEK--LAVSREANSKadpslnpeQL 230
Cdd:cd07651    89 EKL-----AAFASSYT---QKRKKIQSHMEKLLKKKQDQEKYLEKAREKYEADCSKINsyTLQSQLTWGK--------EL 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958787453 231 KKLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCQQFEEKRLRF 286
Cdd:cd07651   153 EKNNAKLNKAQSSINSSRRDYQNAVKALRELNEIWNREWKAALDDFQDLEEERIQF 208

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 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIE--DEDEQ--GWCKG-RLDSGQVGLYPANYVEAI 528
Cdd:cd11790     4 KVRATHDYTAEDTDELTFEKGDVILVIPfdDPEEQdeGWLMGvKESTGCRGVFPENFTERI 64

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Nitric Oxide Synthase TRaffic INducer (NOSTRIN); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Nitric Oxide Synthase TRaffic INducer (NOSTRIN) is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). NOSTRIN facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of NOSTRIN may be correlated to preeclampsia. NOSTRIN contains an N-terminal F-BAR domain and a C-terminal SH3 domain. 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. The F-BAR domain of NOSTRIN is necessary and sufficient for its membrane association and is responsible for its subcellular localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453  68 KRTVKRIDDghrLCGDLMNCLHERARIEKAYAQQLTEWARRWRQLVEKGPqyGTVEKAWMAVMSEAERVSELHLEVKASL 147
Cdd:cd07658    11 RRYVKQGGD---FCKELATVLQERAELELNYAKGLSKLSGKLSKASKSVS--GTLSSAWTCVAEEMESEADIHRNLGSAL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958787453 148 MNEDFEKIKNWQkEAFHKqmmggfkeTKEAEDGF-RKAQKPWAKKLKEVDAAKKAHHTACKE-EKL--AVSREANSKADP 223
Cdd:cd07658    86 TEEAIKPLRQVL-DEQHK--------TRKPVENEvDKAAKLLTDWRSEQIKVKKKLHGLAREnEKLqdQVEDNKQSCTKQ 156

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958787453 224 SLNPEQLK----------KLQDKIEKCKQDVLKTKDKYEKALKELDQTTPQYMENMEQVFEQCQQFEEKRLR 285
Cdd:cd07658   157 KMLNKLKKsaevqdkedeKLEAKRKKGEESRLKAENEYYTCCVRLERLRLEWESALRKGLNQYESLEEERLQ 228

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958787453 474 VRALYDYEGQEHDELSFKAGD--ELTKIEdedEQGWCKGRLDsGQVGLYPANYVE 526
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKGDiiTVTQVV---EGGWWEGTLN-GKTGWFPSNYVK 52

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958787453 474 VRALYDYEGQEHDELSFKAGDeLTKIEDEDEQGWCKGRLdSGQVGLYPANYVE 526
Cdd:cd11950     2 VRALYDFEALEDDELGFNSGD-VIEVLDSSNPSWWKGRL-HGKLGLFPANYVA 52

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 1958787453 475 RALYDYEGQEHDELSFKAGDELTKIEDEDEQgWCKGRLDsGQVGLYPANYVE 526
Cdd:cd11786     3 KALYNYEGKEPGDLSFKKGDIILLRKRIDEN-WYHGECN-GKQGFFPASYVQ 52

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958787453 473 RVRALYDYEGQEHDELSFKAGDELtKIEDEDEQGWCKGRLDsGQVGLYPANYVE 526
Cdd:cd11874     1 RCKVLFSYTPQNEDELELKVGDTI-EVLGEVEEGWWEGKLN-GKVGVFPSNFVK 52

N-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 N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958787453 475 RALYDYEGQEHDELSFKAGDELTKIEDEDEQGWCKGRLDsGQVGLYPANYV 525
Cdd:cd11804     3 VAKHDFKATAEDELSFKKGSILKVLNMEDDPNWYKAELD-GKEGLIPKNYI 52

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958787453 474 VRALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLDsGQVGLYPANYVE 526
Cdd:cd11873     2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEE-GWWEGTLN-GKRGMFPDNFVK 52

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. 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 1958787453 469 GTEVRvrALYDYEGQEHDELSFKAGDELTKIEDEDEQGWCKGRLDSGQVGLYPANYVE 526
Cdd:cd11769     1 GTECI--AKYNFNGASEEDLPFKKGDILTIVAVTKDPNWYKAKNKDGREGMIPANYVQ 56

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

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gi 1958787453 474 VRALYDYEGQEHDELSFKAGDELTKIEDEDEqGWCKGRLDSGQVGLYPANYVE 526
Cdd:cd11825     2 VKALYDYRAQRPDELSFCKHAIITNVEKEDG-GWWRGDYGGKKQKWFPANYVE 53

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

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gi 1958787453 473 RVRALYDYEGQEHDELSFKAGDELTKIEDEDEQgWCKGRLdSGQVGLYPANY 524
Cdd:cd11818     1 KARALYDFTGENEDELSFKAGDIITELESIDEE-WMSGEL-RGKSGIFPKNF 50