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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  16 FTAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQTEMNSLRTSFDSLKQQTENVGSAHIQLA 95
Cdd:cd07671    1 FTLNTGYEILLQRLLDGRKMCKDVEELLKQRAQAEERYGKELVQIARKAGGQTEINTLKASFDQLKQQIENIGNSHIQLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  96 LALREELRSLEEFRERQKEQRKKYEAIMDRVQKSKLSLYKKTMESKKAYDQKCRDADDAEQAFERVSANGHQKQVEKSQN 175
Cdd:cd07671   81 GMLREELKSLEEFRERQKEQRKKYEAVMERVQKSKVSLYKKTMESKKTYEQRCREADEAEQTFERSSSTGNPKQSEKSQN 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423 176 KAKQCKESATEAERVYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNALWVHCNQLSMQCVKDDELYEEVRLT 255
Cdd:cd07671  161 KAKQCRDAATEAERVYKQNIEQLDKARTEWETEHILTCEVFQLQEDDRITILRNALWVHCNHFSMQCVKDDELYEEVRTT 240

                 ..
gi 171184423 256 LE 257
Cdd:cd07671  241 LE 242

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Proline-Serine-Threonine Phosphatase-Interacting Protein 1 (PSTPIP1), also known as CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, 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 171184423  16 FTAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQTEMNSLRTSFDSLKQQTENVGSAHIQLA 95
Cdd:cd07671    1 FTLNTGYEILLQRLLDGRKMCKDVEELLKQRAQAEERYGKELVQIARKAGGQTEINTLKASFDQLKQQIENIGNSHIQLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  96 LALREELRSLEEFRERQKEQRKKYEAIMDRVQKSKLSLYKKTMESKKAYDQKCRDADDAEQAFERVSANGHQKQVEKSQN 175
Cdd:cd07671   81 GMLREELKSLEEFRERQKEQRKKYEAVMERVQKSKVSLYKKTMESKKTYEQRCREADEAEQTFERSSSTGNPKQSEKSQN 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423 176 KAKQCKESATEAERVYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNALWVHCNQLSMQCVKDDELYEEVRLT 255
Cdd:cd07671  161 KAKQCRDAATEAERVYKQNIEQLDKARTEWETEHILTCEVFQLQEDDRITILRNALWVHCNHFSMQCVKDDELYEEVRTT 240

                 ..
gi 171184423 256 LE 257
Cdd:cd07671  241 LE 242

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 171184423    12 WCRDFTAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARK----AGGQTEMNSLRTSFDSLKQQTENV 87
Cdd:smart00055   1 MGFWSELDDGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKKlravRDTEPEYGSLSKAWEVLLSETDAL 80

                   ....*..
gi 171184423    88 GSAHIQL 94
Cdd:smart00055  81 AKQHLEL 87

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 171184423   21 GYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQTEMN-----SLRTSFDSLKQQTENVGSAHIQ 93
Cdd:pfam00611   1 GFKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKKKKKPeddggTLKKAWDELLTETEQLAKQHLK 78

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423   37 KDVEELlrQRAQAEERYGKELVQIA---RKAGGQTEMNSLRTSFDSLKQQTENVGSAhiQLALALREELRSLEEFRERQK 113
Cdd:PTZ00121 1405 KKADEL--KKAAAAKKKADEAKKKAeekKKADEAKKKAEEAKKADEAKKKAEEAKKA--EEAKKKAEEAKKADEAKKKAE 1480

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  114 EQRKKYEAimdrvQKSKLSLYKKTMESKKAYDQKcRDADDAEQAFERVSANGHQKQVEKSQnkakqcKESATEAERVyrQ 193
Cdd:PTZ00121 1481 EAKKADEA-----KKKAEEAKKKADEAKKAAEAK-KKADEAKKAEEAKKADEAKKAEEAKK------ADEAKKAEEK--K 1546

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 171184423  194 NIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNA 230
Cdd:PTZ00121 1547 KADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKA 1583

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423    26 LQRLLDGRK-MCKDVEELLRQRAQAEeRYgKELVQIARKAGGQ---TEMNSLRTSFDSLKQQTENVGSAHIQLALALREE 101
Cdd:TIGR02168  188 LDRLEDILNeLERQLKSLERQAEKAE-RY-KELKAELRELELAllvLRLEELREELEELQEELKEAEEELEELTAELQEL 265

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423   102 LRSLEEFRERQKEQRKKYEAIMDRVQKSKLSLYKKTMEsKKAYDQKCRDADDAEQAFERVSANGHQKQVEKSQNKA---- 177
Cdd:TIGR02168  266 EEKLEELRLEVSELEEEIEELQKELYALANEISRLEQQ-KQILRERLANLERQLEELEAQLEELESKLDELAEELAelee 344

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 171184423   178 -----KQCKESATEAERVYRQNIEQLERARTEWEQEHRT 211
Cdd:TIGR02168  345 kleelKEELESLEAELEELEAELEELESRLEELEEQLET 383

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Proline-Serine-Threonine Phosphatase-Interacting Protein 1 (PSTPIP1), also known as CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, 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 171184423  16 FTAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQTEMNSLRTSFDSLKQQTENVGSAHIQLA 95
Cdd:cd07671    1 FTLNTGYEILLQRLLDGRKMCKDVEELLKQRAQAEERYGKELVQIARKAGGQTEINTLKASFDQLKQQIENIGNSHIQLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  96 LALREELRSLEEFRERQKEQRKKYEAIMDRVQKSKLSLYKKTMESKKAYDQKCRDADDAEQAFERVSANGHQKQVEKSQN 175
Cdd:cd07671   81 GMLREELKSLEEFRERQKEQRKKYEAVMERVQKSKVSLYKKTMESKKTYEQRCREADEAEQTFERSSSTGNPKQSEKSQN 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423 176 KAKQCKESATEAERVYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNALWVHCNQLSMQCVKDDELYEEVRLT 255
Cdd:cd07671  161 KAKQCRDAATEAERVYKQNIEQLDKARTEWETEHILTCEVFQLQEDDRITILRNALWVHCNHFSMQCVKDDELYEEVRTT 240

                 ..
gi 171184423 256 LE 257
Cdd:cd07671  241 LE 242

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 2; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Proline-Serine-Threonine Phosphatase-Interacting Protein 2 (PSTPIP2), also known as Macrophage Actin-associated tYrosine Phosphorylated protein (MAYP), is mostly expressed in hematopoietic cells but is also expressed in the brain. It is involved in regulating cell adhesion and motility. Mutations in the gene encoding murine PSTPIP2 can cause autoinflammatory disorders such as chronic multifocal osteomyelitis and macrophage autoinflammatory disease. PSTPIP2 contains an N-terminal F-BAR domain and lacks the PEST motifs and SH3 domain that are found in PSTPIP1. 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 171184423  17 TAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKA-GGQTEMNSLRTSFDSLKQQTENVGSAHIQLA 95
Cdd:cd07672    2 TSTGGYDCIIQHLNDGRKNCKEFEDFLKERASIEEKYGKELLNLSKKKpCGQTEINTLKRSLDVFKQQIDNVGQSHIQLA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  96 LALREELRSLEEFRERQKEQRKKYEAIMDRVQKSKLSLYKKTMESKKAYDQKCRDADDAEQAFERVSANGHQKQVEKSQN 175
Cdd:cd07672   82 QTLRDEAKKMEDFRERQKLARKKIELIMDAIHKQRAMQFKKTMESKKNYEQKCRDKDEAEQAVNRNANLVNVKQQEKLFA 161

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 171184423 176 KAKQCKESATEAERVYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNALWVHCNQLSMQCVKDDELYEEVR 253
Cdd:cd07672  162 KLAQSKQNAEDADRLYMQNISVLDKIREDWQKEHVKACEFFEKQECERINFFRNAVWTHVNQLSQQCVTSDEMYEEVR 239

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 171184423  21 GYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQTEMNSLRTSFDSLKQQTENVGSAHIQLALALRE 100
Cdd:cd07651    6 GFDVIQTRIKDSLRTLEELRSFYKERASIEEEYAKRLEKLSRKSLGGSEEGGLKNSLDTLRLETESMAKSHLKFAKQIRQ 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423 101 ELRS-LEEFRERQKEQRKKYEAIMDRVQKSKLSLYKKTMESKKAYDQKCRDAddaeQAFERVSANGHQKQVEKSQNKAKQ 179
Cdd:cd07651   86 DLEEkLAAFASSYTQKRKKIQSHMEKLLKKKQDQEKYLEKAREKYEADCSKI----NSYTLQSQLTWGKELEKNNAKLNK 161

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 171184423 180 CKESATEAERVYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNALWVHCNQLSMQCVKDDELYEEVRL 254
Cdd:cd07651  162 AQSSINSSRRDYQNAVKALRELNEIWNREWKAALDDFQDLEEERIQFLKSNCWTFANNISTLCVDDDESCERIRS 236

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCH domain Only proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Proteins in this group have been named FCH domain Only (FCHO) proteins. Vertebrates have two members, FCHO1 and FCHO2. These proteins contain an F-BAR domain and a C-terminal domain of unknown function named SAFF which is also present in endophilin interacting protein 1. 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 171184423  19 HTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQTEMNSLRTSFDSLKQQTENVGSAHIQLALAL 98
Cdd:cd07648    4 NNGFDVLYHNMKHGQIAVKELADFLRERATIEETYSKALNKLAKQASNSSQLGTFAPLWLVLRVSTEKLSELHLQLVQKL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  99 REELRSLEEFRERQKEQRKKY--------EAIMdRVQKSKLSLYKktmeSKKAYDQKCRDADDAEQafervsANGHQKQV 170
Cdd:cd07648   84 QELIKDVQKYGEEQHKKHKKVkeeesgtaEAVQ-AIQTTTAALQK----AKEAYHARCLELERLRR------ENASPKEI 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423 171 EKSQNKAKQCKESateaervYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNALWVHCNQLSMQCVKDDELYE 250
Cdd:cd07648  153 EKAEAKLKKAQDE-------YKALVEKYNNIRADFETKMTDSCKRFQEIEESHLRQMKEFLASYAEVLSENHSAVGQVHE 225

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 171184423 251 EVRLTLEGCDVEGDINGFIQSKSTGREPPAPVPYQ 285
Cdd:cd07648  226 EFKRQVDELTVDKLLRQFVESKGTGTEKPELIEFE 260

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Growth Arrest Specific protein 7; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Growth Arrest Specific protein 7 (GAS7) is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. 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 171184423  17 TAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQTEMNSLRTSFDSLKQQTENVGSAHIQLAL 96
Cdd:cd07649    2 TTVTGFEILLQKQLKGKQMQKEMAEFIRERIKIEEEYAKNLSKLSQSSLAAQEEGTLGEAWAQVKKSLADEAEVHLKFSS 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  97 ALREEL-RSLEEFRERQKEQRKKYEAIMDRVQKSKLSLYKKTMESKKAYDQKCRDADDAEQAFERVSANGHQKQVEKSQN 175
Cdd:cd07649   82 KLQSEVeKPLLNFRENFKKDMKKLDHHIADLRKQLASRYAAVEKARKALLERQKDLEGKTQQLEIKLSNKTEEDIKKARR 161

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 171184423 176 KAKQCKESATEAERVYRQnieqlerARTEWEQEHRTTCEAFQLQEFDRLTILRNAL 231
Cdd:cd07649  162 KSTQAGDDLMRCVDLYNQ-------AQSKWFEEMVTTSLELERLEVERIEMIRQHL 210

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 171184423    12 WCRDFTAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARK----AGGQTEMNSLRTSFDSLKQQTENV 87
Cdd:smart00055   1 MGFWSELDDGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKKlravRDTEPEYGSLSKAWEVLLSETDAL 80

                   ....*..
gi 171184423    88 GSAHIQL 94
Cdd:smart00055  81 AKQHLEL 87

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 171184423 363 YRALYDYTAQNSDELDISAGDILAVILEGEDGWWTVE-RNGQRGFVPGSY 411
Cdd:cd00174    2 ARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGElNGGREGLFPANY 51

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. 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 171184423 363 YRALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLEK 414
Cdd:cd11856    2 YVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLEP 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 171184423 363 YRALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLE 413
Cdd:cd11772    2 FRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVE 52

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 171184423 364 RALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLE 413
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVE 52

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 171184423  16 FTAHTGYEVLLQRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKA--GGQTEMNSLRTSFDSLKQQTENVGSAHIQ 93
Cdd:cd07658    1 FMGQKGFEELRRYVKQGGDFCKELATVLQERAELELNYAKGLSKLSGKLskASKSVSGTLSSAWTCVAEEMESEADIHRN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423  94 LALALREEL-RSLEEFRERQKEQRKKYEAIMDRV-----------QKSKLSLYKKTMESKKAYDQKCRDADDAEQAFERV 161
Cdd:cd07658   81 LGSALTEEAiKPLRQVLDEQHKTRKPVENEVDKAaklltdwrseqIKVKKKLHGLARENEKLQDQVEDNKQSCTKQKMLN 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 171184423 162 ----SANGHQKQVEKSQNKAKQCKESATEAERVYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNAL 231
Cdd:cd07658  161 klkkSAEVQDKEDEKLEAKRKKGEESRLKAENEYYTCCVRLERLRLEWESALRKGLNQYESLEEERLQHLKHSL 234

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 171184423 363 YRALYDYTAQNSDELDISAGDILAVILE-GEDGWWT-VERNGQRGFVPGSYLE 413
Cdd:cd11763    2 VRALYDFDSQPSGELSLRAGEVLTITRQdVGDGWLEgRNSRGEVGLFPSSYVE 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 171184423 362 DYRALYDYTAQNSDELDISAGDILAVILEGEDGWW--TVERNGQRGFVPGSYLEK 414
Cdd:cd11789    1 RYRAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMegTVQRTGQSGMLPANYVEL 55

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. 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 171184423 363 YRALYDYTAQNSDELDISAGDILAVILEGEDGWWTVER-NGQRGFVPGSYLEK 414
Cdd:cd11770    2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAENsKGNRGLVPKTYLKV 54

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 171184423  363 YRALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLEKL 415
Cdd:pfam07653   2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEEI 54

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. 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 171184423 361 QDYRALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLEK 414
Cdd:cd12076    1 EKYTVIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLKK 54

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 171184423 364 RALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLE 413
Cdd:cd11840    3 IALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVE 52

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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 171184423 363 YRALYDYTAQNSDELDISAGDILAVILEGEDGWWTVE--RNGQRGFVPGSY 411
Cdd:cd11845    2 YVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARhlSTGKEGYIPSNY 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 171184423 364 RALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLE 413
Cdd:cd11874    3 KVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVK 52

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 171184423  27 QRLLDGRKMCKDVEELLRQRAQAEERYGKELVQIARKAGGQT----EMNSLRTSFDSLKQQTENVGSAHIQlalaLREEL 102
Cdd:cd07655   12 KRIEDGHKLCDDLMKMVQERAEIEKAYAKKLKEWAKKWRDLIekgpEYGTLETAWKGLLSEAERLSELHLS----IRDKL 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171184423 103 RSL--EEFRERQKE-----------QRKKYEAIMDRVQKSKLSLYKKTMESKKAYDQKCRDADDAEQAfERVSA---NGH 166
Cdd:cd07655   88 LNDvvEEVKTWQKEnyhksmmggfkETKEAEDGFAKAQKPWAKLLKKVEKAKKAYHAACKAEKSAQKQ-ENNAKsdtSLS 166

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 171184423 167 QKQVEKSQNKAKQCKESATEAERVYRQNIEQLERARTEWEQEHRTTCEAFQLQEFDRLTILRNAL 231
Cdd:cd07655  167 PDQVKKLQDKVEKCKQEVSKTKDKYEKALEDLNKYNPRYMEDMEQVFDKCQEFEEKRLDFFKEIL 231

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. 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 171184423 364 RALYDYTAQNSDELDISAGDILAVILE-GEDGWWTVERN-GQRGFVPGSYLE 413
Cdd:cd11911    3 TALYDFDGTSEGTLSMEEGEILLVLEEdGGDGWTRVRKNnGDEGYVPTSYIE 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 171184423 363 YRALYDYTAQNSDELDISAGDILAVILEGEDGWW--TVERNGQRGFVPGSYLEKL 415
Cdd:cd11916    4 YQALYSYAPQNDDELELRDGDIVDVMEKCDDGWFvgTSRRTKQFGTFPGNYVKLL 58

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 171184423 363 YRALYDYTAQNSDELDISAGDILAVILE--GEDGWWTVERNGQRGFVPGSYLE 413
Cdd:cd12142    2 CRVLFDYNPVAPDELALKKGDVIEVISKetEDEGWWEGELNGRRGFFPDNFVM 54

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. 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 171184423 365 ALYDYTAQNSDELDISAGDILAVILEGEDGWWTVERNGQRGFVPGSYLEK 414
Cdd:cd11808    4 ALYDYQEKSPREVSMKKGDILTLLNSSNKDWWKVEVNDRQGFVPAAYVKK 53