ADF homology domain of drebrin and actin-binding protein 1 (abp1); Actin depolymerization factor/cofilin-like domains (ADF domains) are present in a family of essential eukaryotic actin regulatory proteins. Many of these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments. Abp1 and drebrin (developmentally regulated brain protein) are multidomain proteins with an N-terminal ADF homology domain and one or more C-terminal SH3 domains. They have been shown to interact with polymeric F-actin, but not with monomeric G-actin, and do not appear to promote the disassembly of actin filaments. Drebrin rather stabilizes actin filaments by inducing changes in the helical twist and may promote or interfere with the interactions of other proteins with actin filaments.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361670   3 ANLSRNGPALQEAYVRVVTEKSPTDWALFTYEGNSNDIRVAGTGEGGLEEMVEELNSGKVMYAFCRVKDPNSGLPKFVLI 82
Cdd:cd11281   1 IDLSTNSPEILAAYEDVVDGKSSTDWALFTYEGKSNDLKVADTGDGGLEELVEEFSDGKVQYGFARVKDPNSGLPKFVLI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 21361670  83 NWTGEGVNDVRKGACASHVSTMASFLKGAHVTINARAEEDVEPECIMEKVAKASGA 138
Cdd:cd11281  81 NWCGEGVPDARKGSFASHVAAVANFLKGAHVQINARSEDDLDEDAILKKVSKASGA 136

ADF homology domain of drebrin and actin-binding protein 1 (abp1); Actin depolymerization factor/cofilin-like domains (ADF domains) are present in a family of essential eukaryotic actin regulatory proteins. Many of these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments. Abp1 and drebrin (developmentally regulated brain protein) are multidomain proteins with an N-terminal ADF homology domain and one or more C-terminal SH3 domains. They have been shown to interact with polymeric F-actin, but not with monomeric G-actin, and do not appear to promote the disassembly of actin filaments. Drebrin rather stabilizes actin filaments by inducing changes in the helical twist and may promote or interfere with the interactions of other proteins with actin filaments.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361670   3 ANLSRNGPALQEAYVRVVTEKSPTDWALFTYEGNSNDIRVAGTGEGGLEEMVEELNSGKVMYAFCRVKDPNSGLPKFVLI 82
Cdd:cd11281   1 IDLSTNSPEILAAYEDVVDGKSSTDWALFTYEGKSNDLKVADTGDGGLEELVEEFSDGKVQYGFARVKDPNSGLPKFVLI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 21361670  83 NWTGEGVNDVRKGACASHVSTMASFLKGAHVTINARAEEDVEPECIMEKVAKASGA 138
Cdd:cd11281  81 NWCGEGVPDARKGSFASHVAAVANFLKGAHVQINARSEDDLDEDAILKKVSKASGA 136

Cofilin/tropomyosin-type actin-binding protein; Severs actin filaments and binds to actin monomers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361670    12 LQEAYVRVVTEKSpTDWALFTYEGNSNDIRVAGTGEGGL--EEMVEELNSGKVMYAFCRVK---DPNSGLPKFVLINWTG 86
Cdd:pfam00241   1 CKEAYQELRSDKK-TNWIIFKIDDDKEEIVVEETGEGGLsyDEFLEELPDDEPRYAVYRFEythDDGSKRSKLVFITWCP 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 21361670    87 EGVNDVRKGACASHVSTMASFLKGAHVTINARAEEDVEPECIME 130
Cdd:pfam00241  80 DGAPIKRKMLYASSKAALKRELKGIHVEIQATDPSELTEEEILE 123

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 21361670    377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHFGMFPANYVE 428
Cdd:smart00326   5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56

ADF homology domain of drebrin and actin-binding protein 1 (abp1); Actin depolymerization factor/cofilin-like domains (ADF domains) are present in a family of essential eukaryotic actin regulatory proteins. Many of these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments. Abp1 and drebrin (developmentally regulated brain protein) are multidomain proteins with an N-terminal ADF homology domain and one or more C-terminal SH3 domains. They have been shown to interact with polymeric F-actin, but not with monomeric G-actin, and do not appear to promote the disassembly of actin filaments. Drebrin rather stabilizes actin filaments by inducing changes in the helical twist and may promote or interfere with the interactions of other proteins with actin filaments.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361670   3 ANLSRNGPALQEAYVRVVTEKSPTDWALFTYEGNSNDIRVAGTGEGGLEEMVEELNSGKVMYAFCRVKDPNSGLPKFVLI 82
Cdd:cd11281   1 IDLSTNSPEILAAYEDVVDGKSSTDWALFTYEGKSNDLKVADTGDGGLEELVEEFSDGKVQYGFARVKDPNSGLPKFVLI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 21361670  83 NWTGEGVNDVRKGACASHVSTMASFLKGAHVTINARAEEDVEPECIMEKVAKASGA 138
Cdd:cd11281  81 NWCGEGVPDARKGSFASHVAAVANFLKGAHVQINARSEDDLDEDAILKKVSKASGA 136

Cofilin/tropomyosin-type actin-binding protein; Severs actin filaments and binds to actin monomers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361670    12 LQEAYVRVVTEKSpTDWALFTYEGNSNDIRVAGTGEGGL--EEMVEELNSGKVMYAFCRVK---DPNSGLPKFVLINWTG 86
Cdd:pfam00241   1 CKEAYQELRSDKK-TNWIIFKIDDDKEEIVVEETGEGGLsyDEFLEELPDDEPRYAVYRFEythDDGSKRSKLVFITWCP 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 21361670    87 EGVNDVRKGACASHVSTMASFLKGAHVTINARAEEDVEPECIME 130
Cdd:pfam00241  80 DGAPIKRKMLYASSKAALKRELKGIHVEIQATDPSELTEEEILE 123

Actin depolymerisation factor/cofilin -like domains; Severs actin filaments and binds to actin monomers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361670      7 RNGPALQEAYVRVVTeKSPTDWALFTYegNSNDIRV-AGTGEGGLEEMVEELNSGKVMYAFCRVKDP--NSGLPKFVLIN 83
Cdd:smart00102   1 EDCKEAFNELKKKRK-HSAIIFKIDKD--NEEIVVEeVGSTEDSYDEFVEELPEDECRYALYDYKFTteESKKSKIVFIF 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 21361670     84 WTGEGVNDVRKGACASHVSTMASFLKGAHVTINARAEEDVEPECIMEKV 132
Cdd:smart00102  78 WSPDGAPVKSKMLYASSKDTLKKELGGIQVEVQATDEDDLDEEALKEKL 126

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 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGpDGHFGMFPANYVEL 429
Cdd:cd11959   2 AVALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVC-RGKYGLFPANYVEL 53

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 21361670 375 LCARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGpDGHFGMFPANYVEL 429
Cdd:cd12073   1 ICAVALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTC-HGHRGLFPANYVEL 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 21361670 378 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGP-DGHFGMFPANYVEL 429
Cdd:cd11789   3 RAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGTVQrTGQSGMLPANYVEL 55

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 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHFGMFPANY 426
Cdd:cd00174   2 ARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGREGLFPANY 51

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 21361670 378 RALYDYQAADDTEISFDPENLITGIEVIDEGWWrgYGP---DGHFGMFPANYVELI 430
Cdd:cd11934   6 RAVYDYNAADEDEVSFQDGDTIVNVQQIDDGWM--YGTverTGDTGMLPANYVEAI 59

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 21361670 378 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRG-YGPDGHFGMFPANYVELI 430
Cdd:cd11935   4 RAMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGtVQRTGRTGMLPANYIEFV 57

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHFGMFPANYVEL 429
Cdd:cd11962   2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTNSKGESGLFPSNYVEL 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 21361670 378 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHfGMFPANYV 427
Cdd:cd11820   4 RALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGE-GLFPANFV 52

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 21361670 376 CARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVELI 430
Cdd:cd11803   2 CCRALYDFEPENEGELGFKEGDIITLTNQIDENWYEGM-VNGQSGFFPVNYVEVL 55

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 21361670   379 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGyGPDGHFGMFPANYVE 428
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEG-INTGRTGLVPANYVE 49

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 21361670 378 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVEL 429
Cdd:cd11840   3 IALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGE-LNGQTGLFPSNYVEP 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 21361670 378 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVE 428
Cdd:cd11826   3 VALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGV-LNGVTGLFPGNYVE 52

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 21361670 377 ARALYDYQAADDTEISFdPENLITGI-----EVIDEGWWRGYgPDGHFGMFPANYVE 428
Cdd:cd11762   2 VRALYDYEAQSDEELSF-PEGAIIRIlrkddNGVDDGWWEGE-FNGRVGVFPSLVVE 56

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 21361670 374 GLCARALYDYQAADDTEISFDP-ENLITGIEVIDEGWWRGYGPDGHFGMFPANYVE 428
Cdd:cd11997   1 GVRVRALYDYTGQEADELSFKAgEELLKIGEEDEQGWCKGRLLSGRIGLYPANYVE 56

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 21361670 377 ARALYDYQAADD--TEISFDPENLItgiEVIDEG--WWRGYGPDGHFGMFPANYVEL 429
Cdd:cd11855   2 ARALYPYDASPDdpNELSFEKGEIL---EVSDTSgkWWQARKSNGETGICPSNYLQL 55

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 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDE-GWWRGYgPDGHFGMFPANYVEL 429
Cdd:cd11882   2 ARALYACKAEDESELSFEPGQIITNVQPSDEpGWLEGT-LNGRTGLIPENYVEF 54

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. 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. 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 21361670 378 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRG-YGPDGHFgMFPANYVE 428
Cdd:cd11969   3 KALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGdYGGKVQH-YFPSNYVE 53

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 21361670 376 CARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVE 428
Cdd:cd11786   1 CAKALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGE-CNGKQGFFPASYVQ 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The 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 21361670 379 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVEL 429
Cdd:cd11995   5 GMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE-LNGQVGLFPSNYVKL 54

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which 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.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 21361670 379 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVEL 429
Cdd:cd11996   5 AMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGE-INGVTGLFPSNYVKM 54

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

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                ....*....|....*....|....*....|....*....|....*....|....*
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGI--EVIDEGWWRGYgPDGHFGMFPANYVEL 429
Cdd:cd11875   2 ARVLFDYEAENEDELTLREGDIVTILskDCEDKGWWKGE-LNGKRGVFPDNFVEP 55

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 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. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGyGPDGHFGMFPANYVE 428
Cdd:cd11949   2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKG-ACHGQTGMFPRNYVT 52

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 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGyGPDGHFGMFPANY 426
Cdd:cd11818   2 ARALYDFTGENEDELSFKAGDIITELESIDEEWMSG-ELRGKSGIFPKNF 50

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

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                ....*....|....*....|....*....|....*....|....*....|..
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVE 428
Cdd:cd11950   2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGR-LHGKLGLFPANYVA 52

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. 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 21361670 379 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDgHFGMFPANYV 427
Cdd:cd11833   4 ALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIED-RVGFFPANFV 51

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. 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 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPdGHFGMFPANYVE 428
Cdd:cd11766   2 AVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECN-GQVGWFPSNYVT 52

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

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                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGIEV-----IDEGWWRGYGP-DGHFGMFPANYVELI 430
Cdd:cd11790   5 VRATHDYTAEDTDELTFEKGDVILVIPFddpeeQDEGWLMGVKEsTGCRGVFPENFTERI 64

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYV 427
Cdd:cd11951   2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGR-ISGRVGFFPRNYV 51

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

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                ....*....|....*....|....*....|....*....|....*....|....
gi 21361670 377 ARALYDYQAADDTEISF-DPENLITGIEVIDEGWWRGYGPDGHFGMFPANYVEL 429
Cdd:cd11896   2 ARALYSFQSENKEEINIqENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 55

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 21361670 378 RALYDYQAADDTE-ISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYV 427
Cdd:cd11829   3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDGGWWEGE-KDGLRGWFPASYV 52

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. 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. 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.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 21361670 379 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGpDGHFGMFPANYVELI 430
Cdd:cd11971   4 AIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVC-NGVTGLFPGNYVESI 54

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

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                ....*....|....*....|....*....|....*....|....*....|....*
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGIE--VIDEGWWRGYGPDGHFGMFPANYVEL 429
Cdd:cd11767   2 VVALYPFTGENDEELSFEKGERLEIIEkpEDDPDWWKARNALGTTGLVPRNYVEV 56

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.

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                ....*....|....*....|....*....|....*....|....*....|...
gi 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVEL 429
Cdd:cd11874   2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGK-LNGKVGVFPSNFVKE 53

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                ....*....|....*....|....*....|....*....|....*....|....*...
gi 21361670 372 GQGLCARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHfGMFPANYVEL 429
Cdd:cd11973  15 GSVVCAEALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSE-GWFPASFVRL 71

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. 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 21361670 377 ARALYDYQAADDTEISFDPENLITGIEVIDE-GWWRG--YGpdgHFGMFPANYVE 428
Cdd:cd11976   2 AKARYDFCARDRSELSLKEGDIIKILNKKGQqGWWRGeiYG---RVGWFPANYVE 53

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.

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 21361670 376 CARALYDYQAADDTEISFDPENLITGI--EVIDEGWWRGYgPDGHFGMFPANYVEL 429
Cdd:cd12142   1 YCRVLFDYNPVAPDELALKKGDVIEVIskETEDEGWWEGE-LNGRRGFFPDNFVMP 55