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 568918916 365 GVRVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11997    1 GVRVRALYDYTGQEADELSFKAGEELLKIGEEDEQGWCKGRLLSGRIGLYPANYVE 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 568918916 365 GVRVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11997    1 GVRVRALYDYTGQEADELSFKAGEELLKIGEEDEQGWCKGRLLSGRIGLYPANYVE 56

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568918916   22 YRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGAVEKG-PQYGTLEKAWHAFFTAAERLSELHLE 97
Cdd:pfam00611   2 FKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKKKKKPeDDGGTLKKAWDELLTETEQLAKQHLK 78

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568918916  370 ALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRG-DVITVIEESEDGWWEGIN-TGRTGLVPANYVE 49

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 568918916  16 FWEAGNYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGAVEKGPQYGTLEKAWHAFFTAAERLSELH 95
Cdd:cd07655    1 FWEVGNYKRTVKRIEDGHKLCDDLMKMVQERAEIEKAYAKKLKEWAKKWRDLIEKGPEYGTLETAWKGLLSEAERLSELH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918916  96 LEVREKLHGPDSERVRTWQRGAFHRPVLGGFRESRAAEDGFRKAQKPWLKRLKEVEASKKSYHTARKDEKTAQTRESHAK 175
Cdd:cd07655   81 LSIRDKLLNDVVEEVKTWQKENYHKSMMGGFKETKEAEDGFAKAQKPWAKLLKKVEKAKKAYHAACKAEKSAQKQENNAK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918916 176 ADSSMSQEQLRKLQERVGRCTKEAEKMKTQYEQTLAELNRYTPRYMEDMEQAFESCQAAERQRLLFFKDVLLTLHQHLDL 255
Cdd:cd07655  161 SDTSLSPDQVKKLQDKVEKCKQEVSKTKDKYEKALEDLNKYNPRYMEDMEQVFDKCQEFEEKRLDFFKEILLSYHRHLDL 240

                        250
                 ....*....|....*...
gi 568918916 256 SSSDKFHELHRDLQQSIE 273
Cdd:cd07655  241 STNPSFKAIYRDLQQTII 258

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSIN 1 or Syndapin I is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. It contains an N-terminal F-BAR domain and a C-terminal SH3 domain. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918916  16 FWEAGNYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGAVEKGPQYGTLEKAWHAFFTAAERLSELH 95
Cdd:cd07680    1 FWEVGNYKRTVKRIDDGHRLCNDLMNCVQERAKIEKAYGQQLTDWAKRWRQLIEKGPQYGSLERAWGAIMTEADKVSELH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918916  96 LEVREKLHGPDSERVRTWQRGAFHRPVLGGFRESRAAEDGFRKAQKPWLKRLKEVEASKKSYHTARKDEKTAQTRESHAK 175
Cdd:cd07680   81 QEVKNNLLNEDLEKVKNWQKDAYHKQIMGGFKETKEAEDGFRKAQKPWAKKMKELEAAKKAYHLACKEEKLAMTREANSK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918916 176 ADSSMSQEQLRKLQERVGRCTKEAEKMKTQYEQTLAELNRYTPRYMEDMEQAFESCQAAERQRLLFFKDVLLTLHQHLDL 255
Cdd:cd07680  161 AEQSVTPEQQKKLQDKVDKCKQDVQKTQEKYEKVLDDVGKTTPQYMENMEQVFEQCQQFEEKRLVFLKEVLLDIKRHLNL 240

                        250
                 ....*....|....*..
gi 568918916 256 SSSDKFHELHRDLQQSI 272
Cdd:cd07680  241 AESSSYAHVYRELEQTI 257

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQsGRIGLYPANYVE 420
Cdd:cd11843    1 PVRALYDYEGQESDELSFKAGDILTKLEEEDEQGWCKGRLD-GRVGLYPANYVE 53

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568918916 365 GVRVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11999    1 GVRVRAVYDYTGQEPDELSFKAGEELLKVEDEDEQGWCKGVTDGGAVGLYPANYVE 56

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568918916   22 YRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGAVEKG-PQYGTLEKAWHAFFTAAERLSELHLE 97
Cdd:pfam00611   2 FKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKKKKKPeDDGGTLKKAWDELLTETEQLAKQHLK 78

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 568918916    15 SFWEAG--NYRRTVQRVEDGHRLCGDLVSCFQERARIEKAYAQQLADWARKWRGAVEKGPQYGTLEKAWHAFFTAAERLS 92
Cdd:smart00055   2 GFWSELddGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKKLRAVRDTEPEYGSLSKAWEVLLSETDALA 81

                   ....*.
gi 568918916    93 ELHLEV 98
Cdd:smart00055  82 KQHLEL 87

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). 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 568918916 367 RVRALYDYAGQEADELSFRAGE--ELLKmseEDEQGWCQGQLQsGRIGLYPANYVE 420
Cdd:cd11827    1 QCKALYAYDAQDTDELSFNEGDiiEILK---EDPSGWWTGRLR-GKEGLFPGNYVE 52

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 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLqSGRIGLYPANYVE 420
Cdd:cd11826    1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDD-GWYEGVL-NGVTGLFPGNYVE 52

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568918916  370 ALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRG-DVITVIEESEDGWWEGIN-TGRTGLVPANYVE 49

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11960    1 RARALYDYQAADDTEISFDPGDIITDIEQIDE-GWWRGTGPDGTYGLFPANYVE 53

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 568918916 369 RALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQ-SGRIGLYPANYVECV 422
Cdd:cd11935    4 RAMYDYSAQDEDEVSFRDGDYIVNVQPIDE-GWMYGTVQrTGRTGMLPANYIEFV 57

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 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQsGRIGLYPANYVE 420
Cdd:cd11882    1 RARALYACKAEDESELSFEPGQIITNVQPSDEPGWLEGTLN-GRTGLIPENYVE 53

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 568918916 367 RVRALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:cd11823    1 RCKALYSYTANREDELSLQPG-DIIEVHEKQDDGWWLGEL-NGKKGIFPATYVE 52

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 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQ-SGRIGLYPANYVE 420
Cdd:cd11789    1 RYRAMYDYAAADDDEVSFQEGDVIINVEIIDD-GWMEGTVQrTGQSGMLPANYVE 54

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918916 364 TGVRVRALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQ-SGRIGLYPANYVECV 422
Cdd:cd11934    1 GGKRYRAVYDYNAADEDEVSFQDGDTIVNVQQIDD-GWMYGTVErTGDTGMLPANYVEAI 59

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). 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 568918916 367 RVRALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11758    2 YVRALFDFPGNDDEDLPFKKG-EILTVIRKPEEQWWNARNSEGKTGMIPVPYVE 54

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11896    1 KARALYSFQSENKEEINIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVE 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMS----EEDEQGWCQGQLQS-GRIGLYPANYVE 420
Cdd:cd11790    4 KVRATHDYTAEDTDELTFEKGDVILVIPfddpEEQDEGWLMGVKEStGCRGVFPENFTE 62

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

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gi 568918916 368 VRALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLQsGRIGLYPANYVE 420
Cdd:cd11873    2 VIVEFDYDAEEPDELTLKVG-DIITNVKKMEEGWWEGTLN-GKRGMFPDNFVK 52

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

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gi 568918916 369 RALYDYAGQEADELSFRAGEELLKMSEEDEQGWCQGQlQSGRIGLYPANYV 419
Cdd:cd11804    3 VAKHDFKATAEDELSFKKGSILKVLNMEDDPNWYKAE-LDGKEGLIPKNYI 52

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

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gi 568918916 368 VRALYDYAGQEADELSFRAGE--ELLKMSEEdeqGWCQGQLQsGRIGLYPANYVE 420
Cdd:cd11950    2 VRALYDFEALEDDELGFNSGDviEVLDSSNP---SWWKGRLH-GKLGLFPANYVA 52

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

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gi 568918916 370 ALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQsGRIGLYPANYVE 420
Cdd:cd12073    5 ALYDYQGEGDDEISFDPQETITDIEMVDE-GWWKGTCH-GHRGLFPANYVE 53

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) 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 568918916 368 VRALYDYAGQEADELSFRAGEELLKMSEEDEQgWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11849    2 YRALYDFKSAEPNTLSFSEGETFLLLERSNAH-WWLVTNHSGETGYVPANYVK 53

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

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gi 568918916 368 VRALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:cd11877    2 VRAKFNFEGTNEDELSFDKG-DIITVTQVVEGGWWEGTL-NGKTGWFPSNYVK 52

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. 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 568918916 368 VRALYDYAGQEADELSFRAGE--ELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:cd11894    2 VKALYDYEGQTDDELSFPEGAiiRILNKENQDDDGFWEGEF-NGRIGVFPSVLVE 55

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 568918916 367 RVRALYDYAGQEADELSFRAGEElLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:cd11874    1 RCKVLFSYTPQNEDELELKVGDT-IEVLGEVEEGWWEGKL-NGKVGVFPSNFVK 52

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 568918916 367 RVRALYDY-------AGQEADELSFRAGEELLKMSEEDEQGWCQGQLQSGRIGLYPANYVE 420
Cdd:cd11851    1 LMVALYDYnpetmspNDDPEEELSFHAGDVVRVYGPMDEDGFYYGELEGGRKGLVPSNFVQ 61

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 568918916 370 ALYDYAGQEADELSFRAGEELLKMSEEDEqGWCQGQLQsGRIGLYPANYVE 420
Cdd:cd11959    4 ALYDYQAADDDEISFDPDDIITNIEMIDE-GWWRGVCR-GKYGLFPANYVE 52

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A 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 568918916 369 RALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:cd12054    4 KVLFEYVPQNEDELELKVG-DIIDINEEVEEGWWSGTL-NGKSGLFPSNFVK 53

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 568918916 367 RVRALYDYAGQEADELSFRAGeELLKMSEEDEQGWCQGQLqSGRIGLYPANYVE 420
Cdd:cd11996    2 QVIAMYDYTANNEDELSFSKG-QLINVLNKDDPDWWQGEI-NGVTGLFPSNYVK 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. 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 568918916 367 RVRALYDYAGQEADELSFRAGEELLKMSEEDEQgWCQGQL--QSGRIGLYPANY 418
Cdd:cd11821    1 RVRALYDCQADNDDELTFSEGEIIVVTGEEDDE-WWEGHIegDPSRRGVFPVSF 53