Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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 1390016160 221 HETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 282
Cdd:cd11936     1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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 1390016160 221 HETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 282
Cdd:cd11936     1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Histidine phosphatase superfamily (branch 1); The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The larger branch 1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in branch 1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in branch 1 members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 403 DAPITVFGCMQARLVGEALLESNtiIDHVYCSPSLRCVQTAHNILKGLQqenhLKIRVEPGLFEW--------TKWVAGS 474
Cdd:pfam00300  22 DSPLTELGREQAEALAERLAGEP--FDAIYSSPLKRARQTAEIIAEALG----LPVEIDPRLREIdfgdweglTFEEIAE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 475 TLPAWippselAAANLSVDTTYRPHIPisklvvsESYDTYISRSFQVTKEIISecKSKGNNILIVAHASSLEACTCQLQG 554
Cdd:pfam00300  96 RYPEE------YDAWLADPADYRPPGG-------ESLADVRARVRAALEELAA--RHPGKTVLVVSHGGVIRALLAHLLG 160

                         170
                  ....*....|.
gi 1390016160 555 LSPQNSKDFVQ 565
Cdd:pfam00300 161 LPLEALRRFPL 171

Phosphoglycerate mutase family; Phosphoglycerate mutase (PGAM) and bisphosphoglycerate mutase (BPGM) are structurally related enzymes that catalyse reactions involving the transfer of phospho groups between the three carbon atoms of phosphoglycerate... Both enzymes can catalyse three different reactions with different specificities, the isomerization of 2-phosphoglycerate (2-PGA) to 3-phosphoglycerate (3-PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer of the reaction, the synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer and the degradation of 2,3-DPG to 3-PGA (phosphatase activity). In mammals, PGAM is a dimeric protein with two isoforms, the M (muscle) and B (brain) forms. In yeast, PGAM is a tetrameric protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160  403 DAPITVFGCMQARLVGEALLESNTI-IDHVYCSPSLRCVQTAHNILKGLQQeNHLKIRvEPGLFEwtkwvaGSTLPAWI- 480
Cdd:smart00855  23 DVPLTELGRAQAEALGRLLASLLLPrFDVVYSSPLKRARQTAEALAIALGL-PGLRER-DFGAWE------GLTWDEIAa 94

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1390016160  481 -PPSELAAANLSVDTTYRPHIPisklvVSESYDTYISRSFQVTKEIISECKSKGNNILIVAHASSL 545
Cdd:smart00855  95 kYPEEYLAAWRDPYDPAPPAPP-----GGESLADLVERVEPALDELIATADASGQNVLIVSHGGVI 155

alpha-ribazole phosphatase; Members of this protein family include the known CobC protein of Salmonella and Eschichia coli species, and homologous proteins found in cobalamin biosynthesis regions in other bacteria. This protein is alpha-ribazole phosphatase (EC 3.1.3.73) and, like many phosphatases, can be closely related in sequence to other phosphatases with different functions. Close homologs excluded from this model include proteins with duplications, so this model is built in -g mode to suppress hits to those proteins. [Biosynthesis of cofactors, prosthetic groups, and carriers, Heme, porphyrin, and cobalamin]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 403 DAPITVFGCMQARLVGEALleSNTIIDHVYCSPSLRCVQTAHNILKGLqqenHLKIRVEP-------GLFEWTKWvagST 475
Cdd:TIGR03162  21 DVPLAESGEEQAAALREKL--ADVPFDAVYSSPLSRCRELAEILAERR----GLPIIKDDrlremdfGDWEGRSW---DE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 476 LPAWIPpsELAA-ANLSVdtTYRPHipisklvVSESYDTYISRSFQVTKEIISEckSKGNNILIVAHASSLEACTCQLQG 554
Cdd:TIGR03162  92 IPEAYP--ELDAwAADWQ--HARPP-------GGESFADFYQRVSEFLEELLKA--HEGDNVLIVTHGGVIRALLAHLLG 158

                  ....
gi 1390016160 555 LSPQ 558
Cdd:TIGR03162 159 LPLE 162

phosphoglycerate mutase like-protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 403 DAPITVFGCMQARLVGEALLESNTIIDHVYCSPSLRCVQTAHNILKGLQQ------------ENHLKIRvePGL--FEWT 468
Cdd:PTZ00123   12 DVPLSEKGVQEAREAGKLLKEKGFRFDVVYTSVLKRAIKTAWIVLEELGQlhvpvikswrlnERHYGAL--QGLnkSETA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 469 KWVAGSTLPAW-----IPPSELAAANL---SVDTTYRpHIPISKLVVSESYDTYISRSFQVTKEIISECKSKGNNILIVA 540
Cdd:PTZ00123   90 EKHGEEQVKIWrrsydIPPPPLEKSDErypGNDPVYK-DIPKDALPNTECLKDTVERVLPYWEDHIAPDILAGKKVLVAA 168

                         170
                  ....*....|....*...
gi 1390016160 541 HASSLEACTCQLQGLSPQ 558
Cdd:PTZ00123  169 HGNSLRALVKYLDKMSEE 186

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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 1390016160 221 HETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 282
Cdd:cd11936     1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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 1390016160 222 ETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENY 278
Cdd:cd11937     1 QTLRALFQYKPQNIDELMLSPGDYIFVDPTQQSEASEGWVIGISHRTGCRGFLPENY 57

Histidine phosphatase superfamily (branch 1); The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The larger branch 1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in branch 1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in branch 1 members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 403 DAPITVFGCMQARLVGEALLESNtiIDHVYCSPSLRCVQTAHNILKGLQqenhLKIRVEPGLFEW--------TKWVAGS 474
Cdd:pfam00300  22 DSPLTELGREQAEALAERLAGEP--FDAIYSSPLKRARQTAEIIAEALG----LPVEIDPRLREIdfgdweglTFEEIAE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 475 TLPAWippselAAANLSVDTTYRPHIPisklvvsESYDTYISRSFQVTKEIISecKSKGNNILIVAHASSLEACTCQLQG 554
Cdd:pfam00300  96 RYPEE------YDAWLADPADYRPPGG-------ESLADVRARVRAALEELAA--RHPGKTVLVVSHGGVIRALLAHLLG 160

                         170
                  ....*....|.
gi 1390016160 555 LSPQNSKDFVQ 565
Cdd:pfam00300 161 LPLEALRRFPL 171

Broad specificity phosphatase PhoE [Carbohydrate transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 403 DAPITVFGCMQARLVGEALLESNtiIDHVYCSPSLRCVQTAHNILKGLqqenHLKIRVEPGLFEWtkwvagsTLPAW--I 480
Cdd:COG0406    25 DVPLTELGRAQARALAERLADIP--FDAVYSSPLQRARQTAEALAEAL----GLPVEVDPRLREI-------DFGDWegL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 481 PPSELAAANLSVDTTYRPHIPISKLVVSESYDTYISRSFQVTKEIISecKSKGNNILIVAHASSLEACTCQLQGLSPQNS 560
Cdd:COG0406    92 TFAELEARYPEALAAWLADPAEFRPPGGESLADVQARVRAALEELLA--RHPGGTVLVVTHGGVIRALLAHLLGLPLEAF 169

                  ...
gi 1390016160 561 KDF 563
Cdd:COG0406   170 WRL 172

Phosphoglycerate mutase family; Phosphoglycerate mutase (PGAM) and bisphosphoglycerate mutase (BPGM) are structurally related enzymes that catalyse reactions involving the transfer of phospho groups between the three carbon atoms of phosphoglycerate... Both enzymes can catalyse three different reactions with different specificities, the isomerization of 2-phosphoglycerate (2-PGA) to 3-phosphoglycerate (3-PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer of the reaction, the synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer and the degradation of 2,3-DPG to 3-PGA (phosphatase activity). In mammals, PGAM is a dimeric protein with two isoforms, the M (muscle) and B (brain) forms. In yeast, PGAM is a tetrameric protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160  403 DAPITVFGCMQARLVGEALLESNTI-IDHVYCSPSLRCVQTAHNILKGLQQeNHLKIRvEPGLFEwtkwvaGSTLPAWI- 480
Cdd:smart00855  23 DVPLTELGRAQAEALGRLLASLLLPrFDVVYSSPLKRARQTAEALAIALGL-PGLRER-DFGAWE------GLTWDEIAa 94

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1390016160  481 -PPSELAAANLSVDTTYRPHIPisklvVSESYDTYISRSFQVTKEIISECKSKGNNILIVAHASSL 545
Cdd:smart00855  95 kYPEEYLAAWRDPYDPAPPAPP-----GGESLADLVERVEPALDELIATADASGQNVLIVSHGGVI 155

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1390016160 223 TLQVIYPYTPQNDDELELVPGDFIfmSPMEQtsTSEGWIYGTSLTTGCSGLLPENYI 279
Cdd:cd11916     3 SYQALYSYAPQNDDELELRDGDIV--DVMEK--CDDGWFVGTSRRTKQFGTFPGNYV 55

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390016160 223 TLQVIYPYTPQNDDELELVPGDFI----FMSPMEQtstSEGWIYGTSLTTGCSGLLPENY 278
Cdd:cd11790     4 KVRATHDYTAEDTDELTFEKGDVIlvipFDDPEEQ---DEGWLMGVKESTGCRGVFPENF 60

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 1390016160 227 IYPYTPQNDDELELVPGDFIFmspmEQTSTSEGWIYGTSLTTGCSGLLPENYITK 281
Cdd:cd11789     5 MYDYAAADDDEVSFQEGDVII----NVEIIDDGWMEGTVQRTGQSGMLPANYVEL 55

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 1390016160 223 TLQVIYPYTPQNDDELELVPGDFIF-MSPMEqtstsEGWIYGTSLTTGCSGLLPENYI 279
Cdd:cd11935     2 TYRAMYDYSAQDEDEVSFRDGDYIVnVQPID-----EGWMYGTVQRTGRTGMLPANYI 54

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. 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 1390016160 227 IYPYTPQNDDELELVPGDFIFMSPMEQtstsEGWIYGTSLTTGCSGLLPENYIT 280
Cdd:cd11925     6 LYAYKPQKNDELELRKGEMYRVIEKCQ----DGWFKGTSLRTGVSGVFPGNYVT 55

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1390016160 222 ETLQVIYPYTPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSLTTGCSGLLPENYI 279
Cdd:cd11933     2 KSFRAMYDYRAADDDEVSFKDGDTI----VNVQTIDEGWMYGTVQRTGKTGMLPANYV 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 1390016160 225 QVIYPYTPQNDDELELVPGDFIFMSPMEqtstSEGWIYGTsLTTGCSGLLPENY 278
Cdd:cd00174     3 RALYDYEAQDDDELSFKKGDIITVLEKD----DDGWWEGE-LNGGREGLFPANY 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 1390016160 225 QVIYPYTPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSLTTGCSGLLPENYI 279
Cdd:cd11934     6 RAVYDYNAADEDEVSFQDGDTI----VNVQQIDDGWMYGTVERTGDTGMLPANYV 56

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It 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. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, 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 1390016160 227 IYPYTPQNDDELELVPGDFIFMSPMEQtstsEGWIYGTSLTTGCSGLLPENYIT 280
Cdd:cd11926     5 IYPYTPRKEDELELRKGEMFLVFERCQ----DGWFKGTSMHTSKIGVFPGNYVA 54

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 1390016160 225 QVIYPYTPQNDDELELVPGDFI-FMSPMEqtstsEGWIYGTslTTGCSGLLPENYIT 280
Cdd:cd11874     3 KVLFSYTPQNEDELELKVGDTIeVLGEVE-----EGWWEGK--LNGKVGVFPSNFVK 52

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH 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 1390016160 225 QVIYPYTPQNDDELELVPGDFIFMSpmeqTSTSEGWIYGTSLTTGCSGLLPENY 278
Cdd:cd11793     3 QCVHAYTAQQPDELTLEEGDVVNVL----RKMPDGWYEGERLRDGERGWFPSSY 52

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

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gi 1390016160 227 IYPYTPQNDDELELVPGDFIFMSPMeqtsTSEGWIYGTslTTGCSGLLPENYIT 280
Cdd:cd11772     5 LYDYEAQHPDELSFEEGDLLYISDK----SDPNWWKAT--CGGKTGLIPSNYVE 52

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 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 CIN85. SH3B has been shown to bind Cbl proline-rich peptides and 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 1390016160 225 QVIYPYTPQNDDELELVPGDFI-FMSPMEqtstsEGWIYGtsLTTGCSGLLPENYI 279
Cdd:cd12055     3 QVAFSYLPQNEDELELKVGDIIeVVGEVE-----EGWWEG--VLNGKTGMFPSNFI 51

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 1390016160 225 QVIYPYTPQNDDELELVPGDFIFMspMEQTSTSEGWIYGTslTTGCSGLLPENYI 279
Cdd:cd12142     3 RVLFDYNPVAPDELALKKGDVIEV--ISKETEDEGWWEGE--LNGRRGFFPDNFV 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.

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gi 1390016160 227 IYPYTPQNDDELELVPGDFIFMSPMEqtstSEGWIYGtSLtTGCSGLLPENYI 279
Cdd:cd11823     5 LYSYTANREDELSLQPGDIIEVHEKQ----DDGWWLG-EL-NGKKGIFPATYV 51

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.

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gi 1390016160 225 QVIYPYTPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSlTTGCSGLLPENYI 279
Cdd:cd11962     3 VVLYDYEKDEDNEIELVEGEIV----TNIEMVDEDWWMGTN-SKGESGLFPSNYV 52

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH 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 1390016160 224 LQVIYPYTPQNDDELELVPGDFIFMspmeQTSTSEGWIYGTSLTTGCSGLLPENYI 279
Cdd:cd11940     2 VQCIRSYKAQENDELTLEKADIIMV----RQQSSDGWLEGVRLSDGERGWFPQSHV 53

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 1390016160 225 QVIYPYTPQNDDELELVPGDFIFMspMEqtSTSEGWIYGTSLttGCSGLLPENYITK 281
Cdd:cd11766     3 VVKFNYEAQREDELSLRKGDRVLV--LE--KSSDGWWRGECN--GQVGWFPSNYVTE 53

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

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gi 1390016160 225 QVI--YPYTPQNDDELELVPGDFI-FMSPMEQTstsegWIYGTslTTGCSGLLPENYIT 280
Cdd:cd11840     1 QVIalFPYTAQNEDELSFQKGDIInVLSKDDPD-----WWRGE--LNGQTGLFPSNYVE 52

Src homology 3 domain of Alpha1,6-fucosyltransferase (Fut8); Fut8 catalyzes the alpha1,6-linkage of a fucose residue from a donor substrate to N-linked oligosaccharides on glycoproteins in a process called core fucosylation, which is crucial for growth factor receptor-mediated biological functions. Fut8-deficient mice show severe growth retardation, early death, and a pulmonary emphysema-like phenotype. Fut8 is also implicated to play roles in aging and cancer metastasis. It contains an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The SH3 domain of Fut8 is located in the lumen and its role in glycosyl transfer is unclear. 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 1390016160 226 VIYPYTPQNDDELELVPGDFIFMSPmeqtSTSEGWIYGTSLTTGCSGLLP 275
Cdd:cd11792     4 AIYPHKPRNHDEIELRVGDIIGVAG----NHWDGYSKGRNRRTGKTGLYP 49

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has 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 1390016160 225 QVIYPYTPQNDDELELVPGDFIFMspMEQTSTSEGWIYGTslTTGCSGLLPENYI 279
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTL--ISKDCIDAGWWEGE--LNGRRGVFPDNFV 53

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. 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 1390016160 228 YPYTPQNDDELELVPGDFIFMSPMEQTstseGWIYGTslTTGCSGLLPENYI 279
Cdd:cd12060     8 FNFKQTNEDELSVCKGDIIYVTRVEEG----GWWEGT--LNGKTGWFPSNYV 53

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. 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.

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gi 1390016160 227 IYPYTPQNDDELELVPGDFIFMSPMEqtsTSEGWIYGTSLTTGCSGLLPENY 278
Cdd:cd11878     5 LYDYRAQTPGELSFSKGDFFHVIGEE---DQGEWYEATNPVTGKRGLVPKSY 53

Src Homology 3 domain of Bridging integrator 1 (Bin1), also called Amphiphysin-2; Bin1 isoforms are localized in many different tissues and may function in intracellular vesicle trafficking. It plays a role in the organization and maintenance of the T-tubule network in skeletal muscle. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Bin1 contains an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR) and a C-terminal SH3 domain. The SH3 domain of Bin1 forms transient complexes with actin, myosin filaments, and CDK5, to facilitate sarcomere organization and myofiber maturation. It also binds dynamin and prevents its self-assembly. 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 1390016160 224 LQVIYPYTPQNDDELELVPGDFIFMSPMEQ-TSTSEGWIYGTSLT--------TGCSGLLPENYITK 281
Cdd:cd12139     5 VQAQHDYTATDTDELQLKAGDVVLVIPFQNpEEQDEGWLMGVKESdwnqhkklEKCRGVFPENFTER 71

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 1390016160 227 IYPYTPQNDDELELVPGDFIFMSpmeqTSTSEGWIYGTSltTGCSGLLPENYI 279
Cdd:cd11971     5 IYDYSKDKDDELSFMEGAIIYVI----KKNDDGWYEGVC--NGVTGLFPGNYV 51