First Src homology 3 domain 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1189398057 188 LCVARYSYNPF-DGPNENPEAELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFVDF 248
Cdd:cd12014     1 VFVARYSYNPLrDSPNENPEAELPLNAGDYVYVYGDMDEDGFYEGELLDGRRGLVPSNFVER 62

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189398057   2 REAAERRQQLQLEHDQALAVLSAKQQEIDLLQKAQVEAKKEHEGAVRLLESKVRELEEKCRTQSEQFNLLSRDLEKFRQH 81
Cdd:COG1196   312 RELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEA 391

                  .
gi 1189398057  82 A 82
Cdd:COG1196   392 L 392

First Src homology 3 domain 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1189398057 188 LCVARYSYNPF-DGPNENPEAELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFVDF 248
Cdd:cd12014     1 VFVARYSYNPLrDSPNENPEAELPLNAGDYVYVYGDMDEDGFYEGELLDGRRGLVPSNFVER 62

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1189398057 191 ARYSYNPFDgpnenpEAELPLTAGKYLYVYGDmDEDGFYEGELlDGQRGLVPSNFVD 247
Cdd:pfam14604   1 ALYPYEPKD------DDELSLQRGDVITVIEE-SEDGWWEGIN-TGRTGLVPANYVE 49

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1189398057 410 APSHLRVDNITQISAQLSWLPTNSNYSHVIF-------LNEEEFD---IVKAARYKYQFFNLRPNMAYKVKVLA 473
Cdd:pfam00041   2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGyeveyrpKNSGEPWneiTVPGTTTSVTLTGLKPGTEYEVRVQA 75

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189398057  317 PRKITLIKQLAKSVIVGWEPPAVPPGWGTVSSYNVL---VDKETRMNLTLGSRTKALIEKLNmAACTYRISVQCVTSRGS 393
Cdd:smart00060   4 PSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEyreEGSEWKEVNVTPSSTSYTLTGLK-PGTEYEFRVRAVNGAGE 82

                   .
gi 1189398057  394 S 394
Cdd:smart00060  83 G 83

Domain of unknown function (DUF4200); This family is found in eukaryotes. It is a coiled-coil domain of unknwon function.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1189398057  24 AKQQEIDLLQKAQVEAKKEHEGAVRLLESKVRELEEK---CRTQSEQFNLLSRDLEKFRQHAGKI 85
Cdd:pfam13863   3 EKKREMFLVQLALDAKREEIERLEELLKQREEELEKKeqeLKEDLIKFDKFLKENDAKRRRALKK 67

First Src homology 3 domain 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1189398057 188 LCVARYSYNPF-DGPNENPEAELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFVDF 248
Cdd:cd12014     1 VFVARYSYNPLrDSPNENPEAELPLNAGDYVYVYGDMDEDGFYEGELLDGRRGLVPSNFVER 62

Third Src homology 3 domain 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1189398057 190 VARYSYNPFD-GPNENPEAELPLTAGKYLYVYGDMDEDGFYEGElLDGQRGLVPSNFV 246
Cdd:cd12013     3 VALFDYDPREsSPNVDAEVELSFRAGDIITVFGEMDEDGFYYGE-LNGQRGLVPSNFL 59

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1189398057  185 KVHLCVARYSYNPfdgpnENPEaELPLTAGKYLYVYgDMDEDGFYEGELLDGQRGLVPSNFV 246
Cdd:smart00326   1 EGPQVRALYDYTA-----QDPD-ELSFKKGDIITVL-EKSDDGWWKGRLGRGKEGLFPSNYV 55

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1189398057 191 ARYSYNPFDgpnenpEAELPLTAGKYLYVYGDmDEDGFYEGELlDGQRGLVPSNFVD 247
Cdd:pfam14604   1 ALYPYEPKD------DDELSLQRGDVITVIEE-SEDGWWEGIN-TGRTGLVPANYVE 49

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189398057 298 SAGTLDVNIDDIGEDIVPYPRKITLIKQLAKSVIVGWEPPAVPPGWGTVSSYNVLVDKETRM----NLTLGSRTKALIEK 373
Cdd:COG3401   118 PSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAvattSLTVTSTTLVDGGG 197

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189398057 374 LNMAACTYRISVQCVTSRGSSDE-LQCTLLVGKDVVVAPSHLRVDNITQISAQLSWLPTNSNY--SHVIFL-NEEEFDIV 449
Cdd:COG3401   198 DIEPGTTYYYRVAATDTGGESAPsNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESDatGYRVYRsNSGDGPFT 277

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189398057 450 KAARYK---YQFFNLRPNMAYKVKVLAkphqmpwqlpLEQREKKEAFVEFS--TLPAGPPAPPQDVTVQAgVTPATIRVS 524
Cdd:COG3401   278 KVATVTttsYTDTGLTNGTTYYYRVTA----------VDAAGNESAPSNVVsvTTDLTPPAAPSGLTATA-VGSSSITLS 346

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1189398057 525 WRPpvltptglSNGANVTGYGVY--AKGQRVAEVIFPTADST 564
Cdd:COG3401   347 WTA--------SSDADVTGYNVYrsTSGGGTYTKIAETVTTT 380

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1189398057 410 APSHLRVDNITQISAQLSWLPTNSNYSHVIF-------LNEEEFD---IVKAARYKYQFFNLRPNMAYKVKVLA 473
Cdd:pfam00041   2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGyeveyrpKNSGEPWneiTVPGTTTSVTLTGLKPGTEYEVRVQA 75

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1189398057 202 NENPEAELPLTAGKYLYVYgDMDEDGFYEGELLdGQRGLVPSNFV 246
Cdd:pfam07653   9 VGTDKNGLTLKKGDVVKVL-GKDNDGWWEGETG-GRVGLVPSTAV 51

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1189398057 410 APSHLRVDNITQISAQLSWLPTNSNYSHV----IFLNE------EEFDIVKAARYKYQFFNLRPNMAYKVKVLAK 474
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPEDDGGPItgyvVEYREkgsgdwKEVEVTPGSETSYTLTGLKPGTEYEFRVRAV 77

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1189398057 191 ARYSYnpfDGPNENpeaELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFVD 247
Cdd:cd11998     5 ALYDY---DGQEQD---ELSFKAGDELTKLEDEDEQGWCKGRLDSGQVGLYPANYVE 55

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1189398057 189 CVARYSYNPFdgpneNPEaELPLTAGKYLYVYGDMDED-GFYEGELlDGQRGLVPSNFV 246
Cdd:cd12142     2 CRVLFDYNPV-----APD-ELALKKGDVIEVISKETEDeGWWEGEL-NGRRGFFPDNFV 53

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1189398057 205 PEAELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFV 246
Cdd:cd11763    12 PSGELSLRAGEVLTITRQDVGDGWLEGRNSRGEVGLFPSSYV 53

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189398057   2 REAAERRQQLQLEHDQALAVLSAKQQEIDLLQKAQVEAKKEHEGAVRLLESKVRELEEKCRTQSEQFNLLSRDLEKFRQH 81
Cdd:COG1196   312 RELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEA 391

                  .
gi 1189398057  82 A 82
Cdd:COG1196   392 L 392

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1189398057  410 APSHLRVDNITQISAQLSWLP--TNSNYSHVIFL--------NEEEFDIVKAARYKYQFFNLRPNMAYKVKVLAK 474
Cdd:smart00060   3 PPSNLRVTDVTSTSVTLSWEPppDDGITGYIVGYrveyreegSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1189398057 190 VARYSYNPfdgpneNPEAELPLTAGKYLYVYgDMDEDGFYEGELLDGQRGLVPS 243
Cdd:pfam00018   1 VALYDYTA------QEPDELSFKKGDIIIVL-EKSEDGWWKGRNKGGKEGLIPS 47

Domain of unknown function (DUF4200); This family is found in eukaryotes. It is a coiled-coil domain of unknwon function.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1189398057  24 AKQQEIDLLQKAQVEAKKEHEGAVRLLESKVRELEEK---CRTQSEQFNLLSRDLEKFRQHAGKI 85
Cdd:pfam13863   3 EKKREMFLVQLALDAKREEIERLEELLKQREEELEKKeqeLKEDLIKFDKFLKENDAKRRRALKK 67

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. 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 1189398057 189 CVARYSYNPfdgpnENPEAELPLTAGKYLYVYGDMD----EDGFYEGELLDGQRGLVPSNFV 246
Cdd:cd11771     2 CRALYDFTP-----ENPEMELSLKKGDIVAVLSKTDplgrDSEWWKGRTRDGRIGWFPSNYV 58

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. 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
                  ....*....|....*....|....*....|....*....|....*
gi 1189398057 204 NPEAELPLTAGKYLYVYGDMdEDGFYEGELL-DGQRGLVPSNFVD 247
Cdd:cd11785    11 QSEAELELKEGDIVFVHKKR-EDGWFKGTLQrTGKTGLFPGSFVE 54

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1189398057 208 ELPLTAGKYLYVYGDMDeDGFYEGE-LLDGQRGLVPSNFVDF 248
Cdd:cd11793    15 ELTLEEGDVVNVLRKMP-DGWYEGErLRDGERGWFPSSYTEE 55

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1189398057 189 CVARYSYNPfdgpnENPEaELPLTAGKYLYVYG-DMDEDGFYEGELlDGQRGLVPSNFV 246
Cdd:cd11875     2 ARVLFDYEA-----ENED-ELTLREGDIVTILSkDCEDKGWWKGEL-NGKRGVFPDNFV 53

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1189398057 190 VARYSYNPfdgpneNPEAELPLTAGKYLYVYGDMDEdGFYEGELLDGQRGLVPSNFV 246
Cdd:cd11819     3 KALYDYQA------AEDNEISFVEGDIITQIEQIDE-GWWLGVNAKGQKGLFPANYV 52