Second 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 1958667984 1106 IFVALFDYDPLTMSPNPDAAEEELPFKEGQIIKVYGDKDADGFYRGETCARLGLIPCNMVSE 1167
Cdd:cd12012      1 LFVALFDYDPLTMSPNPDAAEEELPFKEGQLIKVYGDKDADGFYLGEINGRRGLVPCNMVSE 62

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 1958667984  185 LCVARYSYNPF-DGPNENPEAELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFVDF 245
Cdd:cd12014      1 VFVARYSYNPLrDSPNENPEAELPLNAGDYVYVYGDMDEDGFYEGELLDGRRGLVPSNFVER 62

Fibronectin type 3 domain [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  296 GGTLDVNIDDIGEDIVPYPRKITLIKQLAKSVIVGWEPPAVPPGWGTVSSYNVLVDKETRM----SLALGRRTKALIEKL 371
Cdd:COG3401    119 SPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAvattSLTVTSTTLVDGGGD 198

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  372 NTAACTYRISVQCVTSRGNSDE-LQCTLLVGKDVVVAPSQLRVDNITQISAQLSWLPTNSNY--SHIIFLNEEELD---- 444
Cdd:COG3401    199 IEPGTTYYYRVAATDTGGESAPsNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESDatGYRVYRSNSGDGpftk 278

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  445 IVKAARYKYQFFNLRPNMAYKVKVLAqphqmpwqlpLEQREKKEACVEFS--TLPAGPPAPPQDVTVQAgATTASVQVSW 522
Cdd:COG3401    279 VATVTTTSYTDTGLTNGTTYYYRVTA----------VDAAGNESAPSNVVsvTTDLTPPAAPSGLTATA-VGSSSITLSW 347

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1958667984  523 KPPAltptglsnGANVTGYGVY--AKGQRVAEVIAPTADG 560
Cdd:COG3401    348 TASS--------DADVTGYNVYrsTSGGGTYTKIAETVTT 379

tegument protein VP11/12; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  582 SAQGESMDSALAAIPPDLlvPPAPHPRTAPPPKPLASDMDTkdlgPHVKVDESWEQSRPPGPAHGHMLeppdmhstGPGR 661
Cdd:PHA03321   415 SEHYEASLRLLSSRQPPG--APAPRRDNDPPPPPRARPGST----PACARRARAQRARDAGPEYVDPL--------GALR 480

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958667984  662 RSPSPSRILPQPQGAPVSTTVAKAMAREAAQRVAESNRLEKRSLFLEQSSAGPyaNSDEEDGYASPE 728
Cdd:PHA03321   481 RLPAGAAPPPEPAAAPSPATYYTRMGGGPPRLPPRNRATETLRPDWGPPAAAP--PEQMEDPYLEPD 545

Second 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 1958667984 1106 IFVALFDYDPLTMSPNPDAAEEELPFKEGQIIKVYGDKDADGFYRGETCARLGLIPCNMVSE 1167
Cdd:cd12012      1 LFVALFDYDPLTMSPNPDAAEEELPFKEGQLIKVYGDKDADGFYLGEINGRRGLVPCNMVSE 62

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 1958667984  185 LCVARYSYNPF-DGPNENPEAELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFVDF 245
Cdd:cd12014      1 VFVARYSYNPLrDSPNENPEAELPLNAGDYVYVYGDMDEDGFYEGELLDGRRGLVPSNFVER 62

Variant SH3 domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958667984 1213 ALYDYDPREsspnvdvEAELLFCTGDIITVFGEiDEDGFYYGELNGQKGLVPSNFLE 1269
Cdd:pfam14604    1 ALYPYEPKD-------DDELSLQRGDVITVIEE-SEDGWWEGINTGRTGLVPANYVE 49

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958667984 1107 FVALFDYDPltmspnpdAAEEELPFKEGQIIKVYgDKDADGFYRGETCARLGLIPCNMVSEI 1168
Cdd:pfam07653    2 GRVIFDYVG--------TDKNGLTLKKGDVVKVL-GKDNDGWWEGETGGRVGLVPSTAVEEI 54

Variant SH3 domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958667984  188 ARYSYNPFDgpnenpEAELPLTAGKYLYVYGDmDEDGFYEGELlDGQRGLVPSNFVD 244
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 1958667984  296 GGTLDVNIDDIGEDIVPYPRKITLIKQLAKSVIVGWEPPAVPPGWGTVSSYNVLVDKETRM----SLALGRRTKALIEKL 371
Cdd:COG3401    119 SPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAvattSLTVTSTTLVDGGGD 198

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  372 NTAACTYRISVQCVTSRGNSDE-LQCTLLVGKDVVVAPSQLRVDNITQISAQLSWLPTNSNY--SHIIFLNEEELD---- 444
Cdd:COG3401    199 IEPGTTYYYRVAATDTGGESAPsNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESDatGYRVYRSNSGDGpftk 278

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  445 IVKAARYKYQFFNLRPNMAYKVKVLAqphqmpwqlpLEQREKKEACVEFS--TLPAGPPAPPQDVTVQAgATTASVQVSW 522
Cdd:COG3401    279 VATVTTTSYTDTGLTNGTTYYYRVTA----------VDAAGNESAPSNVVsvTTDLTPPAAPSGLTATA-VGSSSITLSW 347

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1958667984  523 KPPAltptglsnGANVTGYGVY--AKGQRVAEVIAPTADG 560
Cdd:COG3401    348 TASS--------DADVTGYNVYrsTSGGGTYTKIAETVTT 379

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 1958667984  407 APSQLRVDNITQISAQLSWLPTNSNYSHI----IFLNE------EELDIVKAARYKYQFFNLRPNMAYKVKVLA 470
Cdd:cd00063      3 PPTNLRVTDVTSTSVTLSWTPPEDDGGPItgyvVEYREkgsgdwKEVEVTPGSETSYTLTGLKPGTEYEFRVRA 76

tegument protein VP11/12; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  582 SAQGESMDSALAAIPPDLlvPPAPHPRTAPPPKPLASDMDTkdlgPHVKVDESWEQSRPPGPAHGHMLeppdmhstGPGR 661
Cdd:PHA03321   415 SEHYEASLRLLSSRQPPG--APAPRRDNDPPPPPRARPGST----PACARRARAQRARDAGPEYVDPL--------GALR 480

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958667984  662 RSPSPSRILPQPQGAPVSTTVAKAMAREAAQRVAESNRLEKRSLFLEQSSAGPyaNSDEEDGYASPE 728
Cdd:PHA03321   481 RLPAGAAPPPEPAAAPSPATYYTRMGGGPPRLPPRNRATETLRPDWGPPAAAP--PEQMEDPYLEPD 545

Hyaluronan mediated motility receptor N-terminal; HMMR_N is the N-terminal region of eukaryotic hyaluronan-mediated motility receptor proteins. The protein is functionally associated with BRCA1 and thus predicted to be a common, low-penetrance breast cancer candidate.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984    4 AAERRQQLELEHEQALAILNAKQQEIQLLQQAqVEAKKEHegavqlLESKVRELEEKCRV-QSEQFNLLSRDLEKFRQHA 82
Cdd:pfam15905  234 VSEQVEKYKLDIAQLEELLKEKNDEIESLKQS-LEEKEQE------LSKQIKDLNEKCKLlESEKEELLREYEEKEQTLN 306

                   ....*.
gi 1958667984   83 GSIDLL 88
Cdd:pfam15905  307 AELEEL 312

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  458 LRPNMAyKVKVLAQPHQMPwqlpLEQREKKEACVEFSTLPAGP-------PAPPQDVTVQAGATTASVQVSWKPPALTPT 530
Cdd:PHA03247  2688 ARPTVG-SLTSLADPPPPP----PTPEPAPHALVSATPLPPGPaaarqasPALPAAPAPPAVPAGPATPGGPARPARPPT 2762

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  531 GLSNGANVTGYGVYAKGQRVAEVIAPTADGAAVELVRLRSLEAKAVSVRTLSAQGESMDSALAAI--PPDLLVPPAPHPR 608
Cdd:PHA03247  2763 TAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPlpPPTSAQPTAPPPP 2842

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984  609 TAPPPKPLASDMDTKDLGPHVKVDESweQSRPPGPAHG------HMLEPPDMHSTGPGRRSPSPSRILPQPQGAPVSTTV 682
Cdd:PHA03247  2843 PGPPPPSLPLGGSVAPGGDVRRRPPS--RSPAAKPAAParppvrRLARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQ 2920

                          250
                   ....*....|
gi 1958667984  683 AKAMAREAAQ 692
Cdd:PHA03247  2921 PQPPPPPQPQ 2930

Second 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 1958667984 1106 IFVALFDYDPLTMSPNPDAAEEELPFKEGQIIKVYGDKDADGFYRGETCARLGLIPCNMVSE 1167
Cdd:cd12012      1 LFVALFDYDPLTMSPNPDAAEEELPFKEGQLIKVYGDKDADGFYLGEINGRRGLVPCNMVSE 62

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 1958667984  185 LCVARYSYNPF-DGPNENPEAELPLTAGKYLYVYGDMDEDGFYEGELLDGQRGLVPSNFVDF 245
Cdd:cd12014      1 VFVARYSYNPLrDSPNENPEAELPLNAGDYVYVYGDMDEDGFYEGELLDGRRGLVPSNFVER 62

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958667984 1210 RMVALYDYDPRESSPNVDVEAELLFCTGDIITVFGEIDEDGFYYGELNG-QKGLVPSNFLEE 1270
Cdd:cd11851      1 LMVALYDYNPETMSPNDDPEEELSFHAGDVVRVYGPMDEDGFYYGELEGgRKGLVPSNFVQE 62

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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958667984 1212 VALYDYDPRESSPNVDVEAELLFCTGDIITVFGEIDEDGFYYGEL-NGQKGLVPSNFLE 1269
Cdd:cd12014      3 VARYSYNPLRDSPNENPEAELPLNAGDYVYVYGDMDEDGFYEGELlDGRRGLVPSNFVE 61

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958667984 1106 IFVALFDYDPLTMSPNPDAaEEELPFKEGQIIKVYGDKDADGFYRGETCARLGLIPCNMVSE 1167
Cdd:cd12013      1 RMVALFDYDPRESSPNVDA-EVELSFRAGDIITVFGEMDEDGFYYGELNGQRGLVPSNFLEE 61

Second 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958667984  187 VARYSYNPFD-GPNENP-EAELPLTAGKYLYVYGDMDEDGFYEGElLDGQRGLVPSNFV 243
Cdd:cd12012      3 VALFDYDPLTmSPNPDAaEEELPFKEGQLIKVYGDKDADGFYLGE-INGRRGLVPCNMV 60

Variant SH3 domain;

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                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958667984 1213 ALYDYDPREsspnvdvEAELLFCTGDIITVFGEiDEDGFYYGELNGQKGLVPSNFLE 1269
Cdd:pfam14604    1 ALYPYEPKD-------DDELSLQRGDVITVIEE-SEDGWWEGINTGRTGLVPANYVE 49

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958667984 1210 RMVALYDYDPREsspnvdvEAELLFCTGDIITVFgEIDEDGFYYGELNGQKGLVPSNFLEE 1270
Cdd:cd11823      1 RCKALYSYTANR-------EDELSLQPGDIIEVH-EKQDDGWWLGELNGKKGIFPATYVEE 53

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958667984 1213 ALYDYDPREsspnvdvEAELLFCTGDIITVFGEIDEDgFYYGELNGQKGLVPSNFLEEV 1271
Cdd:cd11803      5 ALYDFEPEN-------EGELGFKEGDIITLTNQIDEN-WYEGMVNGQSGFFPVNYVEVL 55

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958667984 1210 RMVALYDYDPRESSpnvdveaELLFCTGDIITVFGEIDEDGFYYGELNGQKGLVPSNFLE 1269
Cdd:cd11843      1 PVRALYDYEGQESD-------ELSFKAGDILTKLEEEDEQGWCKGRLDGRVGLYPANYVE 53

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second 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 1958667984 1211 MVALYDYDPresspnvDVEAELLFCTGDIITVFGEIDEDGFYYGELNGQKGLVPSNF 1267
Cdd:cd11778      2 VEALYDYEA-------QGDDEISIRVGDRIAVIRGDDGSGWTYGEINGVKGLFPTSY 51

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958667984 1213 ALYDYDPREsspnvdvEAELLFCTGDIITVFGEIDED-GFYYGELNGQKGLVPSNFLEE 1270
Cdd:cd11875      4 VLFDYEAEN-------EDELTLREGDIVTILSKDCEDkGWWKGELNGKRGVFPDNFVEP 55

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.

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                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958667984  1103 PARIFVALFDYDPltmspnpdAAEEELPFKEGQIIKVYGDKDaDGFYRGETCA-RLGLIPCNMV 1165
Cdd:smart00326    1 EGPQVRALYDYTA--------QDPDELSFKKGDIITVLEKSD-DGWWKGRLGRgKEGLFPSNYV 55

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958667984 1213 ALYDYDPRESSpnvdveaELLFCTGDIITVFGEIDEDgFYYGELNGQKGLVPSNFLE 1269
Cdd:cd11786      4 ALYNYEGKEPG-------DLSFKKGDIILLRKRIDEN-WYHGECNGKQGFFPASYVQ 52

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958667984 1212 VALYDYDPRESSpnvdveaELLFCTGDIITVFgEIDEDGFYYGELN-GQKGLVPS 1265
Cdd:pfam00018    1 VALYDYTAQEPD-------ELSFKKGDIIIVL-EKSEDGWWKGRNKgGKEGLIPS 47

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958667984 1213 ALYDYDPResspNVDveaELLFCTGDIITVFGEIdEDGFYYGELNGQKGLVPSNFLEE 1270
Cdd:cd11874      4 VLFSYTPQ----NED---ELELKVGDTIEVLGEV-EEGWWEGKLNGKVGVFPSNFVKE 53

C-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 C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958667984 1213 ALYDYDPRESSpnvdveaELLFCTGDIITVFGEIDEDgFYYGELNGQKGLVPSNFLEE 1270
Cdd:cd11805      4 ALYDFNPQEPG-------ELEFRRGDIITVLDSSDPD-WWKGELRGRVGIFPANYVQP 53

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958667984 1213 ALYDYDPREsspnvdvEAELLFCTGDIITVFGEID---EDGFYYGELNGQKGLVPSNFLEE 1270
Cdd:cd11762      4 ALYDYEAQS-------DEELSFPEGAIIRILRKDDngvDDGWWEGEFNGRVGVFPSLVVEE 57

First Src Homology 3 domain (SH3A) 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 first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. 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 1958667984 1215 YDYDPREsspnvdvEAELLFCTGDIITVFGEIDEDGFYYGELNGQKGLVPSNFLEEV 1271
Cdd:cd12053      6 YDYDAVH-------EDELTIRVGEIIRNVKKLEEEGWLEGELNGRRGMFPDNFVKEI 55

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958667984 1210 RMVALYDYDPREsspnvdvEAELLFCTGDIITVFGEIDEDGFYYGEL-NGQKGLVPSNFLE 1269
Cdd:cd11998      2 RVRALYDYDGQE-------QDELSFKAGDELTKLEDEDEQGWCKGRLdSGQVGLYPANYVE 55

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 1958667984 1106 IFVALFDYDPltmsPNPDaaeeELPFKEGQIIKVYgDKDADGFYRGETCARLGLIPCNMVSE 1167
Cdd:cd11772      1 VFRALYDYEA----QHPD----ELSFEEGDLLYIS-DKSDPNWWKATCGGKTGLIPSNYVEE 53

Variant SH3 domain;

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                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958667984  188 ARYSYNPFDgpnenpEAELPLTAGKYLYVYGDmDEDGFYEGELlDGQRGLVPSNFVD 244
Cdd:pfam14604    1 ALYPYEPKD------DDELSLQRGDVITVIEE-SEDGWWEGIN-TGRTGLVPANYVE 49

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. 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 1958667984 1109 ALFDYDPLTmspnpdaaEEELPFKEGQIIKVYGDKDADGFYRGETCARLGLIPCNMV 1165
Cdd:cd11774      4 ALYDYDKQT--------EEELSFNEGDTLDVYDDSDSDWILVGFNGTQFGFVPANYI 52

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 1958667984 1212 VALYDYDPREsspnvdvEAELLFCTGDIITVFgEIDEDGFYYGELNGQKGLVPSNFLEE 1270
Cdd:cd11766      3 VVKFNYEAQR-------EDELSLRKGDRVLVL-EKSSDGWWRGECNGQVGWFPSNYVTE 53

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. 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 1958667984 1128 ELPFKEGQIIKVYGDKDADGFYRGETCARLGLIPCNMVSE 1167
Cdd:cd11830     15 ELSLKEGDVVKIYNKKGQQGWWRGEINGRIGWFPSTYVEE 54

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. 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 1958667984 1211 MVALYDYDPREsspnvdvEAELLFCTGDIITVFGEIDEDGFYYGELNGQKGLVPSNFL 1268
Cdd:cd11774      2 AKALYDYDKQT-------EEELSFNEGDTLDVYDDSDSDWILVGFNGTQFGFVPANYI 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. 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 1958667984 1209 RRMVALYDYDPRESSpnvdveaELLFCTGDIITVFGEIDEDgFYYGELNGQKGLVPSNFL 1268
Cdd:cd11964      1 RKVRAIYDFEAAEDN-------ELTFKAGDIITILDDSDPN-WWKGETPQGTGLFPSNFV 52