RUN domain found in RUN and SH3 domain-containing protein 2 (RUSC2) and similar proteins; RUSC2, also called iporin, or interacting protein of Rab1, is a novel interacting molecule for the active GTP-bound conformation of Rab1. It may function as a link between the targeting of endoplasmic reticulum derived vesicles, triggered by the Rab1 GTPase and a signaling pathway regulated by molecules containing SH3 and/or poly-proline regions. This model contains the RUN domain of RUSC2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  996 QKKGLVKAVNTAVDLIVAHFGTSRDPGVKAKLGNSSVSPNVGHLVLKYLCPAVQAVLEDGLKAFVLDVIIGQRKNMPWSV 1075
Cdd:cd17702     1 QKKGLVKAVNIAVDLIVAHFGTSRDPGVKAKLGNSSVSPNVGHLILKYLCPAVRNILQDGLKAYVLDVIIGQRRNKPWSV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919 1076 VEASTQLGPSTKVLHGLYNKVSQFPELTSHTMRFNAFILGLLNIRSLEFWFNHLYNHEDIIQTHYQPWGFLRAAHTVCPG 1155
Cdd:cd17702    81 VEASTQLGPSTKLLHSLVSKVSQYSELTSHSMRFNAFIFGLLNIRSLEFWFNHLYNHEDIITEHYQPWGFLALAHGVCQP 160

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  534 PAALAGPASPPRRVTSFAELAKGRKKAAGSGSPPLRA---------SVGDSSQEFSPIQEAQQDRAAPLDEGTRCSHslP 604
Cdd:PHA03247 2521 PDEPVGEPVHPRMLTWIRGLEELASDDAGDPPPPLPPaappaapdrSVPPPRPAPRPSEPAVTSRARRPDAPPQSAR--P 2598

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  605 SLPLGPSLDLLGPEPwSTPVCQGSQSSEMPLPSLRAAG---QGPLAQLMDPGPAFSGSPATSHTQRDSRARADGGGTE-S 680
Cdd:PHA03247 2599 RAPVDDRGDPRGPAP-PSPLPPDTHAPDPPPPSPSPAAnepDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQaS 2677

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  681 RPVLRYSKEQ-RPTTLPIQPFVFQHHFPKQLAKARALHSLSQLYSLSMPCSRAQQPAPlviSTAQGPAPAPSGEPQPFTS 759
Cdd:PHA03247 2678 SPPQRPRRRAaRPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPAL---PAAPAPPAVPAGPATPGGP 2754

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  760 QASGRGARNAGPEPETSRPSPLGSysPVRSAGPFGSSTDSSASTSCSPPPEQGTAADSVSPWSHTCPPTVRPATSQQPPK 839
Cdd:PHA03247 2755 ARPARPPTTAGPPAPAPPAAPAAG--PPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPT 2832

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  840 EDQKIPtlaeyrlhgtgSLPPLGSWRSGFTRAESLVRGGgegsmanrpnnanhlspqalkwrEYRRKNPLGPPGLSGSLD 919
Cdd:PHA03247 2833 SAQPTA-----------PPPPPGPPPPSLPLGGSVAPGG-----------------------DVRRRPPSRSPAAKPAAP 2878

                         410
                  ....*....|
gi 755505919  920 RRPPEARLAR 929
Cdd:PHA03247 2879 ARPPVRRLAR 2888

RUN domain found in RUN and SH3 domain-containing protein 2 (RUSC2) and similar proteins; RUSC2, also called iporin, or interacting protein of Rab1, is a novel interacting molecule for the active GTP-bound conformation of Rab1. It may function as a link between the targeting of endoplasmic reticulum derived vesicles, triggered by the Rab1 GTPase and a signaling pathway regulated by molecules containing SH3 and/or poly-proline regions. This model contains the RUN domain of RUSC2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  996 QKKGLVKAVNTAVDLIVAHFGTSRDPGVKAKLGNSSVSPNVGHLVLKYLCPAVQAVLEDGLKAFVLDVIIGQRKNMPWSV 1075
Cdd:cd17702     1 QKKGLVKAVNIAVDLIVAHFGTSRDPGVKAKLGNSSVSPNVGHLILKYLCPAVRNILQDGLKAYVLDVIIGQRRNKPWSV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919 1076 VEASTQLGPSTKVLHGLYNKVSQFPELTSHTMRFNAFILGLLNIRSLEFWFNHLYNHEDIIQTHYQPWGFLRAAHTVCPG 1155
Cdd:cd17702    81 VEASTQLGPSTKLLHSLVSKVSQYSELTSHSMRFNAFIFGLLNIRSLEFWFNHLYNHEDIITEHYQPWGFLALAHGVCQP 160

RUN domain; This domain is present in several proteins that are linked to the functions of GTPases in the Rap and Rab families. They could hence play important roles in multiple Ras-like GTPase signalling pathways. The domain is comprises six conserved regions, which in some proteins have considerable insertions between them. The domain core is thought to take up a predominantly alpha fold, with basic amino acids in regions A and D possibly playing a functional role in interactions with Ras GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  1044 LCPAVQAVLEDGLKA---FVLDVIIGQRKNMPWSVVEASTQLGPSTKVLHGLYNKVSQFPELTSHTMRFNAFILGLLNIR 1120
Cdd:pfam02759    2 LCAALEALLSHGLKRsslLILRAAGLLPERSFWALLERVGKLVPPAEELLSSVQELEQIHTPYSPDGRGRAWIRLALNEK 81

                           90       100
                   ....*....|....*....|....*..
gi 755505919  1121 SLEFWFNHLYNHEDIIQTHYQPWGFLR 1147
Cdd:pfam02759   82 LLDQWLKLLLSNKELLSEYYEPWALLA 108

domain involved in Ras-like GTPase signaling;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 755505919   1109 FNAFILGLLNIRSLEFWFNHLYNHEDIIQTHYQPWGFLR 1147
Cdd:smart00593    1 FRAWIRLALNEKLLSSWLNLLLSDEELLSKYYEPWAFLR 39

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
                   ....*....|....*....|....*....|....*....|....*....|
gi 755505919  1459 VQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYV 1508
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAV 51

RUN domain found in RUN and SH3 domain-containing protein 2 (RUSC2) and similar proteins; RUSC2, also called iporin, or interacting protein of Rab1, is a novel interacting molecule for the active GTP-bound conformation of Rab1. It may function as a link between the targeting of endoplasmic reticulum derived vesicles, triggered by the Rab1 GTPase and a signaling pathway regulated by molecules containing SH3 and/or poly-proline regions. This model contains the RUN domain of RUSC2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  996 QKKGLVKAVNTAVDLIVAHFGTSRDPGVKAKLGNSSVSPNVGHLVLKYLCPAVQAVLEDGLKAFVLDVIIGQRKNMPWSV 1075
Cdd:cd17702     1 QKKGLVKAVNIAVDLIVAHFGTSRDPGVKAKLGNSSVSPNVGHLILKYLCPAVRNILQDGLKAYVLDVIIGQRRNKPWSV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919 1076 VEASTQLGPSTKVLHGLYNKVSQFPELTSHTMRFNAFILGLLNIRSLEFWFNHLYNHEDIIQTHYQPWGFLRAAHTVCPG 1155
Cdd:cd17702    81 VEASTQLGPSTKLLHSLVSKVSQYSELTSHSMRFNAFIFGLLNIRSLEFWFNHLYNHEDIITEHYQPWGFLALAHGVCQP 160

RUN domain found in RUN and SH3 domain-containing protein 1 (RUSC1) and similar proteins; RUSC1, also called new molecule containing SH3 at the carboxy-terminus (NESCA), may acts as a signaling adapter that translocates to the nuclear envelope and regulates neurotrophin-induced neurite outgrowth. This model contains the RUN domain of RUSC1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  996 QKKGLVKAVNTAVDLIVAHFGTSRDPGVKAKLGNSSVSPNVGHLVLKYLCPAVQAVLEDGLKAFVLDVIIGQRKNMPWSV 1075
Cdd:cd17701     1 QKKGLLNAVSVSVDKIISHFSSARNLVQKAQLGDSRLSPDVGHLVLQTLCPALYALVADGLKPFQKDLITGRRRSSPWSV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919 1076 VEASTQLGPSTKVLHGLYNKVSQFPELTSHTMRFNAFILGLLNIRSLEFWFNHLYNHEDIIQTHYQPWGFLRAAHTVCPG 1155
Cdd:cd17701    81 VEASVKPGPSTRSLHSLYCQVSRLAQLRSSRSRFNAFIFGLLNTKQLDLWLSHLQKCSDVLSLFYLPTGFFSLARGSCPS 160

                         170       180
                  ....*....|....*....|...
gi 755505919 1156 LFEELLLLLQPLALLPFSLDLLF 1178
Cdd:cd17701   161 LFEELLLLLQPLSVLTFHLDLLF 183

Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that were originally characterized in silico. They are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC2, also called Iporin, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. 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 755505919 1458 EVQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAY 1507
Cdd:cd11810     1 VVRALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50

RUN domain; RUN domain, named after RPIP8 (Rap2 interacting protein 8), UNC-14 and NESCA (new molecule containing SH3 at the carboxyl-terminus), is a less conserved protein motif that comprises six conserved regions, which in some proteins have considerable insertions between them. The domain core is thought to take up a predominantly alpha fold, with basic amino acids in regions A and D possibly playing a functional role in interactions with Ras GTPases. RUN domains are often found in proteins linked particularly to the functions of GTPases in the Rap and Rab families, suggesting the RUN domain may be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. RUN domain-containing proteins could hence play important roles in multiple Ras-like GTPase signalling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919 1006 TAVDLIVAHFGTSRDPGVKAKLgnssvSPNVGHLVLKYLCPAVQAVLEDGLKAFVldviIGQRKNMPWSVVEASTQLGPS 1085
Cdd:cd17671     1 KAVKELLESFADNGEADDSAAL-----TLTDDDPVVGRLCAALEAILSHGLKPKR----FGGGKVSFWDFLEALEKLLPA 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755505919 1086 TKvLHGLYNKVSQFPELTSHTMRFNAFILGLLNIRSLEFWFNHLYNHEDIIQTHYQPWGFLR 1147
Cdd:cd17671    72 PS-LKQAIRDINSLSNVKTDDGRGRAWIRLALNEKSLESYLAALLSDQSLLRKYYEPWALLR 132

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  534 PAALAGPASPPRRVTSFAELAKGRKKAAGSGSPPLRA---------SVGDSSQEFSPIQEAQQDRAAPLDEGTRCSHslP 604
Cdd:PHA03247 2521 PDEPVGEPVHPRMLTWIRGLEELASDDAGDPPPPLPPaappaapdrSVPPPRPAPRPSEPAVTSRARRPDAPPQSAR--P 2598

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  605 SLPLGPSLDLLGPEPwSTPVCQGSQSSEMPLPSLRAAG---QGPLAQLMDPGPAFSGSPATSHTQRDSRARADGGGTE-S 680
Cdd:PHA03247 2599 RAPVDDRGDPRGPAP-PSPLPPDTHAPDPPPPSPSPAAnepDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQaS 2677

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  681 RPVLRYSKEQ-RPTTLPIQPFVFQHHFPKQLAKARALHSLSQLYSLSMPCSRAQQPAPlviSTAQGPAPAPSGEPQPFTS 759
Cdd:PHA03247 2678 SPPQRPRRRAaRPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPAL---PAAPAPPAVPAGPATPGGP 2754

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  760 QASGRGARNAGPEPETSRPSPLGSysPVRSAGPFGSSTDSSASTSCSPPPEQGTAADSVSPWSHTCPPTVRPATSQQPPK 839
Cdd:PHA03247 2755 ARPARPPTTAGPPAPAPPAAPAAG--PPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPT 2832

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  840 EDQKIPtlaeyrlhgtgSLPPLGSWRSGFTRAESLVRGGgegsmanrpnnanhlspqalkwrEYRRKNPLGPPGLSGSLD 919
Cdd:PHA03247 2833 SAQPTA-----------PPPPPGPPPPSLPLGGSVAPGG-----------------------DVRRRPPSRSPAAKPAAP 2878

                         410
                  ....*....|
gi 755505919  920 RRPPEARLAR 929
Cdd:PHA03247 2879 ARPPVRRLAR 2888

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

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 755505919   1455 PPCEVQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPD-TGLVPLAYVT 1509
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGkEGLFPSNYVE 56

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
                   ....*....|....*....|....*....|....*....|....*....|
gi 755505919  1459 VQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYV 1508
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAV 51

Variant SH3 domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 755505919  1461 ALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYVT 1509
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 755505919 1459 VQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYVT 1509
Cdd:cd11805     2 VQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. 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 755505919 1461 ALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAY 1507
Cdd:cd11856     4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASY 50

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. 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 755505919 1458 EVQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYVT 1509
Cdd:cd12047     1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFAV 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, 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
                  ....*....|....*....|....*....|....*....|....*...
gi 755505919 1460 QALCHHLATGPGQLSFHKGDILRVL---GPARGDWLRCSRGPDTGLVP 1504
Cdd:cd12003     4 KALYDNAAESPEELSFRRGDVLMVLkreHGSLPGWWLCSLHGQQGIAP 51

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding 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 755505919 1458 EVQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYVT 1509
Cdd:cd11806     1 EYVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHLH 52

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 755505919 1467 ATGPGQLSFHKGDILRVLGPARG-DWLRCSRGPDTGLVPLAYV 1508
Cdd:cd11804    10 ATAEDELSFKKGSILKVLNMEDDpNWYKAELDGKEGLIPKNYI 52

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 755505919 1459 VQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYVTL 1510
Cdd:cd11828     2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 755505919 1467 ATGPGQLSFHKGDILRVLG-PARGDWLRCSRgPDT---GLVPLAY 1507
Cdd:cd11878    10 AQTPGELSFSKGDFFHVIGeEDQGEWYEATN-PVTgkrGLVPKSY 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 755505919 1457 CEVQALCHHLATGPGQLSFHKGDILRVLGPARGDWLRCSRGPDTGLVPLAYVTL 1510
Cdd:cd11996     1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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 755505919 1467 ATGPGQLSFHKGDILRVLGPARGDW--LRCSRGPDTGLVPLAY 1507
Cdd:cd11845    10 ARTDDDLSFKKGDRLQILDDSDGDWwlARHLSTGKEGYIPSNY 52

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. 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 755505919 1459 VQALCHHLATG-PGQLSFHKGDILRVLGP-ARGDWL--RCSRGPDTGLVPLAYV 1508
Cdd:cd11914     3 VRAIVSHPAGSnPTLLRFNRGDIITVLVPeARNGWLygKLEGSSRQGWFPEAYV 56

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  727 MPCSRAQQPAPLVISTAQGPAPAPSGEPQPFTSQASGRGARNAGPEPE-TSRPSPLGSYSPVRSAGPFGSSTDSSASTSC 805
Cdd:PRK12323  386 APAAAAPAAAAPAPAAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALaAARQASARGPGGAPAPAPAPAAAPAAAARPA 465

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755505919  806 SPPPEQGTAADSVSPWSHTCPPTVRPATSQQPPKEDQKiPTLAEYRLHGTGSLPPLGSWRSGFTRAESLVRGGGEGSMAN 885
Cdd:PRK12323  466 AAGPRPVAAAAAAAPARAAPAAAPAPADDDPPPWEELP-PEFASPAPAQPDAAPAGWVAESIPDPATADPDDAFETLAPA 544

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 755505919  886 RPNNANHLSPQALKWREYRRKNPLGPPGLSGSLDRRPPEarLARRNPI 933
Cdd:PRK12323  545 PAAAPAPRAAAATEPVVAPRPPRASASGLPDMFDGDWPA--LAARLPV 590