SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676 1056 PVSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLPP 1125
Cdd:cd09492      1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVSAEQ 70

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1081677676  440 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 496
Cdd:cd11967      1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676 1056 PVSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLPP 1125
Cdd:cd09492      1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVSAEQ 70

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1081677676  440 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 496
Cdd:cd11967      1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

SAM domain (Sterile alpha motif);

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1081677676 1057 VSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFK 1122
Cdd:pfam07647    1 VESWSLESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  664 GQEEGRLGGGLAPDTSKSCDPPGVTGLNKNRR-SLPVSICRSCETLEGPQTVDTWPRSHSLDDLQVEPgaeqDVPTEVTE 742
Cdd:PHA03247  2635 ANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRaRRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPP----PPPPTPEP 2710

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  743 PPPQIVPEVPQKTTASS-------TKAQPLEQDSAVDNALLLTQSKRFSEPqklTTKKLEGSIAASGRGLSPPQCLPRny 815
Cdd:PHA03247  2711 APHALVSATPLPPGPAAarqaspaLPAAPAPPAVPAGPATPGGPARPARPP---TTAGPPAPAPPAAPAAGPPRRLTR-- 2785

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  816 daqPPGAKHGLARTPLEGHRkghefEGTHHPLGTKEGVDAEQRMQPKIPSQPPPVPAKKSRERLANGLHPVPMGPSGAL- 894
Cdd:PHA03247  2786 ---PAVASLSESRESLPSPW-----DPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVa 2857

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1081677676  895 PSPDAPCLPVKRGSPASPTSPSDCP------PALAPRPLSGQAPGSPPSTRPPPWLSELPENTSLQEHGVKLGPAL 964
Cdd:PHA03247  2858 PGGDVRRRPPSRSPAAKPAAPARPPvrrlarPAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPP 2933

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 1081677676  441 RARVHTDFTPspYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 493
Cdd:pfam07653    1 YGRVIFDYVG--TDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAV 51

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1081677676   519 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEY 580
Cdd:smart00454    7 ESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676 1056 PVSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLPP 1125
Cdd:cd09492      1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVSAEQ 70

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1081677676  440 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 496
Cdd:cd11967      1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

Src homology 3 domain of SAM And SH3 Domain Containing Proteins; This subfamily, also called the SLY family, is composed of SAM And SH3 Domain Containing Protein 1 (SASH1), SASH2, SASH3, and similar proteins. These are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as wells as SAM (sterile alpha motif) and SH3 domains. SASH1 is a potential tumor suppressor in breast and colon cancer. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. SASH2 (also called SAMSN-1, SLY2, HACS1 or NASH1) and SASH3 (also called SLY/SLY1) are expressed mainly in hematopoietic cells, although SASH2 is also found in endothelial cells as well as myeloid leukemias and myeloma. SASH2 was found to be differentially expressed in malignant haematopoietic cells and in colorectal tumors, and is a potential tumor suppressor in lung cancer. SASH3 is essential in the full activation of adaptive immunity and is involved in the signaling of T cell receptors. 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 1081677676  441 RARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIY 492
Cdd:cd11822      1 RAKVHTDFTPSPYDTDSLKLKKGDIIDIINKPPMGIWTGMLNNKVGNFKFIY 52

SAM domain of SASH3 subfamily; SAM (sterile alpha motif) domain of SAHS3 (also known as SLY) proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative signaling/adaptor proteins. In addition to SAM, they contain SLY and SH3 domains. They appear to mediate signal transduction in lymphoid tissues. Murine SASH3 is involved in preventing DN thymocytes from premature initiation of programmed cell death and in mTOR (mammalian target of rapamycin) activation via signal integration of the Notch receptor and preTCR (T cell receptor) pathways.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1081677676  519 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 581
Cdd:cd09560      6 KTLHELLERIGLEEHTSTLLLNGYQTLEDFKELRETHLNELNIMDPQHRAKLLTAAELLLDYD 68

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-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 by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1081677676  441 RARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 495
Cdd:cd11759      3 YARVIQKRVPNAYDKTALALEVGDLVKVTKINVSGQWEGELNGKVGHFPFTHVEL 57

SAM domain (Sterile alpha motif);

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1081677676 1057 VSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFK 1122
Cdd:pfam07647    1 VESWSLESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1081677676 1064 SVSDWLISIGLPMYAGTLSTAGFsTLSQVPSLSHTCLQEAGITEERHIRKLLSAAR 1119
Cdd:cd09487      1 DVAEWLESLGLEQYADLFRKNEI-DGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1081677676  441 RARVhtDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 488
Cdd:cd11874      1 RCKV--LFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVF 46

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1081677676  452 PYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 494
Cdd:cd11827     10 AQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52

SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B6 receptors and appears to mediate cell-cell initiated signal transduction. Receptors of this type are highly expressed in embryo and adult nervous system, in thymus and also in T-cells. They are involved in regulation of cell adhesion and migration. (EPH-B6 receptor is unusual; it fails to show catalytic activity due to alteration in kinase domain). EPH-B6 may be considered as a biomarker in some types of tumors; EPH-B6 activates MAP kinase signaling in lung adenocarcinoma, suppresses metastasis formation in non-small cell lung cancer, and slows invasiveness in some breast cancer cell lines.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1081677676 1061 CISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFK 1122
Cdd:cd09555      5 CLDSPQAWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQ 66

SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1081677676 1063 SSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLL 1115
Cdd:cd09491      6 KTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLL 58

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1081677676 1063 SSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSA 1117
Cdd:cd09554      4 GSVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSS 58

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1081677676  443 RVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 488
Cdd:cd12055      1 RCQVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMF 46

Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate chromosome transmission during cell division.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  739 EVTEPPPQIVPEVPQKTTASSTKAQP------LEQdsaVDNALLLtQSKRFSEPQKLTTKKLEGSIAASgrglSPPQCLP 812
Cdd:pfam09770  164 GVAPKKAAAPAPAPQPAAQPASLPAPsrkmmsLEE---VEAAMRA-QAKKPAQQPAPAPAQPPAAPPAQ----QAQQQQQ 235

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  813 RNYDAQPPGAKHGLARTPLEGHRKGHEfegthhplgtkegVDAEQRMQPK--IPSQPPPVPAKKSRERLAnglHPVPMGP 890
Cdd:pfam09770  236 FPPQIQQQQQPQQQPQQPQQHPGQGHP-------------VTILQRPQSPqpDPAQPSIQPQAQQFHQQP---PPVPVQP 299

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1081677676  891 SGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPwLSELPE 949
Cdd:pfam09770  300 TQILQNPNRLSAARVGYPQNPQPGVQPAPAHQAHRQQGSFGRQAPIITHPQQ-LAQLSE 357

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 1081677676  441 RARVHTDFTPSpyDTDSLKLKKGDIIDIISK--PPMGTWMGLLNNKVGTF 488
Cdd:cd11875      1 KARVLFDYEAE--NEDELTLREGDIVTILSKdcEDKGWWKGELNGKRGVF 48

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  799 AASGRGLSPPQCLPRNYD------AQPPGA--KHGLARTPLEghrkghefegthhPLGTKEGVDAEQRMQPKIPSQPPPV 870
Cdd:PHA03247  2562 AAPDRSVPPPRPAPRPSEpavtsrARRPDAppQSARPRAPVD-------------DRGDPRGPAPPSPLPPDTHAPDPPP 2628

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  871 PAKKSRERLANGLHPVPMGPSGA---LPSPDAPCLPVKRGSPASPTSPSDCP-----PALAPR--PLSGQA----PGSPP 936
Cdd:PHA03247  2629 PSPSPAANEPDPHPPPTVPPPERprdDPAPGRVSRPRRARRLGRAAQASSPPqrprrRAARPTvgSLTSLAdpppPPPTP 2708

                          170       180
                   ....*....|....*....|....*..
gi 1081677676  937 STRPPPWLSELPENTSLQEHGVKLGPA 963
Cdd:PHA03247  2709 EPAPHALVSATPLPPGPAAARQASPAL 2735

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

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                   ....*....|....*....|....*....|....*....|
gi 1081677676  454 DTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 493
Cdd:cd11877     12 NEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYV 51

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 1081677676  441 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 493
Cdd:cd11805      1 RVQALYDFNPQ--EPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYV 51

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 1081677676   439 CGRARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMG-LLNNKVGTFKFIYV 493
Cdd:smart00326    2 GPQVRALYDYTAQ--DPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYV 55

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. 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 1081677676  441 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGT--WMGLLNNKVGTFKFIYVDV 495
Cdd:cd11842      1 KAVALYDFAGE--QPGDLAFQKGDIITILKKSDSQNdwWTGRIGGREGIFPANYVEL 55

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.

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gi 1081677676 1064 SVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKL 1123
Cdd:cd09547      5 TVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLRL 64

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 1081677676  456 DSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 494
Cdd:cd11766     14 DELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVT 52

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.

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gi 1081677676 1063 SSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSA 1117
Cdd:cd09551      7 TSVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNS 61

ORF080 virion core protein; Provisional

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  860 QPKIPSQPPPVPAKKsrerlANGLHPVPMGPSGALPS--PDAPCLPVKRGSPASPTSPSDCPPAL---APRPLSGQAPGS 934
Cdd:PHA02682    92 APACPACAPAAPAPA-----VTCPAPAPACPPATAPTcpPPAVCPAPARPAPACPPSTRQCPPAPplpTPKPAPAAKPIF 166

                   ....*...
gi 1081677676  935 PPSTRPPP 942
Cdd:PHA02682   167 LHNQLPPP 174

EBNA-3B; Provisional

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081677676  683 DPPGVTGLNKNRRSLPVSICRSCetlegpqTVDTWPRSHslddlqvePGAEQDVPTEVTEPP----PQIVPEVPQKTTAS 758
Cdd:PHA03378   570 GPLQIQPLTSPTTSQLASSAPSY-------AQTPWPVPH--------PSQTPEPPTTQSHIPetsaPRQWPMPLRPIPMR 634