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 1081682913  934 PVSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLPP 1003
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 1081682913  318 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 374
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 1081682913  934 PVSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLPP 1003
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 1081682913  318 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 374
Cdd:cd11967      1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

SAM domain (Sterile alpha motif);

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1081682913  935 VSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFK 1000
Cdd:pfam07647    1 VESWSLESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  542 GQEEGRLGGGLAPDTSKSCDPPGVTGLNKNRR-SLPVSICRSCETLEGPQTVDTWPRSHSLDDLQVEPgaeqDVPTEVTE 620
Cdd:PHA03247  2635 ANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRaRRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPP----PPPPTPEP 2710

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  621 PPPQIVPEVPQKTTASS-------TKAQPLEQDSAVDNALLLTQSKRFSEPqklTTKKLEGSIAASGRGLSPPQCLPRny 693
Cdd:PHA03247  2711 APHALVSATPLPPGPAAarqaspaLPAAPAPPAVPAGPATPGGPARPARPP---TTAGPPAPAPPAAPAAGPPRRLTR-- 2785

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  694 daqPPGAKHGLARTPLEGHRkghefEGTHHPLGTKEGVDAEQRMQPKIPSQPPPVPAKKSRERLANGLHPVPMGPSGAL- 772
Cdd:PHA03247  2786 ---PAVASLSESRESLPSPW-----DPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVa 2857

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1081682913  773 PSPDAPCLPVKRGSPASPTSPSDCP------PALAPRPLSGQAPGSPPSTRPPPWLSELPENTSLQEHGVKLGPAL 842
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 1081682913  319 RARVHTDFTPspYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 371
Cdd:pfam07653    1 YGRVIFDYVG--TDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAV 51

SAV_2336 family N-terminal domain; This HMM describes an N-terminal domain shared by SAV_2336 (BAC70047.1) whose C-terminal region suggests restriction enzyme activity (PMID: 18456708), and with other proteins with unrelated C-terminal regions. A member protein was also identified in a kanamycin biosynthetic gene cluster (PMID:16766657), while N-terminal regions of two other member proteins were named Trypco1 in a bioinformatic study (PMID:32101166) of predicted bacterial conflict systems.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  757 LANGLHPVPMGPSGALPSPDAPCLPVKRGSPASPTSPSDC---PPALAPRPLSGQAPGSPPSTRPPPWLSELPENTSLQE 833
Cdd:NF041121    11 LAAQMGRAAAPPSPEGPAPTAASQPATPPPPAAPPSPPGDppePPAPEPAPLPAPYPGSLAPPPPPPPGPAGAAPGAALP 90

                           90
                   ....*....|....*..
gi 1081682913  834 HGVKLGPALTRKVSCAR 850
Cdd:NF041121    91 VRVPAPPALPNPLELAR 107

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 1081682913  934 PVSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLPP 1003
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 1081682913  318 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 374
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 1081682913  319 RARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIY 370
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 1081682913  397 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 459
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 1081682913  319 RARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 373
Cdd:cd11759      3 YARVIQKRVPNAYDKTALALEVGDLVKVTKINVSGQWEGELNGKVGHFPFTHVEL 57

SAM domain (Sterile alpha motif);

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1081682913  935 VSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFK 1000
Cdd:pfam07647    1 VESWSLESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  605 QVEPGAEQDVPTEVTEPPPQIVPEVPQKTTASStkaQPLEQDSAVDNALLLTQSKRFSEPQKLTT--KKLEGSIAASGRG 682
Cdd:pfam03154  183 PPSPPPPGTTQAATAGPTPSAPSVPPQGSPATS---QPPNQTQSTAAPHTLIQQTPTLHPQRLPSphPPLQPMTQPPPPS 259

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  683 LSPPQCLPR------------NYDAQPPGAKHGLARTPLEGHRKGHEFEGTHHPLGTKEGVDAEQRMQPkiPSQPPPVPA 750
Cdd:pfam03154  260 QVSPQPLPQpslhgqmppmphSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTP--PSQSQLQSQ 337

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  751 KKSRER-------LANGLHPVPMGPSGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPwLS 823
Cdd:pfam03154  338 QPPREQplppaplSMPHIKPPPTTPIPQLPNPQSHKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTHHPPSAHPPP-LQ 416

                   ....*....
gi 1081682913  824 ELPENTSLQ 832
Cdd:pfam03154  417 LMPQSQQLP 425

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 1081682913  319 RARVhtDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 366
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 1081682913  330 PYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 372
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 1081682913  939 CISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFK 1000
Cdd:cd09555      5 CLDSPQAWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQ 66

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
                   ....*....|....*....|....*....|....*....|....*....
gi 1081682913  325 DFTPSPYDtdSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 373
Cdd:cd11823      7 SYTANRED--ELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVEE 53

SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM1 domain has a potential phosphorylation site for CMGC group of serine/threonine kinases. SAM domains of the AIDA1-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1081682913  942 SVSDWLISIGLPMYAGTLSTAGFSTLSQVPS--LSHTCLQEAGITEERHIRKLLSAARLFKLPP 1003
Cdd:cd09499      4 SVGQWLESIGLPQYESKLLLNGFDDVDFLGSgvMEDQDLKEIGITDEQHRQIILQAARSLPKKK 67

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1081682913  939 CISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLS 994
Cdd:cd09488      1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILN 56

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  941 SSVSDWLISIGLPMYAGTLStAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFK 1000
Cdd:pfam00536    6 EDVGEWLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64

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 1081682913  617 EVTEPPPQIVPEVPQKTTASSTKAQP------LEQdsaVDNALLLtQSKRFSEPQKLTTKKLEGSIAASgrglSPPQCLP 690
Cdd:pfam09770  164 GVAPKKAAAPAPAPQPAAQPASLPAPsrkmmsLEE---VEAAMRA-QAKKPAQQPAPAPAQPPAAPPAQ----QAQQQQQ 235

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  691 RNYDAQPPGAKHGLARTPLEGHRKGHEfegthhplgtkegVDAEQRMQPK--IPSQPPPVPAKKSRERLAnglHPVPMGP 768
Cdd:pfam09770  236 FPPQIQQQQQPQQQPQQPQQHPGQGHP-------------VTILQRPQSPqpDPAQPSIQPQAQQFHQQP---PPVPVQP 299

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1081682913  769 SGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPwLSELPE 827
Cdd:pfam09770  300 TQILQNPNRLSAARVGYPQNPQPGVQPAPAHQAHRQQGSFGRQAPIITHPQQ-LAQLSE 357

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1081682913  332 DTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 371
Cdd:cd11877     12 NEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYV 51

DNA translocase FtsK; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  603 DLQVEPGAEqdVPTEVTEPPPQIVPEVPQKTTASSTKAQPLEQDsavdnallLTQSKRFSEPQKLTTKKLEGSIAASGRG 682
Cdd:PRK10263   359 AWQPVPGPQ--TGEPVIAPAPEGYPQQSQYAQPAVQYNEPLQQP--------VQPQQPYYAPAAEQPAQQPYYAPAPEQP 428

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  683 LSPPQCLPRNYDAQPPGAKHGLARTPLEGHRKGHEFEGTH-HPLGTKEGVDAEQRMQPKIPSQPPPV-----PAK----- 751
Cdd:PRK10263   429 AQQPYYAPAPEQPVAGNAWQAEEQQSTFAPQSTYQTEQTYqQPAAQEPLYQQPQPVEQQPVVEPEPVveetkPARpplyy 508

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  752 ---------KSRERLANGLHPVPMgPSGAlPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPWL 822
Cdd:PRK10263   509 feeveekraREREQLAAWYQPIPE-PVKE-PEPIKSSLKAPSVAAVPPVEAAAAVSPLASGVKKATLATGAAATVAAPVF 586

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  823 SELPENTSLQEHGVKLGPALTRKVScargvdLETLTENKLHAEGIDLTEEPYSDKHGR---CGIPEALVQRYAEDLDQPE 899
Cdd:PRK10263   587 SLANSGGPRPQVKEGIGPQLPRPKR------IRVPTRRELASYGIKLPSQRAAEEKAReaqRNQYDSGDQYNDDEIDAMQ 660

                   ....*
gi 1081682913  900 RDVAA 904
Cdd:PRK10263   661 QDELA 665

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 1081682913  319 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 371
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.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 1081682913   317 CGRARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMG-LLNNKVGTFKFIYV 371
Cdd:smart00326    2 GPQVRALYDYTAQ--DPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYV 55

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. 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 1081682913  321 RVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFK 367
Cdd:cd11883      3 VALYDFTPK--SKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVK 47

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  942 SVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKL 1001
Cdd:cd09547      5 TVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLRL 64

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1081682913  941 SSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSA 995
Cdd:cd09551      7 TSVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNS 61

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) 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. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1081682913  330 PYDT---DSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 366
Cdd:cd11873      7 DYDAeepDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMF 46

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  553 APDTSKSCDPPGVTGLNKNRRSLPVSICRSCETLEGPQTVDTWPRSHSLDDLQvePGAEQDVPTEVTEPPPQIVPEVPQK 632
Cdd:PHA03307   119 PTPPPASPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASDAASSRQ--AALPLSSPEETARAPSSPPAEPPPS 196

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  633 TTASSTKAQPLEQDSavdnalllTQSKRFSEPQKLTTKKLEGSIAASGRGLSPPQCL-----PRNYDAQPPGAKHGLART 707
Cdd:PHA03307   197 TPPAAASPRPPRRSS--------PISASASSPAPAPGRSAADDAGASSSDSSSSESSgcgwgPENECPLPRPAPITLPTR 268

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1081682913  708 PLEGHrkGHEFEGTHHPLGTKEGVDAE-----QRMQPKIPSQPPPVPAKKSRERLANGlhpVPMGPSGALPSPDAPCLPV 782
Cdd:PHA03307   269 IWEAS--GWNGPSSRPGPASSSSSPRErspspSPSSPGSGPAPSSPRASSSSSSSRES---SSSSTSSSSESSRGAAVSP 343

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1081682913  783 KRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPWLSELPENTS 830
Cdd:PHA03307   344 GPSPSRSPSPSRPPPPADPSSPRKRPRPSRAPSSPAASAGRPTRRRAR 391

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1081682913  326 FTPSPYDTDSLKLKKGDIIDIISKPP--MGTWMGLLNNKVGTF 366
Cdd:cd12142      6 FDYNPVAPDELALKKGDVIEVISKETedEGWWEGELNGRRGFF 48

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. 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 C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. 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 1081682913  320 ARVHTDFtpSPYDTDSLKLKKGDIIDIISKP-PMGTWMGLLNNKVGTFKFIYVD 372
Cdd:cd11976      2 AKARYDF--CARDRSELSLKEGDIIKILNKKgQQGWWRGEIYGRVGWFPANYVE 53