SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted 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, relative 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370507734  596 PQPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 661
Cdd:cd09559      1 PQPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  364 SHGRTCSFGGFDLTNRSLHVGSNNSDPMGKEGD---FVYKEVIKSPTASRISLGKKVKSVKETMRKRMSKKYSSSVSEQD 440
Cdd:pfam12485    1 SLQRSSSFGDFDKSRPSSPVVKPEEFNLEEPEDeagEPGPEEAGKPSTSGGKLGKKMRAISRTMRRKMGKKYVKALSEEM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  441 sGLDGMPGSPPPSQPDP----EHLDKPKLKAGGSVESLRsSLSGQSSMSGQTVSTTDSSTSNRESVKSEDgddeEPPYRG 516
Cdd:pfam12485   81 -GEDEEEGSDSPPSPDDpedgPHTEKVSLKASDSEESLY-SPLSGQSSSSSGVTSPSDGTSNRDSLRLEE----EPPYTG 154

                   ..
gi 1370507734  517 PF 518
Cdd:pfam12485  155 PF 156

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 1370507734  807 QVEPGAEQDVPTEVTEPPPQIVPEVPQKTTASStkaQPLEQDSAVDNALLLTQSKRFSEPQKLTT--KKLEGSIAASGRG 884
Cdd:pfam03154  183 PPSPPPPGTTQAATAGPTPSAPSVPPQGSPATS---QPPNQTQSTAAPHTLIQQTPTLHPQRLPSphPPLQPMTQPPPPS 259

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  885 LSPPQCLPR------------NYDAQPPGAKHGLARTPLEGHRKGHEFEGTHHPLGTKEGVDAEQRMQPkiPSQPPPVPA 952
Cdd:pfam03154  260 QVSPQPLPQpslhgqmppmphSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTP--PSQSQLQSQ 337

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  953 KKSRER-------LANGLHPVPMGPSGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPwLS 1025
Cdd:pfam03154  338 QPPREQplppaplSMPHIKPPPTTPIPQLPNPQSHKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTHHPPSAHPPP-LQ 416

                          250       260
                   ....*....|....*....|....
gi 1370507734 1026 ELPENTSLQEHGVKlGPALTRKVS 1049
Cdd:pfam03154  417 LMPQSQQLPPPPAQ-PPVLTQSQS 439

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted 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, relative 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370507734  596 PQPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 661
Cdd:cd09559      1 PQPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  364 SHGRTCSFGGFDLTNRSLHVGSNNSDPMGKEGD---FVYKEVIKSPTASRISLGKKVKSVKETMRKRMSKKYSSSVSEQD 440
Cdd:pfam12485    1 SLQRSSSFGDFDKSRPSSPVVKPEEFNLEEPEDeagEPGPEEAGKPSTSGGKLGKKMRAISRTMRRKMGKKYVKALSEEM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  441 sGLDGMPGSPPPSQPDP----EHLDKPKLKAGGSVESLRsSLSGQSSMSGQTVSTTDSSTSNRESVKSEDgddeEPPYRG 516
Cdd:pfam12485   81 -GEDEEEGSDSPPSPDDpedgPHTEKVSLKASDSEESLY-SPLSGQSSSSSGVTSPSDGTSNRDSLRLEE----EPPYTG 154

                   ..
gi 1370507734  517 PF 518
Cdd:pfam12485  155 PF 156

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 1370507734  1137 VSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLP 1204
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

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 1370507734  807 QVEPGAEQDVPTEVTEPPPQIVPEVPQKTTASStkaQPLEQDSAVDNALLLTQSKRFSEPQKLTT--KKLEGSIAASGRG 884
Cdd:pfam03154  183 PPSPPPPGTTQAATAGPTPSAPSVPPQGSPATS---QPPNQTQSTAAPHTLIQQTPTLHPQRLPSphPPLQPMTQPPPPS 259

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  885 LSPPQCLPR------------NYDAQPPGAKHGLARTPLEGHRKGHEFEGTHHPLGTKEGVDAEQRMQPkiPSQPPPVPA 952
Cdd:pfam03154  260 QVSPQPLPQpslhgqmppmphSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTP--PSQSQLQSQ 337

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  953 KKSRER-------LANGLHPVPMGPSGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPwLS 1025
Cdd:pfam03154  338 QPPREQplppaplSMPHIKPPPTTPIPQLPNPQSHKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTHHPPSAHPPP-LQ 416

                          250       260
                   ....*....|....*....|....
gi 1370507734 1026 ELPENTSLQEHGVKlGPALTRKVS 1049
Cdd:pfam03154  417 LMPQSQQLPPPPAQ-PPVLTQSQS 439

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 1370507734   519 CGRARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMG-LLNNKVGTFKFIYV 573
Cdd:smart00326    2 GPQVRALYDYTAQ--DPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYV 55

Kruppel-like factor (KLF) 9, KLF13, KLF14, KLF16, and similar proteins; Kruppel/Krueppel-like transcription factors (KLFs) belong to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. KLF9, KLF10, KLF11, KLF13, KLF14, and KLF16 share a conserved alpha-helical motif AA/VXXL that mediates their binding to Sin3A and their activities as transcriptional repressors. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the related N-terminal domains of KLF9, KLF13, KLF14, KLF16, and similar proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  907 ARTPLEGHRKGHEfeGTHHPLGTKEGVDAEQRMQPKIPSQPPPVPAKKSRERL--------ANGLHPVPMGP--SGALPS 976
Cdd:cd21975     14 AGAVVHGVRPDPE--GAGLAAGLDVRATREVAKGPGPPGPAWKPDGADSPGLVtaaphllaANVLAPLRGPSveGSSLES 91

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370507734  977 PDAPCLPVKRGSPASPTSPSDCPPalaprplSGQAPGSPPStrpPPWLSELPENTSLqehGVKLGPALTRKVS 1049
Cdd:cd21975     92 GDADMGSDSDVAPASGAAASTSPE-------SSSDAASSPS---PLSLLHPGEAGLE---PERPRPRVRRGVR 151

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 1370507734  959 LANGLHPVPMGPSGALPSPDAPCLPVKRGSPASPTSPSDC---PPALAPRPLSGQAPGSPPSTRPPPWLSELPENTSLQE 1035
Cdd:NF041121    11 LAAQMGRAAAPPSPEGPAPTAASQPATPPPPAAPPSPPGDppePPAPEPAPLPAPYPGSLAPPPPPPPGPAGAAPGAALP 90

                           90
                   ....*....|....*..
gi 1370507734 1036 HGVKLGPALTRKVSCAR 1052
Cdd:NF041121    91 VRVPAPPALPNPLELAR 107

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted 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, relative 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370507734  596 PQPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 661
Cdd:cd09559      1 PQPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  364 SHGRTCSFGGFDLTNRSLHVGSNNSDPMGKEGD---FVYKEVIKSPTASRISLGKKVKSVKETMRKRMSKKYSSSVSEQD 440
Cdd:pfam12485    1 SLQRSSSFGDFDKSRPSSPVVKPEEFNLEEPEDeagEPGPEEAGKPSTSGGKLGKKMRAISRTMRRKMGKKYVKALSEEM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  441 sGLDGMPGSPPPSQPDP----EHLDKPKLKAGGSVESLRsSLSGQSSMSGQTVSTTDSSTSNRESVKSEDgddeEPPYRG 516
Cdd:pfam12485   81 -GEDEEEGSDSPPSPDDpedgPHTEKVSLKASDSEESLY-SPLSGQSSSSSGVTSPSDGTSNRDSLRLEE----EPPYTG 154

                   ..
gi 1370507734  517 PF 518
Cdd:pfam12485  155 PF 156

Src homology 3 domain of Sam And SH3 Domain Containing Protein 3; SASH3, also called SLY/SLY1 (SH3-domain containing protein expressed in lymphocytes), is expressed exclusively in lymhocytes and is essential in the full activation of adaptive immunity. It is involved in the signaling of T cell receptors. It was the first described 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 1370507734  520 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 575
Cdd:cd11968      1 GRARVHTDFIPSPYDGDSLKLQKGDIIQIIEKPPVGTWTGLLNNKVGTFKFIYVDV 56

SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. Proteins of this subfamily are known to be involved in preventing DN thymocytes from premature initiation of programmed cell death and in B cells activation and differentiation. They have been found downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370507734  599 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVEL 656
Cdd:cd09493      3 KTVEELLERINLQEHTSTLLLNGYETLEDFKDLKESHLNELNITDPEHRAKLLTAAEL 60

SAM domain of SAMSN1 subfamily; SAM (sterile alpha motif) domain of SAMSN1 (also known as HACS1 or NASH1) proteins is a predicted protein-protein interaction domain. Members of this group are putative signaling/adaptor proteins. They appear to mediate signal transduction in lymphoid tissues. Murine HACS1 protein likely plays a role in B cell activation and differentiation. Potential binding partners of HACS1 are SLAM, DEC205 and PIR-B receptors and also some unidentified tyrosine-phosphorylated proteins. Proteins of this group were found preferentially expressed in normal hematopietic tissues and in some malignancies including lymphoma, myeloid leukemia and myeloma.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370507734  599 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQE 659
Cdd:cd09561      6 KTLQELLERIHLQEYTSTLLLNGYETLEDLKDLKESHLIELNITDPEDRARLLSAAENLLD 66

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 1370507734  1137 VSPGCISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKLP 1204
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

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 1370507734  807 QVEPGAEQDVPTEVTEPPPQIVPEVPQKTTASStkaQPLEQDSAVDNALLLTQSKRFSEPQKLTT--KKLEGSIAASGRG 884
Cdd:pfam03154  183 PPSPPPPGTTQAATAGPTPSAPSVPPQGSPATS---QPPNQTQSTAAPHTLIQQTPTLHPQRLPSphPPLQPMTQPPPPS 259

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  885 LSPPQCLPR------------NYDAQPPGAKHGLARTPLEGHRKGHEFEGTHHPLGTKEGVDAEQRMQPkiPSQPPPVPA 952
Cdd:pfam03154  260 QVSPQPLPQpslhgqmppmphSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTP--PSQSQLQSQ 337

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  953 KKSRER-------LANGLHPVPMGPSGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPwLS 1025
Cdd:pfam03154  338 QPPREQplppaplSMPHIKPPPTTPIPQLPNPQSHKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTHHPPSAHPPP-LQ 416

                          250       260
                   ....*....|....*....|....
gi 1370507734 1026 ELPENTSLQEHGVKlGPALTRKVS 1049
Cdd:pfam03154  417 LMPQSQQLPPPPAQ-PPVLTQSQS 439

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370507734 1142 ISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAAR 1199
Cdd:cd09545      3 VASVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQ 60

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 1370507734  521 RARVhtDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 568
Cdd:cd11874      1 RCKV--LFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVF 46

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  810 PGAEQDVPTEVTEP---PPQIVPEVPQKTTASSTKAQPLEQDSAVdnALLLTQSKRFSEPQKLTTKKLEGSIAASGRGLS 886
Cdd:PHA03247  2601 PVDDRGDPRGPAPPsplPPDTHAPDPPPPSPSPAANEPDPHPPPT--VPPPERPRDDPAPGRVSRPRRARRLGRAAQASS 2678

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  887 PPQcLPRNYDAQPP-GAKHGLARTPLEGH----RKGHEFEGTHHPLGTKEGVDAEQrmQPKIPSQPPPVPA--------- 952
Cdd:PHA03247  2679 PPQ-RPRRRAARPTvGSLTSLADPPPPPPtpepAPHALVSATPLPPGPAAARQASP--ALPAAPAPPAVPAgpatpggpa 2755

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  953 -KKSRERLANGLHPVPMGPSGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRP----PPWLSEL 1027
Cdd:PHA03247  2756 rPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPagplPPPTSAQ 2835

                   .
gi 1370507734 1028 P 1028
Cdd:PHA03247  2836 P 2836

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 1370507734  532 PYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 574
Cdd:cd11827     10 AQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52

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 1370507734 1143 SSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLL 1195
Cdd:cd09491      6 KTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLL 58

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 1370507734 1144 SVSDWLISIGLPMYAGTLSTAGFSTLSQVPS--LSHTCLQEAGITEERHIRKLLSAARLFKLPP 1205
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 1370507734 1141 CISSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLS 1196
Cdd:cd09488      1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILN 56

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 1370507734  819 EVTEPPPQIVPEVPQKTTASSTKAQP------LEQdsaVDNALLLtQSKRFSEPQKLTTKKLEGSIAASgrglSPPQCLP 892
Cdd:pfam09770  164 GVAPKKAAAPAPAPQPAAQPASLPAPsrkmmsLEE---VEAAMRA-QAKKPAQQPAPAPAQPPAAPPAQ----QAQQQQQ 235

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  893 RNYDAQPPGAKHGLARTPLEGHRKGHEfegthhplgtkegVDAEQRMQPK--IPSQPPPVPAKKSRERLAnglHPVPMGP 970
Cdd:pfam09770  236 FPPQIQQQQQPQQQPQQPQQHPGQGHP-------------VTILQRPQSPqpDPAQPSIQPQAQQFHQQP---PPVPVQP 299

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370507734  971 SGALPSPDAPCLPVKRGSPASPTSPSDCPPALAPRPLSGQAPGSPPSTRPPPwLSELPE 1029
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 1370507734  521 RARVHTDFTPSpyDTDSLKLKKGDIIDIISK--PPMGTWMGLLNNKVGTF 568
Cdd:cd11875      1 KARVLFDYEAE--NEDELTLREGDIVTILSKdcEDKGWWKGELNGKRGVF 48

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 1370507734  534 DTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 573
Cdd:cd11877     12 NEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYV 51

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A 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
                   ....*....|....*....|....*....|....*..
gi 1370507734  532 PYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 568
Cdd:cd12054     11 PQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLF 47

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1370507734 1143 SSVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLL 1195
Cdd:cd09490      4 LDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRIL 56

DNA polymerase III subunits gamma and tau; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  941 PKIPSQPPPVPAKKSRERLANGLHPVPMGPSGALPSPDAPCLPVKRGSPasptsPSDCPPALAPRPLSGQAPGSPPSTRP 1020
Cdd:PRK14951   381 PARPEAAAPAAAPVAQAAAAPAPAAAPAAAASAPAAPPAAAPPAPVAAP-----AAAAPAAAPAAAPAAVALAPAPPAQA 455

                           90       100
                   ....*....|....*....|...
gi 1370507734 1021 PPWLSELPENTSLQEHGVKLGPA 1043
Cdd:PRK14951   456 APETVAIPVRVAPEPAVASAAPA 478

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370507734  521 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGT--WMGLLNNKVGTFKFIYVDV 575
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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734 1144 SVSDWLISIGLPMYAGTLSTAGFSTLSQVPSLSHTCLQEAGITEERHIRKLLSAARLFKL 1203
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.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1370507734  536 DSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 574
Cdd:cd11766     14 DELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVT 52

ORF080 virion core protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370507734  937 QRMQPKIPSQP-PPVPAkksrerlanglhPVPMGPSgalPSPDAPCLPVKRGSPAS---PTSPSDCPPALAPRPLSGQAP 1012
Cdd:PHA02682    74 QRPSGQSPLAPsPACAA------------PAPACPA---CAPAAPAPAVTCPAPAPacpPATAPTCPPPAVCPAPARPAP 138

                           90
                   ....*....|....*.
gi 1370507734 1013 GSPPSTRPPPWLSELP 1028
Cdd:PHA02682   139 ACPPSTRQCPPAPPLP 154