SAM domain of Ph (polyhomeotic) proteins of Polycomb group; SAM (sterile alpha motif) domain of Ph (polyhomeotic) proteins of Polycomb group is a protein-protein interaction domain. Ph1,2,3 proteins are members of PRC1 complex. This complex is involved in transcriptional repression of Hox (Homeobox) cluster genes. It is recruited through methylated H3Lys27 and supports the repression state by mediating monoubiquitination of histone H2A. Proteins of the Ph1,2,3 subfamily contribute to anterior-posterior neural tissue specification during embryogenesis. Additionally, the P2 protein of zebrafish is known to be involved in epiboly and tailbud formation. SAM domains of Ph proteins may interact with each other, forming homooligomers, as well as with SAM domains of other proteins, in particular with the SAM domain of Scm (sex comb on midleg) proteins, forming heterooligomers. Homooligomers are similar to the ones formed by SAM Pointed domains of the TEL proteins. Such SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622904852 877 TEPSIWTVDDVWAFIHSLPGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARINSLKE 945
Cdd:cd09577     1 SNPSKWSVEDVYEFIRSLPGCSDYAEEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICAKINSLKE 69

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 1622904852 183 STSQTQSLTICHNKTTVTSSKISQRDPSPESNKKGESPSLESRSTAVTRTSSIHQLIAPA-SYSPIQPHSLIkhQQIPLH 261
Cdd:pfam03154 160 SSAQQQILQTQPPVLQAQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNqTQSTAAPHTLI--QQTPTL 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 262 SPPSKVSHHQLILQQqqqqiqpitlqnsTQDPPPSQHCI-----PLQNHGLPPAPSNAQSQhcSPIQSHPPPLTVSPNQS 336
Cdd:pfam03154 238 HPQRLPSPHPPLQPM-------------TQPPPPSQVSPqplpqPSLHGQMPPMPHSLQTG--PSHMQHPVPPQPFPLTP 302

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 337 QSAQQSVVVSPPPPHSPSQSPTIIIHPQaliqphplvssalQPGPNLQQSTANQVQPTAQLNLPSHLPLPASPVVHIgPV 416
Cdd:pfam03154 303 QSSQSQVPPGPSPAAPGQSQQRIHTPPS-------------QSQLQSQQPPREQPLPPAPLSMPHIKPPPTTPIPQL-PN 368

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 417 QQSALVSPGQQIVSPshqqYSSLQSSPIPIASPPQMSTS----PPAQIPPLPL----QSMQSLQVQPEILSQGQVLVQNA 488
Cdd:pfam03154 369 PQSHKHPPHLSGPSP----FQMNSNLPPPPALKPLSSLSthhpPSAHPPPLQLmpqsQQLPPPPAQPPVLTQSQSLPPPA 444

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622904852 489 LVSEEELPAAEALVQLPFQT---------------LPPPQTVAVNLQVQPPAPVDPPVGMHL 535
Cdd:pfam03154 445 ASHPPTSGLHQVPSQSPFPQhpfvpggpppitppsGPPTSTSSAMPGIQPPSSASVSSSGPV 506

SAM domain of Ph (polyhomeotic) proteins of Polycomb group; SAM (sterile alpha motif) domain of Ph (polyhomeotic) proteins of Polycomb group is a protein-protein interaction domain. Ph1,2,3 proteins are members of PRC1 complex. This complex is involved in transcriptional repression of Hox (Homeobox) cluster genes. It is recruited through methylated H3Lys27 and supports the repression state by mediating monoubiquitination of histone H2A. Proteins of the Ph1,2,3 subfamily contribute to anterior-posterior neural tissue specification during embryogenesis. Additionally, the P2 protein of zebrafish is known to be involved in epiboly and tailbud formation. SAM domains of Ph proteins may interact with each other, forming homooligomers, as well as with SAM domains of other proteins, in particular with the SAM domain of Scm (sex comb on midleg) proteins, forming heterooligomers. Homooligomers are similar to the ones formed by SAM Pointed domains of the TEL proteins. Such SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622904852 877 TEPSIWTVDDVWAFIHSLPGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARINSLKE 945
Cdd:cd09577     1 SNPSKWSVEDVYEFIRSLPGCSDYAEEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICAKINSLKE 69

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 1622904852  879 PSIWTVDDVWAFIHSLpGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNI-KLGPALKICARINSLKES 946
Cdd:smart00454   1 VSQWSPESVADWLESI-GLEQYADNFRKNGIDGALLLLLTSEEDLKELGItKLGHRKKILKAIQKLKEQ 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 1622904852 183 STSQTQSLTICHNKTTVTSSKISQRDPSPESNKKGESPSLESRSTAVTRTSSIHQLIAPA-SYSPIQPHSLIkhQQIPLH 261
Cdd:pfam03154 160 SSAQQQILQTQPPVLQAQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNqTQSTAAPHTLI--QQTPTL 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 262 SPPSKVSHHQLILQQqqqqiqpitlqnsTQDPPPSQHCI-----PLQNHGLPPAPSNAQSQhcSPIQSHPPPLTVSPNQS 336
Cdd:pfam03154 238 HPQRLPSPHPPLQPM-------------TQPPPPSQVSPqplpqPSLHGQMPPMPHSLQTG--PSHMQHPVPPQPFPLTP 302

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 337 QSAQQSVVVSPPPPHSPSQSPTIIIHPQaliqphplvssalQPGPNLQQSTANQVQPTAQLNLPSHLPLPASPVVHIgPV 416
Cdd:pfam03154 303 QSSQSQVPPGPSPAAPGQSQQRIHTPPS-------------QSQLQSQQPPREQPLPPAPLSMPHIKPPPTTPIPQL-PN 368

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 417 QQSALVSPGQQIVSPshqqYSSLQSSPIPIASPPQMSTS----PPAQIPPLPL----QSMQSLQVQPEILSQGQVLVQNA 488
Cdd:pfam03154 369 PQSHKHPPHLSGPSP----FQMNSNLPPPPALKPLSSLSthhpPSAHPPPLQLmpqsQQLPPPPAQPPVLTQSQSLPPPA 444

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622904852 489 LVSEEELPAAEALVQLPFQT---------------LPPPQTVAVNLQVQPPAPVDPPVGMHL 535
Cdd:pfam03154 445 ASHPPTSGLHQVPSQSPFPQhpfvpggpppitppsGPPTSTSSAMPGIQPPSSASVSSSGPV 506

SAM domain of Ph (polyhomeotic) proteins of Polycomb group; SAM (sterile alpha motif) domain of Ph (polyhomeotic) proteins of Polycomb group is a protein-protein interaction domain. Ph1,2,3 proteins are members of PRC1 complex. This complex is involved in transcriptional repression of Hox (Homeobox) cluster genes. It is recruited through methylated H3Lys27 and supports the repression state by mediating monoubiquitination of histone H2A. Proteins of the Ph1,2,3 subfamily contribute to anterior-posterior neural tissue specification during embryogenesis. Additionally, the P2 protein of zebrafish is known to be involved in epiboly and tailbud formation. SAM domains of Ph proteins may interact with each other, forming homooligomers, as well as with SAM domains of other proteins, in particular with the SAM domain of Scm (sex comb on midleg) proteins, forming heterooligomers. Homooligomers are similar to the ones formed by SAM Pointed domains of the TEL proteins. Such SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622904852 877 TEPSIWTVDDVWAFIHSLPGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARINSLKE 945
Cdd:cd09577     1 SNPSKWSVEDVYEFIRSLPGCSDYAEEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICAKINSLKE 69

SAM domain of Samd7,11 subfamily of Polycomb group; SAM (sterile alpha motif) domain is a protein-protein interaction domain. Phylogenetic analysis suggests that proteins of this subfamily are most closely related to SAM-Ph1,2,3 subfamily of Polycomb group. They are predicted transcriptional repressors in photoreceptor cells and pinealocytes of vertebrates. SAM domain containing protein 11 is also known as Mr-s (major retinal SAM) protein. In mouse, it is predominantly expressed in developing retinal photoreceptors and in adult pineal gland. The SAM domain is involved in homooligomerization of whole proteins (it was shown based on immunoprecipitation assay and mutagenesis), however its repression activity is not due to SAM/SAM interactions but to the C-terminal region.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622904852 882 WTVDDVWAFIHSLPGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARI 940
Cdd:cd09579     4 WTVDDVCSFIGSLPGCAEYAQVFREHSIDGETLPLLTEEHLLNTMGLKLGPALKIRSQV 62

SAM domain of Scm proteins of Polycomb group; SAM (sterile alpha motif) domain of Scm (Sex comb on midleg) subfamily of Polycomb group is a protein-protein interaction domain. Proteins of this subfamily are transcriptional repressors associated with PRC1 complex. This group includes invertebrate Scm protein and chordate Scm homolog 1 and Scm-like 1, 2, 3 proteins. Most have a SAM domain, two MBT repeats, and a DUF3588 domain, except Scm-like 4 proteins which do not have MBT repeats. Originally the Scm protein was described in Drosophila as a regulator required for proper spatial expression of homeotic genes. It plays a major role during early embryogenesis. SAM domains of Scm proteins can interact with each other, forming homooligomers, as well as with SAM domains of other proteins, in particular with SAM domains of Ph (polyhomeotic) proteins, forming heterooligomers. Homooligomers are similar to the ones formed by SAM Pointed domains of the TEL proteins. Such SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Mammalian Scmh1 protein is known be indispensible member of PRC1 complex; it plays a regulatory role for the complex during meiotic prophase of male sperm cells, and is particularly involved in regulation of chromatin modification at the XY chromatin domain of the pachytene spermatocytes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622904852 879 PSIWTVDDVWAFIHSL--PGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARINSLKE 945
Cdd:cd09578     4 PSTWSVEDVVQFIKEAdpQALAPHVDLFRKHEIDGKALLLLNSDMMMKYMGLKLGPALKLCYHIDKLKQ 72

SAM domain of Scm-like-4MBT1,2 proteins of Polycomb group; SAM (sterile alpha motif) domain of Scm-like-4MBT1,2 (Sex comb on midleg, Malignant Brain Tumor) subfamily proteins (also known as Sfmbt1,2 proteins) is a putative protein-protein interaction domain. Proteins of this subfamily are transcriptional regulators belonging to Polycomb group. The majority of them are multidomain proteins: in addition to the C-terminal SAM domain, they contain four MBT repeats and DUF5388 domain. The MBT repeats of the human sfmbt1 protein are responsible for association with the nuclear matrix and for selective binding of H3 histone N-terminal tails, while the exact function of the SAM domain is unclear.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622904852 877 TEPSIWTVDDVWAFIHSlPGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARINSLK 944
Cdd:cd09581    10 SNPLFWSVDDVVRFIKS-TDCAPLAKIFKDQEIDGQALLLLTLPTVQECMELKLGPAIKLCHHIERVK 76

SAM domain of Scm-like-4MBT proteins of Polycomb group; SAM (sterile alpha motif) domain of Scm-like-4MBT (Sex comb on midleg like, Malignant Brain Tumor) subfamily proteins of the polycomb group is a putative protein-protein interaction domain. Additionally to the SAM domain, most of the proteins of this subfamily have 4 MBT repeats. In Drosophila SAM-Scm-like-4MBT protein (known as dSfmbt) is a member of Pho repressive complex (PhoRC). Additionally to dSfmbt, the PhoRC complex includes Pho or Pho-like proteins. This complex is responsible for HOX (Homeobox) gene silencing: Pho or Pho-like proteins bind DNA and dSmbt binds methylated histones. dSmbt can interact with mono- and di-methylated histones H3 and H4 (however this activity has been shown for the MBT repeats, while exact function of the SAM domain is unclear). Besides interaction with histones, dSmbt can interact with Scm (a member of PRC complex), but this interaction also seems to be SAM domain independent.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622904852 879 PSIWTVDDVWAFIhSLPGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARINSLK 944
Cdd:cd09580     1 PSTWGVKDVSQFL-RENDCGAYCECFCRQNIDGKRLLSLTKEQIMTLTGMKVGPSLKIYDLIQQLK 65

SAM domain of WDSUB1 proteins; SAM (sterile alpha motif) domain of WDSUB1 subfamily proteins is a putative protein-protein interaction domain. Proteins of this group contain multiple domains: SAM, one or more WD40 repeats and U-box (derived version of the RING-finger domain). Apparently the WDSUB1 subfamily proteins participate in protein degradation through ubiquitination, since U-box domain are known as a member of E3 ubiquitin ligase family, while SAM and WD40 domains most probably are responsible for an E2 ubiquitin-conjugating enzyme binding and a target protein binding.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622904852 879 PSIWTVDDVWAFIHSLpGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIK-LGPALKICARINSLKES 946
Cdd:cd09505     2 LQDWSEEDVCTWLRSI-GLEQYVEVFRANNIDGKELLNLTKESLSKDLKIEsLGHRNKILRKIEELKMK 69

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 1622904852 886 DVWAFIHSLpGCQDIADEFRAQEIDGQALLLLKEDHLMSAMNIKLGPALKICARIN 941
Cdd:cd09487     1 DVAEWLESL-GLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55

SAM domain of Samd9/Samd9L subfamily; SAM (sterile alpha motif) domain of Samd9/Samd9L subfamily is a putative protein-protein interaction domain. SAM is a widespread domain in signaling proteins. Samd9 is a tumor suppressor gene. It is involved in death signaling of malignant glioblastoma. Samd9 suppression blocks cancer cell death induced by HVJ-E or IFN-beta treatment. Deleterious mutations in Samd9 lead to normophosphatemic familial tumoral calcinosis, a cutaneous disorder characterized by cutaneous calcification or ossification.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622904852 882 WTVDDVWAFIHSLPGCQDIADEFRAQEIDGQALLLLKEDHLMSaMNIKLGPALKIcarINSLKE 945
Cdd:cd09528     3 WTKEHVKQWLIEDLIDKKYAEILYEEEVTGAVLKELTEEDLVD-MGLPHGPALLI---IHSFNE 62

SAM domain of BOI-like fungal subfamily; SAM (sterile alpha motif) domain of BOI-like fungal subfamily is a potential protein-protein interaction domain. Proteins of this subfamily are apparently scaffold proteins, since most contain SH3 and PH domains, which are also protein-protein interaction domains, in addition to SAM domain. BOI-like proteins participate in cell cycle regulation. In particular BOI1 and BOI2 proteins of budding yeast S.cerevisiae are involved in bud formation, and POB1 protein of fission yeast S.pombe plays a role in cell elongation and separation. Among binding partners of BOI-like fungal subfamily members are such proteins as Bem1 and Cdc42 (they are known to be involved in cell polarization and bud formation).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622904852 882 WTVDDVWAFIHSLPGCQDIADEFRAQEIDGQALLLLKEDHLmSAMNIK-LGPALKICARINSLK 944
Cdd:cd09535     3 WSPEQVAEWLLSAGFDDSVCEKFRENEITGDILLELDLEDL-KELDIGsFGKRFKLWNEIKSLR 65

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 181 PKSTSQTQSLTichNKTTVTSSKISQRDPSPESNkkgeSPSLESRSTAVTRT-----SSIH---QLIAPASYSPIqphsl 252
Cdd:pfam05109 400 PKTLIITRTAT---NATTTTHKVIFSKAPESTTT----SPTLNTTGFAAPNTttglpSSTHvptNLTAPASTGPT----- 467

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 253 IKHQQIPLHSPPSKVSHHQLILQQQQQQIQPITLQNSTQDPPPSQHCIPLQNHGLPpapsnaqsqhcSPIQSHPPPLTVS 332
Cdd:pfam05109 468 VSTADVTSPTPAGTTSGASPVTPSPSPRDNGTESKAPDMTSPTSAVTTPTPNATSP-----------TPAVTTPTPNATS 536

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622904852 333 PNQSQSAQQSVVVSPPPPHSPSQSPTIIIHPQALI----QPHPlVSSALQPGPNLQQSTANQVQPTAQLNLPSHLPLPAS 408
Cdd:pfam05109 537 PTLGKTSPTSAVTTPTPNATSPTPAVTTPTPNATIptlgKTSP-TSAVTTPTPNATSPTVGETSPQANTTNHTLGGTSST 615

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622904852 409 PVVHIGPVQQSALVSPGQQIVSPSHQQYSSLQSSPIPIASPPQMSTSPPAQIPPL----PLQSMQSLQVQPEILSQGQV 483
Cdd:pfam05109 616 PVVTSPPKNATSAVTTGQHNITSSSTSSMSLRPSSISETLSPSTSDNSTSHMPLLtsahPTGGENITQVTPASTSTHHV 694

SAM / Pointed domain; A subfamily of the SAM domain

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622904852  879 PSIWTVDDVWAFIhslpgcQDIADEFRAQEID-------GQALLLL-KEDHLMSA 925
Cdd:smart00251  17 PQLWTEDHVLEWL------EWAVKEFSLSPIDfskfdmsGKELCSMsKEEFLERA 65