transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81882526    41 GRRHRPSRSRLRDSTSSAEDGEGSDGPGGKVTDGCGSPLHRLRSPL-HSGPGSPAGGSFCLEPPGLRRSLDEDEPPPSPL 119
Cdd:PHA03307  225 GRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPAPITLPTRIWeASGWNGPSSRPGPASSSSSPRERSPSPSPSSPG 304

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81882526   120 ARYR-PLHNAASHEGLAATSGSPPRSAPSSDSSpsfvrryPRAEPHSEDDSRDASPPEPASPTIGLDKKTRRKFLDLGVT 198
Cdd:PHA03307  305 SGPApSSPRASSSSSSSRESSSSSTSSSSESSR-------GAAVSPGPSPSRSPSPSRPPPPADPSSPRKRPRPSRAPSS 377

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 81882526   199 LRRASTSKSRKEKGSNRLSMGSREsvEGSGRTGGSP 234
Cdd:PHA03307  378 PAASAGRPTRRRARAAVAGRARRR--DATGRFPAGR 411

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 81882526    323 VEHWTSQQVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDG-SKLKSLGLSNSHDRALVKRKLKEL 386
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSeEDLKELGITKLGHRKKILKAIQKL 65

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81882526    41 GRRHRPSRSRLRDSTSSAEDGEGSDGPGGKVTDGCGSPLHRLRSPL-HSGPGSPAGGSFCLEPPGLRRSLDEDEPPPSPL 119
Cdd:PHA03307  225 GRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPAPITLPTRIWeASGWNGPSSRPGPASSSSSPRERSPSPSPSSPG 304

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81882526   120 ARYR-PLHNAASHEGLAATSGSPPRSAPSSDSSpsfvrryPRAEPHSEDDSRDASPPEPASPTIGLDKKTRRKFLDLGVT 198
Cdd:PHA03307  305 SGPApSSPRASSSSSSSRESSSSSTSSSSESSR-------GAAVSPGPSPSRSPSPSRPPPPADPSSPRKRPRPSRAPSS 377

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 81882526   199 LRRASTSKSRKEKGSNRLSMGSREsvEGSGRTGGSP 234
Cdd:PHA03307  378 PAASAGRPTRRRARAAVAGRARRR--DATGRFPAGR 411

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 81882526 330 QVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDGSKLKSLGLSNSHDRALVKRKLKE 385
Cdd:cd09487   1 DVAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQR 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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 81882526   324 EHWTSQQVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDGSKLKSLGLSNSHDR 376
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHR 53

SAM domain of Ste11_fungal subfamily; SAM (sterile alpha motif) domain of Ste11 subfamily is a protein-protein interaction domain. Proteins of this subfamily have SAM domain at the N-terminus and protein kinase domain at the C-terminus. They participate in regulation of mating pheromone response, invasive growth and high osmolarity growth response. MAP triple kinase Ste11 from S.cerevisia is known to interact with Ste20 kinase and Ste50 regulator. These kinases are able to form homodimers interacting through their SAM domains as well as heterodimers or heterogenous complexes when either SAM domain of monomeric or homodimeric form of Ste11 interacts with Ste50 regulator.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 81882526 326 WTSQQVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDGSKLKSLGLSNSHDRALVKRKLKEL 386
Cdd:cd09534   1 WDEEFVEEWLNELNCGQYLDIFEKNLITGDLLLELDKEALKELGITKVGDRIRLLRAIKSL 61

SAM domain ot SARM1-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of SARM1-like adaptor proteins is a protein-protein interaction domain. SARM1-like proteins contain two tandem SAM domains. SARM1-like proteins are involved in TLR (Toll-like receptor) signaling. They are responsible for targeted localization of the whole protein to post-synaptic regions of axons. In humans SARM1 expression is detected in kidney and liver.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 81882526 323 VEHWTSQQVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDGSKLKS-LGLSNSHDRalvKRKLKEL 386
Cdd:cd09501   1 VPLWSVADVQTWLKQIGFEDYAEKFSESQVDGDLLLQLTEDELKQdLGMSSGLLR---KRFLREL 62

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81882526 323 VEHWTSQQVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDGSKLKSLGLSNSHDRALVKRKLKEL 386
Cdd:cd09506   2 VHEWTVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKL 65

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 81882526 329 QQVGQWLHSLNLEQYAAEFAARQVDGPQLLQ---LDGSKLKSLGLSNSHDRALVKRKLKEL 386
Cdd:cd09499   3 QSVGQWLESIGLPQYESKLLLNGFDDVDFLGsgvMEDQDLKEIGITDEQHRQIILQAARSL 63

SAM domain of Ste50_like (ubc2) subfamily; SAM (sterile alpha motif) domain of Ste50-like (or Ubc2 for Ustilago bypass of cyclase) subfamily is a putative protein-protein interaction domain. This group includes only fungal proteins. Basidiomycetes have an N-terminal SAM domain, central UBQ domain, and C-terminal SH3 domain, while Ascomycetes lack the SH3 domain. Ubc2 of Ustilago maydis is a major virulence and maize pathogenicity factor. It is required for filamentous growth (the budding haploid form of Ustilago maydis is a saprophyte, while filamentous dikaryotic form is a pathogen). Also the Ubc2 protein is involved in the pheromone-responsive morphogenesis via the MAP kinase cascade. The SAM domain is necessary for ubc2 function; deletion of SAM eliminates this function. A Lys-to-Glu mutation in the SAM domain of ubc2 gene induces temperature sensitivity.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 81882526 330 QVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDGSKLKSLGLS 371
Cdd:cd09533   1 DVADWLSSLGLPQYEDQFIENGITGDVLVALDHEDLKEMGIT 42

SAM domain of diacylglycerol kinase eta; SAM (sterile alpha motif) domain of DGK-eta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases. The SAM domain is located at the C-terminus of two out of three isoforms of DGK-eta protein. DGK-eta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DCK-eta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-delta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it is responsible for sustained endosomal localization of the protein and resulted in negative regulation of DCK-eta catalytic activity.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81882526 323 VEHWTSQQVGQWLHSLNLEQYAAEFAARQVDGPQLLQLDGSKLKSLGLSNSHDRALVKRKLKEL 386
Cdd:cd09576   2 VQKWGTDEVAAWLDLLSLGEYKEIFIRHDIRGSELLHLERRDLKDLGIPKVGHMKRILQGIKEL 65

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
                ....*....|....*....|....*....|....*....|....*..
gi 81882526 326 WTSQQVGQWLHSLNLEQYAAE-FAARQVDGPQLLQLDGSKLKSLGLS 371
Cdd:cd09535   3 WSPEQVAEWLLSAGFDDSVCEkFRENEITGDILLELDLEDLKELDIG 49

SAM domain of STIM-1,2-like proteins; SAM (sterile alpha motif) domain of STIM-1,2-like (Stromal interaction molecule) proteins is a putative protein-protein interaction domain. STIM1 and STIM2 human proteins are type I transmembrane proteins. The N-terminal part of them includes "hidden" EF-hand and SAM domains. This region is responsible for sensing changes in store-operated and basal cytoplasmic Ca2+ levels and initiates oligomerization. "Hidden" EF hand and SAM domains have a stable intramolecular association, and the SAM domain is a component that regulates stability within STIM proteins. Destabilization of the EF-SAM association during Ca2+ depletion leads to partial unfolding and aggregation (homooligomerization), thus activating the store-operated Ca2+ entry. Immunoprecipitation analysis indicates that STIM1 and STIM2 can form co-precipitable oligomeric associations in vivo. It was suggested that STIM1 and STIM2 are involved in opposite regulation of store operated channels in plasma membrane.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 81882526 323 VEHWTSQQVGQWL-HSLNLEQYAAEFAARQVDG---PQLLQLDGSKLKS-LGLSNSHDR 376
Cdd:cd09504   2 VHNWTVEDTVEWLvNSVELPQYVEAFKENGVDGsalPRLAVNNPSFLTSvLGIKDPIHR 60

SAM domain of aveugle-like subfamily; SAM (sterile alpha motif) domain of SAM_aveugle-like subfamily is a protein-protein interaction domain. In Drosophila, the aveugle (AVE) protein (also known as HYP (Hyphen)) is involved in normal photoreceptor differentiation, and required for epidermal growth factor receptor (EGFR) signaling between ras and raf genes during eye development and wing vein formation. SAM domain of the HYP(AVE) protein interacts with SAM domain of CNK, the multidomain scaffold protein connector enhancer of kinase suppressor of ras. CNK/HYP(AVE) complex interacts with KSR (kinase suppressor of Ras) protein. This interaction leads to stimulation of Ras-dependent Raf activation. This subfamily also includes vertebrate AVE homologs - Samd10 and Samd12 proteins. Their exact function is unknown, but they may play a role in signal transduction during embryogenesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81882526 326 WTSQQVGQWL--H-SLNLEQYAAEFAARQVDGPQLLQLDGSKLKSLGLSNSHDRA-----LVKRKLKE 385
Cdd:cd09510   6 WSVQDVCKWLkrHcPDYYLLYAELFLQHDITGRALLRLNDNKLERMGITDEDHRQdilreILKLRLKT 73

SAM domain of KIF24-like subfamily; SAM (sterile alpha motif) domain of KIF24 subfamily is a putative protein-protein interaction domain. This subfamily includes proteins related to human kinesin-like protein KIF24. SAM domain is located at the N-terminus followed by kinesin motor domain. Kinesins are proteins involved in a number of different cell processes including microtubule dynamics and axonal transport. Kinesins of this group belong to N-type; they drive microtubule plus end-directed transport. SAM apparently plays the role of adaptor or scaffold domain. In many cases SAM is known as a mediator of dimerization/oligomerization.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 81882526 330 QVGQWLHSLNLEQYAAEFAARQVDGPQ-LLQLDGSKLKSLGLSNSHDRalvkRKLKEL 386
Cdd:cd09541   2 VLYEWLEEAGLQHYYPAFAAGGVTSIEaLAQLTMQDYASLGVQDMEDK----QKLFRL 55

SAM domain of Polycomb group; SAM (sterile alpha motif) domain of Polycomb group is a protein-protein interaction domain. The Polycomb group includes transcriptional repressors which are involved in the regulation of some key regulatory genes during development in many organisms. They are best known for silencing Hox (Homeobox) genes. Polycomb proteins work together in large multimeric and chromatin-associated complexes. They organize chromatin of the target genes and maintain repressed states during many cell divisions. Polycomb proteins are classified based on their common function, but not on conserved domains and/or motifs; however many Polycomb proteins (members of PRC1 class complex) contain SAM domains which are more similar to each other inside of the Polycomb group than to SAM domains outside of it. Most information about structure and function of Polycomb SAM domains comes from studies of Ph (Polyhomeotic) and Scm (Sex comb on midleg) proteins. Polycomb SAM domains usually can be found at the C-terminus of the proteins. Some members of this group contain, in addition to the SAM domain, MTB repeats, Zn finger, and/or DUF3588 domains. Polycomb SAM domains can form homo- and/or heterooligomers through ML and EH surfaces. SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Polycomb proteins are known to be highly expressed in some cells years before their cancer pathology; thus they are attractive markers for early cancer therapy.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 81882526 325 HWTSQQVGQWLHSLN-LEQYAAEFAARQVDGPQLLQL 360
Cdd:cd09509   3 KWSVDDVAQFIKSLDgCAEYAEVFREQEIDGQALLLL 39