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 1720421627  961 PVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLL 1026
Cdd:cd09506      1 PVHEWTVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKLL 66

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 1720421627  961 PVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLL 1026
Cdd:cd09506      1 PVHEWTVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKLL 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 1720421627   962 VHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNL-QKEDLIDLGVTRVGHRMNIERALKQLLDR 1028
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLtSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

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 1720421627  961 PVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLL 1026
Cdd:cd09506      1 PVHEWTVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKLL 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 1720421627   962 VHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNL-QKEDLIDLGVTRVGHRMNIERALKQLLDR 1028
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLtSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

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 1720421627  969 DVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALK 1023
Cdd:cd09487      1 DVAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55

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 1720421627  965 WTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1025
Cdd:cd09534      1 WDEEFVEEWLNELNCGQYLDIFEKNLITGDLLLELDKEALKELGITKVGDRIRLLRAIKSL 61

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 1720421627  965 WTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLI-DLGVTRVGHRMNIERALKQLLDR 1028
Cdd:cd09505      5 WSEEDVCTWLRSIGLEQYVEVFRANNIDGKELLNLTKESLSkDLKIESLGHRNKILRKIEELKMK 69

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        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1720421627  969 DVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1025
Cdd:cd09533      1 DVADWLSSLGLPQYEDQFIENGITGDVLVALDHEDLKEMGITSVGHRLTILKAVYEL 57

SAM domain of liprin-beta1,2 proteins repeat 2; SAM (sterile alpha motif) domain repeat 2 of liprin-beta1,2 proteins is a protein-protein interaction domain. Liprin-beta proteins contain three copies (repeats) of SAM domain. They may form heterodimers with liprin-alpha proteins through their SAM domains. It was suggested based on bioinformatic approaches that the second SAM domain of liprin-beta potentially is able to form polymers. Liprins were originally identified as LAR (leukocyte common antigen-related) transmembrane protein-tyrosine phosphatase-interacting proteins. They participate in mammary gland development, in axon guidance, and in the maintenance of lymphatic vessel integrity.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720421627  970 VADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1025
Cdd:cd09566      7 VLRWLDDIGLPQYKDAFSEAKVDGRMLHYLTVDDLLHLKVTSALHHASIRRGIQVL 62

SAM domain of Samd14 subfamily; SAM (sterile alpha motif) domain of SamD14 (or FAM15A) subfamily is a putative protein-protein interaction domain. SAM is widespread domain in proteins involved in signal transduction and regulation. In many cases SAM mediates homodimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720421627  965 WTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLL 1026
Cdd:cd09530      3 WDTEDVAEWIEGLGFPQYRECFTTNFIDGRKLILVDASTLPRMGVTDFEHIKAIARKIRELL 64

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720421627  961 PVHLWTKPDVADWLE-SLNLGEHKETFMDNEIDGSHLPNL--QKEDLI--DLGVTRVGHRMNIE-RAL 1022
Cdd:cd09504      1 EVHNWTVEDTVEWLVnSVELPQYVEAFKENGVDGSALPRLavNNPSFLtsVLGIKDPIHRQKLSlKAM 68

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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720421627  970 VADWLESLNLGEHKETFMDNEIDGSHLPN---LQKEDLIDLGVTRVGHRMNIERALKQL 1025
Cdd:cd09499      5 VGQWLESIGLPQYESKLLLNGFDDVDFLGsgvMEDQDLKEIGITDEQHRQIILQAARSL 63

SAM domain of MLTK subfamily; SAM (sterile alpha motif) domain of MLTK subfamily is a protein-protein interaction domain. Besides SAM domain, these proteins have N-terminal protein tyrosine kinase domain and leucine-zipper motif. Proteins of this group act as mitogen-activated protein triple kinase in a number of MAPK cascades. They can be activated by autophosphorylation in response to stress signals. MLTK-alpha is known to phosphorylate histone H3. In mammals, MLTKs participate in the activation of the JNK/SAPK, p38, ERK5 pathways, the transcriptional factor NF-kB, in the regulation of the cell cycle checkpoint, and in the induction of apoptosis in a hepatoma cell line. Some members of this subfamily are proto-oncogenes, thus MLTK-alpha is involved in neoplasmic cell transformation and/or skin cancer development in athymic nude mice. Based on in vivo coprecipitation experiments in mammalian cells, it has been demonstrated that MLTK proteins might form homodimers/oligomers via their SAM domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720421627  957 FTTKPVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1025
Cdd:cd09529      2 WTEEDVHFWMQQLVRKGGHPSELSQYADLFKENHITGKRLLLLTEEDLRDMGIGSKGHIIHLKSAIEKL 70

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        40
                   ....*....|....*....|....*....|....*....|....
gi 1720421627  965 WTKPDVADWLESLN-LGEHKETFMDNEIDGSHLPNLQKEDLIDL 1007
Cdd:cd09509      4 WSVDDVAQFIKSLDgCAEYAEVFREQEIDGQALLLLTEDDLLKG 47

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 1720421627  962 VHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLI-DLGVTRVGHRMNIERALKQL 1025
Cdd:cd09501      1 VPLWSVADVQTWLKQIGFEDYAEKFSESQVDGDLLLQLTEDELKqDLGMSSGLLRKRFLRELVEL 65

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 1720421627  965 WTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1025
Cdd:cd09580      4 WGVKDVSQFLRENDCGAYCECFCRQNIDGKRLLSLTKEQIMTLTGMKVGPSLKIYDLIQQL 64

SAM domain of ASZ1 subfamily; SAM (sterile alpha motif) domain of ASZ1 (Ankyrin, SAM, leucine Zipper) also known as GASZ (Germ cell-specific Ankyrin, SAM, leucine Zipper) subfamily is a potential protein-protein interaction domain. Proteins of this group are involved in the repression of transposable elements during spermatogenesis, oogenesis, and preimplantation embryogenesis. They support synthesis of PIWI-interacting RNA via association with some PIWI proteins, such as MILI and MIWI. This association is required for initiation and maintenance of retrotransposon repression during the meiosis. In mice lacking ASZ1, DNA damage and delayed germ cell maturation was observed due to retrotransposons releasing from their repressed state.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1720421627  974 LESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1025
Cdd:cd09521     12 LHGLELGHLTPLFKEHDVTFSQLLKMTEEDLEKIGITQPGDQKKILDAIKEV 63

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720421627  970 VADWLESLNLGEHKETFMDNEIDG-SHLPNLQKEDLIDLGVTRVGHRMNIERALKQLLDR 1028
Cdd:cd09554      6 VGEWLRAIKMERYEDSFLQAGFTTfQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGIQ 65

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720421627  969 DVADWLESLNLGEHKETFMDNEI----DGSHLPNlqkEDLIDLGVTRVGHRmniERALKQL 1025
Cdd:cd09490      5 DIAEWLASIHLEQYLDLFREHGYvtatDCQGIND---SRLKQIGISPTGHR---RRILKQL 59

SAM domain of STIM2 subfamily proteins; SAM (sterile alpha motif) domain of STIM2 (Stromal interaction molecule) subfamily 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 STIM2 protein is an inhibitor of store operated channels in plasma membrane.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1720421627  961 PVHLWTKPDVADWL-ESLNLGEHKETFMDNEIDGSHLPNL 999
Cdd:cd09574      1 EVHNWTMEDTLQWLkEFVELPQYEKNFRDNNVKGTTLPRI 40

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 1720421627  970 VADWLESLNLGEHKETFMDNEIDGSHL-PNLQKEDLIDLGVTRVGHRMNI 1018
Cdd:cd09488      5 VGEWLESIKMGRYKENFTAAGYTSLDAvAQMTAEDLTRLGVTLVGHQKKI 54

SAM domain of tumor-p63,p73 proteins; SAM (sterile alpha motif) domain of p63, p73 transcriptional factors is a putative protein-protein interaction domain and lipid-binding domain. p63 and p73 are homologs to the tumor suppressor p53. They have a C-terminal SAM domain in their longest spliced alpha forms, while p53 doesn't have it. p63 or p73 knockout mice show significant developmental abnormalities but no increased cancer susceptibility, suggesting that p63 and p73 play a role in regulation of normal development. It was shown that SAM domain of p73 is able to bind some membrane lipids. The structural rearrangements in SAM are necessary to accomplish the binding. No evidence for homooligomerization through SAM domains was found for p63/p73 subfamily. It was suggested that the partner proteins should be either more distantly related SAM-containing domain proteins or proteins without the SAM domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1720421627  966 TKPDVADWLESLNLGEHKETFMDNEIDG-SHLPNLQKEDLIDLGVTRvGHRMNIERAL 1022
Cdd:cd09503      3 TDNSVASWLTKLGCSNYIDNFHQQGLLSiFQLDEFTLEDLAAMKIPE-QHRNKIWKGL 59