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 768021367 189 NSKKSKTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAENFL 253
Cdd:cd09561    1 RRPKPKTLQELLERIHLQEYTSTLLLNGYETLEDLKDLKESHLIELNITDPEDRARLLSAAENLL 65

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 768021367   17 KPKRSSSFGNFDRFRNNS-LSKPDDST----------------------------------------------------- 42
Cdd:pfam12485   1 SLQRSSSFGDFDKSRPSSpVVKPEEFNleepedeagepgpeeagkpstsggklgkkmraisrtmrrkmgkkyvkalseem 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 768021367   43 -EDEEDGENAHPYRNsDPVIGTHTEKVSLKASDSMDSLYSGQS----SSSGITSCSDGTSNRDSFRLDDDGPYSGPF 114
Cdd:pfam12485  81 gEDEEEGSDSPPSPD-DPEDGPHTEKVSLKASDSEESLYSPLSgqssSSSGVTSPSDGTSNRDSLRLEEEPPYTGPF 156

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 768021367 189 NSKKSKTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAENFL 253
Cdd:cd09561    1 RRPKPKTLQELLERIHLQEYTSTLLLNGYETLEDLKDLKESHLIELNITDPEDRARLLSAAENLL 65

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 768021367   17 KPKRSSSFGNFDRFRNNS-LSKPDDST----------------------------------------------------- 42
Cdd:pfam12485   1 SLQRSSSFGDFDKSRPSSpVVKPEEFNleepedeagepgpeeagkpstsggklgkkmraisrtmrrkmgkkyvkalseem 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 768021367   43 -EDEEDGENAHPYRNsDPVIGTHTEKVSLKASDSMDSLYSGQS----SSSGITSCSDGTSNRDSFRLDDDGPYSGPF 114
Cdd:pfam12485  81 gEDEEEGSDSPPSPD-DPEDGPHTEKVSLKASDSEESLYSPLSgqssSSSGVTSPSDGTSNRDSLRLEEEPPYTGPF 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 768021367   194 KTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAENFL 253
Cdd:smart00454   7 ESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLK 66

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 768021367 189 NSKKSKTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAENFL 253
Cdd:cd09561    1 RRPKPKTLQELLERIHLQEYTSTLLLNGYETLEDLKDLKESHLIELNITDPEDRARLLSAAENLL 65

Src homology 3 domain of SAM And SH3 Domain Containing Proteins; This subfamily, also called the SLY family, is composed of SAM And SH3 Domain Containing Protein 1 (SASH1), SASH2, SASH3, and similar proteins. These are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as wells as SAM (sterile alpha motif) and SH3 domains. SASH1 is a potential tumor suppressor in breast and colon cancer. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. SASH2 (also called SAMSN-1, SLY2, HACS1 or NASH1) and SASH3 (also called SLY/SLY1) are expressed mainly in hematopoietic cells, although SASH2 is also found in endothelial cells as well as myeloid leukemias and myeloma. SASH2 was found to be differentially expressed in malignant haematopoietic cells and in colorectal tumors, and is a potential tumor suppressor in lung cancer. SASH3 is essential in the full activation of adaptive immunity and is involved in the signaling of T cell receptors. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 768021367 117 RARVHTDFTPSPYDTDSLKIKKGDIIDIICKTPMGMWTGMLNNKVGNFKFIY 168
Cdd:cd11822    1 RAKVHTDFTPSPYDTDSLKLKKGDIIDIINKPPMGIWTGMLNNKVGNFKFIY 52

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768021367 116 GRARVHTDFTPSPYDTDSLKIKKGDIIDIICKTPMGMWTGMLNNKVGNFKFIYVDVI 172
Cdd:cd11967    1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

SAM domain of SASH3 subfamily; SAM (sterile alpha motif) domain of SAHS3 (also known as SLY) proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative signaling/adaptor proteins. In addition to SAM, they contain SLY and SH3 domains. They appear to mediate signal transduction in lymphoid tissues. Murine SASH3 is involved in preventing DN thymocytes from premature initiation of programmed cell death and in mTOR (mammalian target of rapamycin) activation via signal integration of the Notch receptor and preTCR (T cell receptor) pathways.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768021367 192 KSKTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAENFL 253
Cdd:cd09560    4 KPKTLHELLERIGLEEHTSTLLLNGYQTLEDFKELRETHLNELNIMDPQHRAKLLTAAELLL 65

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768021367 192 KSKTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAE 250
Cdd:cd09559    2 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVE 60

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 768021367 194 KTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLL 246
Cdd:cd09491    6 KTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLL 58

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 768021367 196 LQEFLERIHLQEYTSTLLLNgYETLEDLKDIKESHLIELNIENPDDRRRLLSAAE 250
Cdd:cd09487    2 VAEWLESLGLEQYADLFRKN-EIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55

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 768021367  195 TLQEFLERIHLQEYTSTlLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAENF 252
Cdd:pfam00536   7 DVGEWLESIGLGQYIDS-FRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

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 768021367 194 KTLQEFLERIHLQEYTSTLLLNGYETLEDLKD--IKESHLIELNIENPDDRRRLLSAAEN 251
Cdd:cd09499    3 QSVGQWLESIGLPQYESKLLLNGFDDVDFLGSgvMEDQDLKEIGITDEQHRQIILQAARS 62

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768021367 194 KTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAENF 252
Cdd:cd09542    5 RSVSEWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPGHQKRILCSIQGF 63

SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and apparently may play a role in neural development, synaptic protein targeting, and regulation of gene expression.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768021367 191 KKSKTLQEFLERIHLQEYTSTLLLNGYE-------TLEDLKDIkeshlielNIENPDDRRRLLS 247
Cdd:cd09497    2 PDAEAIFDWLREFGLEEYTPNFIKAGYDlptisrmTPEDLTAI--------GITKPGHRKKLKS 57

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 768021367 192 KSKTLQEFLERIHLQEYTSTLLLNGYETLEDLKDI 226
Cdd:cd09498    6 PPNDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDL 40