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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958656226   1 MIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAELQK 56
Cdd:cd09498    16 LLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLAIKKLKDLQK 71

Proline rich region of Caskin proteins; This proline rich region is found in Caskin proteins. Caskins are CASK-binding synaptic scaffolding proteins. This region is predicted to be natively unstructured. Its function is not known.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958656226 324 PKKRAHSLNRYAASDSEPERDELLV--PAAAGPYATVQRRVGRSHSVRAPAGTDKNVNRSQSFAVRPRKKGPPP 395
Cdd:pfam16907   1 PKKRSQSLNRYALSDGEPEEEEEPPlgSGTLGSYATLTRRPGRSQLARLQPSPEKNVNRSQSFAVRARKKGPPP 74

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958656226 664 GSARKPVKPPVSPKPILAQPVSKIQGSPTPASKKVPLPGPGSPEVKRAHGTPPPVSPKPPPPPTAPKPAKALAGLQSSSA 743
Cdd:PRK12323  373 GPATAAAAPVAQPAPAAAAPAAAAPAPAAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALAAARQASARGPGGAPAPAP 452

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958656226 744 TPSPVPSPARQPPAAlikpassppsqsasPAKPPSPGAPALQVPTKPPRAAASVVSGPPVASDCasPGDSARQKLEETSA 823
Cdd:PRK12323  453 APAAAPAAAARPAAA--------------GPRPVAAAAAAAPARAAPAAAPAPADDDPPPWEEL--PPEFASPAPAQPDA 516

                         170       180       190
                  ....*....|....*....|....*....|
gi 1958656226 824 CLAAALQAVEEKIRQEDGQGPRPSSIEEKS 853
Cdd:PRK12323  517 APAGWVAESIPDPATADPDDAFETLAPAPA 546

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958656226   1 MIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAELQK 56
Cdd:cd09498    16 LLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLAIKKLKDLQK 71

Proline rich region of Caskin proteins; This proline rich region is found in Caskin proteins. Caskins are CASK-binding synaptic scaffolding proteins. This region is predicted to be natively unstructured. Its function is not known.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958656226 324 PKKRAHSLNRYAASDSEPERDELLV--PAAAGPYATVQRRVGRSHSVRAPAGTDKNVNRSQSFAVRPRKKGPPP 395
Cdd:pfam16907   1 PKKRSQSLNRYALSDGEPEEEEEPPlgSGTLGSYATLTRRPGRSQLARLQPSPEKNVNRSQSFAVRARKKGPPP 74

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 1958656226   2 IGLAQYYKVLVdNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 51
Cdd:pfam00536  15 IGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958656226 664 GSARKPVKPPVSPKPILAQPVSKIQGSPTPASKKVPLPGPGSPEVKRAHGTPPPVSPKPPPPPTAPKPAKALAGLQSSSA 743
Cdd:PRK12323  373 GPATAAAAPVAQPAPAAAAPAAAAPAPAAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALAAARQASARGPGGAPAPAP 452

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958656226 744 TPSPVPSPARQPPAAlikpassppsqsasPAKPPSPGAPALQVPTKPPRAAASVVSGPPVASDCasPGDSARQKLEETSA 823
Cdd:PRK12323  453 APAAAPAAAARPAAA--------------GPRPVAAAAAAAPARAAPAAAPAPADDDPPPWEEL--PPEFASPAPAQPDA 516

                         170       180       190
                  ....*....|....*....|....*....|
gi 1958656226 824 CLAAALQAVEEKIRQEDGQGPRPSSIEEKS 853
Cdd:PRK12323  517 APAGWVAESIPDPATADPDDAFETLAPAPA 546

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958656226   1 MIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAELQK 56
Cdd:cd09498    16 LLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLAIKKLKDLQK 71

Proline rich region of Caskin proteins; This proline rich region is found in Caskin proteins. Caskins are CASK-binding synaptic scaffolding proteins. This region is predicted to be natively unstructured. Its function is not known.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958656226 324 PKKRAHSLNRYAASDSEPERDELLV--PAAAGPYATVQRRVGRSHSVRAPAGTDKNVNRSQSFAVRPRKKGPPP 395
Cdd:pfam16907   1 PKKRSQSLNRYALSDGEPEEEEEPPlgSGTLGSYATLTRRPGRSQLARLQPSPEKNVNRSQSFAVRARKKGPPP 74

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 1958656226   2 IGLAQYYKVLVdNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 51
Cdd:pfam00536  15 IGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHqKKLMLA 47
Cdd:cd09491    15 LGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAH-KRRLLD 59

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 51
Cdd:cd09546    13 IKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEM 62

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
                  ....*....|....*....|....*....|....*....|....
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLM 45
Cdd:cd09488    12 IKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKIL 55

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAE 53
Cdd:cd09527    12 LQLEQYAEKFVDNGYDDLEVCKQIGDPDLDAIGVMNPAHRKRILEAVRRLKE 63

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 51
Cdd:cd09551    16 IKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNSIQSM 65

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVR 49
Cdd:cd09552    16 IKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQ 63

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 51
Cdd:cd09547    13 IKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTL 62

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAE 53
Cdd:cd09543    15 IKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGHQKRIAYSILGLKE 66

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAV 48
Cdd:cd09493    12 INLQEHTSTLLLNGYETLEDFKDLKESHLNELNITDPEHRAKLLTAA 58

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 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 51
Cdd:cd09545    13 IKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGM 62

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1958656226   2 IGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVR 49
Cdd:cd09550    12 IKMGRYKDHFAAGGYSSLGMVMRMNIEDIRRLGITLMGHQKKILTSIQ 59

SAM domain of sphingomyelin synthase related subfamily; SAM (sterile alpha motif) domain of SGMS-like (sphingomyelin synthase) subfamily is a potential protein-protein interaction domain. This group of proteins is related to sphingomyelin synthase 1, and contains an N-terminal SAM domain. The function of SGMS1-like proteins is unknown; they may play a role in sphingolipid metabolism.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958656226   2 IGLAQYYKVLVDNgyENIDFIT--DITWEDLQE--IGITKLGHQKKLMLAVRKL 51
Cdd:cd09515    16 EGFSKYVDLLCNK--HRIDGKVllSLTEEDLRSppLEIKVLGDIKRLWLAIRKL 67

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958656226   1 MIGLAQYYKVLVDNGYeNIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 51
Cdd:cd09534    12 ELNCGQYLDIFEKNLI-TGDLLLELDKEALKELGITKVGDRIRLLRAIKSL 61