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 569000378  42 SAEAVSQWLATFQLQLYAPNFTSAGYDLPTISRMTPEDLTAIGVTKPGHRKKITAEISGLNIPD 105
Cdd:cd09497    3 DAEAIFDWLREFGLEEYTPNFIKAGYDLPTISRMTPEDLTAIGITKPGHRKKLKSEIAQLQIPD 66

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 569000378  443 PKKRAHSLNRYAASDSEPERDELLV--PAAAGPYATVQRRVGRSHSVRAPAGTDKNVNRSQSFAVRPRKKGPPP 514
Cdd:pfam16907   1 PKKRSQSLNRYALSDGEPEEEEEPPlgSGTLGSYATLTRRPGRSQLARLQPSPEKNVNRSQSFAVRARKKGPPP 74

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 569000378  42 SAEAVSQWLATFQLQLYAPNFTSAGYDLPTISRMTPEDLTAIGVTKPGHRKKITAEISGLNIPD 105
Cdd:cd09497    3 DAEAIFDWLREFGLEEYTPNFIKAGYDLPTISRMTPEDLTAIGITKPGHRKKLKSEIAQLQIPD 66

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 569000378  443 PKKRAHSLNRYAASDSEPERDELLV--PAAAGPYATVQRRVGRSHSVRAPAGTDKNVNRSQSFAVRPRKKGPPP 514
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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569000378   42 SAEAVSQWLATFQLQLYAPNFtSAGY-DLPTISRMTPEDLTAIGVTKPGHRKKITAEISGL 101
Cdd:pfam00536   4 SVEDVGEWLESIGLGQYIDSF-RAGYiDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

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 569000378  118 WLSMIGLAQYYKVLVdNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:pfam00536  11 WLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378  192 PQSLEMMAIESPPPSEPA-AAECQSPKMTTFQDSELSGELQAALSGPAEAGAAAVEKSSNHLPPTPRTTSRESSLSGRAR 270
Cdd:PHA03247 2593 PQSARPRAPVDDRGDPRGpAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGR 2672

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378  271 HISSSQELLGDGPPGPGSPMSRSQEylldegMAPGTPPKEVRSSRHGHSVKRASVPPVPGKPRQVLPSGASHFTPPQTPT 350
Cdd:PHA03247 2673 AAQASSPPQRPRRRAARPTVGSLTS------LADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPA 2746

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378  351 -KAQPGSPQALGGPHGPATAKvKPTPQLLPPTDRPMSPRSLPQSPTHRGFAYVLPQPVEGEVGPPAPGPAPPPVPAAVPT 429
Cdd:PHA03247 2747 gPATPGGPARPARPPTTAGPP-APAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPA 2825

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378  430 LCLPPETDVEPGRPkkrahslnryaASDSEPERDELLVPAAAGPYATVQRRVGRSHSVRAPAG-TDKNVNRSQSFAVRPR 508
Cdd:PHA03247 2826 GPLPPPTSAQPTAP-----------PPPPGPPPPSLPLGGSVAPGGDVRRRPPSRSPAAKPAApARPPVRRLARPAVSRS 2894

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378  509 KKGPPPPPPKRSSSAM-ASANLADEPAPDVEAEDGRLGVRAQRRRASDLAGSVDTGSAGSVKSIAAMLELSSIGGGGRAI 587
Cdd:PHA03247 2895 TESFALPPDQPERPPQpQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAV 2974

                         410       420       430
                  ....*....|....*....|....*....|
gi 569000378  588 RR---PPEGHPTPRPASPEPGRVATVLASV 614
Cdd:PHA03247 2975 PRfrvPQPAPSREAPASSTPPLTGHSLSRV 3004

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 569000378  42 SAEAVSQWLATFQLQLYAPNFTSAGYDLPTISRMTPEDLTAIGVTKPGHRKKITAEISGLNIPD 105
Cdd:cd09497    3 DAEAIFDWLREFGLEEYTPNFIKAGYDLPTISRMTPEDLTAIGITKPGHRKKLKSEIAQLQIPD 66

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 569000378  443 PKKRAHSLNRYAASDSEPERDELLV--PAAAGPYATVQRRVGRSHSVRAPAGTDKNVNRSQSFAVRPRKKGPPP 514
Cdd:pfam16907   1 PKKRSQSLNRYALSDGEPEEEEEPPlgSGTLGSYATLTRRPGRSQLARLQPSPEKNVNRSQSFAVRARKKGPPP 74

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
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 569000378   118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAE 173
Cdd:smart00454  12 WLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKE 67

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 569000378    42 SAEAVSQWLATFQLQLYAPNFTSAGYDLPT-ISRMTPEDLTAIGVTKPGHRKKITAEISGL 101
Cdd:smart00454   5 SPESVADWLESIGLEQYADNFRKNGIDGALlLLLTSEEDLKELGITKLGHRKKILKAIQKL 65

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 569000378 112 PANLAVWLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHqKKLMLA 167
Cdd:cd09491    5 PKTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAH-KRRLLD 59

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 569000378  46 VSQWLATFQLQLYAPNFTSAGYDLPTISRMTPEDLTAIGVTKPGHRKKITAEI 98
Cdd:cd09487    2 VAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAI 54

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 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITD--ITWEDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:cd09499    8 WLESIGLPQYESKLLLNGFDDVDFLGSgvMEDQDLKEIGITDEQHRQIILQAARSL 63

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 569000378 114 NLAVWLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:cd09546    5 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEM 62

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 569000378  45 AVSQWLATFQLQLYAPNFTSAGYD-LPTISRMTPEDLTAIGVTKPGHRKKITAEI 98
Cdd:cd09548    9 SVGEWLEAIKMERYKDNFTAAGYNsLESVARMTIEDVMSLGITLVGHQKKIMSSI 63

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 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLM 165
Cdd:cd09488    8 WLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKIL 55

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 569000378  45 AVSQWLATFQLQLYAPNFTSAGY-DLPTISRMTPEDLTAIGVTKPGHRKKITAEISGL 101
Cdd:cd09545    5 SVDDWLQAIKMERYKDNFTAAGYtTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGM 62

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 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAE 173
Cdd:cd09527    8 WLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLDAIGVMNPAHRKRILEAVRRLKE 63

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 569000378  46 VSQWLATFQLQLYAPNFTSAGY-DLPTISRMTPEDLTAIGVTKPGHRKKITAEISGLNI 103
Cdd:cd09553    9 VGDWLDAIKMGRYKENFVSAGFaSFDLVAQMTAEDLLRIGVTLAGHQKKILSSIQDMRL 67

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569000378  45 AVSQWLATFQLQLYAPNFTSAGY-DLPTISRMTPEDLTAIGVTKPGHRKKITAEISGL 101
Cdd:cd09549    9 SVGEWLEALDLCRYKDNFAAAGYgSLEAVARMTAQDVLSLGITSLEHQELLLAGIQAL 66

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 569000378  42 SAEAVSQWLATFQLQLYAPNFTSAGY-DLPTISRMTPEDLTAIGVTKPGHRKKITAEISGLNI 103
Cdd:cd09554    2 SCGSVGEWLRAIKMERYEDSFLQAGFtTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGI 64

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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVR 169
Cdd:cd09552   12 WLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQ 63

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 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 the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-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 569000378  42 SAEAVSQWLATFQLQLYAPNFTSAGY-DLPTISRMTPEDLTAI-GVTKPGHRKKITAEISG 100
Cdd:cd09500    4 SPASVSEWLDSIGLGDYIETFLKHGYtSMERVKRIWEVELTNVlEINKLGHRKRILASLAD 64

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 569000378  44 EAVSQWLATFQLQLYAPNFTSAGYD-LPTISRMTPEDLTAIGVTKPGHRKKITAEI 98
Cdd:cd09546    4 RSVGEWLEAIKMGRYTEIFMENGYSsMDAVAQVTLEDLRRLGVTLVGHQKKIMNSI 59

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 569000378  42 SAEAVSQWLATFQLQLYAPNFTSAGYDLPTISRMTPEDLTAIGVTKPGHRKKITAEISGL 101
Cdd:cd09506    6 TVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKL 65

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:cd09554    9 WLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAM 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 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKLAE 173
Cdd:cd09543   11 WLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGHQKRIAYSILGLKE 66

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 569000378 113 ANLAVWLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:cd09545    4 ASVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGM 62

SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain of DGK-eta-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DGK proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers between the SAM domains of DGK delta and eta proteins. The oligomerization plays a role in the regulation of DGK intracellular localization.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378 102 NIPDWLPEhkpaNLAVWLSMIGLAQYYKVLVDNGYENIDFITdITWEDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:cd09507    1 PVTNWTTE----EVGAWLESLQLGEYRDIFARNDIRGSELLH-LERRDLKDLGITKVGHVKRILQAIKDL 65

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.

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                 ....*....|....*....|....*....|....*....|....*..
gi 569000378  49 WLATFQLQLYAPNFTSAGYD-LPTISRMTPEDLTAIGVTKPGHRKKI 94
Cdd:cd09498   13 WLSLLGLPQYHKVLVENGYDsIDFVTDLTWEDLQDIGITKLGHQKKL 59

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.

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVR 169
Cdd:cd09550    8 WLDSIKMGRYKDHFAAGGYSSLGMVMRMNIEDIRRLGITLMGHQKKILTSIQ 59

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.

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                 ....*....|....*....|....*....|....*....|....*....|
gi 569000378  46 VSQWLATFQLQLYAPNFTSAGYDLPTISR-MTPEDLTAIGVTKPGHRKKI 94
Cdd:cd09490    6 IAEWLASIHLEQYLDLFREHGYVTATDCQgINDSRLKQIGISPTGHRRRI 55

SAM domain of BICC1 (bicaudal) subfamily; SAM (sterile alpha motif) domain of BICC1 (bicaudal) subfamily is a protein-protein interaction domain. Proteins of this group have N-terminal K homology RNA-binding vigilin-like repeats and a C-terminal SAM domain. BICC1 is involved in the regulation of embryonic differentiation. It plays a role in the regulation of Dvl (Dishevelled) signaling, particularly in the correct cilia orientation and nodal flow generation. In Drosophila, disruption of BICC1 can disturb the normal migration direction of the anterior follicle cell of oocytes; the specific function of SAM is to recruit whole protein to the periphery of P-bodies. In mammals, mutations in this gene are associated with polycystic kidney disease and it was suggested that the BICC1 protein can indirectly interact with ANKS6 protein (ANKS6 is also associated with polycystic kidney disease) through some protein and RNA intermediates.

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 569000378 119 LSMIGLAQYYKVLVDNgyeNID---FITdITWEDLQEIGITKLGHQKKLMLAVRKLAEL 174
Cdd:cd09520   11 LAKLGLEKYIDLFAQQ---EIDlqtFLT-LTDQDLKELGITAFGARRKMLLAISELNKR 65

104 kDa microneme/rhoptry antigen; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378 252 LPPT-PRTTSRESSLSGRARHISSSQEllgdgppgpgsPMSRSQEYLLDEGMAPGtPPKEVRSSRHGHSVKRASVPPVPG 330
Cdd:PTZ00449 519 LPPKaPGDKEGEEGEHEDSKESDEPKE-----------GGKPGETKEGEVGKKPG-PAKEHKPSKIPTLSKKPEFPKDPK 586

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569000378 331 KPRQVL-PSGASHFTPPQTPTKAQ-PGSPQALGGPHGPATAKVKPTPQLLPPTDRPMSPRSlPQSP 394
Cdd:PTZ00449 587 HPKDPEePKKPKRPRSAQRPTRPKsPKLPELLDIPKSPKRPESPKSPKRPPPPQRPSSPER-PEGP 651

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.

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                 ....*....|....*....|....*....|....*....|....*...
gi 569000378 118 WLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLM 165
Cdd:cd09548   13 WLEAIKMERYKDNFTAAGYNSLESVARMTIEDVMSLGITLVGHQKKIM 60

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569000378 115 LAVWLSMIGLAQYYKVLVDNGYENIDFItDITWEDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:cd09576   10 VAAWLDLLSLGEYKEIFIRHDIRGSELL-HLERRDLKDLGIPKVGHMKRILQGIKEL 65

SAM (Sterile alpha motif ); SAM (sterile alpha motif) domain of Smaug-like subfamily proteins is an RNA binding domain. SAM interacts with stem-loop structures in target mRNAs. Proteins of this subfamily are post-transcriptional regulators involved in mRNA silencing and deadenylation; they can be implicated in transcript stability regulation and vacuolar protein transport as well. SAM_Smaug-like domain-containing proteins are found in metazoa from yeast to human. In animals they are active during early embryogenesis.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000378 114 NLAVWLSMIGLAQYYKVLVDNGYENIDFITDitwEDLQEIGITKLGHQKKLMLAVRKLAE 173
Cdd:cd09489    1 GIPMWLKSLRLHKYSDAFKGTTWEELLYLTE---ETLEKKGVLTLGARRKLLKAFGIVKE 57

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569000378 118 WLSMIGLAQYYKVLVDNgyeNID--FITDITWEDLQ-EIGITKLGHQKKLMlavRKLAELQKAEYS 180
Cdd:cd09505   13 WLRSIGLEQYVEVFRAN---NIDgkELLNLTKESLSkDLKIESLGHRNKIL---RKIEELKMKSDS 72

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569000378 109 EHKPANLAVWLSMIGLAQYYKVLVDNgyenidfitDITW--------EDLQEIGITKLGHQKKLMLAVRKL 171
Cdd:cd09521    2 YSKLDDLELFLHGLELGHLTPLFKEH---------DVTFsqllkmteEDLEKIGITQPGDQKKILDAIKEV 63

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.

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                 ....*....|....*....|....*....|....*....|....*....|
gi 569000378 115 LAVWLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKL 164
Cdd:cd09541    3 LYEWLEEAGLQHYYPAFAAGGVTSIEALAQLTMQDYASLGVQDMEDKQKL 52