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 291406707 539 LQWSPERVAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISRHTRELLGIE 605
Cdd:cd09530    1 LSWDTEDVAEWIEGLGFPQYRECFTTNFIDGRKLILVDASTLPRMGVTDFEHIKAIARKIRELLGIE 67

LPXTG-anchored aggregation substance; Aggregation substances, as described in Enterococcus, are LPXTG-anchored large surface proteins that contribute to virulence. Several closely related paralogs may be found in a single strain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291406707  218 ETDLEP------PEMTDPEIAEETQREFPEDKPTESTETVPEP--LEEIKSEFFEEESRKPSlepseesevpeetrrnSN 289
Cdd:NF033875   45 ELDTQPgtttvqPDNPDPQSGSETPKTAVSEEATVQKDTTSQPtkVEEVASEKNGAEQSSAT----------------PN 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291406707  290 EGVETKPPEATGLTPLQEVQEQTQRKSPRQVLEPTEDAPSEDQTKKQTQSTEEIGLPQKSKTEETLGDSTEETSLEPPEQ 369
Cdd:NF033875  109 DTTNAQQPTVGAEKSAQEQPVVSPETTNEPLGQPTEVAPAENEANKSTSIPKEFETPDVDKAVDEAKKDPNITVVEKPAE 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291406707  370 IKPEFPEKEPGKPAEETGQVPPQQTEPEAQEKTITKPAEER----SLELPDETKQRETRVDfsqgdrsEPVASGDKDELE 445
Cdd:NF033875  189 DLGNVSSKDLAAKEKEVDQLQKEQAKKIAQQAAELKAKNEKiakeNAEIAAKNKAEKERYE-------KEVAEYNKHKNE 261

                         250       260
                  ....*....|....*....|....*....
gi 291406707  446 H---PENLKKDIALESVI---DSEVISVT 468
Cdd:NF033875  262 NgyvNEAISKNLVFDQSVvtkDTKISSIK 290

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 291406707 539 LQWSPERVAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISRHTRELLGIE 605
Cdd:cd09530    1 LSWDTEDVAEWIEGLGFPQYRECFTTNFIDGRKLILVDASTLPRMGVTDFEHIKAIARKIRELLGIE 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 291406707   538 YLQWSPERVAEWISELGFPQYKECFTANFISGRKLIHVNCSN-LPQMGITDFEHMKAISRHTRELL 602
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEdLKELGITKLGHRKKILKAIQKLK 66

LPXTG-anchored aggregation substance; Aggregation substances, as described in Enterococcus, are LPXTG-anchored large surface proteins that contribute to virulence. Several closely related paralogs may be found in a single strain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291406707  218 ETDLEP------PEMTDPEIAEETQREFPEDKPTESTETVPEP--LEEIKSEFFEEESRKPSlepseesevpeetrrnSN 289
Cdd:NF033875   45 ELDTQPgtttvqPDNPDPQSGSETPKTAVSEEATVQKDTTSQPtkVEEVASEKNGAEQSSAT----------------PN 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291406707  290 EGVETKPPEATGLTPLQEVQEQTQRKSPRQVLEPTEDAPSEDQTKKQTQSTEEIGLPQKSKTEETLGDSTEETSLEPPEQ 369
Cdd:NF033875  109 DTTNAQQPTVGAEKSAQEQPVVSPETTNEPLGQPTEVAPAENEANKSTSIPKEFETPDVDKAVDEAKKDPNITVVEKPAE 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291406707  370 IKPEFPEKEPGKPAEETGQVPPQQTEPEAQEKTITKPAEER----SLELPDETKQRETRVDfsqgdrsEPVASGDKDELE 445
Cdd:NF033875  189 DLGNVSSKDLAAKEKEVDQLQKEQAKKIAQQAAELKAKNEKiakeNAEIAAKNKAEKERYE-------KEVAEYNKHKNE 261

                         250       260
                  ....*....|....*....|....*....
gi 291406707  446 H---PENLKKDIALESVI---DSEVISVT 468
Cdd:NF033875  262 NgyvNEAISKNLVFDQSVvtkDTKISSIK 290

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 291406707 539 LQWSPERVAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISRHTRELLGIE 605
Cdd:cd09530    1 LSWDTEDVAEWIEGLGFPQYRECFTTNFIDGRKLILVDASTLPRMGVTDFEHIKAIARKIRELLGIE 67

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 291406707  540 QWSPERVAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISRHTREL 601
Cdd:pfam00536   2 GWSVEDVGEWLESIGLGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

SAM domain (Sterile alpha motif);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 291406707  541 WSPERVAEWISELGFPQYKECFTANFISGRKLI-HVNCSNLPQMGITDFEHMKAISRHTRELL 602
Cdd:pfam07647   4 WSLESVADWLRSIGLEQYTDNFRDQGITGAELLlRLTLEDLKRLGITSVGHRRKILKKIQELK 66

SAM domain of diacylglycerol kinase delta; SAM (sterile alpha motif) domain of DGK-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-delta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. In particular DGK-delta is involved in the regulation of clathrin-dependent endocytosis. The SAM domain of DGK-delta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-eta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it inhibits the translocation of the protein to the plasma membrane from the cytoplasm. The SAM domain also can bind Zn at multiple (not conserved) sites driving the formation of highly ordered large sheets of polymers, thus suggesting that Zn may play important role in the function of DCK-delta.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 291406707 540 QWSPERVAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISRHTREL 601
Cdd:cd09575    4 LWGTEEVAAWLEHLSLCEYKDIFTRHDVRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 65

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 291406707 546 VAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAI 594
Cdd:cd09533    2 VADWLSSLGLPQYEDQFIENGITGDVLVALDHEDLKEMGITSVGHRLTI 50

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 291406707 546 VAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISR 596
Cdd:cd09566    7 VLRWLDDIGLPQYKDAFSEAKVDGRMLHYLTVDDLLHLKVTSALHHASIRR 57

SAM domain of SAM_Neurabin-like subfamily; SAM (sterile alpha motif) domain of Neurabin-like (Neural actin-binding) subfamily is a putative protein-protein interaction domain. This group currently includes the SAM domains of neurobin-I, SAMD14 and neurobin-I/SAMD14-like proteins. Most are multidomain proteins and in addition to SAM domain they contain other protein-binding domains such as PDZ and actin-binding domains. Members of this subfamily participate in signal transduction. Neurabin-I is involved in the regulation of Ca signaling intensity in alpha-adrenergic receptors; it forms a functional pair of opposing regulators with neurabin-II. Neurabins are expressed almost exclusively in neuronal cells. They are known to interact with protein phosphatase 1 and inhibit its activity; they also can bind actin filaments; however, the exact role of the SAM domain is unclear, since SAM doesn't participate in these interactions.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 291406707 541 WSPERVAEWISELGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISRHTREL 601
Cdd:cd09512    7 WSVQQVCQWLMGLGLEQYIPEFTANNIDGQQLLQLDSSKLKALGITSSSDRSLLKKKLKEL 67

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 291406707 540 QWSPERVAEWISE---LGFPQYKECFTANFISGRKLIHVNCSNLPQMGITDFEHMKAISRH 597
Cdd:cd09510    5 LWSVQDVCKWLKRhcpDYYLLYAELFLQHDITGRALLRLNDNKLERMGITDEDHRQDILRE 65

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 291406707 546 VAEWISELGFPQYKECFT-ANFISGRKLIHVNCSNLPQMGITDFEHMKAI 594
Cdd:cd09545    6 VDDWLQAIKMERYKDNFTaAGYTTLEAVVHMNQDDLARIGISAIAHQNKI 55

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
                 ....*....|....*....|....*....|....*
gi 291406707 540 QWSPERVAEWISELGFPQYKECFTANF-ISGRKLI 573
Cdd:cd09515    3 EWTCEDVAKWLKKEGFSKYVDLLCNKHrIDGKVLL 37

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
                 ....*....|....*....|....*....|....*.
gi 291406707 541 WSPERVAEWISELGFPQYKECFTANFISGRKLIHVN 576
Cdd:cd09505    5 WSEEDVCTWLRSIGLEQYVEVFRANNIDGKELLNLT 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 291406707 546 VAEWISELGFPQYKECFT-ANFISGRKLIHVNCSNLPQMGITDFEHMKAI 594
Cdd:cd09488    5 VGEWLESIKMGRYKENFTaAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKI 54