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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 156119597  72 KPVALWTQQDVCKWLKKHCPNQYQIYSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQLKVREEV 146
Cdd:cd09510    1 KPVYLWSVQDVCKWLKRHCPDYYLLYAELFLQHDITGRALLRLNDNKLERMGITDEDHRQDILREILKLRLKTEI 75

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 156119597  72 KPVALWTQQDVCKWLKKHCPNQYQIYSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQLKVREEV 146
Cdd:cd09510    1 KPVYLWSVQDVCKWLKRHCPDYYLLYAELFLQHDITGRALLRLNDNKLERMGITDEDHRQDILREILKLRLKTEI 75

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.

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gi 156119597    74 VALWTQQDVCKWLKKHcpnQYQIYSESFKQHDITGRALLRLTDK-KLERMGIAQENLRQHILQQVLQLK 141
Cdd:smart00454   1 VSQWSPESVADWLESI---GLEQYADNFRKNGIDGALLLLLTSEeDLKELGITKLGHRKKILKAIQKLK 66

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 156119597  72 KPVALWTQQDVCKWLKKHCPNQYQIYSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQLKVREEV 146
Cdd:cd09510    1 KPVYLWSVQDVCKWLKRHCPDYYLLYAELFLQHDITGRALLRLNDNKLERMGITDEDHRQDILREILKLRLKTEI 75

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.

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gi 156119597  81 DVCKWLKKHCPNQYqiySESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQV 137
Cdd:cd09487    1 DVAEWLESLGLEQY---ADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAI 54

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

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gi 156119597  77 WTQQDVCKWLKKH-----CPNQYQIYSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQLK 141
Cdd:cd09529    2 WTEEDVHFWMQQLvrkggHPSELSQYADLFKENHITGKRLLLLTEEDLRDMGIGSKGHIIHLKSAIEKLT 71

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 156119597  77 WTQQDVCKWLKKHCPNQYqiySESFKQHDITGRALLRLTDKKLER-MGIAQENLRQHILQQVLQLKVRE 144
Cdd:cd09505    5 WSEEDVCTWLRSIGLEQY---VEVFRANNIDGKELLNLTKESLSKdLKIESLGHRNKILRKIEELKMKS 70

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.

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gi 156119597  71 SKPVALWTQQDVCKWLkkHCPNQYQiYSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQLK 141
Cdd:cd09512    1 SRPVSEWSVQQVCQWL--MGLGLEQ-YIPEFTANNIDGQQLLQLDSSKLKALGITSSSDRSLLKKKLKELK 68

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.

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gi 156119597  77 WTQQDVCKWLKKH-CpnqyQIYSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQLK 141
Cdd:cd09534    1 WDEEFVEEWLNELnC----GQYLDIFEKNLITGDLLLELDKEALKELGITKVGDRIRLLRAIKSLR 62

SAM domain ot SARM1-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of SARM1-like adaptor proteins is a protein-protein interaction domain. SARM1-like proteins contain two tandem SAM domains. SARM1-like proteins are involved in TLR (Toll-like receptor) signaling. They are responsible for targeted localization of the whole protein to post-synaptic regions of axons. In humans SARM1 expression is detected in kidney and liver.

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gi 156119597  74 VALWTQQDVCKWLKKhcpNQYQIYSESFKQHDITGRALLRLTDKKLER-MGIAQENLRQHILQQVLQLKV 142
Cdd:cd09501    1 VPLWSVADVQTWLKQ---IGFEDYAEKFSESQVDGDLLLQLTEDELKQdLGMSSGLLRKRFLRELVELKT 67

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.

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gi 156119597  74 VALWTQQDVCKWLKKhcpNQYQIYSESF-KQHDITGRALLRLTDKKL 119
Cdd:cd09515    1 VHEWTCEDVAKWLKK---EGFSKYVDLLcNKHRIDGKVLLSLTEEDL 44

Sterile alpha motif (SAM)/Pointed domain;

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gi 156119597   76 LWTQQDVCKWLkKHCPNQYQIYSESFKQHDITGRALLRLTDKK-LERMGIAQENLRQHILQ 135
Cdd:pfam02198  19 LWTKDHVLEWL-EWAVDEFDLSKIDFSQFDMNGKALCSLGKEEfLQRAPGPGDILWSHLQI 78

SAM domain of Scm proteins of Polycomb group; SAM (sterile alpha motif) domain of Scm (Sex comb on midleg) subfamily of Polycomb group is a protein-protein interaction domain. Proteins of this subfamily are transcriptional repressors associated with PRC1 complex. This group includes invertebrate Scm protein and chordate Scm homolog 1 and Scm-like 1, 2, 3 proteins. Most have a SAM domain, two MBT repeats, and a DUF3588 domain, except Scm-like 4 proteins which do not have MBT repeats. Originally the Scm protein was described in Drosophila as a regulator required for proper spatial expression of homeotic genes. It plays a major role during early embryogenesis. SAM domains of Scm proteins can interact with each other, forming homooligomers, as well as with SAM domains of other proteins, in particular with SAM domains of Ph (polyhomeotic) proteins, forming heterooligomers. Homooligomers are similar to the ones formed by SAM Pointed domains of the TEL proteins. Such SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Mammalian Scmh1 protein is known be indispensible member of PRC1 complex; it plays a regulatory role for the complex during meiotic prophase of male sperm cells, and is particularly involved in regulation of chromatin modification at the XY chromatin domain of the pachytene spermatocytes.

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gi 156119597  71 SKPVALWTQQDVCKWLKKHCPNQYQIYSESFKQHDITGRALLRLT-DKKLERMGI 124
Cdd:cd09578    1 SKDPSTWSVEDVVQFIKEADPQALAPHVDLFRKHEIDGKALLLLNsDMMMKYMGL 55

SAM domain of Samd9/Samd9L subfamily; SAM (sterile alpha motif) domain of Samd9/Samd9L subfamily is a putative protein-protein interaction domain. SAM is a widespread domain in signaling proteins. Samd9 is a tumor suppressor gene. It is involved in death signaling of malignant glioblastoma. Samd9 suppression blocks cancer cell death induced by HVJ-E or IFN-beta treatment. Deleterious mutations in Samd9 lead to normophosphatemic familial tumoral calcinosis, a cutaneous disorder characterized by cutaneous calcification or ossification.

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gi 156119597  77 WTQQDVCKWLKKHCPNQYqiYSESFKQHDITGRALLRLTDKKLERMGI 124
Cdd:cd09528    3 WTKEHVKQWLIEDLIDKK--YAEILYEEEVTGAVLKELTEEDLVDMGL 48

SAM domain of BAR subfamily; SAM (sterile alpha motif) domain of BAR (Bifunctional Apoptosis Regulator) subfamily is a protein-protein interaction domain. In addition to the SAM domain, this type of regulator has a RING finger domain. Proteins of this subfamily are involved in the apoptosis signal network. Their overexpression in human neuronal cells significantly protects cells from a broad range of cell death stimuli. SAM domain can interact with Caspase8, Bcl-2 and Bcl-X resulting in suppression of Bax-induced cell death.

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gi 156119597  74 VALWTQQDVCKWLKKHCPnQYQIYSESFKQHDITGRALLRLTDKKLER--MGIAQENLRQHILQQVLQLK 141
Cdd:cd09513    1 VSKWTPEEVVLWLEQLGP-WASLYRERFLSENVNGRLLLTLTEEELSKppFNIENSLHRRAILTELERVK 69

SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK (connector enhancer of kinase suppressor of ras (Ksr)) subfamily is a protein-protein interaction domain. CNK proteins are multidomain scaffold proteins containing a few protein-protein interaction domains and are required for connecting Rho and Ras signaling pathways. In Drosophila, the SAM domain of CNK is known to interact with the SAM domain of the aveugle protein, forming a heterodimer. Mutation of the SAM domain in human CNK1 abolishes the ability to cooperate with the Ras effector, supporting the idea that this interaction is necessary for proper Ras signal transduction.

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gi 156119597  74 VALWTQQDVCKWLKKhCPNQYQIYSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQL 140
Cdd:cd09511    1 VAKWSPKQVTDWLKG-LDDCLQQYIYTFEREKVTGEQLLNLSPQDLENLGVTKIGHQELILEAVELL 66

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 156119597 101 FKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQL 140
Cdd:cd09521   24 FKEHDVTFSQLLKMTEEDLEKIGITQPGDQKKILDAIKEV 63

Sterile alpha motif (SAM)/Pointed domain; Sterile alpha motif (SAM)/Pointed domain is found in about 40% of transcriptional regulators of ETS family (initially named for Erythroblastosis virus, E26-E Twenty Six). SAM Pointed domain containing proteins of this family additionally have a C-terminal ETS DNA-binding domain. In a few cases, SAM Pointed domain appears as a single domain protein. Members of this group are mostly involved in regulation of embryonic development and growth control in eukaryotes. SAM Pointed domains mediate protein-protein interactions. Depending on the subgroup, they can interact with other SAM Pointed domains forming homo or hetero dimers/oligomers and/or they can recruit a protein kinase to its target which can be a SAM Pointed domain containing protein itself or another protein that has no kinase docking site. Thus, SAM Pointed domains participate in transcriptional regulation and signal transduction. Some genes coding ETS family transcriptional regulators are proto-oncogenes. They are prone to chromosomal translocations resulting in gene fusions. Chimeric proteins with SAM Pointed domains were found in a number of different human tumors including myeloid leukemia, lymphoblastic leukemia, Ewing's sarcoma and primitive neuroectodermal tumor. Members of this family are potential targets for cancer therapy.

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gi 156119597  76 LWTQQDVCKWLkKHCPNQYQIYSESFKQHDITGRALLRLTD 116
Cdd:cd08203    4 EWTPEHVQQWL-SWVSKKFSLDPIDPDRFPMNGKELCALSK 43

SAM domain of TAL subfamily; SAM (sterile alpha motif) domain of TAL (Tsg101-associated ligase) proteins, also known as LRSAM1 (Leucine-rich repeat and sterile alpha motif-containing) proteins, is a putative protein-protein interaction domain. Proteins of this subfamily participate in the regulation of retrovirus budding and receptor endocytosis. They show E3 ubiquitin ligase activity. Human TAL protein interacts with Tsg101 and TAL's C-terminal ring finger domain is essential for the multiple monoubiquitylation of Tsg101.

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gi 156119597  97 YSESFKQHDITGRALLRLTDKKLERMGIAQENLRQHILQQVLQLK 141
Cdd:cd09523   20 YLPVFARHRITMETLSTMTDEDLKKIGIHEIGLRKEILRAAQELL 64