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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017484030 448 KWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQFLK 510
Cdd:cd09566     1 KLDTHWVLRWLDDIGLPQYKDAFSEAKVDGRMLHYLTVDDLLHLKVTSALHHASIRRGIQVLR 63

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017484030 448 KWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQFLK 510
Cdd:cd09566     1 KLDTHWVLRWLDDIGLPQYKDAFSEAKVDGRMLHYLTVDDLLHLKVTSALHHASIRRGIQVLR 63

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 1017484030  448 KWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLT-ANDAVEMKVVNAHHYATLARSIQFLKK 511
Cdd:smart00454   3 QWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTsEEDLKELGITKLGHRKKILKAIQKLKE 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 1017484030 377 WRSEQLADWIAEIGYPQYMNEVSRHVRSGRHFLNMSMNEYEGvLNIKNPVHRKRVAILLRRI 438
Cdd:pfam00536   3 WSVEDVGEWLESIGLGQYIDSFRAGYIDGDALLQLTEDDLLK-LGVTLLGHRKKILYAIQRL 63

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 1017484030  374 FVDWRSEQLADWIAEIGYPQYMNEVSRHVRSGRHFLNMSMNEYEGVLNIKNPVHRKRVAILLRRIEED 441
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017484030 448 KWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQFLK 510
Cdd:cd09566     1 KLDTHWVLRWLDDIGLPQYKDAFSEAKVDGRMLHYLTVDDLLHLKVTSALHHASIRRGIQVLR 63

SAM domain of kazrin proteins repeat 3; SAM (sterile alpha motif) domain repeat 3 of kazrin proteins is a protein-protein interaction domain. The long isoform of kazrins contains three copies (repeats) of SAM domain. Kazrin can interact with periplakin. It is involved in interplay between desmosomes and in adheren junctions. Additionally kazrins play a role in regulation of intercellular differentiation, junction assembly, and cytoskeletal organization.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017484030 535 DVVVrWTHSATCEWLRKIDLAEFTQNLLFAGVPGALMIYEPSFTAESLAEILQMPPHKTLLRRHLTSHFNQLL 607
Cdd:cd09570     1 DPVV-WTNQRVIKWARSIDLKEYADNLRDSGVHGALMVLEPSFNSDTMATALGIPSSKNIIRRHLTTEMEALV 72

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 1017484030  448 KWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLT-ANDAVEMKVVNAHHYATLARSIQFLKK 511
Cdd:smart00454   3 QWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTsEEDLKELGITKLGHRKKILKAIQKLKE 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 1017484030 377 WRSEQLADWIAEIGYPQYMNEVSRHVRSGRHFLNMSMNEYEGvLNIKNPVHRKRVAILLRRI 438
Cdd:pfam00536   3 WSVEDVGEWLESIGLGQYIDSFRAGYIDGDALLQLTEDDLLK-LGVTLLGHRKKILYAIQRL 63

SAM domain of liprin/kazrin proteins repeat 2; SAM (sterile alpha motif) domain repeat 2 of liprin/kazrin proteins is a protein-protein interaction domain. The long form of liprin/kazrin proteins contains three copies (repeats) of SAM domain. Liprin-alpha may form heterodimers with liprin-beta through their SAM domains. Liprins were originally identified as LAR (leukocyte common antigen-related) transmembrane protein-tyrosine phosphatase-interacting proteins. They participate in mammary gland development and in axon guidance. In particular, liprin-alpha is involved in formation of the presynaptic active zone; liprin-beta is involved in the maintenance of lymphatic vessel integrity. Kazrins are involved in interplay between desmosomes and in adheren junctions; additionally they play a role in regulation of intercellular differentiation, junction assembly, and cytoskeletal organization.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1017484030 456 RWLDDIGLPQYKDVFAENVVDGPLLLSLTAND-AVEMKVVNAHHYATLARSIQFLK 510
Cdd:cd09495     5 RWLDDIGLPQYKDQFHESLVDRRMLQYLTVNDlLVHLKVTSQLHHLSLKCGIHVLH 60

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 1017484030 457 WLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQ 507
Cdd:cd09487     5 WLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55

SAM domain (Sterile alpha motif);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1017484030 449 WDVHQTLRWLDDIGLPQYKDVFAENVVDGP-LLLSLTANDAVEMKVVNAHHYATLARSIQFLK 510
Cdd:pfam07647   4 WSLESVADWLRSIGLEQYTDNFRDQGITGAeLLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

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 1017484030 445 PANKWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQFLKKA 512
Cdd:cd09512     3 PVSEWSVQQVCQWLMGLGLEQYIPEFTANNIDGQQLLQLDSSKLKALGITSSSDRSLLKKKLKELKAQ 70

SAM domain of liprin-alpha1,2,3,4 proteins repeat 2; SAM (sterile alpha motif) domain repeat 2 of liprin-alpha1,2,3,4 proteins is a protein-protein interaction domain. Liprin-alpha proteins contain three copies (repeats) of SAM domain. They may form heterodimers with liprin-beta proteins through their SAM domains. Liprins were originally identified as LAR (leukocyte common antigen-related) transmembrane protein-tyrosine phosphatase-interacting proteins. They participate in mammary gland development, and in axon guidance; in particular, liprin-alpha is involved in formation of the presynaptic active zone.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1017484030 457 WLDDIGLPQYKDVFAENVVDGPLLLSLTAND-AVEMKVVNAHHYATLARSIQFLKK 511
Cdd:cd09565    10 WLPSLGLPQYRSYFMECLVDARMLDHLTKKDlRTHLKMVDSFHRTSLQYGILCLKR 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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1017484030 450 DVHQtlrWLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQFLK 510
Cdd:cd09533     1 DVAD---WLSSLGLPQYEDQFIENGITGDVLVALDHEDLKEMGITSVGHRLTILKAVYELK 58

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        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1017484030 449 WDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTAND-AVEMKVVNAHHYATLARSIQFLKK 511
Cdd:cd09505     5 WSEEDVCTWLRSIGLEQYVEVFRANNIDGKELLNLTKESlSKDLKIESLGHRNKILRKIEELKM 68

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017484030 381 QLADWIAEIGYPQYMNEVSRHVRSGRHFLNMSMNEYEGvLNIKNPVHRKRvaiLLRRIEE 440
Cdd:cd09487     1 DVAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKE-LGITSPGHRKK---ILRAIQR 56

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.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1017484030 449 WDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTAND 487
Cdd:cd09501     4 WSVADVQTWLKQIGFEDYAEKFSESQVDGDLLLQLTEDE 42

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1017484030 445 PANKWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQFL 509
Cdd:cd09576     1 PVQKWGTDEVAAWLDLLSLGEYKEIFIRHDIRGSELLHLERRDLKDLGIPKVGHMKRILQGIKEL 65

SAM domain of STIM2 subfamily proteins; SAM (sterile alpha motif) domain of STIM2 (Stromal interaction molecule) subfamily proteins is a putative protein-protein interaction domain. STIM1 and STIM2 human proteins are type I transmembrane proteins. The N-terminal part of them includes "hidden" EF-hand and SAM domains. This region is responsible for sensing changes in store-operated and basal cytoplasmic Ca2+ levels and initiates oligomerization. "Hidden" EF hand and SAM domains have a stable intramolecular association, and the SAM domain is a component that regulates stability within STIM proteins. Destabilization of the EF-SAM association during Ca2+ depletion leads to partial unfolding and aggregation (homooligomerization), thus activating the store-operated Ca2+ entry. Immunoprecipitation analysis indicates that STIM1 and STIM2 can form co-precipitable oligomeric associations in vivo. It was suggested that STIM2 protein is an inhibitor of store operated channels in plasma membrane.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1017484030 445 PANKWDVHQTLRWLDD-IGLPQYKDVFAENVVDGPLLLSLTANDAVEM----KVVNAHH 498
Cdd:cd09574     1 EVHNWTMEDTLQWLKEfVELPQYEKNFRDNNVKGTTLPRIAVNEPSFMisqlKILDRSH 59

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 1017484030 445 PANKWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTANDAVEMKVVNAHHYATLARSIQFL 509
Cdd:cd09575     1 PVHLWGTEEVAAWLEHLSLCEYKDIFTRHDVRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 65

SAM domain of Atherin/Atherin-like subfamily; SAM (sterile alpha motif) domain of SAM_Atherin and Atherin-like subfamily proteins is a putative protein-protein and/or protein-lipid interaction domain. In addition to the C-terminal SAM domain, the majority of proteins belonging to this group also have PHD (or Zn finger) domain. As potential members of the polycomb group, these proteins may be involved in regulation of some key regulatory genes during development. Atherin can be recruited by Ruk/CIN85 kinase-binding proteins via its SH3 domains thus participating in the signal transferring kinase cascades. Also, atherin was found associated with low density lipids (LDL) in atherosclerotic lesions in human. It was suggested that atherin plays an essential role in atherogenesis via immobilization of LDL in the arterial wall. SAM domains of atherins are predicted to form polymers. Inhibition of polymer formation could be a potential antiatherosclerotic therapy.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1017484030 445 PANkWDVHQTLRWLDDIGLPQYKDVFAENVVDGPLLLSLTAND 487
Cdd:cd09583     1 PSN-WSVEDVVQYFKTAGFPEEANAFKEQEIDGKSLLLLTRSD 42