PDZ domain of connector enhancer of kinase suppressor of ras 1 (CNK1), CNK2, CNK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CNK1 (also known as connector enhancer of KSR 1 (CNKSR1), CNK homolog protein 1, connector enhancer of KSR-like), CNK2 (also known as CNKSR2, CNK homolog protein 2), and CNK3 (also known as CNKSR3, CNK homolog protein 3, CNKSR family member 3, maguin-like). CNK proteins modulate Ras-mediated signaling, acting downstream of Ras as a scaffold for the Raf/MEK/ERK kinase cascade. They also modulate signaling mediated via Rho family small GTPases, through interactions with various guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and modulate the insulin signaling pathway through interactions with the Arf guanine nucleotide exchange factors. CNK proteins also regulate cell proliferation and migration by acting as scaffolds for the PI3K/Akt and JNK signaling cascades. CNK2 plays a role in the molecular processes that govern morphology of the postsynaptic density (PSD), and influences subcellular localization of the regulatory NCK-interacting kinase TNIK. TNIK binds a region of CNK2 including the PDZ and the DUF domain; this region also binds the kinase MINK1. CNK2 may also influence the membrane localization of MINK1. CNK3 plays a part in transepithelial sodium transport; it coordinates assembly of an epithelial sodium channel (ENaC)-regulatory complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This CNK1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509417 195 QKAVLESVQVDDPSGLEIHTTSNCLHFVSRVGVQ--AATSSQILPGDEIVQVNEQVVVGWSHKNMLRELLREPAKVSLVL 272
Cdd:cd06748    1 ELVQLTNKKPEEGLGLEIKSTYNGLHVITGTKENspADRCGKIHAGDEVIQVNYQTVVGWQLKNLVRALREDPHGVTLTL 80

                 .
gi 755509417 273 K 273
Cdd:cd06748   81 K 81

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 755509417   4 VEAWTPGKVAAWLRGLDDALQ--DYPFEDWQLPGKYLLQLCPQSLEALTVWPLGHQELILDGVEQLRAL 70
Cdd:cd09511    1 VAKWSPKQVTDWLKGLDDCLQqyIYTFEREKVTGEQLLNLSPQDLENLGVTKIGHQELILEAVELLCAL 69

PDZ domain of connector enhancer of kinase suppressor of ras 1 (CNK1), CNK2, CNK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CNK1 (also known as connector enhancer of KSR 1 (CNKSR1), CNK homolog protein 1, connector enhancer of KSR-like), CNK2 (also known as CNKSR2, CNK homolog protein 2), and CNK3 (also known as CNKSR3, CNK homolog protein 3, CNKSR family member 3, maguin-like). CNK proteins modulate Ras-mediated signaling, acting downstream of Ras as a scaffold for the Raf/MEK/ERK kinase cascade. They also modulate signaling mediated via Rho family small GTPases, through interactions with various guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and modulate the insulin signaling pathway through interactions with the Arf guanine nucleotide exchange factors. CNK proteins also regulate cell proliferation and migration by acting as scaffolds for the PI3K/Akt and JNK signaling cascades. CNK2 plays a role in the molecular processes that govern morphology of the postsynaptic density (PSD), and influences subcellular localization of the regulatory NCK-interacting kinase TNIK. TNIK binds a region of CNK2 including the PDZ and the DUF domain; this region also binds the kinase MINK1. CNK2 may also influence the membrane localization of MINK1. CNK3 plays a part in transepithelial sodium transport; it coordinates assembly of an epithelial sodium channel (ENaC)-regulatory complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This CNK1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509417 195 QKAVLESVQVDDPSGLEIHTTSNCLHFVSRVGVQ--AATSSQILPGDEIVQVNEQVVVGWSHKNMLRELLREPAKVSLVL 272
Cdd:cd06748    1 ELVQLTNKKPEEGLGLEIKSTYNGLHVITGTKENspADRCGKIHAGDEVIQVNYQTVVGWQLKNLVRALREDPHGVTLTL 80

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gi 755509417 273 K 273
Cdd:cd06748   81 K 81

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 755509417   4 VEAWTPGKVAAWLRGLDDALQ--DYPFEDWQLPGKYLLQLCPQSLEALTVWPLGHQELILDGVEQLRAL 70
Cdd:cd09511    1 VAKWSPKQVTDWLKGLDDCLQqyIYTFEREKVTGEQLLNLSPQDLENLGVTKIGHQELILEAVELLCAL 69

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755509417    5 EAWTPGKVAAWLRGLDdaLQDY--PFEDWQLPGKYLLQLCPQSLEALTVWPLGHQELILDGVEQLR 68
Cdd:pfam00536   1 DGWSVEDVGEWLESIG--LGQYidSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64

PDZ domain of connector enhancer of kinase suppressor of ras 1 (CNK1), CNK2, CNK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CNK1 (also known as connector enhancer of KSR 1 (CNKSR1), CNK homolog protein 1, connector enhancer of KSR-like), CNK2 (also known as CNKSR2, CNK homolog protein 2), and CNK3 (also known as CNKSR3, CNK homolog protein 3, CNKSR family member 3, maguin-like). CNK proteins modulate Ras-mediated signaling, acting downstream of Ras as a scaffold for the Raf/MEK/ERK kinase cascade. They also modulate signaling mediated via Rho family small GTPases, through interactions with various guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and modulate the insulin signaling pathway through interactions with the Arf guanine nucleotide exchange factors. CNK proteins also regulate cell proliferation and migration by acting as scaffolds for the PI3K/Akt and JNK signaling cascades. CNK2 plays a role in the molecular processes that govern morphology of the postsynaptic density (PSD), and influences subcellular localization of the regulatory NCK-interacting kinase TNIK. TNIK binds a region of CNK2 including the PDZ and the DUF domain; this region also binds the kinase MINK1. CNK2 may also influence the membrane localization of MINK1. CNK3 plays a part in transepithelial sodium transport; it coordinates assembly of an epithelial sodium channel (ENaC)-regulatory complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This CNK1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509417 195 QKAVLESVQVDDPSGLEIHTTSNCLHFVSRVGVQ--AATSSQILPGDEIVQVNEQVVVGWSHKNMLRELLREPAKVSLVL 272
Cdd:cd06748    1 ELVQLTNKKPEEGLGLEIKSTYNGLHVITGTKENspADRCGKIHAGDEVIQVNYQTVVGWQLKNLVRALREDPHGVTLTL 80

                 .
gi 755509417 273 K 273
Cdd:cd06748   81 K 81

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755509417   4 VEAWTPGKVAAWLRGLDDALQ--DYPFEDWQLPGKYLLQLCPQSLEALTVWPLGHQELILDGVEQLRAL 70
Cdd:cd09511    1 VAKWSPKQVTDWLKGLDDCLQqyIYTFEREKVTGEQLLNLSPQDLENLGVTKIGHQELILEAVELLCAL 69

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 755509417 220 HFVSRV--GVQAATSSQILPGDEIVQVNEQVVVGWSHKNMLRELLREPAKVSLVLK 273
Cdd:cd00136   26 IFVSRVepGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTVR 81

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 755509417   220 HFVSRVGVQ-AATSSQILPGDEIVQVNEQVVVGWSHKNMLRELLREPAKVSLVLK 273
Cdd:smart00228  28 VVVSSVVPGsPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTVL 82

SAM domain (Sterile alpha motif);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755509417    4 VEAWTPGKVAAWLRGLDdaLQDYP--FEDWQLPGKY-LLQLCPQSLEALTVWPLGHQELILDGVEQLR 68
Cdd:pfam07647   1 VESWSLESVADWLRSIG--LEQYTdnFRDQGITGAElLLRLTLEDLKRLGITSVGHRRKILKKIQELK 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 755509417   3 PVEAWTPGKVAAWLRGLddALQDYP--FEDWQLPGKYLLQLCPQSLEALTVWPLGHQELILDGVEQL 67
Cdd:cd09575    1 PVHLWGTEEVAAWLEHL--SLCEYKdiFTRHDVRGSELLHLERRDLKDLGVTKVGHMKRILCGIKEL 65

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 755509417   3 PVEAWTPGKVAAWLRGLDDALQDYPFEDWQLPGKYLLQLCPQSLEALTVWPLGHQELILDGVEQL 67
Cdd:cd09576    1 PVQKWGTDEVAAWLDLLSLGEYKEIFIRHDIRGSELLHLERRDLKDLGIPKVGHMKRILQGIKEL 65

PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight junction (PATJ), PDZ domain 2 of Drosophila melanogaster inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 8 of MUPP1, PDZ domain 7 of PATJ, and PDZ domain 2 of Drosophila melanogaster INAD, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ8 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 755509417 221 FVsrVGVQ----AATSSQILPGDEIVQVNEQVVVGWSHKNMLRELLREPAKVSLVL 272
Cdd:cd06672   29 FV--VGIDpdgaAGKDGRIQVGDELLEINGQVLYGRSHLNASAIIKSAPSKVKIVF 82