SAM domain of sec23ip; SAM (sterile alpha motif) domain of Sec23ip (Sec23 interacting protein) group is a potential protein-protein interaction domain. Sec23ip proteins (also known as p125) contain an N-terminal proline-rich region, a central region containing a SAM domain and a C-terminal region with a predicted metal-binding domain. Sec23ip interacts with Sec23p/Sec24p part of COPII-coated vesicles complex involved in protein transport from the ER to the Golgi apparatus. The proline-rich region plays an essential role in this interaction. Overexpression of Sec23ip leads to disorganization of ER/Golgi intermediate compartment.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 55584014  638 DLVVENKEVLTLQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVEH 702
Cdd:cd09584    1 RLNEEEEDVPSLQSVLEALSLSEYKSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVKE 65

SAM domain of sec23ip; SAM (sterile alpha motif) domain of Sec23ip (Sec23 interacting protein) group is a potential protein-protein interaction domain. Sec23ip proteins (also known as p125) contain an N-terminal proline-rich region, a central region containing a SAM domain and a C-terminal region with a predicted metal-binding domain. Sec23ip interacts with Sec23p/Sec24p part of COPII-coated vesicles complex involved in protein transport from the ER to the Golgi apparatus. The proline-rich region plays an essential role in this interaction. Overexpression of Sec23ip leads to disorganization of ER/Golgi intermediate compartment.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 55584014  638 DLVVENKEVLTLQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVEH 702
Cdd:cd09584    1 RLNEEEEDVPSLQSVLEALSLSEYKSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVKE 65

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 55584014     641 VENKEVLTLQETLEALSLSEYFSTFEKEKIDMESLL-MCTVDDLKEMGI-PLGPRKKIANFVE 701
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLlLTSEEDLKELGItKLGHRKKILKAIQ 63

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55584014    168 FGNQPQGIPQPGYNPYRHTPGSSRANPYIAPPQLQQCQTPGPPAHpppsgppvqMYQMPPGSLPPVPSSVQSPAQQQVPA 247
Cdd:TIGR01628  409 FNGQPLGWPRMSMMPTPMGPGGPLRPNGLAPMNAVRAPSRNAQNA---------AQKPPMQPVMYPPNYQSLPLSQDLPQ 479

                           90
                   ....*....|....*.
gi 55584014    248 RPGAPSVQVPSPFLLQ 263
Cdd:TIGR01628  480 PQSTASQGGQNKKLAQ 495

SAM domain of sec23ip; SAM (sterile alpha motif) domain of Sec23ip (Sec23 interacting protein) group is a potential protein-protein interaction domain. Sec23ip proteins (also known as p125) contain an N-terminal proline-rich region, a central region containing a SAM domain and a C-terminal region with a predicted metal-binding domain. Sec23ip interacts with Sec23p/Sec24p part of COPII-coated vesicles complex involved in protein transport from the ER to the Golgi apparatus. The proline-rich region plays an essential role in this interaction. Overexpression of Sec23ip leads to disorganization of ER/Golgi intermediate compartment.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 55584014  638 DLVVENKEVLTLQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVEH 702
Cdd:cd09584    1 RLNEEEEDVPSLQSVLEALSLSEYKSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVKE 65

SAM domain of DDHD2; SAM (sterile alpha motif) domain of DDHD2 group is a potential protein-protein interaction domain. DDHD2 proteins contain at least two domains:a SAM domain and a predicted metal-binding domain. Phospholipase A1 activity was demonstrated for the mammalian DDHD2 protein. Mutation of the putative catalytic serine resulted in elimination of activity. Unlike SEC23IP, DDHD2 proteins do not have an N-terminal proline-rich region and correspondingly they are not able to interact with Sec23p/Sec24p complex. Overexpression of DDHD2 is the cause of dispersion of ER/Golgi intermediate compartment and dispersion of tethering proteins located in the Golgi region, leading to aggregation in the endoplasmic reticulum.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 55584014  648 TLQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVEH 702
Cdd:cd09585   11 TLEETLKKLGLSEYCDVFEKEKIDLEALALCQERDLKDLGIPLGPRKKILNYIRR 65

SAM domain of USH1G_HARP family; SAM (sterile alpha motif) domain of USH1G/HARP (Usher syndrome type-1G/ Harmonin-interacting Ankyrin Repeat-containing protein) family is a protein-protein interaction domain. Members of this family have an N-terminal ankyrin repeat region and a C-terminal SAM domain. In mammals these proteins can interact via the SAM domain with the PDZ domain of harmonin to form a scaffolding complex that facilitates signal transduction in epithelial and inner ear sensory cells. It was suggested that USH1G and HARP can be tissue specific partners of harmonin. Mutations in ush1g genes lead to Usher syndrome type 1G. This syndrome is the cause of deaf-blindness in humans.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 55584014  649 LQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVE 701
Cdd:cd09517    5 LERFLTSNHLEEYLPVFEREKIDLEALMLLTDEDLQSLKLPLGPRRKLLNAIA 57

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 55584014  649 LQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGI-PLGPRKKIANFVEH 702
Cdd:cd09487    2 VAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGItSPGHRKKILRAIQR 56

SAM domain of HARP subfamily; SAM (sterile alpha motif) domain of HARP (Harmonin-interacting Ankyrin Repeat-containing) proteins, also known as ANKS4B, is a protein-protein interaction domain. Proteins of this subfamily have an N-terminal ankyrin repeat region and C-terminal SAM. In mouse epithelial tissues, HARP protein interacts with the PDZ domain of harmonin. This scaffolding complex facilitates signal transduction in epithelia. HARP was found co-expressed with harmonin in a number of epithelial cells including pancreatic ductal epithelium, embryonic epithelia of the lung, kidney, salivary glands, and cochlea.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 55584014  649 LQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFV 700
Cdd:cd09587    5 LEVFLSSQHLEEFLPIFMREQIDLEALMLCSDEDLQNIQMQLGPRKKILSAV 56

SAM domain of ANKS6 (or SamCystin) subfamily; SAM (sterile alpha motif) domain of ANKS6 (or SamCystin) subfamily is a potential protein-protein interaction domain. Proteins of this subfamily have N-terminal ankyrin repeats and a C-terminal SAM domain. They are able to form self-associated complexes and both (SAM and ANK) domains play a role in such interactions. Mutations in Anks6 gene are associated with polycystic kidney disease. They cause formation of renal cysts in rodent models. It was suggested that the ANKS6 protein can interact indirectly (through RNA and protein intermediates) with BICC1, another polycystic kidney disease-associated protein.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 55584014  649 LQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGIPL-GPRKKI 696
Cdd:cd09518    8 LSGILRKLSLEKYQPIFEEQEVDMEAFLTLTDGDLKELGIKTdGPRQQI 56

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 55584014  649 LQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGI-PLGPRKKIAN 698
Cdd:cd09534    6 VEEWLNELNCGQYLDIFEKNLITGDLLLELDKEALKELGItKVGDRIRLLR 56

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 55584014  648 TLQETLEALSLSEYFSTFEKEKID-MESLLMCTVDDLKEMGIPL-GPRKKI 696
Cdd:cd09542    6 SVSEWLESIRMKRYILHFRSAGLDtMECVLELTAEDLTQMGITLpGHQKRI 56

SAM domain of Polycomb group; SAM (sterile alpha motif) domain of Polycomb group is a protein-protein interaction domain. The Polycomb group includes transcriptional repressors which are involved in the regulation of some key regulatory genes during development in many organisms. They are best known for silencing Hox (Homeobox) genes. Polycomb proteins work together in large multimeric and chromatin-associated complexes. They organize chromatin of the target genes and maintain repressed states during many cell divisions. Polycomb proteins are classified based on their common function, but not on conserved domains and/or motifs; however many Polycomb proteins (members of PRC1 class complex) contain SAM domains which are more similar to each other inside of the Polycomb group than to SAM domains outside of it. Most information about structure and function of Polycomb SAM domains comes from studies of Ph (Polyhomeotic) and Scm (Sex comb on midleg) proteins. Polycomb SAM domains usually can be found at the C-terminus of the proteins. Some members of this group contain, in addition to the SAM domain, MTB repeats, Zn finger, and/or DUF3588 domains. Polycomb SAM domains can form homo- and/or heterooligomers through ML and EH surfaces. SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Polycomb proteins are known to be highly expressed in some cells years before their cancer pathology; thus they are attractive markers for early cancer therapy.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 55584014  657 SLSEYFSTFEKEKIDMESLLMCTVDDL-KEMGIPLGPRKKIANFVE 701
Cdd:cd09509   18 GCAEYAEVFREQEIDGQALLLLTEDDLlKGMGLKLGPALKIYNHIV 63

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 55584014  649 LQETLEALSLSEYFSTFEKEKIDMESLLMCTVDDLKEMGI-PLGPRKKIANFVE 701
Cdd:cd09523    8 LVNLLNELSAEHYLPVFARHRITMETLSTMTDEDLKKIGIhEIGLRKEILRAAQ 61

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55584014    168 FGNQPQGIPQPGYNPYRHTPGSSRANPYIAPPQLQQCQTPGPPAHpppsgppvqMYQMPPGSLPPVPSSVQSPAQQQVPA 247
Cdd:TIGR01628  409 FNGQPLGWPRMSMMPTPMGPGGPLRPNGLAPMNAVRAPSRNAQNA---------AQKPPMQPVMYPPNYQSLPLSQDLPQ 479

                           90
                   ....*....|....*.
gi 55584014    248 RPGAPSVQVPSPFLLQ 263
Cdd:TIGR01628  480 PQSTASQGGQNKKLAQ 495

SAM domain of tumor-p63,p73 proteins; SAM (sterile alpha motif) domain of p63, p73 transcriptional factors is a putative protein-protein interaction domain and lipid-binding domain. p63 and p73 are homologs to the tumor suppressor p53. They have a C-terminal SAM domain in their longest spliced alpha forms, while p53 doesn't have it. p63 or p73 knockout mice show significant developmental abnormalities but no increased cancer susceptibility, suggesting that p63 and p73 play a role in regulation of normal development. It was shown that SAM domain of p73 is able to bind some membrane lipids. The structural rearrangements in SAM are necessary to accomplish the binding. No evidence for homooligomerization through SAM domains was found for p63/p73 subfamily. It was suggested that the partner proteins should be either more distantly related SAM-containing domain proteins or proteins without the SAM domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 55584014  648 TLQETLEALSLSEYFSTFEKEKID-MESLLMCTVDDLKEMGIPLGPRKKI 696
Cdd:cd09503    6 SVASWLTKLGCSNYIDNFHQQGLLsIFQLDEFTLEDLAAMKIPEQHRNKI 55