Summary: SAM domain (Sterile alpha motif)
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Sterile alpha motif Edit Wikipedia article
|SAM domain (Sterile alpha motif)|
|SCOP2||1b0x / SCOPe / SUPFAM|
|SCOP2||1uqv / SCOPe / SUPFAM|
In molecular biology, the protein domain Sterile alpha motif (or SAM) is a putative protein interaction module present in a wide variety of proteins involved in many biological processes. The SAM domain that spreads over around 70 residues is found in diverse eukaryotic organisms. SAM domains have been shown to homo- and hetero-oligomerise, forming multiple self-association architectures and also binding to various non-SAM domain-containing proteins, nevertheless with a low affinity constant.
SAM domains also appear to possess the ability to bind RNA. Smaug, a protein that helps to establish a morphogen gradient in Drosophila embryos by repressing the translation of nanos (nos) mRNA, binds to the 3' untranslated region (UTR) of nos mRNA via two similar hairpin structures. The 3D crystal structure of the Smaug RNA-binding region shows a cluster of positively charged residues on the Smaug-SAM domain, which could be the RNA-binding surface. This electropositive potential is unique among all previously determined SAM-domain structures and is conserved among Smaug-SAM homologs. These results suggest that the SAM domain might have a primary role in RNA binding.
Structural analyses show that the SAM domain is arranged in a small five-helix bundle with two large interfaces. In the case of the SAM domain of EPHB2, each of these interfaces is able to form dimers. The presence of these two distinct intermonomers binding surface suggest that SAM could form extended polymeric structures.
In molecular biology, the protein domain Ste50p mainly in fungi and some other types of eukaryotes. It plays a role in the mitogen-activated protein kinase cascades, a type of cell signalling that helps the cell respond to external stimuli, more specifically mating, cell growth, and osmo-tolerance  in fungi.
The protein domain Ste50p has a role in detecting pheromones for mating. It is thought to be found bound to Ste11p in order to prolong the pheromone-induced signaling response. Furthermore, it is also involved in aiding the cell to respond to nitrogen starvation.
The fungal Ste50p SAM consists of six helices, which form a compact, globular fold. It is a monomer in solution and often undergoes heterodimerisation (and in some cases oligomerisation) of the protein.
The SAM domain of Ste50p often interacts with the SAM domain of Ste11p. They form bonds through this association. It is important to note that the SAM domain of one protein will bind to the SAM of a different protein. SAM domains do not self-associate in vitro. There is significant evidence for Ste50p oligomerization in vivo.
Human proteins containing this domain
ANKS1A; ANKS1B; ANKS3; ANKS4B; ANKS6; BFAR; BICC1; CASKIN1; CASKIN2; CENTD1; CNKSR2; CNKSR3; DDHD2; EPHA1; EPHA10; EPHA2; EPHA5; EPHA6; EPHA7; EPHA8; EPHB1; EPHB2; EPHB3; EPHB4; FAM59A; HPH2; INPPL1; L3MBTL3; PHC1; PHC2; PHC3; PPFIA1; PPFIA2; PPFIA3; PPFIA4; PPFIBP1; PPFIBP2; SAMD1; SAMD13; SAMD14; SAMD3; SAMD4A; SAMD4B; SAMD5; SAMD7; SAMD8; SAMD9; SCMH1; SCML1; SCML2; SEC23IP; SGMS1; SHANK1; SHANK2; SHANK3; STARD13; UBP1; USH1G; ZCCHC14; p63; p73;
- Bork P, Ponting CP, Hofmann K, Schultz J (1997). "SAM as a protein interaction domain involved in developmental regulation". Protein Sci. 6 (1): 249â€“253. doi:10.1002/pro.5560060128. PMCÂ 2143507. PMIDÂ 9007998.
- Pawson T, Stapleton D, Balan I, Sicheri F (1999). "The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization". Nat. Struct. Biol. 6 (1): 44â€“49. doi:10.1038/4917. PMIDÂ 9886291. S2CIDÂ 1202526.
- Simon J, Peterson AJ, Kyba M, Bornemann D, Morgan K, Brock HW (1997). "A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions". Mol. Cell. Biol. 17 (11): 6683â€“6692. doi:10.1128/MCB.17.11.6683. PMCÂ 232522. PMIDÂ 9343432.
- Goodwill KE, Thanos CD, Bowie JU (1999). "Oligomeric structure of the human EphB2 receptor SAM domain". Science. 283 (5403): 833â€“836. doi:10.1126/science.283.5403.833. PMIDÂ 9933164.
- Bowie JU, Kim CA (2003). "SAM domains: uniform structure, diversity of function". Trends Biochem. Sci. 28 (12): 625â€“628. doi:10.1016/j.tibs.2003.11.001. PMIDÂ 14659692.
- Posas, F.; Witten, E. A.; Saito, H. (1998). "Requirement of STE50 for osmostress-induced activation of the STE11 mitogen-activated protein kinase kinase kinase in the high-osmolarity glycerol response pathway". Molecular and Cellular Biology. 18 (10): 5788â€“5796. doi:10.1128/mcb.18.10.5788. PMCÂ 109165. PMIDÂ 9742096.
- Grimshaw SJ, Mott HR, Stott KM, Nielsen PR, Evetts KA, Hopkins LJ, Nietlispach D, Owen D (January 2004). "Structure of the sterile alpha motif (SAM) domain of the Saccharomyces cerevisiae mitogen-activated protein kinase pathway-modulating protein STE50 and analysis of its interaction with the STE11 SAM". J. Biol. Chem. 279 (3): 2192â€“201. doi:10.1074/jbc.M305605200. PMIDÂ 14573615.
- Slaughter, BD; Huff JM; Wiegraebe W; Schwartz JW; Li R (2008). "SAM domain-based protein oligomerization observed by live-cell fluorescence fluctuation spectroscopy". PLOS ONE. 3 (4): e1931. doi:10.1371/journal.pone.0001931. PMCÂ 2291563. PMIDÂ 18431466.
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SAM domain (Sterile alpha motif) Provide feedback
No Pfam abstract.
Stapleton D, Balan I, Pawson T, Sicheri F; , Nat Struct Biol 1999;6:44-49.: The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization. PUBMED:9886291 EPMC:9886291
Internal database links
|SCOOP:||NCD1 SAM_1 SAM_3 SAM_4 SAM_KSR1 SAM_PNT SAM_Ste50p|
|Similarity to PfamA using HHSearch:||SAM_1 IGR SAM_3|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001660
The sterile alpha motif (SAM) domain is a putative protein interaction module present in a wide variety of proteins [ PUBMED:9007998 ] involved in many biological processes. The SAM domain that spreads over around 70 residues is found in diverse eukaryotic organisms [ PUBMED:9886291 ]. SAM domains have been shown to homo- and hetero-oligomerise, forming multiple self-association architectures and also binding to various non-SAM domain-containing proteins [ PUBMED:9343432 ], nevertheless with a low affinity constant [ PUBMED:9933164 ]. SAM domains also appear to possess the ability to bind RNA [ PUBMED:14659692 ]. Smaug, a protein that helps to establish a morphogen gradient in Drosophila embryos by repressing the translation of nanos (nos) mRNA, binds to the 3' untranslated region (UTR) of nos mRNA via two similar hairpin structures. The 3D crystal structure of the Smaug RNA-binding region shows a cluster of positively charged residues on the Smaug-SAM domain, which could be the RNA-binding surface. This electropositive potential is unique among all previously determined SAM-domain structures and is conserved among Smaug-SAM homologues. These results suggest that the SAM domain might have a primary role in RNA binding.
Structural analyses show that the SAM domain is arranged in a small five-helix bundle with two large interfaces [ PUBMED:9343432 ]. In the case of the SAM domain of EphB2, each of these interfaces is able to form dimers. The presence of these two distinct intermonomers binding surface suggest that SAM could form extended polymeric structures [ PUBMED:9933164 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||protein binding (GO:0005515)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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SAM domains are found in a diverse set of proteins, which include scaffolding proteins, transcription regulators, translational regulators tyrosine kinases and serine/threonine kinases [1-3]. SAM domains are found in all eukaryotes and some bacteria  . Structures of SAM domains reveal a common five helical structure. The SAM domain is involved in a variety of functions. The most widespread function is in domain-domain interactions. The SAM domain performs domain-domain interactions using multifarious arrangements of the SAM domain. More recently, the SAM domain within the Smaug protein has been demonstrated to bind to the Nanos 3' UTR translation control element (Rfam:RF00161) . This clan currently only represents the diverse SAM domain family and does not contain the more divergent SAM/Pointed family (Pfam:PF02198).
The clan contains the following 12 members:IGR NCD1 SAM_1 SAM_2 SAM_3 SAM_4 SAM_DrpA SAM_Exu SAM_KSR1 SAM_LFY SAM_PNT SAM_Ste50p
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Number in seed:||46|
|Number in full:||26807|
|Average length of the domain:||65.20 aa|
|Average identity of full alignment:||21 %|
|Average coverage of the sequence by the domain:||7.70 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||20|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the SAM_2 domain has been found. There are 308 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.