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71  structures 310  species 2  interactions 6213  sequences 406  architectures

Family: SAM_1 (PF00536)

Summary: SAM domain (Sterile alpha motif)

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Sterile alpha motif Edit Wikipedia article

SAM domain (Sterile alpha motif)
Identifiers
Symbol SAM_1
Pfam PF00536
InterPro IPR001660
SMART SAM
SCOP 1b0x
SUPERFAMILY 1b0x
CDD cd09487
Ste50p-SAM
PDB 1uqv EBI.jpg
SAM domain from fungal protein Ste50p
Identifiers
Symbol Ste50p-SAM
Pfam PF09235
Pfam clan CL0003
InterPro IPR015316
SCOP 1uqv
SUPERFAMILY 1uqv

In molecular biology, the protein domain Sterile alpha motif (or SAM) is a putative protein interaction module present in a wide variety of proteins[1] involved in many biological processes. The SAM domain that spreads over around 70 residues is found in diverse eukaryotic organisms.[2] 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,[3] nevertheless with a low affinity constant.[4]

SAM domains also appear to possess the ability to bind RNA.[5] 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.[3] 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.[4]

Fungal SAM[edit]

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 [6] in fungi.

Function[edit]

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.[7]

Structure[edit]

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.[7]

Protein interaction[edit]

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.[7] There is significant evidence for Ste50p oligomerization in vivo.[8]

Human proteins containing this domain[edit]

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;

References[edit]

  1. ^ Bork P, Ponting CP, Hofmann K, Schultz J (1997). "SAM as a protein interaction domain involved in developmental regulation". Protein Sci. 6 (1): 249–253. doi:10.1002/pro.5560060128. PMC 2143507. PMID 9007998. 
  2. ^ 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): 44–49. doi:10.1038/4917. PMID 9886291. 
  3. ^ a b 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): 6683–6692. PMC 232522. PMID 9343432. 
  4. ^ a b Goodwill KE, Thanos CD, Bowie JU (1999). "Oligomeric structure of the human EphB2 receptor SAM domain". Science 283 (5403): 833–836. doi:10.1126/science.283.5403.833. PMID 9933164. 
  5. ^ Bowie JU, Kim CA (2003). "SAM domains: uniform structure, diversity of function". Trends Biochem. Sci. 28 (12): 625–628. doi:10.1016/j.tibs.2003.11.001. PMID 14659692. 
  6. ^ 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): 5788–5796. PMC 109165. PMID 9742096.  edit
  7. ^ a b c 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): 2192–201. doi:10.1074/jbc.M305605200. PMID 14573615. 
  8. ^ 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: e1931. doi:10.1371/journal.pone.0001931. PMID 18431466. 

This article incorporates text from the public domain Pfam and InterPro IPR001660

Structural evolution of p53, p63, and p73: Implication for heterotetramer formation

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SAM domain (Sterile alpha motif) Provide feedback

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.

Literature references

  1. Ponting CP; , Protein Sci 1995;4:1928-1930.: SAM: a novel motif in yeast sterile and Drosophila polyhomeotic proteins. PUBMED:8528090 EPMC:8528090

  2. Schultz J, Ponting CP, Hofmann K, Bork P; , Protein Sci 1997;6:249-253.: SAM as a protein interaction domain involved in developmental regulation. PUBMED:9007998 EPMC:9007998

  3. 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

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR021129

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 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 [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].

This entry represents type 1 SAM domains.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan SAM (CL0003), which has the following description:

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 [3] . 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) [3]. 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 5 members:

KSR1-SAM SAM_1 SAM_2 SAM_PNT Ste50p-SAM

Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(65)
Full
(6213)
Representative proteomes NCBI
(7526)
Meta
(101)
RP15
(782)
RP35
(1136)
RP55
(2102)
RP75
(3366)
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  Seed
(65)
Full
(6213)
Representative proteomes NCBI
(7526)
Meta
(101)
RP15
(782)
RP35
(1136)
RP55
(2102)
RP75
(3366)
Alignment:
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  Seed
(65)
Full
(6213)
Representative proteomes NCBI
(7526)
Meta
(101)
RP15
(782)
RP35
(1136)
RP55
(2102)
RP75
(3366)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Trees

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

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Curation View help on the curation process

Seed source: [1],[2]
Previous IDs: SAM_1;
Type: Domain
Author: Bateman A
Number in seed: 65
Number in full: 6213
Average length of the domain: 63.10 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 9.07 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 64
Family (HMM) version: 25
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

SAM_1 SAM_2

Structures

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_1 domain has been found. There are 71 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 seqence.

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