molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

, the

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of ...

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 Smaug () is a dragon and the main antagonist in J. R. R. Tolkien's 1937 novel ''The Hobbit'', his treasure and the mountain he lives in being the goal of the quest. Powerful and fearsome, he invaded the Dwarf kingdom of Erebor 150 years prior ...

, a protein that helps to establish a

morphogen A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various ...

gradient in ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'' embryos by repressing the translation of nanos (nos) mRNA, binds to the

3' untranslated region In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...

(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 Ephrin type-B receptor 2 is a protein that in humans is encoded by the ''EPHB2'' gene. Function Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their stru ...

, 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.

Fungal SAM

, the

Ste50p mainly in

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

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.

Function

The protein domain Ste50p has a role in detecting

pheromones A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

for

mating In biology, mating is the pairing of either opposite- sex or hermaphroditic organisms for the purposes of sexual reproduction. ''Fertilization'' is the fusion of two gametes. ''Copulation'' is the union of the sex organs of two sexually reprod ...

. 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 Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

starvation.

Structure

The

fungal A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...

Ste50p SAM consists of six

helices A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined 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 Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

Protein interaction

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 CNKSR family member 3 is a protein that in humans is encoded by the CNKSR3 gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''bi ...

; DDHD2;

EPHA1 EPH receptor A1 (ephrin type-A receptor 1) is a protein that in humans is encoded by the ''EPHA1'' gene. This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated ...

; EPHA10;

EPHA2 EPH receptor A2 (ephrin type-A receptor 2) is a protein that in humans is encoded by the ''EPHA2'' gene. Function This gene belongs to the ephrin receptor subfamily of the protein- tyrosine kinase family. EPH and EPH-related receptors have be ...

;

EPHA5 EPH receptor A5 (ephrin type-A receptor 5) is a protein that in humans is encoded by the ''EPHA5'' gene. This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicate ...

;

EPHA6 Ephrin type-A receptor 6 is a protein that in humans is encoded by the ''EPHA6'' gene. EphA6 may serve an important role in breast carcinogenesis and may pose as a novel prognostic indicator and therapeutic target for breast cancer Breast ...

;

EPHA7 Ephrin type-A receptor 7 is a protein that in humans is encoded by the ''EPHA7'' gene. This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating devel ...

; EPHA8; EPHB1;

;

EPHB3 Ephrin type-B receptor 3 is a protein that in humans is encoded by the ''EPHB3'' gene. Function Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their struct ...

;

EPHB4 Ephrin type-B receptor 4 is a protein that in humans is encoded by the ''EPHB4'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...

; FAM59A; HPH2;

INPPL1 SH2-domain containing Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 is an enzyme that in humans is encoded by the ''INPPL1'' gene. INPPL1 encodes inositol polyphosphate-5 phosphatase-like 1, a protein that in addition to the phosphatase ...

; L3MBTL3;

PHC1 Polyhomeotic-like protein 1 is a protein that in humans is encoded by the ''PHC1'' gene. Function This gene is a homolog of the ''Drosophila'' polyhomeotic gene, which is a member of the Polycomb group of genes. The gene product is a component ...

;

PHC2 Polyhomeotic-like protein 2 is a protein that in humans is encoded by the ''PHC2'' gene. Function In Drosophila melanogaster, the 'Polycomb' group (PcG) of genes are part of a cellular memory system that is responsible for the stable inheritan ...

; PHC3; PPFIA1; PPFIA2; PPFIA3;

PPFIA4 Liprin-alpha-4 is a protein that in humans is encoded by the ''PPFIA4'' gene. Interactions PPFIA4 has been shown to Protein-protein interaction, interact with: * ERC2 (gene), ERC2, * GIT1, and * Nuclear receptor coactivator 2. References ...

; PPFIBP1; PPFIBP2; SAMD1; SAMD13; SAMD14; SAMD3; SAMD4A; SAMD4B; SAMD5; SAMD7; SAMD8; SAMD9;

SARM1 Sterile alpha and TIR motif containing 1 Is an enzyme that in humans is encoded by the ''SARM1'' gene. It is the most evolutionarily conserved member of the Toll/Interleukin receptor-1 (TIR) family. SARM1's TIR domain has intrinsic NADase enzym ...

; SCMH1; SCML1; SCML2; SEC23IP; SGMS1;

SHANK1 SH3 and multiple ankyrin repeat domains protein 1 is a protein that in humans is encoded by the ''SHANK1'' gene. Interactions SHANK1 has been shown to interact with: * ARHGEF7, * BAIAP2, * DNM2, * SPTAN1 Alpha II-spectrin, also known as S ...

;

SHANK2 SH3 and multiple ankyrin repeat domains protein 2 is a protein that in humans is encoded by the ''SHANK2'' gene. Two alternative splice variants, encoding distinct isoforms, are reported. Additional splice variants exist but their full-length natur ...

;

SHANK3 SH3 and multiple ankyrin repeat domains 3 (Shank3), also known as proline-rich synapse-associated protein 2 (ProSAP2), is a protein that in humans is encoded by the ''SHANK3'' gene on chromosome 22. Additional isoforms have been described for thi ...

; STARD13; UBP1; USH1G; ZCCHC14; p63; p73;

References

{{InterPro content, IPR001660
Structural evolution of p53, p63, and p73: Implication for heterotetramer formation
Protein domains Protein structural motifs