P31153 · METK2_HUMAN
- ProteinS-adenosylmethionine synthase isoform type-2
- GeneMAT2A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids395 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate.
Miscellaneous
Protein expression is regulated by post-transcriptional regulation: in presence of S-adenosyl-L-methionine, METTL16 binds and methylates the first hairpin of the 3'-UTR region of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase (PubMed:28525753, PubMed:29262316, PubMed:33930289).
In S-adenosyl-L-methionine-limiting conditions, METTL16 binds the 3'-UTR region of MAT2A mRNA without methylating it due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753).
In S-adenosyl-L-methionine-limiting conditions, METTL16 binds the 3'-UTR region of MAT2A mRNA without methylating it due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753).
Catalytic activity
- ATP + H2O + L-methionine = diphosphate + phosphate + S-adenosyl-L-methionine
Cofactor
Protein has several cofactor binding sites:
Note: Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.
Note: Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.
Pathway
Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis; S-adenosyl-L-methionine from L-methionine: step 1/1.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 29 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: H | ||||||
Binding site | 31 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 57 | K+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 70 | L-methionine (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: E | ||||||
Binding site | 113 | L-methionine (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: Q | ||||||
Binding site | 179-181 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: DSK | ||||||
Binding site | 247-250 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: SGRF | ||||||
Binding site | 258 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: D | ||||||
Binding site | 258 | L-methionine (UniProtKB | ChEBI); ligand shared between two neighboring subunits | ||||
Sequence: D | ||||||
Binding site | 264-265 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: RK | ||||||
Binding site | 281 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits | ||||
Sequence: A | ||||||
Binding site | 285 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits | ||||
Sequence: K | ||||||
Binding site | 289 | L-methionine (UniProtKB | ChEBI); ligand shared between two neighboring subunits; in other chain | ||||
Sequence: K | ||||||
Binding site | 291 | ATP (UniProtKB | ChEBI); ligand shared between two neighboring subunits | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | methionine adenosyltransferase complex | |
Molecular Function | ATP binding | |
Molecular Function | identical protein binding | |
Molecular Function | metal ion binding | |
Molecular Function | methionine adenosyltransferase activity | |
Molecular Function | small molecule binding | |
Biological Process | cellular response to leukemia inhibitory factor | |
Biological Process | cellular response to methionine | |
Biological Process | one-carbon metabolic process | |
Biological Process | positive regulation of TORC1 signaling | |
Biological Process | protein heterooligomerization | |
Biological Process | protein hexamerization | |
Biological Process | S-adenosylmethionine biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameS-adenosylmethionine synthase isoform type-2
- EC number
- Short namesAdoMet synthase 2
- Alternative names
Gene names
- Community suggested namesMAT2A
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP31153
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 207 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000174435 | 1-395 | UniProt | S-adenosylmethionine synthase isoform type-2 | |||
Sequence: MNGQLNGFHEAFIEEGTFLFTSESVGEGHPDKICDQISDAVLDAHLQQDPDAKVACETVAKTGMILLAGEITSRAAVDYQKVVREAVKHIGYDDSSKGFDYKTCNVLVALEQQSPDIAQGVHLDRNEEDIGAGDQGLMFGYATDETEECMPLTIVLAHKLNAKLAELRRNGTLPWLRPDSKTQVTVQYMQDRGAVLPIRVHTIVISVQHDEEVCLDEMRDALKEKVIKAVVPAKYLDEDTIYHLQPSGRFVIGGPQGDAGLTGRKIIVDTYGGWGAHGGGAFSGKDYTKVDRSAAYAARWVAKSLVKGGLCRRVLVQVSYAIGVSHPLSISIFHYGTSQKSERELLEIVKKNFDLRPGVIVRDLDLKKPIYQRTAAYGHFGRDSFPWEVPKKLKY | |||||||
Modified residue | 81 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 114 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 114 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 228 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 234 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 242 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 384 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 384 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Detected in kidney.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Heterotrimer; composed of a catalytic MAT2A homodimer that binds one regulatory MAT2B chain (PubMed:10644686, PubMed:23189196).
Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain (PubMed:25075345).
Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain (PubMed:25075345).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 113-125 | Flexible loop | ||||
Sequence: QSPDIAQGVHLDR |
Sequence similarities
Belongs to the AdoMet synthase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P31153-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length395
- Mass (Da)43,661
- Last updated1993-07-01 v1
- Checksum2E7D1B91CC4F7BDD
P31153-2
- Name2
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X68836 EMBL· GenBank· DDBJ | CAA48726.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ083239 EMBL· GenBank· DDBJ | AAY85355.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291126 EMBL· GenBank· DDBJ | BAF83815.1 EMBL· GenBank· DDBJ | mRNA | ||
AK297758 EMBL· GenBank· DDBJ | BAG60107.1 EMBL· GenBank· DDBJ | mRNA | ||
AK316411 EMBL· GenBank· DDBJ | BAH14782.1 EMBL· GenBank· DDBJ | mRNA | ||
AC016753 EMBL· GenBank· DDBJ | AAY24339.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAW99511.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAW99513.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001686 EMBL· GenBank· DDBJ | AAH01686.1 EMBL· GenBank· DDBJ | mRNA | ||
BC001854 EMBL· GenBank· DDBJ | AAH01854.1 EMBL· GenBank· DDBJ | mRNA |