UniProtKB - P31153 (METK2_HUMAN)
Protein
S-adenosylmethionine synthase isoform type-2
Gene
MAT2A
Organism
Homo sapiens (Human)
Status
Functioni
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.3 Publications
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, impairing MAT2A expression (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). Consequences of N6-methylation of MAT2A are however subject to discussion: According to a report, N6-methylation of MAT2A affects MAT2A mRNA splicing (PubMed:28525753). According to a second report, N6-methylation of MAT2A affects MAT2A mRNA stability (By similarity).By similarity1 Publication
Catalytic activityi
- EC:2.5.1.63 Publications
Cofactori
Protein has several cofactor binding sites:- Mg2+By similarityNote: Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.2 Publications
- K+By similarityNote: Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.1 Publication
: S-adenosyl-L-methionine biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes S-adenosyl-L-methionine from L-methionine.3 PublicationsProteins known to be involved in this subpathway in this organism are:
- Methionine adenosyltransferase 2 subunit beta (MAT2B), Methionine adenosyltransferase 2 subunit beta, S-adenosylmethionine synthase isoform type-1 (MAT1A), S-adenosylmethionine synthase, S-adenosylmethionine synthase, Methionine adenosyltransferase, Methionine adenosyltransferase 2 subunit beta, Methionine adenosyltransferase 2 subunit beta (MAT2B), Methionine adenosyltransferase 2 subunit beta (MAT2B), S-adenosylmethionine synthase isoform type-2 (MAT2A), Methionine adenosyltransferase 2 subunit beta, S-adenosylmethionine synthase (MAT2A)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes S-adenosyl-L-methionine from L-methionine, the pathway S-adenosyl-L-methionine biosynthesis and in Amino-acid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 29 | ATPCombined sources2 Publications | 1 | |
Metal bindingi | 31 | MagnesiumCombined sources2 Publications | 1 | |
Metal bindingi | 57 | PotassiumBy similarity | 1 | |
Binding sitei | 70 | MethionineCombined sources1 Publication | 1 | |
Binding sitei | 113 | Methionine1 Publication | 1 | |
Binding sitei | 258 | ATPCombined sources2 Publications | 1 | |
Binding sitei | 258 | Methionine; shared with neighboring subunitCombined sources2 Publications | 1 | |
Binding sitei | 281 | ATP; via amide nitrogen; shared with neighboring subunitCombined sources1 Publication | 1 | |
Binding sitei | 285 | ATP; shared with neighboring subunitCombined sources2 Publications | 1 | |
Binding sitei | 289 | MethionineBy similarity | 1 | |
Binding sitei | 291 | ATP; shared with neighboring subunitCombined sources2 Publications | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 179 – 181 | ATPCombined sources2 Publications | 3 | |
Nucleotide bindingi | 247 – 250 | ATPCombined sources2 Publications | 4 | |
Nucleotide bindingi | 264 – 265 | ATPCombined sources2 Publications | 2 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- metal ion binding Source: UniProtKB-KW
- methionine adenosyltransferase activity Source: UniProtKB
GO - Biological processi
- cellular response to leukemia inhibitory factor Source: Ensembl
- methylation Source: Reactome
- one-carbon metabolic process Source: UniProtKB-KW
- protein heterooligomerization Source: UniProtKB
- protein hexamerization Source: UniProtKB
- S-adenosylmethionine biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Biological process | One-carbon metabolism |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium |
Enzyme and pathway databases
BioCyci | MetaCyc:HS09847-MONOMER |
BRENDAi | 2.5.1.6, 2681 |
PathwayCommonsi | P31153 |
Reactomei | R-HSA-156581, Methylation |
UniPathwayi | UPA00315;UER00080 |
Names & Taxonomyi
Protein namesi | Recommended name: S-adenosylmethionine synthase isoform type-2 (EC:2.5.1.63 Publications)Short name: AdoMet synthase 2 Alternative name(s): Methionine adenosyltransferase 2 Short name: MAT 21 Publication Methionine adenosyltransferase II Short name: MAT-II |
Gene namesi | Name:MAT2A Synonyms:AMS2, MATA2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000168906.12 |
HGNCi | HGNC:6904, MAT2A |
MIMi | 601468, gene |
neXtProti | NX_P31153 |
Subcellular locationi
Cytosol
- cytosol Source: GO_Central
Other locations
- methionine adenosyltransferase complex Source: UniProtKB
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 4144 |
MalaCardsi | MAT2A |
OpenTargetsi | ENSG00000168906 |
Orphaneti | 91387, Familial thoracic aortic aneurysm and aortic dissection |
PharmGKBi | PA30647 |
Miscellaneous databases
Pharosi | P31153, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3313835 |
DrugBanki | DB00118, Ademetionine DB00134, Methionine |
Polymorphism and mutation databases
BioMutai | MAT2A |
DMDMi | 400245 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000174435 | 1 – 395 | S-adenosylmethionine synthase isoform type-2Add BLAST | 395 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 81 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 114 | PhosphoserineCombined sources | 1 | |
Cross-linki | 228 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 234 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 384 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-234 CPTAC-235 |
EPDi | P31153 |
jPOSTi | P31153 |
MassIVEi | P31153 |
MaxQBi | P31153 |
PaxDbi | P31153 |
PeptideAtlasi | P31153 |
PRIDEi | P31153 |
ProteomicsDBi | 4670 54763 [P31153-1] |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00010157 |
PTM databases
iPTMneti | P31153 |
MetOSitei | P31153 |
PhosphoSitePlusi | P31153 |
SwissPalmi | P31153 |
Expressioni
Tissue specificityi
Detected in kidney.1 Publication
Gene expression databases
Bgeei | ENSG00000168906, Expressed in adenohypophysis and 249 other tissues |
ExpressionAtlasi | P31153, baseline and differential |
Genevisiblei | P31153, HS |
Organism-specific databases
HPAi | ENSG00000168906, Tissue enhanced (pancreas) |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsP31153
With | #Exp. | IntAct |
---|---|---|
MAT1A [Q00266] | 7 | EBI-1050743,EBI-967087 |
itself | 8 | EBI-1050743,EBI-1050743 |
MAT2B [Q9NZL9] | 3 | EBI-1050743,EBI-10317491 |
PRC1 [O43663] | 3 | EBI-1050743,EBI-741137 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 110314, 84 interactors |
CORUMi | P31153 |
IntActi | P31153, 53 interactors |
MINTi | P31153 |
STRINGi | 9606.ENSP00000303147 |
Miscellaneous databases
RNActi | P31153, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P31153 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P31153 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 113 – 125 | Flexible loopBy similarityAdd BLAST | 13 |
Sequence similaritiesi
Belongs to the AdoMet synthase family.Curated
Phylogenomic databases
eggNOGi | KOG1506, Eukaryota |
GeneTreei | ENSGT00950000183185 |
HOGENOMi | CLU_041802_0_1_1 |
InParanoidi | P31153 |
OMAi | MPYLRPD |
PhylomeDBi | P31153 |
TreeFami | TF300511 |
Family and domain databases
HAMAPi | MF_00086, S_AdoMet_synth1, 1 hit |
InterProi | View protein in InterPro IPR022631, ADOMET_SYNTHASE_CS IPR022630, S-AdoMet_synt_C IPR022629, S-AdoMet_synt_central IPR022628, S-AdoMet_synt_N IPR002133, S-AdoMet_synthetase IPR022636, S-AdoMet_synthetase_sfam |
PANTHERi | PTHR11964, PTHR11964, 1 hit |
Pfami | View protein in Pfam PF02773, S-AdoMet_synt_C, 1 hit PF02772, S-AdoMet_synt_M, 1 hit PF00438, S-AdoMet_synt_N, 1 hit |
PIRSFi | PIRSF000497, MAT, 1 hit |
SUPFAMi | SSF55973, SSF55973, 3 hits |
TIGRFAMsi | TIGR01034, metK, 1 hit |
PROSITEi | View protein in PROSITE PS00376, ADOMET_SYNTHASE_1, 1 hit PS00377, ADOMET_SYNTHASE_2, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: P31153-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNGQLNGFHE AFIEEGTFLF TSESVGEGHP DKICDQISDA VLDAHLQQDP
60 70 80 90 100
DAKVACETVA KTGMILLAGE ITSRAAVDYQ KVVREAVKHI GYDDSSKGFD
110 120 130 140 150
YKTCNVLVAL EQQSPDIAQG VHLDRNEEDI GAGDQGLMFG YATDETEECM
160 170 180 190 200
PLTIVLAHKL NAKLAELRRN GTLPWLRPDS KTQVTVQYMQ DRGAVLPIRV
210 220 230 240 250
HTIVISVQHD EEVCLDEMRD ALKEKVIKAV VPAKYLDEDT IYHLQPSGRF
260 270 280 290 300
VIGGPQGDAG LTGRKIIVDT YGGWGAHGGG AFSGKDYTKV DRSAAYAARW
310 320 330 340 350
VAKSLVKGGL CRRVLVQVSY AIGVSHPLSI SIFHYGTSQK SERELLEIVK
360 370 380 390
KNFDLRPGVI VRDLDLKKPI YQRTAAYGHF GRDSFPWEVP KKLKY
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056186 | 1 – 63 | Missing in isoform 2. 1 PublicationAdd BLAST | 63 | |
Alternative sequenceiVSP_056187 | 363 – 395 | Missing in isoform 2. 1 PublicationAdd BLAST | 33 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X68836 mRNA Translation: CAA48726.1 DQ083239 mRNA Translation: AAY85355.1 AK291126 mRNA Translation: BAF83815.1 AK297758 mRNA Translation: BAG60107.1 AK316411 mRNA Translation: BAH14782.1 AC016753 Genomic DNA Translation: AAY24339.1 CH471053 Genomic DNA Translation: EAW99511.1 CH471053 Genomic DNA Translation: EAW99513.1 BC001686 mRNA Translation: AAH01686.1 BC001854 mRNA Translation: AAH01854.1 |
CCDSi | CCDS1977.1 [P31153-1] |
PIRi | S27257 |
RefSeqi | NP_005902.1, NM_005911.5 [P31153-1] |
Genome annotation databases
Ensembli | ENST00000306434; ENSP00000303147; ENSG00000168906 [P31153-1] ENST00000409017; ENSP00000386353; ENSG00000168906 [P31153-2] |
GeneIDi | 4144 |
KEGGi | hsa:4144 |
UCSCi | uc002spr.4, human [P31153-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X68836 mRNA Translation: CAA48726.1 DQ083239 mRNA Translation: AAY85355.1 AK291126 mRNA Translation: BAF83815.1 AK297758 mRNA Translation: BAG60107.1 AK316411 mRNA Translation: BAH14782.1 AC016753 Genomic DNA Translation: AAY24339.1 CH471053 Genomic DNA Translation: EAW99511.1 CH471053 Genomic DNA Translation: EAW99513.1 BC001686 mRNA Translation: AAH01686.1 BC001854 mRNA Translation: AAH01854.1 |
CCDSi | CCDS1977.1 [P31153-1] |
PIRi | S27257 |
RefSeqi | NP_005902.1, NM_005911.5 [P31153-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2P02 | X-ray | 1.21 | A | 1-395 | [»] | |
4KTT | X-ray | 2.59 | A/B/C/D | 1-395 | [»] | |
4KTV | X-ray | 3.30 | A/B/C/D | 1-395 | [»] | |
4NDN | X-ray | 2.34 | A/B/C/D | 1-395 | [»] | |
5A19 | X-ray | 2.34 | A | 1-395 | [»] | |
5A1G | X-ray | 1.83 | A | 1-395 | [»] | |
5A1I | X-ray | 1.09 | A | 1-395 | [»] | |
5UGH | X-ray | 2.06 | A/B/C/D | 1-395 | [»] | |
6FAJ | X-ray | 1.95 | A/B | 1-395 | [»] | |
6FBN | X-ray | 2.70 | A/B | 1-395 | [»] | |
6FBO | X-ray | 1.80 | A | 1-395 | [»] | |
6FBP | X-ray | 1.65 | A/B | 1-395 | [»] | |
6FCB | X-ray | 2.70 | A | 1-395 | [»] | |
6FCD | X-ray | 1.70 | A | 1-395 | [»] | |
6FWB | X-ray | 1.79 | A/B/C/D | 1-394 | [»] | |
6G6R | X-ray | 1.35 | A | 1-395 | [»] | |
6P9V | X-ray | 2.05 | A | 1-395 | [»] | |
SMRi | P31153 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110314, 84 interactors |
CORUMi | P31153 |
IntActi | P31153, 53 interactors |
MINTi | P31153 |
STRINGi | 9606.ENSP00000303147 |
Chemistry databases
ChEMBLi | CHEMBL3313835 |
DrugBanki | DB00118, Ademetionine DB00134, Methionine |
PTM databases
iPTMneti | P31153 |
MetOSitei | P31153 |
PhosphoSitePlusi | P31153 |
SwissPalmi | P31153 |
Polymorphism and mutation databases
BioMutai | MAT2A |
DMDMi | 400245 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00010157 |
Proteomic databases
CPTACi | CPTAC-234 CPTAC-235 |
EPDi | P31153 |
jPOSTi | P31153 |
MassIVEi | P31153 |
MaxQBi | P31153 |
PaxDbi | P31153 |
PeptideAtlasi | P31153 |
PRIDEi | P31153 |
ProteomicsDBi | 4670 54763 [P31153-1] |
Protocols and materials databases
Antibodypediai | 31867, 356 antibodies |
DNASUi | 4144 |
Genome annotation databases
Ensembli | ENST00000306434; ENSP00000303147; ENSG00000168906 [P31153-1] ENST00000409017; ENSP00000386353; ENSG00000168906 [P31153-2] |
GeneIDi | 4144 |
KEGGi | hsa:4144 |
UCSCi | uc002spr.4, human [P31153-1] |
Organism-specific databases
CTDi | 4144 |
DisGeNETi | 4144 |
EuPathDBi | HostDB:ENSG00000168906.12 |
GeneCardsi | MAT2A |
HGNCi | HGNC:6904, MAT2A |
HPAi | ENSG00000168906, Tissue enhanced (pancreas) |
MalaCardsi | MAT2A |
MIMi | 601468, gene |
neXtProti | NX_P31153 |
OpenTargetsi | ENSG00000168906 |
Orphaneti | 91387, Familial thoracic aortic aneurysm and aortic dissection |
PharmGKBi | PA30647 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1506, Eukaryota |
GeneTreei | ENSGT00950000183185 |
HOGENOMi | CLU_041802_0_1_1 |
InParanoidi | P31153 |
OMAi | MPYLRPD |
PhylomeDBi | P31153 |
TreeFami | TF300511 |
Enzyme and pathway databases
UniPathwayi | UPA00315;UER00080 |
BioCyci | MetaCyc:HS09847-MONOMER |
BRENDAi | 2.5.1.6, 2681 |
PathwayCommonsi | P31153 |
Reactomei | R-HSA-156581, Methylation |
Miscellaneous databases
BioGRID-ORCSi | 4144, 726 hits in 847 CRISPR screens |
ChiTaRSi | MAT2A, human |
EvolutionaryTracei | P31153 |
GenomeRNAii | 4144 |
Pharosi | P31153, Tbio |
PROi | PR:P31153 |
RNActi | P31153, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000168906, Expressed in adenohypophysis and 249 other tissues |
ExpressionAtlasi | P31153, baseline and differential |
Genevisiblei | P31153, HS |
Family and domain databases
HAMAPi | MF_00086, S_AdoMet_synth1, 1 hit |
InterProi | View protein in InterPro IPR022631, ADOMET_SYNTHASE_CS IPR022630, S-AdoMet_synt_C IPR022629, S-AdoMet_synt_central IPR022628, S-AdoMet_synt_N IPR002133, S-AdoMet_synthetase IPR022636, S-AdoMet_synthetase_sfam |
PANTHERi | PTHR11964, PTHR11964, 1 hit |
Pfami | View protein in Pfam PF02773, S-AdoMet_synt_C, 1 hit PF02772, S-AdoMet_synt_M, 1 hit PF00438, S-AdoMet_synt_N, 1 hit |
PIRSFi | PIRSF000497, MAT, 1 hit |
SUPFAMi | SSF55973, SSF55973, 3 hits |
TIGRFAMsi | TIGR01034, metK, 1 hit |
PROSITEi | View protein in PROSITE PS00376, ADOMET_SYNTHASE_1, 1 hit PS00377, ADOMET_SYNTHASE_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | METK2_HUMAN | |
Accessioni | P31153Primary (citable) accession number: P31153 Secondary accession number(s): A8K511 Q53SP5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1993 |
Last sequence update: | July 1, 1993 | |
Last modified: | December 2, 2020 | |
This is version 211 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM