Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

S-adenosylmethionine synthase isoform type-1

Gene

MAT1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.1 Publication

Catalytic activityi

ATP + L-methionine + H2O = phosphate + diphosphate + S-adenosyl-L-methionine.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarityNote: Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.By similarity
  • K+By similarityNote: Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.By similarity

Pathwayi: S-adenosyl-L-methionine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes S-adenosyl-L-methionine from L-methionine.1 Publication
Proteins known to be involved in this subpathway in this organism are:
  1. Methionine adenosyltransferase 2 subunit beta (MAT2B), S-adenosylmethionine synthase isoform type-1 (MAT1A), S-adenosylmethionine synthase, S-adenosylmethionine synthase, S-adenosylmethionine synthase isoform type-2 (MAT2A), S-adenosylmethionine synthase (MAT2A)
This subpathway is part of the pathway S-adenosyl-L-methionine biosynthesis, which is itself part of Amino-acid biosynthesis.
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 keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi23MagnesiumBy similarity1
Binding sitei29ATPCombined sources1 Publication1
Metal bindingi57PotassiumBy similarity1
Binding sitei70MethionineBy similarity1
Binding sitei113MethionineBy similarity1
Binding sitei258ATPCombined sources1 Publication1
Binding sitei258Methionine; shared with neighboring subunitBy similarity1
Binding sitei281ATP; via amide nitrogen; shared with neighboring subunitBy similarity1
Binding sitei285ATP; shared with neighboring subunitBy similarity1
Binding sitei289ATP; shared with neighboring subunitBy similarity1
Binding sitei289MethionineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi179 – 181ATPCombined sources1 Publication3
Nucleotide bindingi247 – 250ATPCombined sources1 Publication4
Nucleotide bindingi264 – 265ATPBy similarity2

GO - Molecular functioni

GO - Biological processi

  • methionine catabolic process Source: UniProtKB
  • methylation Source: Reactome
  • one-carbon metabolic process Source: UniProtKB-KW
  • protein homotetramerization Source: UniProtKB
  • S-adenosylmethionine biosynthetic process Source: UniProtKB
  • selenium compound metabolic process Source: Reactome
  • sulfur amino acid metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

One-carbon metabolism

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium

Enzyme and pathway databases

BioCyciZFISH:HS07715-MONOMER.
ReactomeiR-HSA-156581. Methylation.
R-HSA-1614635. Sulfur amino acid metabolism.
R-HSA-2408508. Metabolism of ingested SeMet, Sec, MeSec into H2Se.
UniPathwayiUPA00315; UER00080.

Names & Taxonomyi

Protein namesi
Recommended name:
S-adenosylmethionine synthase isoform type-1 (EC:2.5.1.61 Publication)
Short name:
AdoMet synthase 1
Alternative name(s):
Methionine adenosyltransferase 1
Short name:
MAT 1
Methionine adenosyltransferase I/III
Short name:
MAT-I/III
Gene namesi
Name:MAT1A
Synonyms:AMS1, MATA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:6903. MAT1A.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Methionine adenosyltransferase deficiency (MATD)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some neurologic symptoms may be present in rare cases with severe loss of methionine adenosyltransferase activity.
See also OMIM:250850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03124238S → N in MATD; abolishes enzyme activity. 1 Publication1
Natural variantiVAR_00693555A → D in MATD. 1 PublicationCorresponds to variant rs118204002dbSNPEnsembl.1
Natural variantiVAR_006936199R → C in MATD; retains 11% of wild-type activity. 1 PublicationCorresponds to variant rs773267230dbSNPEnsembl.1
Natural variantiVAR_031243264R → C in MATD; has virtually no enzymatic activity. 1 PublicationCorresponds to variant rs118204005dbSNPEnsembl.1
Natural variantiVAR_006937264R → H in MATD; dominant mutation. 2 PublicationsCorresponds to variant rs72558181dbSNPEnsembl.1
Natural variantiVAR_006938305L → P in MATD. 1 PublicationCorresponds to variant rs118204004dbSNPEnsembl.1
Natural variantiVAR_006939322I → M in MATD; diminishes but do not completely abolishes enzyme activity; 46% of the level of the wild-type enzyme. 2 PublicationsCorresponds to variant rs118204001dbSNPEnsembl.1
Natural variantiVAR_031244336G → R in MATD; retains significant enzymatic activity; 23% of the level of the wild-type enzyme. 1 PublicationCorresponds to variant rs118204006dbSNPEnsembl.1
Natural variantiVAR_031245344E → A in MATD; diminishes but do not completely abolishes enzyme activity; 12% of the level of the wild-type enzyme. 1 Publication1
Natural variantiVAR_006940356R → Q in MATD. 1 PublicationCorresponds to variant rs138742870dbSNPEnsembl.1
Natural variantiVAR_006941357P → L in MATD. 1 PublicationCorresponds to variant rs118204003dbSNPEnsembl.1
Natural variantiVAR_006942378G → S in MATD. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4143.
MalaCardsiMAT1A.
MIMi250850. phenotype.
OpenTargetsiENSG00000151224.
Orphaneti168598. Brain demyelination due to methionine adenosyltransferase deficiency.
PharmGKBiPA30646.

Chemistry databases

DrugBankiDB00134. L-Methionine.
DB00118. S-Adenosylmethionine.

Polymorphism and mutation databases

BioMutaiMAT1A.
DMDMi417297.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001744321 – 395S-adenosylmethionine synthase isoform type-1Add BLAST395

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 60By similarity
Modified residuei120S-nitrosocysteineBy similarity1

Post-translational modificationi

S-nitrosylation of Cys-120 inactivates the enzyme.By similarity
An intrachain disulfide bond can be formed. The protein structure shows that the relevant Cys residues are in a position that would permit formation of a disulfide bond.By similarity

Keywords - PTMi

Disulfide bond, S-nitrosylation

Proteomic databases

EPDiQ00266.
MaxQBiQ00266.
PaxDbiQ00266.
PeptideAtlasiQ00266.
PRIDEiQ00266.

PTM databases

iPTMnetiQ00266.
PhosphoSitePlusiQ00266.

Expressioni

Tissue specificityi

Expressed in liver.1 Publication

Gene expression databases

BgeeiENSG00000151224.
CleanExiHS_MAT1A.
ExpressionAtlasiQ00266. baseline and differential.
GenevisibleiQ00266. HS.

Organism-specific databases

HPAiHPA048627.

Interactioni

Subunit structurei

Homotetramer (MAT-I); dimer of dimers (PubMed:23425511). Homodimer (MAT-III) (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MAT2AP311534EBI-967087,EBI-1050743

Protein-protein interaction databases

BioGridi110313. 12 interactors.
IntActiQ00266. 1 interactor.
STRINGi9606.ENSP00000361280.

Structurei

Secondary structure

1395
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi18 – 25Combined sources8
Helixi30 – 48Combined sources19
Beta strandi53 – 61Combined sources9
Beta strandi64 – 72Combined sources9
Helixi79 – 90Combined sources12
Helixi95 – 97Combined sources3
Turni101 – 103Combined sources3
Beta strandi105 – 111Combined sources7
Helixi115 – 121Combined sources7
Turni122 – 124Combined sources3
Helixi127 – 129Combined sources3
Beta strandi132 – 134Combined sources3
Beta strandi136 – 143Combined sources8
Helixi152 – 170Combined sources19
Beta strandi171 – 173Combined sources3
Beta strandi176 – 191Combined sources16
Beta strandi194 – 209Combined sources16
Beta strandi211 – 213Combined sources3
Helixi215 – 224Combined sources10
Helixi227 – 230Combined sources4
Helixi233 – 235Combined sources3
Beta strandi241 – 245Combined sources5
Helixi254 – 256Combined sources3
Turni266 – 273Combined sources8
Helixi290 – 307Combined sources18
Beta strandi312 – 320Combined sources9
Beta strandi328 – 333Combined sources6
Helixi342 – 352Combined sources11
Helixi357 – 363Combined sources7
Turni364 – 367Combined sources4
Helixi371 – 374Combined sources4
Beta strandi375 – 377Combined sources3
Beta strandi379 – 381Combined sources3
Helixi386 – 388Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OBVX-ray2.05A16-395[»]
ProteinModelPortaliQ00266.
SMRiQ00266.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00266.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni113 – 125Flexible loopBy similarityAdd BLAST13

Sequence similaritiesi

Belongs to the AdoMet synthase family.Curated

Phylogenomic databases

eggNOGiKOG1506. Eukaryota.
COG0192. LUCA.
GeneTreeiENSGT00500000044811.
HOGENOMiHOG000245710.
HOVERGENiHBG001562.
InParanoidiQ00266.
KOiK00789.
OMAiIQDNGAV.
OrthoDBiEOG091G08Z2.
PhylomeDBiQ00266.
TreeFamiTF300511.

Family and domain databases

HAMAPiMF_00086. S_AdoMet_synth1. 1 hit.
InterProiIPR022631. 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.
[Graphical view]
PANTHERiPTHR11964. PTHR11964. 1 hit.
PfamiPF02773. S-AdoMet_synt_C. 1 hit.
PF02772. S-AdoMet_synt_M. 1 hit.
PF00438. S-AdoMet_synt_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000497. MAT. 1 hit.
SUPFAMiSSF55973. SSF55973. 3 hits.
TIGRFAMsiTIGR01034. metK. 1 hit.
PROSITEiPS00376. ADOMET_SYNTHASE_1. 1 hit.
PS00377. ADOMET_SYNTHASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q00266-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNGPVDGLCD HSLSEGVFMF TSESVGEGHP DKICDQISDA VLDAHLKQDP
60 70 80 90 100
NAKVACETVC KTGMVLLCGE ITSMAMVDYQ RVVRDTIKHI GYDDSAKGFD
110 120 130 140 150
FKTCNVLVAL EQQSPDIAQC VHLDRNEEDV GAGDQGLMFG YATDETEECM
160 170 180 190 200
PLTIILAHKL NARMADLRRS GLLPWLRPDS KTQVTVQYMQ DNGAVIPVRI
210 220 230 240 250
HTIVISVQHN EDITLEEMRR ALKEQVIRAV VPAKYLDEDT VYHLQPSGRF
260 270 280 290 300
VIGGPQGDAG VTGRKIIVDT YGGWGAHGGG AFSGKDYTKV DRSAAYAARW
310 320 330 340 350
VAKSLVKAGL CRRVLVQVSY AIGVAEPLSI SIFTYGTSQK TERELLDVVH
360 370 380 390
KNFDLRPGVI VRDLDLKKPI YQKTACYGHF GRSEFPWEVP RKLVF
Length:395
Mass (Da):43,648
Last modified:October 1, 1993 - v2
Checksum:iB3462A5670A5B0D4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti272 – 273GG → AA in BAA08355 (PubMed:1772450).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03124238S → N in MATD; abolishes enzyme activity. 1 Publication1
Natural variantiVAR_00693555A → D in MATD. 1 PublicationCorresponds to variant rs118204002dbSNPEnsembl.1
Natural variantiVAR_028944119Q → H.Corresponds to variant rs1143693dbSNPEnsembl.1
Natural variantiVAR_006936199R → C in MATD; retains 11% of wild-type activity. 1 PublicationCorresponds to variant rs773267230dbSNPEnsembl.1
Natural variantiVAR_031243264R → C in MATD; has virtually no enzymatic activity. 1 PublicationCorresponds to variant rs118204005dbSNPEnsembl.1
Natural variantiVAR_006937264R → H in MATD; dominant mutation. 2 PublicationsCorresponds to variant rs72558181dbSNPEnsembl.1
Natural variantiVAR_006938305L → P in MATD. 1 PublicationCorresponds to variant rs118204004dbSNPEnsembl.1
Natural variantiVAR_006939322I → M in MATD; diminishes but do not completely abolishes enzyme activity; 46% of the level of the wild-type enzyme. 2 PublicationsCorresponds to variant rs118204001dbSNPEnsembl.1
Natural variantiVAR_031244336G → R in MATD; retains significant enzymatic activity; 23% of the level of the wild-type enzyme. 1 PublicationCorresponds to variant rs118204006dbSNPEnsembl.1
Natural variantiVAR_031245344E → A in MATD; diminishes but do not completely abolishes enzyme activity; 12% of the level of the wild-type enzyme. 1 Publication1
Natural variantiVAR_006940356R → Q in MATD. 1 PublicationCorresponds to variant rs138742870dbSNPEnsembl.1
Natural variantiVAR_006941357P → L in MATD. 1 PublicationCorresponds to variant rs118204003dbSNPEnsembl.1
Natural variantiVAR_006942378G → S in MATD. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49357 mRNA. Translation: BAA08355.1.
X69078 mRNA. Translation: CAA48822.1.
AL359195 Genomic DNA. Translation: CAI13695.1.
CH471142 Genomic DNA. Translation: EAW80396.1.
CH471142 Genomic DNA. Translation: EAW80397.1.
BC018359 mRNA. Translation: AAH18359.1.
CCDSiCCDS7365.1.
PIRiS27363.
RefSeqiNP_000420.1. NM_000429.2.
XP_005269899.1. XM_005269842.4.
UniGeneiHs.282670.

Genome annotation databases

EnsembliENST00000372213; ENSP00000361287; ENSG00000151224.
GeneIDi4143.
KEGGihsa:4143.
UCSCiuc001kbw.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49357 mRNA. Translation: BAA08355.1.
X69078 mRNA. Translation: CAA48822.1.
AL359195 Genomic DNA. Translation: CAI13695.1.
CH471142 Genomic DNA. Translation: EAW80396.1.
CH471142 Genomic DNA. Translation: EAW80397.1.
BC018359 mRNA. Translation: AAH18359.1.
CCDSiCCDS7365.1.
PIRiS27363.
RefSeqiNP_000420.1. NM_000429.2.
XP_005269899.1. XM_005269842.4.
UniGeneiHs.282670.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OBVX-ray2.05A16-395[»]
ProteinModelPortaliQ00266.
SMRiQ00266.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110313. 12 interactors.
IntActiQ00266. 1 interactor.
STRINGi9606.ENSP00000361280.

Chemistry databases

DrugBankiDB00134. L-Methionine.
DB00118. S-Adenosylmethionine.

PTM databases

iPTMnetiQ00266.
PhosphoSitePlusiQ00266.

Polymorphism and mutation databases

BioMutaiMAT1A.
DMDMi417297.

Proteomic databases

EPDiQ00266.
MaxQBiQ00266.
PaxDbiQ00266.
PeptideAtlasiQ00266.
PRIDEiQ00266.

Protocols and materials databases

DNASUi4143.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372213; ENSP00000361287; ENSG00000151224.
GeneIDi4143.
KEGGihsa:4143.
UCSCiuc001kbw.4. human.

Organism-specific databases

CTDi4143.
DisGeNETi4143.
GeneCardsiMAT1A.
HGNCiHGNC:6903. MAT1A.
HPAiHPA048627.
MalaCardsiMAT1A.
MIMi250850. phenotype.
610550. gene.
neXtProtiNX_Q00266.
OpenTargetsiENSG00000151224.
Orphaneti168598. Brain demyelination due to methionine adenosyltransferase deficiency.
PharmGKBiPA30646.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1506. Eukaryota.
COG0192. LUCA.
GeneTreeiENSGT00500000044811.
HOGENOMiHOG000245710.
HOVERGENiHBG001562.
InParanoidiQ00266.
KOiK00789.
OMAiIQDNGAV.
OrthoDBiEOG091G08Z2.
PhylomeDBiQ00266.
TreeFamiTF300511.

Enzyme and pathway databases

UniPathwayiUPA00315; UER00080.
BioCyciZFISH:HS07715-MONOMER.
ReactomeiR-HSA-156581. Methylation.
R-HSA-1614635. Sulfur amino acid metabolism.
R-HSA-2408508. Metabolism of ingested SeMet, Sec, MeSec into H2Se.

Miscellaneous databases

EvolutionaryTraceiQ00266.
GenomeRNAii4143.
PROiQ00266.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151224.
CleanExiHS_MAT1A.
ExpressionAtlasiQ00266. baseline and differential.
GenevisibleiQ00266. HS.

Family and domain databases

HAMAPiMF_00086. S_AdoMet_synth1. 1 hit.
InterProiIPR022631. 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.
[Graphical view]
PANTHERiPTHR11964. PTHR11964. 1 hit.
PfamiPF02773. S-AdoMet_synt_C. 1 hit.
PF02772. S-AdoMet_synt_M. 1 hit.
PF00438. S-AdoMet_synt_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000497. MAT. 1 hit.
SUPFAMiSSF55973. SSF55973. 3 hits.
TIGRFAMsiTIGR01034. metK. 1 hit.
PROSITEiPS00376. ADOMET_SYNTHASE_1. 1 hit.
PS00377. ADOMET_SYNTHASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMETK1_HUMAN
AccessioniPrimary (citable) accession number: Q00266
Secondary accession number(s): D3DWD5, Q5QP09
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: October 1, 1993
Last modified: November 30, 2016
This is version 182 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.