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Q00266 (METK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
S-adenosylmethionine synthase isoform type-1

Short name=AdoMet synthase 1
EC=2.5.1.6
Alternative name(s):
Methionine adenosyltransferase 1
Short name=MAT 1
Methionine adenosyltransferase I/III
Short name=MAT-I/III
Gene names
Name:MAT1A
Synonyms:AMS1, MATA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length395 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the formation of S-adenosylmethionine from methionine and ATP. HAMAP-Rule MF_00086

Catalytic activity

ATP + L-methionine + H2O = phosphate + diphosphate + S-adenosyl-L-methionine. HAMAP-Rule MF_00086

Cofactor

Binds 2 divalent ions per subunit. Magnesium or cobalt By similarity.

Binds 1 potassium ion per subunit By similarity. HAMAP-Rule MF_00086

Pathway

Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis; S-adenosyl-L-methionine from L-methionine: step 1/1. HAMAP-Rule MF_00086

Subunit structure

Homotetramer (MAT-I) or homodimer (MAT-III).

Tissue specificity

Expressed in liver.

Post-translational modification

S-nitrosylation of Cys-120 inactivates the enzyme By similarity. HAMAP-Rule MF_00086

Involvement in disease

Methionine adenosyltransferase deficiency (MATD) [MIM:250850]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10 Ref.11

Sequence similarities

Belongs to the AdoMet synthase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 395395S-adenosylmethionine synthase isoform type-1 HAMAP-Rule MF_00086
PRO_0000174432

Regions

Nucleotide binding131 – 1366ATP Potential

Sites

Metal binding311Magnesium By similarity
Metal binding571Potassium By similarity
Metal binding2831Potassium By similarity
Metal binding2911Magnesium By similarity
Binding site291Substrate
Binding site1591ATP Potential
Binding site1791Substrate
Binding site2471Substrate
Binding site2491Substrate; via carbonyl oxygen
Binding site2581Substrate

Amino acid modifications

Modified residue1201S-nitrosocysteine By similarity
Disulfide bond34 ↔ 60 By similarity

Natural variations

Natural variant381S → N in MATD; abolishes enzyme activity. Ref.11
VAR_031242
Natural variant551A → D in MATD. Ref.8
VAR_006935
Natural variant1191Q → H.
Corresponds to variant rs1143693 [ dbSNP | Ensembl ].
VAR_028944
Natural variant1991R → C in MATD; retains 11% of wild-type activity. Ref.9
VAR_006936
Natural variant2641R → C in MATD; has virtually no enzymatic activity. Ref.11
VAR_031243
Natural variant2641R → H in MATD; dominant mutation. Ref.10 Ref.11
VAR_006937
Natural variant3051L → P in MATD. Ref.8
VAR_006938
Natural variant3221I → M in MATD; diminishes but do not completely abolishes enzyme activity; 46% of the level of the wild-type enzyme. Ref.8 Ref.11
VAR_006939
Natural variant3361G → R in MATD; retains significant enzymatic activity; 23% of the level of the wild-type enzyme. Ref.11
VAR_031244
Natural variant3441E → A in MATD; diminishes but do not completely abolishes enzyme activity; 12% of the level of the wild-type enzyme. Ref.11
VAR_031245
Natural variant3561R → Q in MATD. Ref.9
Corresponds to variant rs138742870 [ dbSNP | Ensembl ].
VAR_006940
Natural variant3571P → L in MATD. Ref.8
VAR_006941
Natural variant3781G → S in MATD. Ref.9
VAR_006942

Experimental info

Sequence conflict272 – 2732GG → AA in BAA08355. Ref.2

Secondary structure

................................................................. 395
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q00266 [UniParc].

Last modified October 1, 1993. Version 2.
Checksum: B3462A5670A5B0D4

FASTA39543,648
        10         20         30         40         50         60 
MNGPVDGLCD HSLSEGVFMF TSESVGEGHP DKICDQISDA VLDAHLKQDP NAKVACETVC 

        70         80         90        100        110        120 
KTGMVLLCGE ITSMAMVDYQ RVVRDTIKHI GYDDSAKGFD FKTCNVLVAL EQQSPDIAQC 

       130        140        150        160        170        180 
VHLDRNEEDV GAGDQGLMFG YATDETEECM PLTIILAHKL NARMADLRRS GLLPWLRPDS 

       190        200        210        220        230        240 
KTQVTVQYMQ DNGAVIPVRI HTIVISVQHN EDITLEEMRR ALKEQVIRAV VPAKYLDEDT 

       250        260        270        280        290        300 
VYHLQPSGRF VIGGPQGDAG VTGRKIIVDT YGGWGAHGGG AFSGKDYTKV DRSAAYAARW 

       310        320        330        340        350        360 
VAKSLVKAGL CRRVLVQVSY AIGVAEPLSI SIFTYGTSQK TERELLDVVH KNFDLRPGVI 

       370        380        390 
VRDLDLKKPI YQKTACYGHF GRSEFPWEVP RKLVF 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of a full-length cDNA encoding human liver S-adenosylmethionine synthetase: tissue-specific gene expression and mRNA levels in hepatopathies."
Alvarez L., Corrales F., Mato J.M.
Biochem. J. 293:481-486(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular cloning and nucleotide sequence of cDNA encoding the human liver S-adenosylmethionine synthetase."
Horikawa S., Tsukada K.
Biochem. Int. 25:81-90(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph.
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Crystal structure of the human s-adenosylmethionine synthetase 1 in complex with the product."
Structural genomics consortium (SGC)
Submitted (JUL-2007) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 14-395 IN COMPLEX WITH SUBSTRATE.
[8]"Molecular mechanisms of an inborn error of methionine pathway. Methionine adenosyltransferase deficiency."
Ubagai T., Lei K.-J., Huang S., Mudd S.H., Levy H.L., Chou J.Y.
J. Clin. Invest. 96:1943-1947(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MATD ASP-55; PRO-305; MET-322 AND LEU-357.
[9]"Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency."
Chamberlin M.E., Ubagai T., Mudd S.H., Wilson W.G., Leonard J.V., Chou J.Y.
J. Clin. Invest. 98:1021-1027(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MATD CYS-199; GLN-356 AND SER-378.
[10]"Dominant inheritance of isolated hypermethioninemia is associated with a mutation in the human methionine adenosyltransferase 1A gene."
Chamberlin M.E., Ubagai T., Mudd S.H., Levy H.L., Chou J.Y.
Am. J. Hum. Genet. 60:540-546(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MATD HIS-264.
[11]"Methionine adenosyltransferase I/III deficiency: novel mutations and clinical variations."
Chamberlin M.E., Ubagai T., Mudd S.H., Thomas J., Pao V.Y., Nguyen T.K., Levy H.L., Greene C., Freehauf C., Chou J.Y.
Am. J. Hum. Genet. 66:347-355(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MATD ASN-38; CYS-264; HIS-264; MET-322; ARG-336 AND ALA-344, CHARACTERIZATION OF VARIANTS MATD ASN-38; CYS-264; HIS-264; MET-322; ARG-336 AND ALA-344.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS27363.
RefSeqNP_000420.1. NM_000429.2.
XP_005269899.1. XM_005269842.2.
UniGeneHs.282670.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2OBVX-ray2.05A16-395[»]
ProteinModelPortalQ00266.
SMRQ00266. Positions 14-395.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110313. 4 interactions.
STRING9606.ENSP00000361287.

Chemistry

DrugBankDB00134. L-Methionine.
DB00118. S-Adenosylmethionine.

PTM databases

PhosphoSiteQ00266.

Polymorphism databases

DMDM417297.

Proteomic databases

PaxDbQ00266.
PRIDEQ00266.

Protocols and materials databases

DNASU4143.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372213; ENSP00000361287; ENSG00000151224.
GeneID4143.
KEGGhsa:4143.
UCSCuc001kbw.3. human.

Organism-specific databases

CTD4143.
GeneCardsGC10M082021.
HGNCHGNC:6903. MAT1A.
HPAHPA048627.
MIM250850. phenotype.
610550. gene.
neXtProtNX_Q00266.
Orphanet168598. Brain demyelination due to methionine adenosyltransferase deficiency.
PharmGKBPA30646.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0192.
HOGENOMHOG000245710.
HOVERGENHBG001562.
InParanoidQ00266.
KOK00789.
OMAINPTGRY.
OrthoDBEOG7TF79H.
PhylomeDBQ00266.
TreeFamTF300511.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00315; UER00080.

Gene expression databases

ArrayExpressQ00266.
BgeeQ00266.
CleanExHS_MAT1A.
GenevestigatorQ00266.

Family and domain databases

HAMAPMF_00086. S_AdoMet_synth1.
InterProIPR022631. 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]
PANTHERPTHR11964. PTHR11964. 1 hit.
PfamPF02773. S-AdoMet_synt_C. 1 hit.
PF02772. S-AdoMet_synt_M. 1 hit.
PF00438. S-AdoMet_synt_N. 1 hit.
[Graphical view]
PIRSFPIRSF000497. MAT. 1 hit.
SUPFAMSSF55973. SSF55973. 3 hits.
TIGRFAMsTIGR01034. metK. 1 hit.
PROSITEPS00376. ADOMET_SYNTHASE_1. 1 hit.
PS00377. ADOMET_SYNTHASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ00266.
GenomeRNAi4143.
NextBio16272.
PROQ00266.
SOURCESearch...

Entry information

Entry nameMETK1_HUMAN
AccessionPrimary (citable) accession number: Q00266
Secondary accession number(s): D3DWD5, Q5QP09
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: October 1, 1993
Last modified: April 16, 2014
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM