Q00266 (METK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Catalytic activity	ATP + L-methionine + H2O = phosphate + diphosphate + S-adenosyl-L-methionine.
Cofactor	Binds 2 divalent ions per subunit. Magnesium or cobalt By similarity. Binds 1 potassium ion per subunit By similarity.
Pathway	Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis; S-adenosyl-L-methionine from L-methionine: step 1/1.
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.
Involvement in disease	Defects in MAT1A are the cause of methionine adenosyltransferase deficiency (MATD) [MIM:250850]; also called MAT I/III deficiency. MATD is 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. Ref.7 Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the AdoMet synthase family.

Ontologies

Keywords
Biological process	One-carbon metabolism
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Cobalt Magnesium Metal-binding Nucleotide-binding Potassium
Molecular function	Transferase
PTM	Disulfide bond S-nitrosylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	S-adenosylmethionine biosynthetic process Inferred from electronic annotation. Source: InterPro methylation Traceable author statement. Source: Reactome xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW methionine adenosyltransferase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 395

395

S-adenosylmethionine synthase isoform type-1

PRO_0000174432

Regions

Nucleotide binding

131 – 136

6

ATP Potential

Sites

Metal binding

31

1

Magnesium By similarity

Metal binding

57

1

Potassium By similarity

Metal binding

283

1

Potassium By similarity

Metal binding

291

1

Magnesium By similarity

Binding site

29

1

Substrate

Binding site

159

1

ATP Potential

Binding site

179

1

Substrate

Binding site

247

1

Substrate

Binding site

249

1

Substrate; via carbonyl oxygen

Binding site

258

1

Substrate

Amino acid modifications

Modified residue

120

1

S-nitrosocysteine By similarity

Disulfide bond

34 ↔ 60

By similarity

Natural variations

Natural variant

38

1

S → N in MATD; abolishes enzyme activity. Ref.10

VAR_031242

Natural variant

55

1

A → D in MATD. Ref.7

VAR_006935

Natural variant

119

1

Q → H.
Corresponds to variant rs1143693 [ dbSNP | Ensembl ].

VAR_028944

Natural variant

199

1

R → C in MATD; retains 11% of wild-type activity. Ref.8

VAR_006936

Natural variant

264

1

R → C in MATD; has virtually no enzymatic activity. Ref.10

VAR_031243

Natural variant

264

1

R → H in MATD; dominant mutation. Ref.9 Ref.10

VAR_006937

Natural variant

305

1

L → P in MATD. Ref.7

VAR_006938

Natural variant

322

1

I → M in MATD; diminishes but do not completely abolishes enzyme activity; 46% of the level of the wild-type enzyme. Ref.7 Ref.10

VAR_006939

Natural variant

336

1

G → R in MATD; retains significant enzymatic activity; 23% of the level of the wild-type enzyme. Ref.10

VAR_031244

Natural variant

344

1

E → A in MATD; diminishes but do not completely abolishes enzyme activity; 12% of the level of the wild-type enzyme. Ref.10

VAR_031245

Natural variant

356

1

R → Q in MATD. Ref.8

VAR_006940

Natural variant

357

1

P → L in MATD. Ref.7

VAR_006941

Natural variant

378

1

G → S in MATD. Ref.8

VAR_006942

Experimental info

Sequence conflict

272 – 273

2

GG → AA in BAA08355. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

395

Helix Strand Turn

Details...

Beta strand

18 – 25

8

Helix

30 – 48

19

Beta strand

53 – 61

9

Beta strand

64 – 72

9

Helix

79 – 90

12

Helix

95 – 97

3

Turn

101 – 103

3

Beta strand

105 – 111

7

Helix

115 – 121

7

Turn

122 – 124

3

Helix

127 – 129

3

Beta strand

132 – 134

3

Beta strand

136 – 143

8

Helix

152 – 170

19

Beta strand

171 – 173

3

Beta strand

176 – 191

16

Beta strand

194 – 209

16

Beta strand

211 – 213

3

Helix

215 – 224

10

Helix

227 – 230

4

Helix

233 – 235

3

Beta strand

241 – 245

5

Helix

254 – 256

3

Turn

266 – 273

8

Helix

290 – 307

18

Beta strand

312 – 320

9

Beta strand

328 – 333

6

Helix

342 – 352

11

Helix

357 – 363

7

Turn

364 – 367

4

Helix

371 – 374

4

Beta strand

375 – 377

3

Beta strand

379 – 381

3

Helix

386 – 388

3

Sequences

	Sequence		Length	Mass (Da)
	Q00266 [UniParc]. Last modified October 1, 1993. Version 2. Checksum: B3462A5670A5B0D4	FASTA	395	43,648
	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

References

	« Hide 'large scale' referencesShow '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: 8393662] [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: 1772450] [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. , 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: 15164054] [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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[6]	"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.
[7]	"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: 7560086] [Abstract] Cited for: VARIANTS MATD ASP-55; PRO-305; MET-322 AND LEU-357.
[8]	"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: 8770875] [Abstract] Cited for: VARIANTS MATD CYS-199; GLN-356 AND SER-378.
[9]	"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: 9042912] [Abstract] Cited for: VARIANT MATD HIS-264.
[10]	"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: 10677294] [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

GeneReviews

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.

IPI

IPI00021772.

PIR

S27363.

RefSeq

NP_000420.1. NM_000429.2.

UniGene

Hs.282670.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2OBV	X-ray	2.05	A	16-395	[»]

ProteinModelPortal

Q00266.

SMR

Q00266. Positions 14-395.

ModBase

Search...

Protein-protein interaction databases

STRING

Q00266.

PTM databases

PhosphoSite

Q00266.

Polymorphism databases

DMDM

417297.

Proteomic databases

PRIDE

Q00266.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372213; ENSP00000361287; ENSG00000151224.

GeneID

4143.

KEGG

hsa:4143.

UCSC

uc001kbw.1. human.

Organism-specific databases

CTD

4143.

GeneCards

GC10M082021.

H-InvDB

HIX0021631.

HGNC

HGNC:6903. MAT1A.

MIM

250850. phenotype.
610550. gene.

neXtProt

NX_Q00266.

Orphanet

168598. Brain demyelination due to methionine adenosyltransferase deficiency.

PharmGKB

PA30646.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17444.

GeneTree

ENSGT00500000044811.

HOGENOM

HBG443662.

HOVERGEN

HBG001562.

InParanoid

Q00266.

OMA

SEFPWEI.

OrthoDB

EOG4QVCC3.

PhylomeDB

Q00266.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q00266.

Bgee

Q00266.

CleanEx

HS_MAT1A.

Genevestigator

Q00266.

GermOnline

ENSG00000151224. Homo sapiens.

Family and domain databases

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.
[Graphical view]

KO

K00789.

PANTHER

PTHR11964. S-AdoMet_synt. 1 hit.

Pfam

PF02773. S-AdoMet_synt_C. 1 hit.
PF02772. S-AdoMet_synt_M. 1 hit.
PF00438. S-AdoMet_synt_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000497. MAT. 1 hit.

SUPFAM

SSF55973. S-AdoMet_synt. 3 hits.

TIGRFAMs

TIGR01034. MetK. 1 hit.

PROSITE

PS00376. ADOMET_SYNTHASE_1. 1 hit.
PS00377. ADOMET_SYNTHASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00134. L-Methionine.
DB00118. S-Adenosylmethionine.

NextBio

16272.

SOURCE

Search...

Entry information

Entry name

METK1_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.