METK1_MOUSE
ID METK1_MOUSE Reviewed; 396 AA.
AC Q91X83;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=S-adenosylmethionine synthase isoform type-1;
DE Short=AdoMet synthase 1;
DE EC=2.5.1.6 {ECO:0000269|PubMed:8314764};
DE AltName: Full=Methionine adenosyltransferase 1;
DE Short=MAT 1;
GN Name=Mat1a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC TISSUE=Liver;
RX PubMed=8314764; DOI=10.1016/s0021-9258(19)85198-0;
RA Sakata S.F., Shelly L.L., Ruppert S., Schutz G., Chou J.Y.;
RT "Cloning and expression of murine S-adenosylmethionine synthetase.";
RL J. Biol. Chem. 268:13978-13986(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the formation of S-adenosylmethionine from
CC methionine and ATP. The reaction comprises two steps that are both
CC catalyzed by the same enzyme: formation of S-adenosylmethionine
CC (AdoMet) and triphosphate, and subsequent hydrolysis of the
CC triphosphate. {ECO:0000269|PubMed:8314764}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-methionine = diphosphate + phosphate + S-
CC adenosyl-L-methionine; Xref=Rhea:RHEA:21080, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57844, ChEBI:CHEBI:59789; EC=2.5.1.6;
CC Evidence={ECO:0000269|PubMed:8314764};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P13444};
CC Note=Binds 2 magnesium ions per subunit. The magnesium ions interact
CC primarily with the substrate. {ECO:0000250|UniProtKB:P13444};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:P13444};
CC Note=Binds 1 potassium ion per subunit. The potassium ion interacts
CC primarily with the substrate. {ECO:0000250|UniProtKB:P13444};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis;
CC S-adenosyl-L-methionine from L-methionine: step 1/1.
CC {ECO:0000269|PubMed:8314764}.
CC -!- SUBUNIT: Homotetramer (MAT-I); dimer of dimers. Homodimer (MAT-III).
CC {ECO:0000250|UniProtKB:P13444}.
CC -!- PTM: S-nitrosylation of Cys-121 inactivates the enzyme.
CC {ECO:0000250|UniProtKB:P13444}.
CC -!- PTM: An intrachain disulfide bond can be formed. The protein structure
CC shows that the relevant Cys residues are in a position that would
CC permit formation of a disulfide bond. {ECO:0000250|UniProtKB:P13444}.
CC -!- SIMILARITY: Belongs to the AdoMet synthase family. {ECO:0000305}.
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DR EMBL; AK149542; BAE28947.1; -; mRNA.
DR EMBL; AK153832; BAE32202.1; -; mRNA.
DR EMBL; BC011211; AAH11211.1; -; mRNA.
DR CCDS; CCDS26959.1; -.
DR PIR; A47151; A47151.
DR RefSeq; NP_598414.1; NM_133653.3.
DR RefSeq; XP_006518513.1; XM_006518450.2.
DR AlphaFoldDB; Q91X83; -.
DR SMR; Q91X83; -.
DR BioGRID; 198092; 1.
DR ComplexPortal; CPX-3182; Methionine adenosyltransferase complex variant 1.
DR ComplexPortal; CPX-3183; Methionine adenosyltransferase complex variant 3.
DR DIP; DIP-45874N; -.
DR IntAct; Q91X83; 2.
DR STRING; 10090.ENSMUSP00000044288; -.
DR iPTMnet; Q91X83; -.
DR PhosphoSitePlus; Q91X83; -.
DR SwissPalm; Q91X83; -.
DR REPRODUCTION-2DPAGE; Q91X83; -.
DR jPOST; Q91X83; -.
DR MaxQB; Q91X83; -.
DR PaxDb; Q91X83; -.
DR PeptideAtlas; Q91X83; -.
DR PRIDE; Q91X83; -.
DR ProteomicsDB; 295725; -.
DR Antibodypedia; 29977; 259 antibodies from 33 providers.
DR DNASU; 11720; -.
DR Ensembl; ENSMUST00000047286; ENSMUSP00000044288; ENSMUSG00000037798.
DR Ensembl; ENSMUST00000225720; ENSMUSP00000153488; ENSMUSG00000037798.
DR GeneID; 11720; -.
DR KEGG; mmu:11720; -.
DR UCSC; uc007tcm.2; mouse.
DR CTD; 4143; -.
DR MGI; MGI:88017; Mat1a.
DR VEuPathDB; HostDB:ENSMUSG00000037798; -.
DR eggNOG; KOG1506; Eukaryota.
DR GeneTree; ENSGT00950000183185; -.
DR HOGENOM; CLU_041802_0_1_1; -.
DR InParanoid; Q91X83; -.
DR OMA; INPTGRY; -.
DR OrthoDB; 685006at2759; -.
DR PhylomeDB; Q91X83; -.
DR TreeFam; TF300511; -.
DR BRENDA; 2.5.1.6; 3474.
DR Reactome; R-MMU-156581; Methylation.
DR Reactome; R-MMU-1614635; Sulfur amino acid metabolism.
DR Reactome; R-MMU-2408508; Metabolism of ingested SeMet, Sec, MeSec into H2Se.
DR UniPathway; UPA00315; UER00080.
DR BioGRID-ORCS; 11720; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q91X83; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q91X83; protein.
DR Bgee; ENSMUSG00000037798; Expressed in left lobe of liver and 52 other tissues.
DR ExpressionAtlas; Q91X83; baseline and differential.
DR Genevisible; Q91X83; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0048269; C:methionine adenosyltransferase complex; ISO:MGI.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0043531; F:ADP binding; ISO:MGI.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0004478; F:methionine adenosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0009087; P:methionine catabolic process; ISS:UniProtKB.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051289; P:protein homotetramerization; ISO:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; ISS:UniProtKB.
DR HAMAP; MF_00086; S_AdoMet_synth1; 1.
DR InterPro; IPR022631; ADOMET_SYNTHASE_CS.
DR InterPro; IPR022630; S-AdoMet_synt_C.
DR InterPro; IPR022629; S-AdoMet_synt_central.
DR InterPro; IPR022628; S-AdoMet_synt_N.
DR InterPro; IPR002133; S-AdoMet_synthetase.
DR InterPro; IPR022636; S-AdoMet_synthetase_sfam.
DR PANTHER; PTHR11964; PTHR11964; 1.
DR Pfam; PF02773; S-AdoMet_synt_C; 1.
DR Pfam; PF02772; S-AdoMet_synt_M; 1.
DR Pfam; PF00438; S-AdoMet_synt_N; 1.
DR PIRSF; PIRSF000497; MAT; 1.
DR SUPFAM; SSF55973; SSF55973; 3.
DR TIGRFAMs; TIGR01034; metK; 1.
DR PROSITE; PS00376; ADOMET_SYNTHASE_1; 1.
DR PROSITE; PS00377; ADOMET_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Disulfide bond; Magnesium; Metal-binding; Nucleotide-binding;
KW One-carbon metabolism; Potassium; Reference proteome; S-nitrosylation;
KW Transferase.
FT CHAIN 1..396
FT /note="S-adenosylmethionine synthase isoform type-1"
FT /id="PRO_0000174433"
FT REGION 114..126
FT /note="Flexible loop"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 24
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P13444"
FT BINDING 30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P13444"
FT BINDING 58
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 71
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 114
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 180..182
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q00266"
FT BINDING 248..251
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q00266"
FT BINDING 259
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P13444"
FT BINDING 259
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 265..266
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P13444"
FT BINDING 286
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P13444"
FT BINDING 290
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P13444"
FT BINDING 290
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT MOD_RES 121
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P13444"
FT DISULFID 35..61
FT /evidence="ECO:0000250|UniProtKB:P13444"
SQ SEQUENCE 396 AA; 43509 MW; AAA593A669551EB8 CRC64;
MNGPVDGLCD HSLSEEGAFM FTSESVGEGH PDKICDQISD AVLDAHLKQD PNAKVACETV
CKTGMVLLCG EITSVAMVDY QRVVRDTIKH IGYDDSAKGF DFKTCNVLVA LEQQSPDIAQ
CVHLDRNEED VGAGDQGLMF GYATDETEEC MPLTIVLAHK LNTRIADLRR SGVLPWLRPD
SKTQVTVQYM QDNGAVIPVR IHTIVISVQH NEDITLEAMQ EALKEQVIKA VVPAKYLDED
TVYHLQPSGR FVIGGPQGDA GVTGRKIIVD TYGGWGAHGG GAFSGKDYTK VDRSAAYAAR
WVAKSLVKAG LCRRVLVQVS YAIGVAEPLS ISIFTYGTSN KTERELLEVV NKNFDLRPGV
IVRDLDLKKP IYQKTACYGH FGRSEFPWEV PKKLVF
