METK1_RAT
ID METK1_RAT Reviewed; 397 AA.
AC P13444; Q5FVU2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=S-adenosylmethionine synthase isoform type-1;
DE Short=AdoMet synthase 1;
DE EC=2.5.1.6 {ECO:0000269|PubMed:10873471, ECO:0000269|PubMed:1517209, ECO:0000269|PubMed:9755242};
DE AltName: Full=Methionine adenosyltransferase 1;
DE Short=MAT 1;
DE AltName: Full=Methionine adenosyltransferase I/III;
DE Short=MAT-I/III;
GN Name=Mat1a; Synonyms=Ams1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=2806235; DOI=10.1111/j.1432-1033.1989.tb15042.x;
RA Horikawa S., Ishikawa M., Ozasa H., Tsukada K.;
RT "Isolation of a cDNA encoding the rat liver S-adenosylmethionine
RT synthetase.";
RL Eur. J. Biochem. 184:497-501(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1915866; DOI=10.1016/0014-5793(91)81245-4;
RA Alvarez L., Asuncion M., Corrales F., Pajares M.A., Mato J.M.;
RT "Analysis of the 5' non-coding region of rat liver S-adenosylmethionine
RT synthetase mRNA and comparison of the Mr deduced from the cDNA sequence and
RT the purified enzyme.";
RL FEBS Lett. 290:142-146(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 SUBUNIT, CATALYTIC ACTIVITY, FUNCTION, PATHWAY, AND TISSUE SPECIFICITY.
RX PubMed=1517209; DOI=10.1016/s0021-9258(19)37084-x;
RA Pajares M.A., Duran C., Corrales F., Pliego M.M., Mato J.M.;
RT "Modulation of rat liver S-adenosylmethionine synthetase activity by
RT glutathione.";
RL J. Biol. Chem. 267:17598-17605(1992).
RN [5]
RP S-NITROSYLATION, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, AND PATHWAY.
RX PubMed=9755242; DOI=10.1002/hep.510280420;
RA Ruiz F., Corrales F.J., Miqueo C., Mato J.M.;
RT "Nitric oxide inactivates rat hepatic methionine adenosyltransferase In
RT vivo by S-nitrosylation.";
RL Hepatology 28:1051-1057(1998).
RN [6]
RP S-NITROSYLATION AT CYS-121.
RX PubMed=10358060; DOI=10.1074/jbc.274.24.17075;
RA Perez-Mato I., Castro C., Ruiz F.A., Corrales F.J., Mato J.M.;
RT "Methionine adenosyltransferase S-nitrosylation is regulated by the basic
RT and acidic amino acids surrounding the target thiol.";
RL J. Biol. Chem. 274:17075-17079(1999).
RN [7]
RP DISULFIDE BOND.
RX PubMed=10601859; DOI=10.1046/j.1432-1327.2000.00974.x;
RA Martinez-Chantar M.L., Pajares M.A.;
RT "Assignment of a single disulfide bridge in rat liver methionine
RT adenosyltransferase.";
RL Eur. J. Biochem. 267:132-137(2000).
RN [8] {ECO:0007744|PDB:1QM4}
RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) IN COMPLEX WITH METHIONINE ANALOG;
RP POTASSIUM AND MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT,
RP MUTAGENESIS OF ASP-180; LYS-182 AND PHE-251, AND DISULFIDE BOND.
RX PubMed=10873471; DOI=10.1006/jmbi.2000.3858;
RA Gonzalez B., Pajares M.A., Hermoso J.A., Alvarez L., Garrido F.,
RA Sufrin J.R., Sanz-Aparicio J.;
RT "The crystal structure of tetrameric methionine adenosyltransferase from
RT rat liver reveals the methionine-binding site.";
RL J. Mol. Biol. 300:363-375(2000).
RN [9] {ECO:0007744|PDB:1O90, ECO:0007744|PDB:1O92, ECO:0007744|PDB:1O93, ECO:0007744|PDB:1O9T}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEXES WITH ATP; METHIONINE
RP POTASSIUM AND MAGNESIUM, AND SUBUNIT.
RX PubMed=12888348; DOI=10.1016/s0022-2836(03)00728-9;
RA Gonzalez B., Pajares M.A., Hermoso J.A., Guillerm D., Guillerm G.,
RA Sanz-Aparicio J.;
RT "Crystal structures of methionine adenosyltransferase complexed with
RT substrates and products reveal the methionine-ATP recognition and give
RT insights into the catalytic mechanism.";
RL J. Mol. Biol. 331:407-416(2003).
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:10873471, ECO:0000269|PubMed:1517209,
CC ECO:0000269|PubMed:9755242}.
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:10873471, ECO:0000269|PubMed:1517209,
CC ECO:0000269|PubMed:9755242};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:10873471};
CC Note=Binds 2 magnesium ions per subunit. The magnesium ions interact
CC primarily with the substrate. {ECO:0000305|PubMed:10873471};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000305|PubMed:10873471};
CC Note=Binds 1 potassium ion per subunit. The potassium ion interacts
CC primarily with the substrate. {ECO:0000305|PubMed:10873471};
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:10873471, ECO:0000269|PubMed:1517209,
CC ECO:0000269|PubMed:9755242}.
CC -!- SUBUNIT: Homotetramer (MAT-I); dimer of dimers (PubMed:1517209,
CC PubMed:9755242, PubMed:10873471, PubMed:12888348). Homodimer (MAT-III)
CC (PubMed:1517209, PubMed:9755242). {ECO:0000269|PubMed:10873471,
CC ECO:0000269|PubMed:12888348, ECO:0000269|PubMed:1517209,
CC ECO:0000305|PubMed:9755242}.
CC -!- INTERACTION:
CC P13444; P13444: Mat1a; NbExp=2; IntAct=EBI-961260, EBI-961260;
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level)
CC (PubMed:1517209). Expressed in liver (PubMed:2806235).
CC {ECO:0000269|PubMed:1517209, ECO:0000269|PubMed:2806235}.
CC -!- PTM: S-nitrosylation of Cys-121 inactivates the enzyme.
CC {ECO:0000269|PubMed:10358060, ECO:0000269|PubMed:9755242}.
CC -!- PTM: An intrachain disulfide bond can be formed (PubMed:10601859). The
CC protein structure shows that the relevant Cys residues are in a
CC position that would permit formation of a disulfide bond
CC (PubMed:10873471). {ECO:0000269|PubMed:10601859,
CC ECO:0000269|PubMed:10873471}.
CC -!- SIMILARITY: Belongs to the AdoMet synthase family. {ECO:0000305}.
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DR EMBL; X15734; CAA33754.1; -; mRNA.
DR EMBL; X60822; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC089770; AAH89770.1; -; mRNA.
DR PIR; S06114; S06114.
DR RefSeq; NP_036992.2; NM_012860.2.
DR PDB; 1O90; X-ray; 3.10 A; A/B=1-397.
DR PDB; 1O92; X-ray; 3.19 A; A/B=1-397.
DR PDB; 1O93; X-ray; 3.49 A; A/B=1-397.
DR PDB; 1O9T; X-ray; 2.90 A; A/B=1-397.
DR PDB; 1QM4; X-ray; 2.66 A; A/B=1-397.
DR PDBsum; 1O90; -.
DR PDBsum; 1O92; -.
DR PDBsum; 1O93; -.
DR PDBsum; 1O9T; -.
DR PDBsum; 1QM4; -.
DR AlphaFoldDB; P13444; -.
DR SMR; P13444; -.
DR BioGRID; 247370; 2.
DR ComplexPortal; CPX-58; Methionine adenosyltransferase complex variant 1.
DR ComplexPortal; CPX-59; Methionine adenosyltransferase complex variant 3.
DR STRING; 10116.ENSRNOP00000015190; -.
DR BindingDB; P13444; -.
DR ChEMBL; CHEMBL2195; -.
DR iPTMnet; P13444; -.
DR PhosphoSitePlus; P13444; -.
DR jPOST; P13444; -.
DR PaxDb; P13444; -.
DR PRIDE; P13444; -.
DR GeneID; 25331; -.
DR KEGG; rno:25331; -.
DR UCSC; RGD:3050; rat.
DR CTD; 4143; -.
DR RGD; 3050; Mat1a.
DR eggNOG; KOG1506; Eukaryota.
DR InParanoid; P13444; -.
DR OrthoDB; 685006at2759; -.
DR PhylomeDB; P13444; -.
DR BioCyc; MetaCyc:MON-8568; -.
DR BRENDA; 2.5.1.6; 5301.
DR Reactome; R-RNO-156581; Methylation.
DR Reactome; R-RNO-1614635; Sulfur amino acid metabolism.
DR Reactome; R-RNO-2408508; Metabolism of ingested SeMet, Sec, MeSec into H2Se.
DR UniPathway; UPA00315; UER00080.
DR EvolutionaryTrace; P13444; -.
DR PRO; PR:P13444; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0048269; C:methionine adenosyltransferase complex; ISO:RGD.
DR GO; GO:0016363; C:nuclear matrix; IDA:RGD.
DR GO; GO:0043531; F:ADP binding; IDA:RGD.
DR GO; GO:0016597; F:amino acid binding; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; IDA:RGD.
DR GO; GO:0004478; F:methionine adenosyltransferase activity; IDA:RGD.
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:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:RGD.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IDA:RGD.
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 3D-structure; ATP-binding; Disulfide bond; Magnesium; Metal-binding;
KW Nucleotide-binding; One-carbon metabolism; Potassium; Reference proteome;
KW S-nitrosylation; Transferase.
FT CHAIN 1..397
FT /note="S-adenosylmethionine synthase isoform type-1"
FT /id="PRO_0000174434"
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:0007744|PDB:1O92, ECO:0007744|PDB:1O9T"
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:0000269|PubMed:12888348,
FT ECO:0007744|PDB:1O92, ECO:0007744|PDB:1O93,
FT ECO:0007744|PDB:1O9T"
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:0000269|PubMed:12888348,
FT ECO:0007744|PDB:1O92, ECO:0007744|PDB:1O9T"
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:0000305|PubMed:10873471,
FT ECO:0000305|PubMed:12888348, ECO:0007744|PDB:1QM4"
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:0007744|PDB:1O92"
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:0000269|PubMed:12888348,
FT ECO:0007744|PDB:1O9T"
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:0007744|PDB:1O92"
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:0000269|PubMed:12888348,
FT ECO:0007744|PDB:1O92, ECO:0007744|PDB:1O9T"
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:0000269|PubMed:12888348,
FT ECO:0007744|PDB:1O92, ECO:0007744|PDB:1O9T"
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:0000269|PubMed:10358060"
FT DISULFID 35..61
FT /evidence="ECO:0000269|PubMed:10601859,
FT ECO:0000305|PubMed:10873471"
FT MUTAGEN 180
FT /note="D->G: Loss of S-adenosylmethionine synthase
FT activity, but does not abolish polyphosphatase activity."
FT /evidence="ECO:0000269|PubMed:10873471"
FT MUTAGEN 182
FT /note="K->G: Loss of S-adenosylmethionine synthase
FT activity, but does not abolish polyphosphatase activity."
FT /evidence="ECO:0000269|PubMed:10873471"
FT MUTAGEN 251
FT /note="F->D,G: Loss of S-adenosylmethionine synthase
FT activity, but does not abolish polyphosphatase activity."
FT /evidence="ECO:0000269|PubMed:10873471"
FT CONFLICT 345
FT /note="Missing (in Ref. 3; AAH89770)"
FT /evidence="ECO:0000305"
FT STRAND 19..26
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 31..47
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 63..73
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 80..91
FT /evidence="ECO:0007829|PDB:1QM4"
FT TURN 96..99
FT /evidence="ECO:0007829|PDB:1QM4"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 137..144
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 153..171
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 177..190
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 197..210
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 216..225
FT /evidence="ECO:0007829|PDB:1QM4"
FT TURN 226..231
FT /evidence="ECO:0007829|PDB:1QM4"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:1QM4"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:1QM4"
FT TURN 267..274
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 291..308
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 313..321
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 331..335
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 347..354
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 359..365
FT /evidence="ECO:0007829|PDB:1QM4"
FT TURN 366..369
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 373..376
FT /evidence="ECO:0007829|PDB:1QM4"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:1O9T"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:1QM4"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:1QM4"
SQ SEQUENCE 397 AA; 43698 MW; A847A8CCBB2007BA CRC64;
MNGPVDGLCD HSLSEEGAFM FTSESVGEGH PDKICDQISD AVLDAHLKQD PNAKVACETV
CKTGMVLLCG EITSMAMIDY QRVVRDTIKH IGYDDSAKGF DFKTCNVLVA LEQQSPDIAQ
CVHLDRNEED VGAGDQGLMF GYATDETEEC MPLTIVLAHK LNTRMADLRR SGVLPWLRPD
SKTQVTVQYV QDNGAVIPVR VHTIVISVQH NEDITLEAMR EALKEQVIKA VVPAKYLDED
TIYHLQPSGR FVIGGPQGDA GVTGRKIIVD TYGGWGAHGG GAFSGKDYTK VDRSAAYAAR
WVAKSLVKAG LCRRVLVQVS YAIGVAEPLS ISIFTYGTSK KTERDELLEV VNKNFDLRPG
VIVRDLDLKK PIYQKTACYG HFGRSEFPWE VPKKLVF
