METK2_RAT
ID METK2_RAT Reviewed; 395 AA.
AC P18298;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=S-adenosylmethionine synthase isoform type-2;
DE Short=AdoMet synthase 2;
DE EC=2.5.1.6 {ECO:0000250|UniProtKB:P31153};
DE AltName: Full=Methionine adenosyltransferase 2;
DE Short=MAT 2;
DE AltName: Full=Methionine adenosyltransferase II;
DE Short=MAT-II;
GN Name=Mat2a; Synonyms=Ams2;
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].
RC STRAIN=Wistar; TISSUE=Kidney;
RX PubMed=1696256; DOI=10.1016/s0021-9258(18)77403-6;
RA Horikawa S., Sasuga J., Shimizu K., Ozasa H., Tsukada K.;
RT "Molecular cloning and nucleotide sequence of cDNA encoding the rat kidney
RT S-adenosylmethionine synthetase.";
RL J. Biol. Chem. 265:13683-13686(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9461287; DOI=10.1111/j.1432-1033.1997.00653.x;
RA Hiroki T., Horikawa S., Tsukada K.;
RT "Structure of the rat methionine adenosyltransferase 2A gene and its
RT promoter.";
RL Eur. J. Biochem. 250:653-660(1997).
RN [3]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15504733; DOI=10.1074/jbc.m408438200;
RA Kim J.S., Coon S.L., Blackshaw S., Cepko C.L., Moller M., Mukda S.,
RA Zhao W.Q., Charlton C.G., Klein D.C.;
RT "Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily
RT rhythm in pineal expression.";
RL J. Biol. Chem. 280:677-684(2005).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19103603; DOI=10.1074/jbc.m808394200;
RA Bailey M.J., Coon S.L., Carter D.A., Humphries A., Kim J.S., Shi Q.,
RA Gaildrat P., Morin F., Ganguly S., Hogenesch J.B., Weller J.L., Rath M.F.,
RA Moller M., Baler R., Sugden D., Rangel Z.G., Munson P.J., Klein D.C.;
RT "Night/day changes in pineal expression of >600 genes: central role of
RT adrenergic/cAMP signaling.";
RL J. Biol. Chem. 284:7606-7622(2009).
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:0000250|UniProtKB:P31153}.
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:0000250|UniProtKB:P31153};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0A817};
CC Note=Binds 2 magnesium ions per subunit. The magnesium ions interact
CC primarily with the substrate. {ECO:0000250|UniProtKB:P31153};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:P0A817};
CC Note=Binds 1 potassium ion per subunit. The potassium ion interacts
CC primarily with the substrate. {ECO:0000250|UniProtKB:P31153};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis;
CC S-adenosyl-L-methionine from L-methionine: step 1/1.
CC {ECO:0000250|UniProtKB:P31153}.
CC -!- SUBUNIT: Heterotrimer; composed of a catalytic MAT2A homodimer that
CC binds one regulatory MAT2B chain. Heterohexamer; composed of a central,
CC catalytic MAT2A homotetramer flanked on either side by a regulatory
CC MAT2B chain. {ECO:0000250|UniProtKB:P31153}.
CC -!- TISSUE SPECIFICITY: In mammalian tissues, there are three distinct
CC forms of AdoMet synthases designated as alpha, beta, and gamma. Alpha
CC and beta are expressed only in adult liver, while gamma is widely
CC distributed in extrahepatic tissues. In addition, the gamma form
CC predominantly exists in fetal rat liver and is progressively replaced
CC by the alpha and beta forms during development. In the brain, highly
CC expressed at night in pinealocytes (at protein level). Low expression
CC in the medial habenular nucleus, granular layer of the cerebellum,
CC layer II of the neocortex and the pyramidal cells and granular cells of
CC the hippocampal formation. {ECO:0000269|PubMed:15504733,
CC ECO:0000269|PubMed:19103603}.
CC -!- INDUCTION: Exhibits night/day variations with a 5-fold increased
CC expression at night in the pineal gland (at protein level). Up-
CC regulation is due to a large degree to the release of norepinephrine
CC from nerve terminals in the pineal gland and cAMP signaling pathway.
CC {ECO:0000269|PubMed:15504733, ECO:0000269|PubMed:19103603}.
CC -!- SIMILARITY: Belongs to the AdoMet synthase family. {ECO:0000305}.
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DR EMBL; J05571; AAA42106.1; -; mRNA.
DR EMBL; AB000717; BAA19170.1; -; Genomic_DNA.
DR PIR; A37118; A37118.
DR RefSeq; NP_599178.1; NM_134351.1.
DR AlphaFoldDB; P18298; -.
DR SMR; P18298; -.
DR BioGRID; 251193; 1.
DR STRING; 10116.ENSRNOP00000018170; -.
DR BindingDB; P18298; -.
DR ChEMBL; CHEMBL2838; -.
DR CarbonylDB; P18298; -.
DR iPTMnet; P18298; -.
DR PhosphoSitePlus; P18298; -.
DR jPOST; P18298; -.
DR PaxDb; P18298; -.
DR PRIDE; P18298; -.
DR GeneID; 171347; -.
DR KEGG; rno:171347; -.
DR UCSC; RGD:619985; rat.
DR CTD; 4144; -.
DR RGD; 619985; Mat2a.
DR eggNOG; KOG1506; Eukaryota.
DR InParanoid; P18298; -.
DR OrthoDB; 685006at2759; -.
DR PhylomeDB; P18298; -.
DR BRENDA; 2.5.1.6; 5301.
DR Reactome; R-RNO-156581; Methylation.
DR SABIO-RK; P18298; -.
DR UniPathway; UPA00315; UER00080.
DR PRO; PR:P18298; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0048269; C:methionine adenosyltransferase complex; ISS:UniProtKB.
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; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004478; F:methionine adenosyltransferase activity; IDA:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; IDA:RGD.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051291; P:protein heterooligomerization; ISS:UniProtKB.
DR GO; GO:0034214; P:protein hexamerization; ISS:UniProtKB.
DR GO; GO:0051591; P:response to cAMP; IDA:RGD.
DR GO; GO:0009725; P:response to hormone; IDA:RGD.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; 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 Acetylation; ATP-binding; Isopeptide bond; Magnesium; Metal-binding;
KW Nucleotide-binding; One-carbon metabolism; Phosphoprotein; Potassium;
KW Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..395
FT /note="S-adenosylmethionine synthase isoform type-2"
FT /id="PRO_0000174439"
FT REGION 113..125
FT /note="Flexible loop"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 29
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:P31153"
FT BINDING 31
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 57
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 70
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:P31153"
FT BINDING 113
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:P31153"
FT BINDING 179..181
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:P31153"
FT BINDING 247..250
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:P31153"
FT BINDING 258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 258
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:P31153"
FT BINDING 264..265
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:P31153"
FT BINDING 281
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 285
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 289
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 291
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT MOD_RES 81
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT CROSSLNK 228
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT CROSSLNK 234
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P31153"
SQ SEQUENCE 395 AA; 43716 MW; 4DA9AFABF7D09C79 CRC64;
MNGQLNGFHE AFIEEGTFLF TSESVGEGHP DKICDQINDA VLDAHLQQDP DAKVACETVA
KTGMILLAGE ITSRAAIDYQ KVVREAIKHI GYDDSSKGFD YKTCNVLVAL EQQSPDIAQG
VHLDRNEEDI GAGDQGLMFG YATDETEECM PLTIVLAHKL NAKLAELRRN GTLPWLRPDS
KTQVTVQYMQ DRGAVIPIRV HTIVISVQHD EEVCLDEMRD ALKEKLIKAV VPAKYLDEDT
IYHLQPSGRF VIGGPQGDAG LTGRKIIVDT YGGWGAHGGG AFSGKDYTKV DRSAAYAARW
VAKSLVKGGL CRRVLVQVSY AIGVSHPLSI SIFHYGTSQK SERELLEIVK NNFDLRPGVI
VRDLDLKKPI YQRTAAYGHF GRDSFPWEVP KKLKY
