MTHR2_ARATH
ID MTHR2_ARATH Reviewed; 594 AA.
AC O80585; Q56ZL2; Q94JZ1; Q9SE59; Q9SUJ0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2002, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Methylenetetrahydrofolate reductase 2;
DE Short=AtMTHFR2;
DE EC=1.5.1.20;
GN Name=MTHFR2; OrderedLocusNames=At2g44160; ORFNames=F6E13.29;
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ravanel S., Rebeille F., Douce R.;
RT "Folate metabolism in higher plants: cloning of a cDNA for 5,10-
RT methylenetetrahydrofolate reductase in Arabidopsis thaliana.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=10593891; DOI=10.1074/jbc.274.51.36089;
RA Roje S., Wang H., McNeil S.D., Raymond R.K., Appling D.R., Shachar-Hill Y.,
RA Bohnert H.J., Hanson A.D.;
RT "Isolation, characterization, and functional expression of cDNAs encoding
RT NADH-dependent methylenetetrahydrofolate reductase from higher plants.";
RL J. Biol. Chem. 274:36089-36096(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=10617197; DOI=10.1038/45471;
RA Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D.,
RA Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V.,
RA Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., Moffat K.S.,
RA Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J.,
RA Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M.,
RA Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O.,
RA Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C.;
RT "Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.";
RL Nature 402:761-768(1999).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-594.
RC STRAIN=cv. Columbia;
RA Totoki Y., Seki M., Ishida J., Nakajima M., Enju A., Kamiya A.,
RA Narusaka M., Shin-i T., Nakagawa M., Sakamoto N., Oishi K., Kohara Y.,
RA Kobayashi M., Toyoda A., Sakaki Y., Sakurai T., Iida K., Akiyama K.,
RA Satou M., Toyoda T., Konagaya A., Carninci P., Kawai J., Hayashizaki Y.,
RA Shinozaki K.;
RT "Large-scale analysis of RIKEN Arabidopsis full-length (RAFL) cDNAs.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: The probable reversibility of the MTHFR reaction in plants
CC suggests that they can metabolize the methyl group of 5,10-
CC methylenetetrahydrofolate to serine, sugars and starch.
CC {ECO:0000269|PubMed:10593891}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-
CC methylene-5,6,7,8-tetrahydrofolate + H(+) + NADPH;
CC Xref=Rhea:RHEA:19817, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.20;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10-
CC methylene-5,6,7,8-tetrahydrofolate + H(+) + NADH;
CC Xref=Rhea:RHEA:19821, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.5.1.20;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Plant MTHFRs strongly prefer NADH over NADPH. Not
CC inhibited by methionine or S-adenosylmethionine.
CC {ECO:0000269|PubMed:10593891}.
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; AJ245414; CAB53783.1; -; mRNA.
DR EMBL; AF181967; AAD55788.1; -; mRNA.
DR EMBL; AC004005; AAC23420.2; -; Genomic_DNA.
DR EMBL; CP002685; AEC10384.1; -; Genomic_DNA.
DR EMBL; AY050434; AAK91450.1; -; mRNA.
DR EMBL; AF370515; AAK43892.1; -; mRNA.
DR EMBL; AK220952; BAD94483.1; -; mRNA.
DR PIR; T00696; T00696.
DR RefSeq; NP_566011.1; NM_129979.3.
DR AlphaFoldDB; O80585; -.
DR SMR; O80585; -.
DR BioGRID; 4358; 14.
DR IntAct; O80585; 2.
DR STRING; 3702.AT2G44160.1; -.
DR iPTMnet; O80585; -.
DR PaxDb; O80585; -.
DR PRIDE; O80585; -.
DR ProteomicsDB; 250908; -.
DR EnsemblPlants; AT2G44160.1; AT2G44160.1; AT2G44160.
DR GeneID; 819022; -.
DR Gramene; AT2G44160.1; AT2G44160.1; AT2G44160.
DR KEGG; ath:AT2G44160; -.
DR Araport; AT2G44160; -.
DR TAIR; locus:2051789; AT2G44160.
DR eggNOG; KOG0564; Eukaryota.
DR HOGENOM; CLU_025841_2_2_1; -.
DR InParanoid; O80585; -.
DR OMA; EQWVSNT; -.
DR OrthoDB; 338303at2759; -.
DR PhylomeDB; O80585; -.
DR BioCyc; ARA:AT2G44160-MON; -.
DR BRENDA; 1.5.1.20; 399.
DR BRENDA; 1.5.1.54; 399.
DR UniPathway; UPA00193; -.
DR PRO; PR:O80585; -.
DR Proteomes; UP000006548; Chromosome 2.
DR ExpressionAtlas; O80585; baseline and differential.
DR Genevisible; O80585; AT.
DR GO; GO:0005829; C:cytosol; HDA:TAIR.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0004489; F:methylenetetrahydrofolate reductase (NAD(P)H) activity; IBA:GO_Central.
DR GO; GO:0106312; F:methylenetetrahydrofolate reductase NADH activity; IEA:RHEA.
DR GO; GO:0106313; F:methylenetetrahydrofolate reductase NADPH activity; IEA:RHEA.
DR GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR CDD; cd00537; MTHFR; 1.
DR InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR InterPro; IPR004621; Fadh2_euk.
DR InterPro; IPR003171; Mehydrof_redctse-like.
DR Pfam; PF02219; MTHFR; 1.
DR SUPFAM; SSF51730; SSF51730; 1.
DR TIGRFAMs; TIGR00677; fadh2_euk; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..594
FT /note="Methylenetetrahydrofolate reductase 2"
FT /id="PRO_0000190250"
FT ACT_SITE 21
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 21..26
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 52..53
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 52..53
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 81
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 111..113
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 153
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 157..160
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 182
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 193
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 285
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 72
FT /note="N -> S (in Ref. 1; CAB53783)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="P -> H (in Ref. 5; AAK43892)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="A -> V (in Ref. 1; CAB53783)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 594 AA; 66802 MW; E2F4F919FCE10EF8 CRC64;
MKVIDKIQSL ADEGKTAFSF EFFPPKTEDG VDNLFERMDR MVAYGPTFCD ITWGAGGSTA
DLTLDIASRM QNVVCVESMM HLTCTNMPVE KIDHALETIR SNGIQNVLAL RGDPPHGQDK
FVQVEGGFDC ALDLVNHIRS KYGDYFGITV AGYPEAHPDV IGENGLASNE AYQSDLEYLK
KKIDAGADLI VTQLFYDTDI FLKFVNDCRQ IGISCPIVPG IMPINNYRGF LRMTGFCKTK
IPVEVMAALE PIKDNEEAVK AYGIHLGTEM CKKMLAHGVK SLHLYTLNME KSALAILMNL
GMIDESKISR SLPWRRPANV FRTKEDVRPI FWANRPKSYI SRTKGWEDFP QGRWGDSRSA
SYGALSDHQF SRPRARDKKL QQEWVVPLKS VEDIQEKFKE LCLGNLKSSP WSELDGLQPE
TRIINEQLIK VNSKGFLTIN SQPSVNAERS DSPTVGWGGP VGYVYQKAYL EFFCSKEKLD
AVVEKCKALP SITYMAVNKG EQWVSNTAQA DVNAVTWGVF PAKEIIQPTI VDPASFNVWK
DEAFETWSRS WANLYPEADP SRNLLEEVKN SYYLVSLVEN DYINGDIFAV FADL
