MTHR1_ARATH
ID MTHR1_ARATH Reviewed; 592 AA.
AC Q9SE60; Q3EAG9;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Methylenetetrahydrofolate reductase 1;
DE Short=AtMTHFR1;
DE EC=1.5.1.20;
GN Name=MTHFR1; OrderedLocusNames=At3g59970; ORFNames=F24G16.240;
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] (ISOFORM 1), FUNCTION, SUBUNIT, AND ACTIVITY
RP 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130713; DOI=10.1038/35048706;
RA Salanoubat M., Lemcke K., Rieger M., Ansorge W., Unseld M., Fartmann B.,
RA Valle G., Bloecker H., Perez-Alonso M., Obermaier B., Delseny M.,
RA Boutry M., Grivell L.A., Mache R., Puigdomenech P., De Simone V.,
RA Choisne N., Artiguenave F., Robert C., Brottier P., Wincker P.,
RA Cattolico L., Weissenbach J., Saurin W., Quetier F., Schaefer M.,
RA Mueller-Auer S., Gabel C., Fuchs M., Benes V., Wurmbach E., Drzonek H.,
RA Erfle H., Jordan N., Bangert S., Wiedelmann R., Kranz H., Voss H.,
RA Holland R., Brandt P., Nyakatura G., Vezzi A., D'Angelo M., Pallavicini A.,
RA Toppo S., Simionati B., Conrad A., Hornischer K., Kauer G., Loehnert T.-H.,
RA Nordsiek G., Reichelt J., Scharfe M., Schoen O., Bargues M., Terol J.,
RA Climent J., Navarro P., Collado C., Perez-Perez A., Ottenwaelder B.,
RA Duchemin D., Cooke R., Laudie M., Berger-Llauro C., Purnelle B., Masuy D.,
RA de Haan M., Maarse A.C., Alcaraz J.-P., Cottet A., Casacuberta E.,
RA Monfort A., Argiriou A., Flores M., Liguori R., Vitale D., Mannhaupt G.,
RA Haase D., Schoof H., Rudd S., Zaccaria P., Mewes H.-W., Mayer K.F.X.,
RA Kaul S., Town C.D., Koo H.L., Tallon L.J., Jenkins J., Rooney T., Rizzo M.,
RA Walts A., Utterback T., Fujii C.Y., Shea T.P., Creasy T.H., Haas B.,
RA Maiti R., Wu D., Peterson J., Van Aken S., Pai G., Militscher J.,
RA Sellers P., Gill J.E., Feldblyum T.V., Preuss D., Lin X., Nierman W.C.,
RA Salzberg S.L., White O., Venter J.C., Fraser C.M., Kaneko T., Nakamura Y.,
RA Sato S., Kato T., Asamizu E., Sasamoto S., Kimura T., Idesawa K.,
RA Kawashima K., Kishida Y., Kiyokawa C., Kohara M., Matsumoto M., Matsuno A.,
RA Muraki A., Nakayama S., Nakazaki N., Shinpo S., Takeuchi C., Wada T.,
RA Watanabe A., Yamada M., Yasuda M., Tabata S.;
RT "Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana.";
RL Nature 408:820-822(2000).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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).
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:0000269|PubMed:10593891}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9SE60-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9SE60-2; Sequence=VSP_018093, VSP_018094;
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; AF181966; AAD55787.1; -; mRNA.
DR EMBL; AL138647; CAB75816.1; -; Genomic_DNA.
DR EMBL; CP002686; AEE79992.1; -; Genomic_DNA.
DR EMBL; CP002686; AEE79994.1; -; Genomic_DNA.
DR EMBL; AY122922; AAM67455.1; -; mRNA.
DR EMBL; AY070034; AAL49791.1; -; mRNA.
DR PIR; T47821; T47821.
DR RefSeq; NP_191556.1; NM_115860.4. [Q9SE60-1]
DR RefSeq; NP_850723.1; NM_180392.1. [Q9SE60-2]
DR AlphaFoldDB; Q9SE60; -.
DR SMR; Q9SE60; -.
DR BioGRID; 10481; 13.
DR IntAct; Q9SE60; 1.
DR STRING; 3702.AT3G59970.3; -.
DR MetOSite; Q9SE60; -.
DR PaxDb; Q9SE60; -.
DR PRIDE; Q9SE60; -.
DR ProteomicsDB; 250811; -. [Q9SE60-1]
DR EnsemblPlants; AT3G59970.1; AT3G59970.1; AT3G59970. [Q9SE60-2]
DR EnsemblPlants; AT3G59970.3; AT3G59970.3; AT3G59970. [Q9SE60-1]
DR GeneID; 825167; -.
DR Gramene; AT3G59970.1; AT3G59970.1; AT3G59970. [Q9SE60-2]
DR Gramene; AT3G59970.3; AT3G59970.3; AT3G59970. [Q9SE60-1]
DR KEGG; ath:AT3G59970; -.
DR Araport; AT3G59970; -.
DR TAIR; locus:2080477; AT3G59970.
DR eggNOG; KOG0564; Eukaryota.
DR HOGENOM; CLU_025841_2_2_1; -.
DR InParanoid; Q9SE60; -.
DR OMA; EFFCSRD; -.
DR PhylomeDB; Q9SE60; -.
DR BioCyc; ARA:AT3G59970-MON; -.
DR BRENDA; 1.5.1.54; 399.
DR SABIO-RK; Q9SE60; -.
DR UniPathway; UPA00193; -.
DR PRO; PR:Q9SE60; -.
DR Proteomes; UP000006548; Chromosome 3.
DR ExpressionAtlas; Q9SE60; baseline and differential.
DR Genevisible; Q9SE60; 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 InterPro; IPR004620; MTHF_reductase_bac.
DR Pfam; PF02219; MTHFR; 1.
DR SUPFAM; SSF51730; SSF51730; 1.
DR TIGRFAMs; TIGR00676; fadh2; 1.
DR TIGRFAMs; TIGR00677; fadh2_euk; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; FAD; Flavoprotein; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..592
FT /note="Methylenetetrahydrofolate reductase 1"
FT /id="PRO_0000190249"
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 VAR_SEQ 397..421
FT /note="KFKELCIGNLKSSPWSELDGLQPET -> VGFTLRTLVQIVSISFPHTHLHI
FT FM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_018093"
FT VAR_SEQ 422..592
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_018094"
SQ SEQUENCE 592 AA; 66288 MW; 72D7453AF1AF1573 CRC64;
MKVVDKIKSV TEQGQTAFSF EFFPPKTEDG VENLFERMDR LVSYGPTFCD ITWGAGGSTA
DLTLEIASRM QNVICVETMM HLTCTNMPIE KIDHALETIR SNGIQNVLAL RGDPPHGQDK
FVQVEGGFAC ALDLVNHIRS KYGDYFGITV AGYPEAHPDV IEADGLATPE SYQSDLAYLK
KKVDAGADLI VTQLFYDTDI FLKFVNDCRQ IGINCPIVPG IMPISNYKGF LRMAGFCKTK
IPAELTAALE PIKDNDEAVK AYGIHFATEM CKKILAHGIT SLHLYTLNVD KSAIGILMNL
GLIDESKISR SLPWRRPANV FRTKEDVRPI FWANRPKSYI SRTKGWNDFP HGRWGDSHSA
AYSTLSDYQF ARPKGRDKKL QQEWVVPLKS IEDVQEKFKE LCIGNLKSSP WSELDGLQPE
TKIINEQLGK INSNGFLTIN SQPSVNAAKS DSPAIGWGGP GGYVYQKAYL EFFCSKDKLD
TLVEKSKAFP SITYMAVNKS ENWVSNTGES DVNAVTWGVF PAKEVIQPTI VDPASFKVWK
DEAFEIWSRS WANLYPEDDP SRKLLEEVKN SYYLVSLVDN NYINGDIFSV FA
