MTHR_CAEEL
ID MTHR_CAEEL Reviewed; 663 AA.
AC Q17693; G8JXY2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Probable methylenetetrahydrofolate reductase;
DE EC=1.5.1.20;
GN Name=mthf-1 {ECO:0000312|WormBase:C06A8.1a};
GN ORFNames=C06A8.1 {ECO:0000312|WormBase:C06A8.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
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 Evidence={ECO:0000250|UniProtKB:P42898};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19819;
CC Evidence={ECO:0000250|UniProtKB:P42898};
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 Evidence={ECO:0000250|UniProtKB:P42898};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19823;
CC Evidence={ECO:0000250|UniProtKB:P42898};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P42898};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000250|UniProtKB:P42898}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:C06A8.1a};
CC IsoId=Q17693-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C06A8.1b};
CC IsoId=Q17693-2; Sequence=VSP_057655;
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; FO080131; CCD61458.1; -; Genomic_DNA.
DR EMBL; FO080131; CCD61459.1; -; Genomic_DNA.
DR PIR; T15423; T15423.
DR RefSeq; NP_741027.1; NM_171024.4. [Q17693-1]
DR RefSeq; NP_741028.1; NM_171025.6. [Q17693-2]
DR AlphaFoldDB; Q17693; -.
DR SMR; Q17693; -.
DR BioGRID; 39587; 6.
DR DIP; DIP-26125N; -.
DR IntAct; Q17693; 3.
DR STRING; 6239.C06A8.1a; -.
DR iPTMnet; Q17693; -.
DR EPD; Q17693; -.
DR PaxDb; Q17693; -.
DR PeptideAtlas; Q17693; -.
DR PRIDE; Q17693; -.
DR EnsemblMetazoa; C06A8.1a.1; C06A8.1a.1; WBGene00015512. [Q17693-1]
DR EnsemblMetazoa; C06A8.1b.1; C06A8.1b.1; WBGene00015512. [Q17693-2]
DR EnsemblMetazoa; C06A8.1b.2; C06A8.1b.2; WBGene00015512. [Q17693-2]
DR GeneID; 174254; -.
DR KEGG; cel:CELE_C06A8.1; -.
DR UCSC; C06A8.1a.1; c. elegans. [Q17693-1]
DR CTD; 174254; -.
DR WormBase; C06A8.1a; CE30593; WBGene00015512; mthf-1. [Q17693-1]
DR WormBase; C06A8.1b; CE31291; WBGene00015512; mthf-1. [Q17693-2]
DR eggNOG; KOG0564; Eukaryota.
DR GeneTree; ENSGT00390000012490; -.
DR InParanoid; Q17693; -.
DR OMA; HPVHGWG; -.
DR OrthoDB; 338303at2759; -.
DR PhylomeDB; Q17693; -.
DR BRENDA; 1.5.1.20; 1045.
DR Reactome; R-CEL-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00193; -.
DR PRO; PR:Q17693; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00015512; Expressed in larva and 4 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0004489; F:methylenetetrahydrofolate reductase (NAD(P)H) activity; ISS:UniProtKB.
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; ISS:UniProtKB.
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 3: Inferred from homology;
KW Alternative splicing; FAD; Flavoprotein; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..663
FT /note="Probable methylenetetrahydrofolate reductase"
FT /id="PRO_0000190248"
FT ACT_SITE 76
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 76..81
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 107..108
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 107..108
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 141
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 171..173
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 187..188
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 210
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 214..217
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 223
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 230
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 241
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 334
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 338
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 477..480
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 497..501
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 578
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 591
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 465
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT VAR_SEQ 1..28
FT /note="MTNTGETKVIESHGTIKKIDSLSTMPYC -> MAVLSKN (in isoform
FT b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057655"
SQ SEQUENCE 663 AA; 75487 MW; EA94806A2C3BC1CD CRC64;
MTNTGETKVI ESHGTIKKID SLSTMPYCGV ETDENAVVEE KITLESGKSW SPKHYELLHE
RIERLIDEKQ QFFSLEFFPP RFVNGVPNFL ERVERLSEGG SVFVDMTWHM GSDPANVDKV
TSSSSIAASM LDYCGVDTML HMTCVQYNKA DTLKHLEQAK AMGLRSILAL RGDLPPGTEL
EDTHQFRALD MIRWIREEYG NYFSIGCAGY PLGHPQAPSY KADLMYLKAK CDAGANFVIT
QLFFEAETFE KFVRDCREIG ITQPIIPGIM PIMGYESIKR IAKLSQLEIP QHILDDLEPI
KHDDDAVQKY GTERCIEMCR RLLDNGTAPS IHLYTMNREG SIREILKSLG LWKLEGDRVF
PWKNRSQHPI RCLESVRPIY WSFRPRSYIT RTRDWDQFPN GRWGNSSSPA FGDVSSYYLS
NLTTVRNADD RLAMFGANIE SFEDVKRVFI NYITQAPNAD GVKVTVLPWT EAETGVQPET
SLISEQLVWC NENGILTVNS QPSVNGAPST DPLVGWGKPG GYCYQKAYLE CFMTAELSDK
LIQIIEREFP VRVNYHAINK DSTFDKTNSE ETTPIAVTWG VFPGSEIAQP TVVDPLSFRA
WRDEAYQMWM AQWGDFYPKE SKSYGVIKAV HDEFRLVTLV DNDFQKPSVL FDVLQKALDE
LKK
