MTHR1_YEAST
ID MTHR1_YEAST Reviewed; 657 AA.
AC P46151; D6W3Y9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Methylenetetrahydrofolate reductase 1;
DE EC=1.5.1.20;
GN Name=MET12; OrderedLocusNames=YPL023C; ORFNames=LPB8C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169875;
RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA Vo D.H., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL Nature 387:103-105(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-131.
RX PubMed=6095044; DOI=10.1128/mcb.4.10.2161-2169.1984;
RA Yang E., Friedberg E.C.;
RT "Molecular cloning and nucleotide sequence analysis of the Saccharomyces
RT cerevisiae RAD1 gene.";
RL Mol. Cell. Biol. 4:2161-2169(1984).
RN [4]
RP IDENTIFICATION.
RX PubMed=7920641; DOI=10.1038/ng0694-195;
RA Goyette P., Sumner J.S., Milos R., Duncan A.M.V., Rosenblatt D.S.,
RA Matthews R.G., Rozen R.;
RT "Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and
RT mutation identification.";
RL Nat. Genet. 7:195-200(1994).
RN [5]
RP ERRATUM OF PUBMED:7920641.
RX PubMed=7951330;
RA Goyette P., Sumner J.S., Milos R., Duncan A.M.V., Rosenblatt D.S.,
RA Matthews R.G., Rozen R.;
RL Nat. Genet. 7:551-551(1994).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120 AND SER-301, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
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 -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC -!- INTERACTION:
CC P46151; P53128: MET13; NbExp=2; IntAct=EBI-11567, EBI-11572;
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; U36624; AAB68164.1; -; Genomic_DNA.
DR EMBL; K02070; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BK006949; DAA11405.1; -; Genomic_DNA.
DR PIR; S63459; S63459.
DR RefSeq; NP_015302.1; NM_001183837.1.
DR PDB; 6FNU; X-ray; 1.56 A; A=1-302.
DR PDBsum; 6FNU; -.
DR AlphaFoldDB; P46151; -.
DR SMR; P46151; -.
DR BioGRID; 36154; 139.
DR DIP; DIP-2825N; -.
DR IntAct; P46151; 5.
DR MINT; P46151; -.
DR STRING; 4932.YPL023C; -.
DR iPTMnet; P46151; -.
DR MaxQB; P46151; -.
DR PaxDb; P46151; -.
DR PRIDE; P46151; -.
DR EnsemblFungi; YPL023C_mRNA; YPL023C; YPL023C.
DR GeneID; 856084; -.
DR KEGG; sce:YPL023C; -.
DR SGD; S000005944; MET12.
DR VEuPathDB; FungiDB:YPL023C; -.
DR eggNOG; KOG0564; Eukaryota.
DR HOGENOM; CLU_025841_2_2_1; -.
DR InParanoid; P46151; -.
DR OMA; YPEGHAD; -.
DR BioCyc; YEAST:YPL023C-MON; -.
DR UniPathway; UPA00193; -.
DR PRO; PR:P46151; -.
DR Proteomes; UP000002311; Chromosome XVI.
DR RNAct; P46151; protein.
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; IDA:SGD.
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 3D-structure; FAD; Flavoprotein; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..657
FT /note="Methylenetetrahydrofolate reductase 1"
FT /id="PRO_0000190255"
FT REGION 308..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 18
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 18..23
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 49..50
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 49..50
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 78
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 108..110
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 110
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 129..130
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 152
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 286
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT CONFLICT 110..111
FT /note="DP -> NL (in Ref. 3; K02070)"
FT /evidence="ECO:0000305"
FT CONFLICT 115..116
FT /note="ED -> VV (in Ref. 3; K02070)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="D -> V (in Ref. 3; K02070)"
FT /evidence="ECO:0000305"
FT CONFLICT 124..131
FT /note="ESPFKYAV -> RLLNMRLF (in Ref. 3; K02070)"
FT /evidence="ECO:0000305"
FT HELIX 3..9
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 14..19
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 25..38
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 57..71
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 130..141
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 168..180
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 185..190
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 194..207
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 224..234
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 240..243
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 254..275
FT /evidence="ECO:0007829|PDB:6FNU"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:6FNU"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:6FNU"
FT HELIX 292..300
FT /evidence="ECO:0007829|PDB:6FNU"
SQ SEQUENCE 657 AA; 73942 MW; D75612EA92D67500 CRC64;
MSIRDLYHAR ASPFISLEFF PPKTELGTRN LMERMHRMTA LDPLFITVTW GAGGTTAEKT
LTLASLAQQT LNIPVCMHLT CTNTEKAIID DALDRCYNAG IRNILALRGD PPIGEDWLDS
QSNESPFKYA VDLVRYIKQS YGDKFCVGVA AYPEGHCEGE AEGHEQDPLK DLVYLKEKVE
AGADFVITQL FYDVEKFLTF EMLFRERISQ DLPLFPGLMP INSYLLFHRA AKLSHASIPP
AILSRFPPEI QSDDNAVKSI GVDILIELIQ EIYQRTSGRI KGFHFYTLNL EKAIAQIVSQ
SPVLSHIVNE SSEEEGEDET SGEIGSIENV PIEDADGDIV LDDSNEETVA NRKRRRHSSL
DSAKLIFNRA IVTEKGLRYN NENGSMPSKK ALISISKGHG TLGRDATWDE FPNGRFGDSR
SPAYGEIDGY GPSIKVSKSK ALELWGIPKT IGDLKDIFIK YLEGSTDAIP WSDLGLSAET
ALIQEELIQL NYRGYLTLAS QPATNATLSS DKIFGWGPAK GRLYQKAFVE MFIHRQQWET
TLKPKLDHYG RRKFSYYAGD SSGSFETNLD PHSSSVVTWG VFPNSPVKQT TIIEEESFKA
WRDEAFSIWS EWAKLFPRNT PANILLRLVH KDYCLVSIVH HDFKETDELW EMLLDQA
