MTHR2_SCHPO
ID MTHR2_SCHPO Reviewed; 641 AA.
AC O74927; P78770; Q9UT80;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Methylenetetrahydrofolate reductase 2;
DE EC=1.5.1.20;
GN Name=met11; Synonyms=mthfr2; ORFNames=SPAC343.10;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=12112238; DOI=10.1002/yea.877;
RA Naula N., Walther C., Baumann D., Schweingruber M.E.;
RT "Two non-complementing genes encoding enzymatically active
RT methylenetetrahydrofolate reductases control methionine requirement in
RT fission yeast Schizosaccharomyces pombe.";
RL Yeast 19:841-848(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-641.
RC STRAIN=PR745;
RX PubMed=9501991; DOI=10.1093/dnares/4.6.363;
RA Yoshioka S., Kato K., Nakai K., Okayama H., Nojima H.;
RT "Identification of open reading frames in Schizosaccharomyces pombe
RT cDNAs.";
RL DNA Res. 4:363-369(1997).
CC -!- FUNCTION: Major methylenetetrahydrofolate reductase required to
CC generate the methyl groups necessary for methionine synthetase to
CC convert homocysteine to methionine. Performs 15 to 20 percent of the
CC total methylenetetrahydrofolate reductase activity of the cells.
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:0000269|PubMed:12112238};
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:0000269|PubMed:12112238};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC -!- DISRUPTION PHENOTYPE: Leads to partial auxotrophy for methionine.
CC {ECO:0000269|PubMed:12112238}.
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; AJ011686; CAA09738.1; -; Genomic_DNA.
DR EMBL; CU329670; CAB52273.1; -; Genomic_DNA.
DR EMBL; D89118; BAA13780.1; -; mRNA.
DR PIR; T38659; T38659.
DR RefSeq; NP_593430.1; NM_001018863.2.
DR AlphaFoldDB; O74927; -.
DR SMR; O74927; -.
DR BioGRID; 279537; 10.
DR STRING; 4896.SPAC343.10.1; -.
DR iPTMnet; O74927; -.
DR MaxQB; O74927; -.
DR PaxDb; O74927; -.
DR PRIDE; O74927; -.
DR EnsemblFungi; SPAC343.10.1; SPAC343.10.1:pep; SPAC343.10.
DR GeneID; 2543105; -.
DR KEGG; spo:SPAC343.10; -.
DR PomBase; SPAC343.10; met11.
DR VEuPathDB; FungiDB:SPAC343.10; -.
DR eggNOG; KOG0564; Eukaryota.
DR HOGENOM; CLU_025841_2_1_1; -.
DR InParanoid; O74927; -.
DR OMA; YPEGHAD; -.
DR PhylomeDB; O74927; -.
DR UniPathway; UPA00193; -.
DR PRO; PR:O74927; -.
DR Proteomes; UP000002485; Chromosome I.
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; IMP:PomBase.
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; IMP:PomBase.
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; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..641
FT /note="Methylenetetrahydrofolate reductase 2"
FT /id="PRO_0000190254"
FT ACT_SITE 20
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 20..25
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 172
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 190
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 202
FT /note="E -> D (in Ref. 3; BAA13780)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="G -> A (in Ref. 3; BAA13780)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="A -> V (in Ref. 3; BAA13780)"
FT /evidence="ECO:0000305"
FT CONFLICT 537..641
FT /note="QVTYYAGNNKSEFLTNAPKDGASAVTWGVYPGREIIQSTIIAEVSFKAWLSE
FT SFQVWGEWANLYSKNTPSRKLLENCINDRWLVTVIHHDFMDKNGLWKVLEIDF -> HV
FT RSNFSSSISDSTCFQRLVSKPLFLRIRATDRSKFSVQK (in Ref. 3;
FT BAA13780)"
FT /evidence="ECO:0000305"
FT CONFLICT 614
FT /note="I -> L (in Ref. 1; CAA09738)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 641 AA; 72140 MW; E7AFFDD1F2C1C8A4 CRC64;
MKIVDLIDKI PNGNAFYSFE YFPPKTTVGL ENLSSRITRM SRNMMPLFSS VTWGTAGSTA
EVSIYLAKML EQHHKIPACL HLTCTNVDKA IIDKALETAK EYGIRNILAL RGDPPLNSDH
WEGKVSEFEH AVDLVRYIRE KYGDYFCIGV AAYPEGHVDS NVPELSKDPL RDIPFLIEKV
EAGADFIITQ IFYEPEAFIK FENFVRNHSS NALRNIPIIP AIMPIQSYGS LKRMTRLCGC
SVPSSLMQRL NAAKPDDEAI KNIGVEHIVD MIKKIMDNVQ GRVHGFHFCT LNLERSVALI
LKNSGLLTKR WKQVESEMED EKLLRTTRKR LSLDEPAELH NQVVVPSQQP VADKSSNLFV
TSKQSSVSGH KDNLTEEAPF SVSEGSGVLG RQANWDDFTN GRFGDPRSPA YGEIDGYGPT
LHFPPSEALK LWGYPVDESD ITSLFQKHIM SDISAIPWID EPVEVETKTI AKYLLKLNGN
SWWTVGSQPA VNGAPSADPV FGWGPKGGRV FQKAFVECFV NGKDLKDFIT KWHDNPQVTY
YAGNNKSEFL TNAPKDGASA VTWGVYPGRE IIQSTIIAEV SFKAWLSESF QVWGEWANLY
SKNTPSRKLL ENCINDRWLV TVIHHDFMDK NGLWKVLEID F
