ID Q5SNW7_HUMAN Unreviewed; 696 AA.
AC Q5SNW7;
DT 21-DEC-2004, integrated into UniProtKB/TrEMBL.
DT 05-DEC-2018, sequence version 10.
DT 27-MAR-2024, entry version 112.
DE RecName: Full=Methylenetetrahydrofolate reductase {ECO:0000256|RuleBase:RU003862};
DE EC=1.5.1.53 {ECO:0000256|RuleBase:RU003862};
GN Name=MTHFR {ECO:0000313|Ensembl:ENSP00000398908.3};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000398908.3, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000398908.3, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H.,
RA Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C.,
RA Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R.,
RA Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.,
RA Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.,
RA Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R.,
RA Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D.,
RA Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A.,
RA Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S., McLaren S., Milne S.,
RA Mistry S., Moore M.J., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A.,
RA Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S.,
RA Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G.,
RA Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A.,
RA Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L.,
RA Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z.,
RA Coulson A., Vaudin M., Sulston J.E., Durbin R., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R., Banerjee R., Bryant S.P., Burford D.C.,
RA Burrill W.D., Clegg S.M., Dhami P., Dovey O., Faulkner L.M., Gribble S.M.,
RA Langford C.F., Pandian R.D., Porter K.M., Prigmore E.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2] {ECO:0007829|PubMed:21269460}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Burckstummer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [3] {ECO:0000313|Ensembl:ENSP00000398908.3}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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=1.5.1.53;
CC Evidence={ECO:0000256|ARBA:ARBA00034452};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19819;
CC Evidence={ECO:0000256|ARBA:ARBA00034452};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|ARBA:ARBA00001974,
CC ECO:0000256|RuleBase:RU003862};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000256|ARBA:ARBA00004777, ECO:0000256|RuleBase:RU003862}.
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000256|ARBA:ARBA00006743, ECO:0000256|RuleBase:RU003862}.
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DR EMBL; AL953897; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_011539797.1; XM_011541495.2.
DR AlphaFoldDB; Q5SNW7; -.
DR SMR; Q5SNW7; -.
DR MassIVE; Q5SNW7; -.
DR PeptideAtlas; Q5SNW7; -.
DR ProteomicsDB; 63768; -.
DR Antibodypedia; 28242; 468 antibodies from 38 providers.
DR DNASU; 4524; -.
DR Ensembl; ENST00000423400.7; ENSP00000398908.3; ENSG00000177000.13.
DR UCSC; uc057chs.1; human.
DR HGNC; HGNC:7436; MTHFR.
DR VEuPathDB; HostDB:ENSG00000177000; -.
DR GeneTree; ENSGT00390000012490; -.
DR HOGENOM; CLU_3092636_0_0_1; -.
DR OrthoDB; 1381745at2759; -.
DR UniPathway; UPA00193; -.
DR ChiTaRS; MTHFR; human.
DR Proteomes; UP000005640; Chromosome 1.
DR Bgee; ENSG00000177000; Expressed in corpus epididymis and 177 other cell types or tissues.
DR ExpressionAtlas; Q5SNW7; baseline and differential.
DR GO; GO:0106313; F:methylenetetrahydrofolate reductase NADPH activity; IEA:RHEA.
DR GO; GO:0006555; P:methionine metabolic process; IEA:InterPro.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
DR CDD; cd00537; MTHFR; 1.
DR Gene3D; 3.20.20.220; -; 1.
DR InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR InterPro; IPR004621; Fadh2_euk.
DR InterPro; IPR003171; Mehydrof_redctse-like.
DR NCBIfam; TIGR00677; fadh2_euk; 1.
DR PANTHER; PTHR45754; METHYLENETETRAHYDROFOLATE REDUCTASE; 1.
DR PANTHER; PTHR45754:SF3; METHYLENETETRAHYDROFOLATE REDUCTASE; 1.
DR Pfam; PF02219; MTHFR; 1.
DR SUPFAM; SSF51730; FAD-linked oxidoreductase; 1.
PE 1: Evidence at protein level;
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|RuleBase:RU003862};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630,
KW ECO:0000256|RuleBase:RU003862};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|RuleBase:RU003862};
KW Proteomics identification {ECO:0007829|EPD:Q5SNW7,
KW ECO:0007829|MaxQB:Q5SNW7};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640}.
FT REGION 38..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..73
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 696 AA; 78878 MW; 32639F020D1E313D CRC64;
MDHRKARVLP AGHYCPSLGI WASQVGSVRS SVPPSIRNPA MVNEARGNSS LNPCLEGSAS
SGSESSKDSS RCSTPGLDPE RHERLREKMR RRLESGDKWF SLEFFPPRTA EGAVNLISRF
DRMAAGGPLY IDVTWHPAGD PGSDKETSSM MIASTAVNYC GLETILHMTC CRQRLEEITG
HLHKAKQLGL KNIMALRGDP IGDQWEEEEG GFNYAVDLVK HIRSEFGDYF DICVAGYPKG
HPEAGSFEAD LKHLKEKVSA GADFIITQLF FEADTFFRFV KACTDMGITC PIVPGIFPIQ
GYHSLRQLVK LSKLEVPQEI KDVIEPIKDN DAAIRNYGIE LAVSLCQELL ASGLVPGLHF
YTLNREMATT EVLKRLGMWT EDPRRPLPWA LSAHPKRREE DVRPIFWASR PKSYIYRTQE
WDEFPNGRWG NSSSPAFGEL KDYYLFYLKS KSPKEELLKM WGEELTSEES VFEVFVLYLS
GEPNRNGHKV TCLPWNDEPL AAETSLLKEE LLRVNRQGIL TINSQPNING KPSSDPIVGW
GPSGGYVFQK AYLEFFTSRE TAEALLQVLK KYELRVNYHL VNVKGENITN APELQPNAVT
WGIFPGREII QPTVVDPVSF MFWKDEAFAL WIERWGKLYE EESPSRTIIQ YIHDNYFLVN
LVDNDFPLDN CLWQVVEDTL ELLNRPTQNA RETEAP
//
