ID A0A286YF17_HUMAN Unreviewed; 549 AA.
AC A0A286YF17;
DT 22-NOV-2017, integrated into UniProtKB/TrEMBL.
DT 22-NOV-2017, sequence version 1.
DT 27-MAR-2024, entry version 32.
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:ENSP00000493262.1};
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:ENSP00000493262.1, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000493262.1, 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:ENSP00000493262.1}
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 AlphaFoldDB; A0A286YF17; -.
DR SMR; A0A286YF17; -.
DR MassIVE; A0A286YF17; -.
DR PeptideAtlas; A0A286YF17; -.
DR Ensembl; ENST00000641446.1; ENSP00000493262.1; ENSG00000177000.13.
DR HGNC; HGNC:7436; MTHFR.
DR VEuPathDB; HostDB:ENSG00000177000; -.
DR GeneTree; ENSGT00390000012490; -.
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; A0A286YF17; 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:A0A286YF17,
KW ECO:0007829|MaxQB:A0A286YF17};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640}.
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..33
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 549 AA; 62000 MW; 8410E116AA89EB85 CRC64;
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
VNVKANHSG
//
