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P42898

- MTHR_HUMAN

UniProt

P42898 - MTHR_HUMAN

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Protein

Methylenetetrahydrofolate reductase

Gene

MTHFR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.

Catalytic activityi

5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H.

Cofactori

FAD.

Enzyme regulationi

Allosterically regulated by S-adenosylmethionine.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei63 – 631Proton donor/acceptorBy similarity
Binding sitei127 – 1271FADBy similarity
Binding sitei159 – 1591SubstrateBy similarity
Binding sitei197 – 1971FADBy similarity
Binding sitei210 – 2101FADBy similarity
Binding sitei217 – 2171FADBy similarity
Binding sitei228 – 2281SubstrateBy similarity
Binding sitei321 – 3211SubstrateBy similarity
Binding sitei325 – 3251SubstrateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi63 – 686NADBy similarity
Nucleotide bindingi94 – 952NAD and FADBy similarity
Nucleotide bindingi157 – 1593FADBy similarity
Nucleotide bindingi174 – 1752FADBy similarity
Nucleotide bindingi201 – 2044FADBy similarity

GO - Molecular functioni

  1. flavin adenine dinucleotide binding Source: Ensembl
  2. methylenetetrahydrofolate reductase (NAD(P)H) activity Source: Reactome
  3. modified amino acid binding Source: UniProtKB
  4. NADP binding Source: Ensembl

GO - Biological processi

  1. blood circulation Source: ProtInc
  2. cellular amino acid metabolic process Source: ProtInc
  3. folic acid metabolic process Source: Reactome
  4. homocysteine metabolic process Source: UniProtKB
  5. methionine biosynthetic process Source: Ensembl
  6. response to drug Source: Ensembl
  7. response to folic acid Source: Ensembl
  8. response to hypoxia Source: Ensembl
  9. response to interleukin-1 Source: Ensembl
  10. response to vitamin B2 Source: Ensembl
  11. S-adenosylmethionine metabolic process Source: Ensembl
  12. small molecule metabolic process Source: Reactome
  13. tetrahydrofolate interconversion Source: UniProtKB-UniPathway
  14. vitamin metabolic process Source: Reactome
  15. water-soluble vitamin metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein, NADP

Enzyme and pathway databases

ReactomeiREACT_11167. Metabolism of folate and pterines.
SABIO-RKP42898.
UniPathwayiUPA00193.

Names & Taxonomyi

Protein namesi
Recommended name:
Methylenetetrahydrofolate reductase (EC:1.5.1.20)
Gene namesi
Name:MTHFR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:7436. MTHFR.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. neuron projection Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Methylenetetrahydrofolate reductase deficiency (MTHFRD) [MIM:236250]: Autosomal recessive disorder with a wide range of features including homocysteinuria, homocysteinemia [MIM:603174], developmental delay, severe mental retardation, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders.4 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti51 – 511R → P in MTHFRD. 1 Publication
Corresponds to variant rs201618781 [ dbSNP | Ensembl ].
VAR_009530
Natural varianti52 – 521R → Q in MTHFRD. 1 Publication
VAR_004319
Natural varianti157 – 1571R → Q in MTHFRD. 1 Publication
VAR_004320
Natural varianti227 – 2271T → M in MTHFRD. 1 Publication
VAR_004321
Natural varianti251 – 2511P → L in MTHFRD. 1 Publication
VAR_004322
Natural varianti323 – 3231L → P in MTHFRD. 1 Publication
VAR_009531
Natural varianti324 – 3241N → S in MTHFRD. 1 Publication
VAR_009532
Natural varianti325 – 3251R → C in MTHFRD. 1 Publication
VAR_004323
Natural varianti335 – 3351R → C in MTHFRD. 1 Publication
VAR_004324
Natural varianti339 – 3391W → G in MTHFRD. 1 Publication
VAR_009533
Natural varianti357 – 3571R → C in MTHFRD. 1 Publication
VAR_004325
Natural varianti377 – 3771R → C in MTHFRD. 1 Publication
VAR_009534
Natural varianti387 – 3871G → D in MTHFRD. 1 Publication
VAR_009535
Natural varianti572 – 5721P → L in MTHFRD. 1 Publication
VAR_009536
Natural varianti586 – 5861E → K in MTHFRD. 1 Publication
VAR_009537
Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.1 Publication
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly.3 Publications
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti222 – 2221A → V Common polymorphism; thermolabile; 50% reduced activity; at homozygosity reduces the risk for colorectal cancer in individuals with adequate folate status; decreased risk for adult acute leukemia; increased risk for FS-NTD. 5 Publications
Corresponds to variant rs1801133 [ dbSNP | Ensembl ].
VAR_009528

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi236250. phenotype.
601367. phenotype.
601634. phenotype.
603174. phenotype.
Orphaneti268392. Cervical spina bifida aperta.
268762. Cervical spina bifida cystica.
268397. Cervicothoracic spina bifida aperta.
268766. Cervicothoracic spina bifida cystica.
395. Homocystinuria due to methylene tetrahydrofolate reductase deficiency.
1048. Isolated anencephaly/exencephaly.
268388. Lumbosacral spina bifida aperta.
268758. Lumbosacral spina bifida cystica.
90070. Methotrexate poisoning.
64738. Non rare thrombophilia.
240977. Susceptibility to adverse reaction due to methotrexate treatment.
268384. Thoracolumbosacral spina bifida aperta.
268752. Thoracolumbosacral spina bifida cystica.
268377. Total spina bifida aperta.
268748. Total spina bifida cystica.
268740. Upper thoracic spina bifida aperta.
268770. Upper thoracic spina bifida cystica.
PharmGKBiPA245.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 656656Methylenetetrahydrofolate reductasePRO_0000190245Add
BLAST

Proteomic databases

MaxQBiP42898.
PaxDbiP42898.
PRIDEiP42898.

PTM databases

PhosphoSiteiP42898.

Expressioni

Gene expression databases

BgeeiP42898.
CleanExiHS_MTHFR.
ExpressionAtlasiP42898. baseline and differential.
GenevestigatoriP42898.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi110624. 7 interactions.
IntActiP42898. 1 interaction.
STRINGi9606.ENSP00000365775.

Structurei

3D structure databases

ProteinModelPortaliP42898.
SMRiP42898. Positions 60-338.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0685.
GeneTreeiENSGT00390000012490.
HOGENOMiHOG000246234.
HOVERGENiHBG006414.
InParanoidiP42898.
KOiK00297.
OMAiYLEFFVS.
OrthoDBiEOG7TF7B4.
PhylomeDBiP42898.
TreeFamiTF105665.

Family and domain databases

Gene3Di3.20.20.220. 1 hit.
InterProiIPR029041. FAD-linked_oxidoreductase-like.
IPR004621. Fadh2_euk.
IPR003171. Mehydrof_redctse.
[Graphical view]
PfamiPF02219. MTHFR. 1 hit.
[Graphical view]
SUPFAMiSSF51730. SSF51730. 1 hit.
TIGRFAMsiTIGR00677. fadh2_euk. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P42898-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVNEARGNSS LNPCLEGSAS SGSESSKDSS RCSTPGLDPE RHERLREKMR
60 70 80 90 100
RRLESGDKWF SLEFFPPRTA EGAVNLISRF DRMAAGGPLY IDVTWHPAGD
110 120 130 140 150
PGSDKETSSM MIASTAVNYC GLETILHMTC CRQRLEEITG HLHKAKQLGL
160 170 180 190 200
KNIMALRGDP IGDQWEEEEG GFNYAVDLVK HIRSEFGDYF DICVAGYPKG
210 220 230 240 250
HPEAGSFEAD LKHLKEKVSA GADFIITQLF FEADTFFRFV KACTDMGITC
260 270 280 290 300
PIVPGIFPIQ GYHSLRQLVK LSKLEVPQEI KDVIEPIKDN DAAIRNYGIE
310 320 330 340 350
LAVSLCQELL ASGLVPGLHF YTLNREMATT EVLKRLGMWT EDPRRPLPWA
360 370 380 390 400
LSAHPKRREE DVRPIFWASR PKSYIYRTQE WDEFPNGRWG NSSSPAFGEL
410 420 430 440 450
KDYYLFYLKS KSPKEELLKM WGEELTSEES VFEVFVLYLS GEPNRNGHKV
460 470 480 490 500
TCLPWNDEPL AAETSLLKEE LLRVNRQGIL TINSQPNING KPSSDPIVGW
510 520 530 540 550
GPSGGYVFQK AYLEFFTSRE TAEALLQVLK KYELRVNYHL VNVKGENITN
560 570 580 590 600
APELQPNAVT WGIFPGREII QPTVVDPVSF MFWKDEAFAL WIERWGKLYE
610 620 630 640 650
EESPSRTIIQ YIHDNYFLVN LVDNDFPLDN CLWQVVEDTL ELLNRPTQNA

RETEAP
Length:656
Mass (Da):74,597
Last modified:December 7, 2004 - v3
Checksum:iF16E774833D054B8
GO
Isoform 2 (identifier: P42898-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDHRKARVLPAGHYCPSLGIWASQVGSVRSSVPPSISRNPAM

Show »
Length:697
Mass (Da):78,965
Checksum:i53BD7151AA16F795
GO

Polymorphismi

Genetic variation in MTHFR influences susceptibility to occlusive vascular disease, neural tube defects (NTD), colon cancer and acute leukemia.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti51 – 511R → P in MTHFRD. 1 Publication
Corresponds to variant rs201618781 [ dbSNP | Ensembl ].
VAR_009530
Natural varianti52 – 521R → Q in MTHFRD. 1 Publication
VAR_004319
Natural varianti68 – 681R → Q.1 Publication
Corresponds to variant rs2066472 [ dbSNP | Ensembl ].
VAR_014881
Natural varianti157 – 1571R → Q in MTHFRD. 1 Publication
VAR_004320
Natural varianti222 – 2221A → V Common polymorphism; thermolabile; 50% reduced activity; at homozygosity reduces the risk for colorectal cancer in individuals with adequate folate status; decreased risk for adult acute leukemia; increased risk for FS-NTD. 5 Publications
Corresponds to variant rs1801133 [ dbSNP | Ensembl ].
VAR_009528
Natural varianti227 – 2271T → M in MTHFRD. 1 Publication
VAR_004321
Natural varianti251 – 2511P → L in MTHFRD. 1 Publication
VAR_004322
Natural varianti323 – 3231L → P in MTHFRD. 1 Publication
VAR_009531
Natural varianti324 – 3241N → S in MTHFRD. 1 Publication
VAR_009532
Natural varianti325 – 3251R → C in MTHFRD. 1 Publication
VAR_004323
Natural varianti335 – 3351R → C in MTHFRD. 1 Publication
VAR_004324
Natural varianti339 – 3391W → G in MTHFRD. 1 Publication
VAR_009533
Natural varianti357 – 3571R → C in MTHFRD. 1 Publication
VAR_004325
Natural varianti377 – 3771R → C in MTHFRD. 1 Publication
VAR_009534
Natural varianti387 – 3871G → D in MTHFRD. 1 Publication
VAR_009535
Natural varianti422 – 4221G → R.1 Publication
Corresponds to variant rs45571736 [ dbSNP | Ensembl ].
VAR_018857
Natural varianti428 – 4281E → A Common polymorphism; thermolabile; decreased activity.
VAR_009529
Natural varianti429 – 4291E → A Common polymorphism; thermolabile; decreased activity; decreased risk for adult acute leukemia. 4 Publications
Corresponds to variant rs1801131 [ dbSNP | Ensembl ].
VAR_014882
Natural varianti470 – 4701E → A.1 Publication
VAR_054158
Natural varianti519 – 5191R → C.1 Publication
Corresponds to variant rs45496998 [ dbSNP | Ensembl ].
VAR_018858
Natural varianti519 – 5191R → H.
Corresponds to variant rs45449298 [ dbSNP | Ensembl ].
VAR_050293
Natural varianti566 – 5661G → E.
Corresponds to variant rs2274974 [ dbSNP | Ensembl ].
VAR_050294
Natural varianti572 – 5721P → L in MTHFRD. 1 Publication
VAR_009536
Natural varianti586 – 5861E → K in MTHFRD. 1 Publication
VAR_009537
Natural varianti594 – 5941R → Q.2 Publications
Corresponds to variant rs2274976 [ dbSNP | Ensembl ].
VAR_018859
Natural varianti653 – 6531T → M.1 Publication
Corresponds to variant rs35737219 [ dbSNP | Ensembl ].
VAR_018860

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MDHRKARVLPAGHYCPSLGI WASQVGSVRSSVPPSISRNP AM in isoform 2. 1 PublicationVSP_053744

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U09806 mRNA. Translation: AAA74440.2.
AF105987
, AF105977, AF105978, AF105979, AF105980, AF105981, AF105982, AF105983, AF105984, AF105985, AF105986 Genomic DNA. Translation: AAD17965.1.
AJ237672 mRNA. Translation: CAB41971.1.
AK312907 mRNA. Translation: BAG35753.1.
AY338232 Genomic DNA. Translation: AAP88033.1.
AL953897 Genomic DNA. Translation: CAI15885.1.
CH471130 Genomic DNA. Translation: EAW71709.1.
BC053509 mRNA. Translation: AAH53509.1.
AY046562 mRNA. Translation: AAL17648.1.
AF398930 Genomic DNA. Translation: AAN40865.1.
CCDSiCCDS137.1. [P42898-1]
PIRiS46454.
RefSeqiNP_005948.3. NM_005957.4. [P42898-1]
XP_005263515.1. XM_005263458.1. [P42898-2]
XP_005263517.1. XM_005263460.2. [P42898-1]
XP_005263518.1. XM_005263461.2. [P42898-1]
XP_005263519.1. XM_005263462.2. [P42898-1]
UniGeneiHs.214142.
Hs.737916.

Genome annotation databases

EnsembliENST00000376583; ENSP00000365767; ENSG00000177000. [P42898-2]
ENST00000376585; ENSP00000365770; ENSG00000177000. [P42898-2]
ENST00000376590; ENSP00000365775; ENSG00000177000. [P42898-1]
ENST00000376592; ENSP00000365777; ENSG00000177000. [P42898-1]
GeneIDi4524.
KEGGihsa:4524.
UCSCiuc001atb.1. human.
uc001atc.2. human. [P42898-1]

Polymorphism databases

DMDMi56405339.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Methylenetetrahydrofolate reductase entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U09806 mRNA. Translation: AAA74440.2 .
AF105987
, AF105977 , AF105978 , AF105979 , AF105980 , AF105981 , AF105982 , AF105983 , AF105984 , AF105985 , AF105986 Genomic DNA. Translation: AAD17965.1 .
AJ237672 mRNA. Translation: CAB41971.1 .
AK312907 mRNA. Translation: BAG35753.1 .
AY338232 Genomic DNA. Translation: AAP88033.1 .
AL953897 Genomic DNA. Translation: CAI15885.1 .
CH471130 Genomic DNA. Translation: EAW71709.1 .
BC053509 mRNA. Translation: AAH53509.1 .
AY046562 mRNA. Translation: AAL17648.1 .
AF398930 Genomic DNA. Translation: AAN40865.1 .
CCDSi CCDS137.1. [P42898-1 ]
PIRi S46454.
RefSeqi NP_005948.3. NM_005957.4. [P42898-1 ]
XP_005263515.1. XM_005263458.1. [P42898-2 ]
XP_005263517.1. XM_005263460.2. [P42898-1 ]
XP_005263518.1. XM_005263461.2. [P42898-1 ]
XP_005263519.1. XM_005263462.2. [P42898-1 ]
UniGenei Hs.214142.
Hs.737916.

3D structure databases

ProteinModelPortali P42898.
SMRi P42898. Positions 60-338.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110624. 7 interactions.
IntActi P42898. 1 interaction.
STRINGi 9606.ENSP00000365775.

Chemistry

DrugBanki DB00542. Benazepril.
DB00115. Cyanocobalamin.
DB00544. Fluorouracil.
DB00158. Folic Acid.
DB00134. L-Methionine.
DB00170. Menadione.
DB00563. Methotrexate.
DB00140. Riboflavin.
DB00116. Tetrahydrofolic acid.

PTM databases

PhosphoSitei P42898.

Polymorphism databases

DMDMi 56405339.

Proteomic databases

MaxQBi P42898.
PaxDbi P42898.
PRIDEi P42898.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000376583 ; ENSP00000365767 ; ENSG00000177000 . [P42898-2 ]
ENST00000376585 ; ENSP00000365770 ; ENSG00000177000 . [P42898-2 ]
ENST00000376590 ; ENSP00000365775 ; ENSG00000177000 . [P42898-1 ]
ENST00000376592 ; ENSP00000365777 ; ENSG00000177000 . [P42898-1 ]
GeneIDi 4524.
KEGGi hsa:4524.
UCSCi uc001atb.1. human.
uc001atc.2. human. [P42898-1 ]

Organism-specific databases

CTDi 4524.
GeneCardsi GC01M011845.
HGNCi HGNC:7436. MTHFR.
MIMi 236250. phenotype.
601367. phenotype.
601634. phenotype.
603174. phenotype.
607093. gene.
neXtProti NX_P42898.
Orphaneti 268392. Cervical spina bifida aperta.
268762. Cervical spina bifida cystica.
268397. Cervicothoracic spina bifida aperta.
268766. Cervicothoracic spina bifida cystica.
395. Homocystinuria due to methylene tetrahydrofolate reductase deficiency.
1048. Isolated anencephaly/exencephaly.
268388. Lumbosacral spina bifida aperta.
268758. Lumbosacral spina bifida cystica.
90070. Methotrexate poisoning.
64738. Non rare thrombophilia.
240977. Susceptibility to adverse reaction due to methotrexate treatment.
268384. Thoracolumbosacral spina bifida aperta.
268752. Thoracolumbosacral spina bifida cystica.
268377. Total spina bifida aperta.
268748. Total spina bifida cystica.
268740. Upper thoracic spina bifida aperta.
268770. Upper thoracic spina bifida cystica.
PharmGKBi PA245.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0685.
GeneTreei ENSGT00390000012490.
HOGENOMi HOG000246234.
HOVERGENi HBG006414.
InParanoidi P42898.
KOi K00297.
OMAi YLEFFVS.
OrthoDBi EOG7TF7B4.
PhylomeDBi P42898.
TreeFami TF105665.

Enzyme and pathway databases

UniPathwayi UPA00193 .
Reactomei REACT_11167. Metabolism of folate and pterines.
SABIO-RK P42898.

Miscellaneous databases

ChiTaRSi MTHFR. human.
GeneWikii Methylenetetrahydrofolate_reductase.
GenomeRNAii 4524.
NextBioi 17474.
PROi P42898.
SOURCEi Search...

Gene expression databases

Bgeei P42898.
CleanExi HS_MTHFR.
ExpressionAtlasi P42898. baseline and differential.
Genevestigatori P42898.

Family and domain databases

Gene3Di 3.20.20.220. 1 hit.
InterProi IPR029041. FAD-linked_oxidoreductase-like.
IPR004621. Fadh2_euk.
IPR003171. Mehydrof_redctse.
[Graphical view ]
Pfami PF02219. MTHFR. 1 hit.
[Graphical view ]
SUPFAMi SSF51730. SSF51730. 1 hit.
TIGRFAMsi TIGR00677. fadh2_euk. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "cDNA for human methylenetetrahydrofolate reductase."
    Rozen R., Goyette P.
    Patent number WO9533054, 07-DEC-1995
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR)."
    Goyette P., Pai A., Milos R., Frosst P., Tran P., Chen Z., Chan M., Rozen R.
    Mamm. Genome 9:652-656(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Revised translation initiation site of the human methylenetetrahydrofolate reductase (MTHFR)."
    Homberger A., Linnebank M., Winter C., Rapp B., Koch H.G.
    Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-222.
    Tissue: Subthalamic nucleus.
  5. NIEHS SNPs program
    Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-68; VAL-222; ARG-422; ALA-429; CYS-519; GLN-594 AND MET-653.
  6. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-594.
    Tissue: Lung.
  9. "Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification."
    Goyette P., Sumner J.S., Milos R., Duncan A.M.V., Rosenblatt D.S., Matthews R.G., Rozen R.
    Nat. Genet. 7:195-200(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-415 (ISOFORM 1), VARIANT HOMOCYSTINURIA GLN-157.
    Tissue: Liver.
  10. "Multiple transcription start sites and alternative splicing in the methylenetetrahydrofolate reductase gene result in two enzyme isoforms."
    Tran P., Leclerc D., Chan M., Pai A., Hiou-Tim F., Wu Q., Goyette P., Artigas C., Milos R., Rozen R.
    Mamm. Genome 13:483-492(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-71 (ISOFORM 2), ALTERNATIVE SPLICING.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. "Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency."
    Goyette P., Frosst P., Rosenblatt D.S., Rozen R.
    Am. J. Hum. Genet. 56:1052-1059(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MTHFRD GLN-52; MET-227; LEU-251; CYS-325; CYS-335 AND CYS-357, SEQUENCE REVISION TO 177.
  13. Cited for: ASSOCIATION OF VARIANT VAL-222 WITH SUSCEPTIBILITY TO FS-NTD.
  14. "A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase."
    Frosst P., Blom H.J., Milos R., Goyette P., Sheppard C.A., Matthews R.G., Boers G.J.H., den Heijer M., Kluijtmans L.A.J., van den Heuvel L.P., Rozen R.
    Nat. Genet. 10:111-113(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT VAL-222.
  15. "5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects."
    Ou C.Y., Stevenson R.E., Brown V.K., Schwartz C.E., Allen W.P., Khoury M.J., Rozen R., Oakley G.P. Jr., Adams M.J. Jr.
    Am. J. Med. Genet. 63:610-614(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION OF VARIANT VAL-222 WITH SUSCEPTIBILITY TO FS-NTD.
  16. "Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR."
    Goyette P., Christensen B., Rosenblatt D.S., Rozen R.
    Am. J. Hum. Genet. 59:1268-1275(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MTHFRD PRO-51; PRO-323 AND CYS-377.
  17. "A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer."
    Chen J., Giovannucci E., Kelsey K., Rimm E.B., Stampfer M.J., Colditz G.A., Spiegelman D., Willett W.C., Hunter D.J.
    Cancer Res. 56:4862-4864(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVERSE ASSOCIATION OF VARIANT VAL-222 WITH COLORECTAL CANCER.
  18. "Worldwide distribution of a common methylenetetrahydrofolate reductase mutation."
    Schneider J.A., Rees D.C., Liu Y.-T., Clegg J.B.
    Am. J. Hum. Genet. 62:1258-1260(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT VAL-222.
  19. "A second mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?"
    van der Put N.M.J., Gabreels F., Stevens E.M.B., Smeitink J.A.M., Trijbels F.J.M., Eskes T.K.A.B., van den Heuvel L.P., Blom H.J.
    Am. J. Hum. Genet. 62:1044-1051(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ALA-429.
  20. "Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency."
    Kluijtmans L.A.J., Wendel U., Stevens E.M.B., van den Heuvel L.P.W.J., Trijbels F.J.M., Blom H.J.
    Eur. J. Hum. Genet. 6:257-265(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MTHFRD SER-324 AND GLY-339.
  21. "A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity."
    Weisberg I., Tran P., Christiensen B., Sibani S., Rozen R.
    Mol. Genet. Metab. 64:169-172(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ALA-429.
  22. "Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects."
    Christensen B., Arbour L., Tran P., Leclerc D., Sabbaghian N., Platt R., Gilfix B.M., Rosenblatt D.S., Gravel R.A., Forbes P., Rozen R.
    Am. J. Med. Genet. 84:151-157(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION OF VARIANT VAL-222 WITH SUSCEPTIBILITY TO FS-NTD.
  23. "Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults."
    Skibola C.F., Smith M.T., Kane E., Roman E., Rollinson S., Cartwright R.A., Morgan G.
    Proc. Natl. Acad. Sci. U.S.A. 96:12810-12815(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS VAL-222 AND ALA-429, ASSOCIATION WITH SUSCEPTIBILITY TO ACUTE LEUKEMIA.
  24. "Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria."
    Sibani S., Christensen B., O'Ferrall E., Saadi I., Hiou-Tim F., Rosenblatt D.S., Rozen R.
    Hum. Mutat. 15:280-287(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MTHFRD ASP-387; LEU-572 AND LYS-586.
  25. "Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls."
    Casas J.P., Hingorani A.D., Bautista L.E., Sharma P.
    Arch. Neurol. 61:1652-1661(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION OF VARIANT VAL-222 WITH SUSCEPTIBILITY TO ISCHSTR.
  26. Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-470.

Entry informationi

Entry nameiMTHR_HUMAN
AccessioniPrimary (citable) accession number: P42898
Secondary accession number(s): B2R7A6
, Q5SNW6, Q5SNW9, Q7Z6M6, Q8IU73, Q9UQR2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 7, 2004
Last modified: October 29, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3