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P42898

- MTHR_HUMAN

UniProt

P42898 - MTHR_HUMAN

Protein

Methylenetetrahydrofolate reductase

Gene

MTHFR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 3 (07 Dec 2004)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiP42898.
    BgeeiP42898.
    CleanExiHS_MTHFR.
    GenevestigatoriP42898.

    Interactioni

    Subunit structurei

    Homodimer.

    Protein-protein interaction databases

    BioGridi110624. 1 interaction.
    IntActiP42898. 1 interaction.
    STRINGi9606.ENSP00000365775.

    Structurei

    3D structure databases

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

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0685.
    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

    MVNEARGNSS LNPCLEGSAS SGSESSKDSS RCSTPGLDPE RHERLREKMR    50
    RRLESGDKWF SLEFFPPRTA EGAVNLISRF DRMAAGGPLY IDVTWHPAGD 100
    PGSDKETSSM MIASTAVNYC GLETILHMTC CRQRLEEITG HLHKAKQLGL 150
    KNIMALRGDP IGDQWEEEEG GFNYAVDLVK HIRSEFGDYF DICVAGYPKG 200
    HPEAGSFEAD LKHLKEKVSA GADFIITQLF FEADTFFRFV KACTDMGITC 250
    PIVPGIFPIQ GYHSLRQLVK LSKLEVPQEI KDVIEPIKDN DAAIRNYGIE 300
    LAVSLCQELL ASGLVPGLHF YTLNREMATT EVLKRLGMWT EDPRRPLPWA 350
    LSAHPKRREE DVRPIFWASR PKSYIYRTQE WDEFPNGRWG NSSSPAFGEL 400
    KDYYLFYLKS KSPKEELLKM WGEELTSEES VFEVFVLYLS GEPNRNGHKV 450
    TCLPWNDEPL AAETSLLKEE LLRVNRQGIL TINSQPNING KPSSDPIVGW 500
    GPSGGYVFQK AYLEFFTSRE TAEALLQVLK KYELRVNYHL VNVKGENITN 550
    APELQPNAVT WGIFPGREII QPTVVDPVSF MFWKDEAFAL WIERWGKLYE 600
    EESPSRTIIQ YIHDNYFLVN LVDNDFPLDN CLWQVVEDTL ELLNRPTQNA 650
    RETEAP 656
    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.
    UCSCiuc001atc.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. 1 interaction.
    IntActi P42898. 1 interaction.
    STRINGi 9606.ENSP00000365775.

    Chemistry

    DrugBanki DB00542. Benazepril.
    DB00115. Cyanocobalamin.
    DB00158. Folic Acid.
    DB00134. L-Methionine.
    DB00170. Menadione.
    DB00563. Methotrexate.
    DB00114. Pyridoxal Phosphate.
    DB00165. Pyridoxine.
    DB00293. Raltitrexed.
    DB00140. Riboflavin.
    DB00118. S-Adenosylmethionine.
    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 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.
    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

    ArrayExpressi P42898.
    Bgeei P42898.
    CleanExi HS_MTHFR.
    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

    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 1, 2014
    This is version 143 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