Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P11586 (C1TC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 167. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-1-tetrahydrofolate synthase, cytoplasmic

Short name=C1-THF synthase

Including the following 3 domains:

  1. Methylenetetrahydrofolate dehydrogenase
    EC=1.5.1.5
  2. Methenyltetrahydrofolate cyclohydrolase
    EC=3.5.4.9
  3. Formyltetrahydrofolate synthetase
    EC=6.3.4.3
Gene names
Name:MTHFD1
Synonyms:MTHFC, MTHFD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length935 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. HAMAP-Rule MF_01543

5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. HAMAP-Rule MF_01543

ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate. HAMAP-Rule MF_01543

Pathway

One-carbon metabolism; tetrahydrofolate interconversion. HAMAP-Rule MF_01543

Subunit structure

Homodimer. Ref.13

Subcellular location

Cytoplasm HAMAP-Rule MF_01543.

Tissue specificity

Ubiquitous.

Domain

This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity. HAMAP-Rule MF_01543

Involvement in disease

Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.16

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Sequence similarities

In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.

In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.

Ontologies

Keywords
   Biological processAmino-acid biosynthesis
Histidine biosynthesis
Methionine biosynthesis
One-carbon metabolism
Purine biosynthesis
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandATP-binding
NADP
Nucleotide-binding
   Molecular functionHydrolase
Ligase
Oxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processfolic acid metabolic process

Traceable author statement. Source: Reactome

folic acid-containing compound biosynthetic process

Inferred from electronic annotation. Source: InterPro

histidine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

methionine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

one-carbon metabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

purine nucleotide biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

small molecule metabolic process

Traceable author statement. Source: Reactome

tetrahydrofolate interconversion

Inferred from electronic annotation. Source: UniProtKB-UniPathway

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337PubMed 23376485. Source: UniProt

mitochondrion

Traceable author statement PubMed 3528153. Source: ProtInc

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

formate-tetrahydrofolate ligase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

methenyltetrahydrofolate cyclohydrolase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

methylenetetrahydrofolate dehydrogenase (NADP+) activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 935935C-1-tetrahydrofolate synthase, cytoplasmic HAMAP-Rule MF_01543
PRO_0000423280
Initiator methionine11Removed; alternate Ref.1 Ref.6 Ref.7
Chain2 – 935934C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed HAMAP-Rule MF_01543
PRO_0000199321

Regions

Nucleotide binding172 – 1743NADP HAMAP-Rule MF_01543
Nucleotide binding380 – 3878ATP By similarity
Region2 – 305304Methylenetetrahydrofolate dehydrogenase and cyclohydrolase HAMAP-Rule MF_01543
Region52 – 565Substrate binding HAMAP-Rule MF_01543
Region99 – 1013Substrate binding HAMAP-Rule MF_01543
Region272 – 2765Substrate binding HAMAP-Rule MF_01543
Region306 – 935630Formyltetrahydrofolate synthetase HAMAP-Rule MF_01543

Sites

Binding site1971NADP

Amino acid modifications

Modified residue11N-acetylmethionine Ref.8 Ref.10 Ref.11

Natural variations

Natural variant1341R → K Associated with increased risk of colorectal cancer. Ref.15 Ref.16 Ref.17
Corresponds to variant rs1950902 [ dbSNP | Ensembl ].
VAR_016232
Natural variant1621P → L.
Corresponds to variant rs4902283 [ dbSNP | Ensembl ].
VAR_055458
Natural variant2931R → H Associated with susceptibility to FS-NTD. Ref.14
Corresponds to variant rs34181110 [ dbSNP | Ensembl ].
VAR_010241
Natural variant6531R → Q May be associated with susceptibility to FS-NTD; decreases enzyme stability and increases risk for congenital heart defects. Ref.2 Ref.4 Ref.5 Ref.14 Ref.15 Ref.16 Ref.18
Corresponds to variant rs2236225 [ dbSNP | Ensembl ].
VAR_010251
Natural variant7611T → M.
Corresponds to variant rs10813 [ dbSNP | Ensembl ].
VAR_032789
Natural variant7691L → F. Ref.5
Corresponds to variant rs17857382 [ dbSNP | Ensembl ].
VAR_032790

Experimental info

Mutagenesis491S → A: No effect on dehydrogenase and cyclohydrolase activity. Strong increase of Km for NADP. Ref.13
Mutagenesis491S → Q: Reduces dehydrogenase by 75% and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. Ref.13
Mutagenesis521Y → A or S: Reduces dehydrogenase activity by 99%. Reduces cyclohydrolase activity by 70%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. Ref.13
Mutagenesis521Y → F: Slightly reduces dehydrogenase and cyclohydrolase activity. Increase of Km for NADP and for 5,10-methenyltetrahydrofolate. Ref.13
Mutagenesis561K → A, I, S or T: Decreases dehydrogenase activity over 90%. Loss of cyclohydrolase activity. Ref.13
Mutagenesis561K → E, M or Q: Moderate decrease of dehydrogenase activity. Loss of cyclohydrolase activity. Strong increase of Km for NADP. Decrease of Km for 5,10-methenyltetrahydrofolate. Ref.13
Mutagenesis561K → R: Reduces dehydrogenase and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. Ref.13
Mutagenesis1471C → Q: Reduces dehydrogenase activity by 50% and cyclohydrolase activity by 87%. Ref.13

Secondary structure

............................................. 935
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11586 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 29AE1C04B4922885

FASTA935101,559
        10         20         30         40         50         60 
MAPAEILNGK EISAQIRARL KNQVTQLKEQ VPGFTPRLAI LQVGNRDDSN LYINVKLKAA 

        70         80         90        100        110        120 
EEIGIKATHI KLPRTTTESE VMKYITSLNE DSTVHGFLVQ LPLDSENSIN TEEVINAIAP 

       130        140        150        160        170        180 
EKDVDGLTSI NAGRLARGDL NDCFIPCTPK GCLELIKETG VPIAGRHAVV VGRSKIVGAP 

       190        200        210        220        230        240 
MHDLLLWNNA TVTTCHSKTA HLDEEVNKGD ILVVATGQPE MVKGEWIKPG AIVIDCGINY 

       250        260        270        280        290        300 
VPDDKKPNGR KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP 

       310        320        330        340        350        360 
GKWMIQYNNL NLKTPVPSDI DISRSCKPKP IGKLAREIGL LSEEVELYGE TKAKVLLSAL 

       370        380        390        400        410        420 
ERLKHRPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH LYQNVFACVR QPSQGPTFGI 

       430        440        450        460        470        480 
KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT AANNLVAAAI DARIFHELTQ TDKALFNRLV 

       490        500        510        520        530        540 
PSVNGVRRFS DIQIRRLKRL GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF 

       550        560        570        580        590        600 
LRKITIGQAP TEKGHTRTAQ FDISVASEIM AVLALTTSLE DMRERLGKMV VASSKKGEPV 

       610        620        630        640        650        660 
SAEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG 

       670        680        690        700        710        720 
PEGFVVTEAG FGADIGMEKF FNIKCRYSGL CPHVVVLVAT VRALKMHGGG PTVTAGLPLP 

       730        740        750        760        770        780 
KAYIQENLEL VEKGFSNLKK QIENARMFGI PVVVAVNAFK TDTESELDLI SRLSREHGAF 

       790        800        810        820        830        840 
DAVKCTHWAE GGKGALALAQ AVQRAAQAPS SFQLLYDLKL PVEDKIRIIA QKIYGADDIE 

       850        860        870        880        890        900 
LLPEAQHKAE VYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFILPIRD IRASVGAGFL 

       910        920        930 
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF 

« Hide

References

« Hide 'large scale' references
[1]"Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase."
Hum D.W., Bell A.W., Rozen R., Mackenzie R.E.
J. Biol. Chem. 263:15946-15950(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-31.
Tissue: Liver.
[2]"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. expand/collapse author list , 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], VARIANT GLN-653.
Tissue: Amygdala.
[3]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLN-653.
[5]"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], VARIANTS GLN-653 AND PHE-769.
Tissue: Brain, Eye and Lymph.
[6]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-17.
Tissue: Platelet.
[7]Bienvenut W.V., Gao M., Leug H., Campbell A., Ozanne B.W.
Submitted (JUL-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-17; 251-264; 314-324; 355-362; 596-616 AND 722-733, CLEAVAGE OF INITIATOR METHIONINE, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Foreskin fibroblast and Prostatic carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5-A resolution."
Allaire M., Li Y., Mackenzie R.E., Cygler M.
Structure 6:173-182(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-302.
[13]"Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase."
Schmidt A., Wu H., MacKenzie R.E., Chen V.J., Bewly J.R., Ray J.E., Toth J.E., Cygler M.
Biochemistry 39:6325-6335(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-306 IN COMPLEX WITH NADP AND SUBSTRATE ANALOGS, SUBUNIT, MUTAGENESIS OF SER-49; TYR-52; LYS-56 AND CYS-147.
[14]"Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects."
Hol F.A., van der Put N.M.J., Geurds M.P.A., Heil S.G., Trijbels F.J.M., Hamel B.C.J., Mariman E.C.M., Blom H.J.
Clin. Genet. 53:119-125(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT HIS-293 WITH SUSCEPTIBILITY TO FS-NTD, VARIANT GLN-653.
[15]"A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group."
Brody L.C., Conley M., Cox C., Kirke P.N., McKeever M.P., Mills J.L., Molloy A.M., O'Leary V.B., Parle-McDermott A., Scott J.M., Swanson D.A.
Am. J. Hum. Genet. 71:1207-1215(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT GLN-653 WITH SUSCEPTIBILITY TO FS-NTD, VARIANT LYS-134.
[16]"Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population."
Parle-McDermott A., Kirke P.N., Mills J.L., Molloy A.M., Cox C., O'Leary V.B., Pangilinan F., Conley M., Cleary L., Brody L.C., Scott J.M.
Eur. J. Hum. Genet. 14:768-772(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT GLN-653 WITH SUSCEPTIBILITY TO FS-NTD, VARIANT LYS-134.
[17]"Search for low penetrance alleles for colorectal cancer through a scan of 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort analysis of 14 704 first-degree relatives."
Webb E.L., Rudd M.F., Sellick G.S., El Galta R., Bethke L., Wood W., Fletcher O., Penegar S., Withey L., Qureshi M., Johnson N., Tomlinson I., Gray R., Peto J., Houlston R.S.
Hum. Mol. Genet. 15:3263-3271(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LYS-134, ASSOCIATION WITH COLORECTAL CANCER SUSCEPTIBILITY.
[18]"The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects."
Christensen K.E., Rohlicek C.V., Andelfinger G.U., Michaud J., Bigras J.-L., Richter A., Mackenzie R.E., Rozen R.
Hum. Mutat. 30:212-220(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT GLN-653, ASSOCIATION WITH RISK OF CONGENITAL HEART DEFECTS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04031 mRNA. Translation: AAA59574.1.
AK312361 mRNA. Translation: BAG35279.1.
AL122035 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW80857.1.
BC001014 mRNA. Translation: AAH01014.2.
BC009806 mRNA. Translation: AAH09806.1.
BC050420 mRNA. Translation: AAH50420.1.
CCDSCCDS9763.1.
PIRA31903.
RefSeqNP_005947.3. NM_005956.3.
UniGeneHs.652308.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A4IX-ray1.50A/B1-301[»]
1DIAX-ray2.20A/B1-306[»]
1DIBX-ray2.70A/B1-306[»]
1DIGX-ray2.20A/B1-306[»]
ProteinModelPortalP11586.
SMRP11586. Positions 2-296, 317-935.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110622. 48 interactions.
IntActP11586. 7 interactions.
MINTMINT-5000922.
STRING9606.ENSP00000216605.

Chemistry

BindingDBP11586.
ChEMBLCHEMBL2541.
DrugBankDB00157. NADH.
DB00116. Tetrahydrofolic acid.

PTM databases

PhosphoSiteP11586.

Polymorphism databases

DMDM115206.

2D gel databases

REPRODUCTION-2DPAGEIPI00218342.
SWISS-2DPAGEP11586.

Proteomic databases

MaxQBP11586.
PaxDbP11586.
PRIDEP11586.

Protocols and materials databases

DNASU4522.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216605; ENSP00000216605; ENSG00000100714.
ENST00000555709; ENSP00000450560; ENSG00000100714.
GeneID4522.
KEGGhsa:4522.

Organism-specific databases

CTD4522.
GeneCardsGC14P064854.
H-InvDBHIX0011731.
HGNCHGNC:7432. MTHFD1.
HPAHPA000704.
HPA001290.
HPA015006.
MIM114500. phenotype.
172460. gene+phenotype.
601634. phenotype.
neXtProtNX_P11586.
Orphanet268392. Cervical spina bifida aperta.
268762. Cervical spina bifida cystica.
268397. Cervicothoracic spina bifida aperta.
268766. Cervicothoracic spina bifida cystica.
268388. Lumbosacral spina bifida aperta.
268758. Lumbosacral spina bifida cystica.
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.
PharmGKBPA31236.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0190.
HOVERGENHBG004916.
InParanoidP11586.
KOK00288.
PhylomeDBP11586.
TreeFamTF300623.

Enzyme and pathway databases

BioCycMetaCyc:HS02138-MONOMER.
BRENDA6.3.4.3. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00193.

Gene expression databases

ArrayExpressP11586.
BgeeP11586.
CleanExHS_MTHFD1.
GenevestigatorP11586.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPMF_01543. FTHFS.
MF_01576. THF_DHG_CYH.
InterProIPR000559. Formate_THF_ligase.
IPR020628. Formate_THF_ligase_CS.
IPR016040. NAD(P)-bd_dom.
IPR027417. P-loop_NTPase.
IPR000672. THF_DH/CycHdrlase.
IPR020630. THF_DH/CycHdrlase_cat_dom.
IPR020867. THF_DH/CycHdrlase_CS.
IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
[Graphical view]
PfamPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSPR00085. THFDHDRGNASE.
SUPFAMSSF52540. SSF52540. 2 hits.
PROSITEPS00721. FTHFS_1. 1 hit.
PS00722. FTHFS_2. 1 hit.
PS00766. THF_DHG_CYH_1. 1 hit.
PS00767. THF_DHG_CYH_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMTHFD1. human.
EvolutionaryTraceP11586.
GeneWikiMTHFD1.
GenomeRNAi4522.
NextBio17468.
PROP11586.
SOURCESearch...

Entry information

Entry nameC1TC_HUMAN
AccessionPrimary (citable) accession number: P11586
Secondary accession number(s): B2R5Y2 expand/collapse secondary AC list , G3V2B8, Q86VC9, Q9BVP5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 167 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM