P11586 (C1TC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	935 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
Pathway	One-carbon metabolism; tetrahydrofolate interconversion.
Subunit structure	Homodimer. Ref.9
Subcellular location	Cytoplasm.
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.
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.10 Ref.11 Ref.12 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 process	Amino-acid biosynthesis Histidine biosynthesis Methionine biosynthesis One-carbon metabolism Purine biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Hydrolase Ligase Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	folic 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 tetrahydrofolate interconversion Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome mitochondrion Traceable author statement PubMed 3528153. Source: ProtInc
Molecular_function	ATP 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

With	Entry	#Exp.	IntAct	Notes
MCC	P23508	1	EBI-709638,EBI-307531
TRAF6	Q9Y4K3	1	EBI-709638,EBI-359276
WDR8	Q9P2S5	1	EBI-709638,EBI-1054904

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1 Ref.5 Ref.6

Chain

2 – 935

934

C-1-tetrahydrofolate synthase, cytoplasmic

PRO_0000199321

Regions

Nucleotide binding

172 – 174

3

NADP

Nucleotide binding

380 – 387

8

ATP By similarity

Region

2 – 305

304

Methylenetetrahydrofolate dehydrogenase and cyclohydrolase

Region

52 – 56

5

Substrate binding

Region

99 – 101

3

Substrate binding

Region

272 – 276

5

Substrate binding

Region

306 – 935

630

Formyltetrahydrofolate synthetase

Sites

Binding site

197

1

NADP

Site

2

1

Not acetylated

Amino acid modifications

Modified residue

786

1

Phosphothreonine By similarity

Natural variations

Natural variant

134

1

R → K Associated with increased risk of colorectal cancer. Ref.11 Ref.12 Ref.13
Corresponds to variant rs1950902 [ dbSNP | Ensembl ].

VAR_016232

Natural variant

162

1

P → L.
Corresponds to variant rs4902283 [ dbSNP | Ensembl ].

VAR_055458

Natural variant

293

1

R → H Associated with susceptibility to FS-NTD. Ref.10
Corresponds to variant rs34181110 [ dbSNP | Ensembl ].

VAR_010241

Natural variant

653

1

R → Q May be associated with susceptibility to FS-NTD; decreases enzyme stability and increases risk for congenital heart defects. Ref.2 Ref.3 Ref.4 Ref.10 Ref.11 Ref.12 Ref.14
Corresponds to variant rs2236225 [ dbSNP | Ensembl ].

VAR_010251

Natural variant

761

1

T → M.
Corresponds to variant rs10813 [ dbSNP | Ensembl ].

VAR_032789

Natural variant

769

1

L → F. Ref.4
Corresponds to variant rs17857382 [ dbSNP | Ensembl ].

VAR_032790

Experimental info

Mutagenesis

49

1

S → A: No effect on dehydrogenase and cyclohydrolase activity. Strong increase of Km for NADP. Ref.9

Mutagenesis

49

1

S → Q: Reduces dehydrogenase by 75% and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. Ref.9

Mutagenesis

52

1

Y → 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.9

Mutagenesis

52

1

Y → F: Slightly reduces dehydrogenase and cyclohydrolase activity. Increase of Km for NADP and for 5,10-methenyltetrahydrofolate. Ref.9

Mutagenesis

56

1

K → A, I, S or T: Decreases dehydrogenase activity over 90%. Loss of cyclohydrolase activity. Ref.9

Mutagenesis

56

1

K → 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.9

Mutagenesis

56

1

K → R: Reduces dehydrogenase and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. Ref.9

Mutagenesis

147

1

C → Q: Reduces dehydrogenase activity by 50% and cyclohydrolase activity by 87%. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

935

Helix Strand Turn

Details...

Helix

9 – 30

22

Beta strand

37 – 44

8

Helix

47 – 63

17

Beta strand

66 – 72

7

Helix

78 – 90

13

Beta strand

96 – 99

4

Helix

111 – 116

6

Helix

120 – 122

3

Helix

129 – 136

8

Helix

147 – 157

11

Turn

158 – 160

3

Beta strand

167 – 171

5

Turn

175 – 177

3

Helix

178 – 187

10

Beta strand

191 – 195

5

Helix

202 – 206

5

Beta strand

210 – 214

5

Helix

224 – 226

3

Beta strand

232 – 235

4

Helix

258 – 261

4

Turn

262 – 264

3

Beta strand

266 – 268

3

Beta strand

271 – 274

4

Helix

275 – 295

21

Sequences

	Sequence		Length	Mass (Da)
	P11586 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 29AE1C04B4922885	FASTA	935	101,559
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	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. , 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.
[4]	"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.
[5]	"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.
[6]	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, LACK OF N-TERMINAL ACETYLATION, MASS SPECTROMETRY. Tissue: Foreskin fibroblast and Prostatic carcinoma.
[7]	"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].
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
CH471061 Genomic DNA. Translation: EAW80857.1.
BC001014 mRNA. Translation: AAH01014.2.
BC009806 mRNA. Translation: AAH09806.1.
BC050420 mRNA. Translation: AAH50420.1.

IPI

IPI00218342.

PIR

A31903.

RefSeq

NP_005947.3. NM_005956.3.

UniGene

Hs.652308.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A4I	X-ray	1.50	A/B	1-301	[»]
1DIA	X-ray	2.20	A/B	1-306	[»]
1DIB	X-ray	2.70	A/B	1-306	[»]
1DIG	X-ray	2.20	A/B	1-306	[»]

ProteinModelPortal

P11586.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11586. 7 interactions.

MINT

MINT-5000922.

STRING

9606.ENSP00000216605.

PTM databases

PhosphoSite

P11586.

Polymorphism databases

DMDM

115206.

2D gel databases

REPRODUCTION-2DPAGE

IPI00218342.

SWISS-2DPAGE

P11586.

Proteomic databases

PaxDb

P11586.

PRIDE

P11586.

Protocols and materials databases

DNASU

4522.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216605; ENSP00000216605; ENSG00000100714.

GeneID

4522.

KEGG

hsa:4522.

UCSC

uc001xhb.3. human.

Organism-specific databases

CTD

4522.

GeneCards

GC14P064854.

H-InvDB

HIX0011731.

HGNC

HGNC:7432. MTHFD1.

HPA

HPA000704.
HPA001290.
HPA015006.

MIM

114500. phenotype.
172460. gene+phenotype.
601634. phenotype.

neXtProt

NX_P11586.

Orphanet

268392. 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.

PharmGKB

PA31236.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0190.

HOVERGEN

HBG004916.

InParanoid

P11586.

KO

K00288.

OrthoDB

EOG4GB75D.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02138-MONOMER.

BRENDA

6.3.4.3. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00193.

Gene expression databases

ArrayExpress

P11586.

Bgee

P11586.

CleanEx

HS_MTHFD1.

Genevestigator

P11586.

GermOnline

ENSG00000100714. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR000559. 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]

Pfam

PF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]

PRINTS

PR00085. THFDHDRGNASE.

SUPFAM

SSF52540. SSF52540. 1 hit.

PROSITE

PS00721. 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]

ProtoNet

Search...

Other

BindingDB

P11586.

ChEMBL

CHEMBL2541.

ChiTaRS

MTHFD1. human.

DrugBank

DB00157. NADH.
DB00116. Tetrahydrofolic acid.

EvolutionaryTrace

P11586.

GenomeRNAi

4522.

NextBio

17468.

SOURCE

Search...

Entry information

Entry name

C1TC_HUMAN

Accession

Primary (citable) accession number: P11586
Secondary accession number(s): B2R5Y2, Q86VC9, Q9BVP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 155 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.