UniProtKB - P11586 (C1TC_HUMAN)

BLAST

>sp|P11586|C1TC_HUMAN C-1-tetrahydrofolate synthase, cytoplasmic OS=Homo sapiens OX=9606 GN=MTHFD1 PE=1 SV=3
MAPAEILNGKEISAQIRARLKNQVTQLKEQVPGFTPRLAILQVGNRDDSNLYINVKLKAA
EEIGIKATHIKLPRTTTESEVMKYITSLNEDSTVHGFLVQLPLDSENSINTEEVINAIAP
EKDVDGLTSINAGRLARGDLNDCFIPCTPKGCLELIKETGVPIAGRHAVVVGRSKIVGAP
MHDLLLWNNATVTTCHSKTAHLDEEVNKGDILVVATGQPEMVKGEWIKPGAIVIDCGINY
VPDDKKPNGRKVVGDVAYDEAKERASFITPVPGGVGPMTVAMLMQSTVESAKRFLEKFKP
GKWMIQYNNLNLKTPVPSDIDISRSCKPKPIGKLAREIGLLSEEVELYGETKAKVLLSAL
ERLKHRPDGKYVVVTGITPTPLGEGKSTTTIGLVQALGAHLYQNVFACVRQPSQGPTFGI
KGGAAGGGYSQVIPMEEFNLHLTGDIHAITAANNLVAAAIDARIFHELTQTDKALFNRLV
PSVNGVRRFSDIQIRRLKRLGIEKTDPTTLTDEEINRFARLDIDPETITWQRVLDTNDRF
LRKITIGQAPTEKGHTRTAQFDISVASEIMAVLALTTSLEDMRERLGKMVVASSKKGEPV
SAEDLGVSGALTVLMKDAIKPNLMQTLEGTPVFVHAGPFANIAHGNSSIIADRIALKLVG
PEGFVVTEAGFGADIGMEKFFNIKCRYSGLCPHVVVLVATVRALKMHGGGPTVTAGLPLP
KAYIQENLELVEKGFSNLKKQIENARMFGIPVVVAVNAFKTDTESELDLISRLSREHGAF
DAVKCTHWAEGGKGALALAQAVQRAAQAPSSFQLLYDLKLPVEDKIRIIAQKIYGADDIE
LLPEAQHKAEVYTKQGFGNLPICMAKTHLSLSHNPEQKGVPTGFILPIRDIRASVGAGFL
YPLVGTMSTMPGLPTRPCFYDIDLDPETEQVNGLF

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History
Entry version 213 (07 Nov 2018)
Sequence version 3 (23 Jan 2007)
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Protein

C-1-tetrahydrofolate synthase, cytoplasmic

Gene

MTHFD1

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

Functionⁱ

Catalytic activityⁱ

5,10-methylenetetrahydrofolate + NADP⁺ = 5,10-methenyltetrahydrofolate + NADPH.

5,10-methenyltetrahydrofolate + H₂O = 10-formyltetrahydrofolate.

ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.

Pathwayⁱ: tetrahydrofolate interconversion

This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.
View all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	197	NADP1 Publication		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	172 – 174	NADP1 Publication		3
Nucleotide bindingⁱ	380 – 387	ATPBy similarity		8

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
formate-tetrahydrofolate ligase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 1881876
methenyltetrahydrofolate cyclohydrolase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 1881876
methylenetetrahydrofolate dehydrogenase (NAD+) activity Source: BHF-UCL
methylenetetrahydrofolate dehydrogenase (NADP+) activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 1881876

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

10-formyltetrahydrofolate biosynthetic process
Source: BHF-UCL
Inferred from direct assayⁱ
- 1881876
embryonic neurocranium morphogenesis Source: BHF-UCL
embryonic viscerocranium morphogenesis Source: BHF-UCL
folic acid metabolic process Source: Reactome
heart development Source: BHF-UCL
histidine biosynthetic process Source: UniProtKB-KW
methionine biosynthetic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 25633902
methionine metabolic process Source: BHF-UCL
neural tube closure Source: BHF-UCL
neutrophil homeostasis Source: Ensembl
one-carbon metabolic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 25633902
purine nucleobase biosynthetic process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
purine nucleotide biosynthetic process Source: BHF-UCL
serine family amino acid biosynthetic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 25633902
serine family amino acid metabolic process Source: BHF-UCL
somite development Source: BHF-UCL
tetrahydrofolate interconversion
Source: BHF-UCL
Inferred from direct assayⁱ
- 1881876
transsulfuration Source: Ensembl

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase, Ligase, Multifunctional enzyme, Oxidoreductase
Biological process	Amino-acid biosynthesis, Histidine biosynthesis, Methionine biosynthesis, One-carbon metabolism, Purine biosynthesis
Ligand	ATP-binding, NADP, Nucleotide-binding

Enzyme and pathway databases

BioCycⁱ	MetaCyc:HS02138-MONOMER
BRENDAⁱ	1.5.1.5 2681 3.5.4.9 2681 6.3.4.3 2681
Reactomeⁱ	R-HSA-196757 Metabolism of folate and pterines
UniPathwayⁱ	UPA00193

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: C-1-tetrahydrofolate synthase, cytoplasmic Short name: C1-THF synthase Cleaved into the following chain: C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed Including the following 3 domains: Methylenetetrahydrofolate dehydrogenase (EC:1.5.1.5) Methenyltetrahydrofolate cyclohydrolase (EC:3.5.4.9) Formyltetrahydrofolate synthetase (EC:6.3.4.3)
Gene namesⁱ	Name:MTHFD1 Synonyms:MTHFC, MTHFD
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 14

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000100714.15
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:7432 MTHFD1
MIMⁱ	172460 gene+phenotype
neXtProtⁱ	NX_P11586

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Neural tube defects, folate-sensitive (NTDFS)3 Publications

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionThe most common NTDs are open spina bifida (myelomeningocele) and anencephaly.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_010241	293	R → H in NTDFS; associated with disease susceptibility. Corresponds to variant dbSNP:rs34181110EnsemblClinVar.		1
Natural variantⁱVAR_010251	653	R → Q in NTDFS; associated with disease susceptibility; increases risk for congenital heart defects; decreases enzyme stability. 5 PublicationsCorresponds to variant dbSNP:rs2236225EnsemblClinVar.		1

Colorectal cancer (CRC)1 Publication

Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Disease descriptionA 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.

Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia (CIMAH)3 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal recessive disorder due to an inborn error of folate metabolism. Variable clinical manifestations include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, and lymphopenia.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	49	S → A: No effect on dehydrogenase and cyclohydrolase activity. Strong increase of Km for NADP. 1 Publication	1
Mutagenesisⁱ	49	S → Q: Reduces dehydrogenase by 75% and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication	1
Mutagenesisⁱ	52	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. 1 Publication	1
Mutagenesisⁱ	52	Y → F: Slightly reduces dehydrogenase and cyclohydrolase activity. Increase of Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication	1
Mutagenesisⁱ	56	K → A, I, S or T: Decreases dehydrogenase activity over 90%. Loss of cyclohydrolase activity. 1 Publication	1
Mutagenesisⁱ	56	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. 1 Publication	1
Mutagenesisⁱ	56	K → R: Reduces dehydrogenase and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication	1
Mutagenesisⁱ	147	C → Q: Reduces dehydrogenase activity by 50% and cyclohydrolase activity by 87%. 1 Publication	1

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	4522
MalaCards human disease database More...MalaCardsⁱ	MTHFD1
MIMⁱ	114500 phenotype 172460 gene+phenotype 601634 phenotype 617780 phenotype
Orphanetⁱ	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
PharmGKBⁱ	PA31236

Chemistry databases

ChEMBLⁱ	CHEMBL2541
Drug and drug target database More...DrugBankⁱ	DB03461 2'-Monophosphoadenosine 5'-Diphosphoribose DB04322 LY249543 DB02358 LY374571 DB00157 NADH DB00116 Tetrahydrofolic acid

Polymorphism and mutation databases

BioMutaⁱ	MTHFD1
DMDMⁱ	115206

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
ChainⁱPRO_0000423280	1 – 935	C-1-tetrahydrofolate synthase, cytoplasmicAdd BLAST	935
Initiator methionineⁱ		Removed; alternate3 Publications
ChainⁱPRO_0000199321	2 – 935	C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processedAdd BLAST	934

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	1	N-acetylmethionineCombined sources	1
Modified residueⁱ	318	PhosphoserineCombined sources	1
Modified residueⁱ	413	PhosphoserineCombined sources	1
Modified residueⁱ	490	PhosphoserineCombined sources	1

Keywords - PTMⁱ

Acetylation, Phosphoprotein

Proteomic databases

EPDⁱ	P11586
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P11586
PaxDbⁱ	P11586
PeptideAtlas More...PeptideAtlasⁱ	P11586
PRIDEⁱ	P11586
ProteomicsDBⁱ	52794

2D gel databases

REPRODUCTION-2DPAGE More...REPRODUCTION-2DPAGEⁱ	IPI00218342
SWISS-2DPAGEⁱ	P11586

PTM databases

iPTMnetⁱ	P11586
PhosphoSitePlusⁱ	P11586
SwissPalmⁱ	P11586

Expressionⁱ

Tissue specificityⁱ

Ubiquitous.

Gene expression databases

Bgeeⁱ	ENSG00000100714 Expressed in 232 organ(s), highest expression level in right lobe of liver
CleanExⁱ	HS_MTHFD1
ExpressionAtlasⁱ	P11586 baseline and differential
Genevisibleⁱ	P11586 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA000704 HPA001290 HPA015006 HPA050052

HPAⁱ

HPA000704
HPA001290
HPA015006
HPA050052

Interactionⁱ

Subunit structureⁱ

Homodimer.1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
	Q9WMX2	3	EBI-709638,EBI-710918	From Hepatitis C virus genotype 1b (isolate Con1).

With

Entry

#Exp.

IntAct

Notes

Q9WMX2

EBI-709638,EBI-710918

From Hepatitis C virus genotype 1b (isolate Con1).

Protein-protein interaction databases

BioGridⁱ	110622, 86 interactors
Database of interacting proteins More...DIPⁱ	DIP-33682N
IntActⁱ	P11586, 22 interactors
Molecular INTeraction database More...MINTⁱ	P11586
STRINGⁱ	9606.ENSP00000450560

Chemistry databases

BindingDBⁱ

P11586

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	9 – 30	Combined sources	22
Beta strandⁱ	37 – 44	Combined sources	8
Helixⁱ	47 – 63	Combined sources	17
Beta strandⁱ	66 – 72	Combined sources	7
Helixⁱ	78 – 90	Combined sources	13
Beta strandⁱ	96 – 99	Combined sources	4
Helixⁱ	111 – 116	Combined sources	6
Helixⁱ	120 – 122	Combined sources	3
Helixⁱ	129 – 136	Combined sources	8
Helixⁱ	147 – 157	Combined sources	11
Turnⁱ	158 – 160	Combined sources	3
Beta strandⁱ	167 – 171	Combined sources	5
Turnⁱ	175 – 177	Combined sources	3
Helixⁱ	178 – 187	Combined sources	10
Beta strandⁱ	191 – 195	Combined sources	5
Helixⁱ	202 – 206	Combined sources	5
Beta strandⁱ	210 – 214	Combined sources	5
Helixⁱ	224 – 226	Combined sources	3
Beta strandⁱ	232 – 235	Combined sources	4
Helixⁱ	258 – 261	Combined sources	4
Turnⁱ	262 – 264	Combined sources	3
Beta strandⁱ	266 – 268	Combined sources	3
Beta strandⁱ	271 – 274	Combined sources	4
Helixⁱ	275 – 295	Combined sources	21

Show more details

3D structure databases

ProteinModelPortalⁱ	P11586
SMRⁱ	P11586
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P11586

EvolutionaryTraceⁱ

P11586

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	2 – 305	Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd BLAST	304
Regionⁱ	52 – 56	Substrate binding	5
Regionⁱ	99 – 101	Substrate binding	3
Regionⁱ	272 – 276	Substrate binding	5
Regionⁱ	306 – 935	Formyltetrahydrofolate synthetaseAdd BLAST	630

Domainⁱ

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.

Sequence similaritiesⁱ

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

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

Phylogenomic databases

eggNOGⁱ	KOG4230 Eukaryota COG0190 LUCA COG2759 LUCA
HOVERGENⁱ	HBG004916
InParanoidⁱ	P11586
KEGG Orthology (KO) More...KOⁱ	K00288
PhylomeDBⁱ	P11586
TreeFamⁱ	TF300623

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00477 FTHFS, 1 hit
HAMAPⁱ	MF_01543 FTHFS, 1 hit MF_01576 THF_DHG_CYH, 1 hit
InterProⁱ	View protein in InterPro IPR000559 Formate_THF_ligase IPR020628 Formate_THF_ligase_CS IPR036291 NAD(P)-bd_dom_sf 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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF01268 FTHFS, 1 hit PF00763 THF_DHG_CYH, 1 hit PF02882 THF_DHG_CYH_C, 1 hit
PRINTSⁱ	PR00085 THFDHDRGNASE
SUPFAMⁱ	SSF51735 SSF51735, 1 hit SSF52540 SSF52540, 1 hit
PROSITEⁱ	View protein in 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

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show all Align All

P11586-1 [UniParc]FASTA Add to basket

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        10         20         30         40         50
MAPAEILNGK EISAQIRARL KNQVTQLKEQ VPGFTPRLAI LQVGNRDDSN 
        60         70         80         90        100
LYINVKLKAA EEIGIKATHI KLPRTTTESE VMKYITSLNE DSTVHGFLVQ 
       110        120        130        140        150
LPLDSENSIN TEEVINAIAP EKDVDGLTSI NAGRLARGDL NDCFIPCTPK 
       160        170        180        190        200
GCLELIKETG VPIAGRHAVV VGRSKIVGAP MHDLLLWNNA TVTTCHSKTA 
       210        220        230        240        250
HLDEEVNKGD ILVVATGQPE MVKGEWIKPG AIVIDCGINY VPDDKKPNGR 
       260        270        280        290        300
KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP 
       310        320        330        340        350
GKWMIQYNNL NLKTPVPSDI DISRSCKPKP IGKLAREIGL LSEEVELYGE 
       360        370        380        390        400
TKAKVLLSAL ERLKHRPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH 
       410        420        430        440        450
LYQNVFACVR QPSQGPTFGI KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT 
       460        470        480        490        500
AANNLVAAAI DARIFHELTQ TDKALFNRLV PSVNGVRRFS DIQIRRLKRL 
       510        520        530        540        550
GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF LRKITIGQAP 
       560        570        580        590        600
TEKGHTRTAQ FDISVASEIM AVLALTTSLE DMRERLGKMV VASSKKGEPV 
       610        620        630        640        650
SAEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII 
       660        670        680        690        700
ADRIALKLVG PEGFVVTEAG FGADIGMEKF FNIKCRYSGL CPHVVVLVAT 
       710        720        730        740        750
VRALKMHGGG PTVTAGLPLP KAYIQENLEL VEKGFSNLKK QIENARMFGI 
       760        770        780        790        800
PVVVAVNAFK TDTESELDLI SRLSREHGAF DAVKCTHWAE GGKGALALAQ 
       810        820        830        840        850
AVQRAAQAPS SFQLLYDLKL PVEDKIRIIA QKIYGADDIE LLPEAQHKAE 
       860        870        880        890        900
VYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFILPIRD IRASVGAGFL 
       910        920        930 
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF

Length:935

Mass (Da):101,559

Last modified:January 23, 2007 - v3

Checksum:ⁱ29AE1C04B4922885

Computationally mapped potential isoform sequencesⁱ

There are 5 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

F5H2F4	F5H2F4_HUMAN	C-1-tetrahydrofolate synthase, cyto... C-1-tetrahydrofolate synthase, cytoplasmic	MTHFD1	1,020	Annotation score:
V9GYY3	V9GYY3_HUMAN	C-1-tetrahydrofolate synthase, cyto... C-1-tetrahydrofolate synthase, cytoplasmic	MTHFD1	107	Annotation score:
V9GY75	V9GY75_HUMAN	C-1-tetrahydrofolate synthase, cyto... C-1-tetrahydrofolate synthase, cytoplasmic	MTHFD1	68	Annotation score:
V9GZ78	V9GZ78_HUMAN	C-1-tetrahydrofolate synthase, cyto... C-1-tetrahydrofolate synthase, cytoplasmic	MTHFD1	25	Annotation score:
V9GZ32	V9GZ32_HUMAN	C-1-tetrahydrofolate synthase, cyto... C-1-tetrahydrofolate synthase, cytoplasmic	MTHFD1	23	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_074075	49	S → F in CIMAH. 1 Publication	1
Natural variantⁱVAR_080873	51	L → P in CIMAH. 1 Publication	1
Natural variantⁱVAR_016232	134	R → K Associated with increased risk of colorectal cancer. Combined sources3 PublicationsCorresponds to variant dbSNP:rs1950902Ensembl.	1
Natural variantⁱVAR_055458	162	P → L. Corresponds to variant dbSNP:rs4902283Ensembl.	1
Natural variantⁱVAR_074076	173	R → C in CIMAH. 1 Publication	1
Natural variantⁱVAR_080874	225 – 935	Missing in CIMAH. 1 PublicationAdd BLAST	711
Natural variantⁱVAR_074077	269	T → I in CIMAH. 1 Publication	1
Natural variantⁱVAR_010241	293	R → H in NTDFS; associated with disease susceptibility. Corresponds to variant dbSNP:rs34181110EnsemblClinVar.	1
Natural variantⁱVAR_010251	653	R → Q in NTDFS; associated with disease susceptibility; increases risk for congenital heart defects; decreases enzyme stability. 5 PublicationsCorresponds to variant dbSNP:rs2236225EnsemblClinVar.	1
Natural variantⁱVAR_032789	761	T → M. Corresponds to variant dbSNP:rs10813Ensembl.	1
Natural variantⁱVAR_032790	769	L → F1 PublicationCorresponds to variant dbSNP:rs17857382Ensembl.	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS9763.1
PIRⁱ	A31903
NCBI Reference Sequences More...RefSeqⁱ	NP_005947.3, NM_005956.3
UniGeneⁱ	Hs.652308

Genome annotation databases

Ensemblⁱ	ENST00000216605; ENSP00000216605; ENSG00000100714 ENST00000555709; ENSP00000450560; ENSG00000100714
GeneIDⁱ	4522
KEGGⁱ	hsa:4522
UCSC genome browser More...UCSCⁱ	uc001xhb.4 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P11586	C-1-tetrahydrofolate synthase, cytoplasmic		MOUSE		935	UniRef90_P11586
C-1-tetrahydrofolate synthase, cytoplasmic		PONAB		935
C-1-tetrahydrofolate synthase, cytoplasmic		RAT		935
Uncharacterized protein		CHLSB		1042
C-1-tetrahydrofolate synthase, cytoplasmic		HUMAN		1020
+186

Protein	Similar proteins		Species	Score	Length	Source
P11586	C-1-tetrahydrofolate synthase, cytoplasmic		MOUSE		935	UniRef50_P11586
C-1-tetrahydrofolate synthase, cytoplasmic		RAT		935
C-1-tetrahydrofolate synthase, cytoplasmic		PONAB		935
Uncharacterized protein		CHLSB		1042
Methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1		PANTR		1020
+238

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
CCDSⁱ	CCDS9763.1
PIRⁱ	A31903
RefSeqⁱ	NP_005947.3, NM_005956.3
UniGeneⁱ	Hs.652308

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB 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	[»]
ProteinModelPortalⁱ	P11586
SMRⁱ	P11586
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	110622, 86 interactors
DIPⁱ	DIP-33682N
IntActⁱ	P11586, 22 interactors
MINTⁱ	P11586
STRINGⁱ	9606.ENSP00000450560

Chemistry databases

BindingDBⁱ	P11586
ChEMBLⁱ	CHEMBL2541
DrugBankⁱ	DB03461 2'-Monophosphoadenosine 5'-Diphosphoribose DB04322 LY249543 DB02358 LY374571 DB00157 NADH DB00116 Tetrahydrofolic acid

PTM databases

iPTMnetⁱ	P11586
PhosphoSitePlusⁱ	P11586
SwissPalmⁱ	P11586

Polymorphism and mutation databases

BioMutaⁱ	MTHFD1
DMDMⁱ	115206

2D gel databases

REPRODUCTION-2DPAGEⁱ	IPI00218342
SWISS-2DPAGEⁱ	P11586

Proteomic databases

EPDⁱ	P11586
MaxQBⁱ	P11586
PaxDbⁱ	P11586
PeptideAtlasⁱ	P11586
PRIDEⁱ	P11586
ProteomicsDBⁱ	52794

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	4522
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000216605; ENSP00000216605; ENSG00000100714 ENST00000555709; ENSP00000450560; ENSG00000100714
GeneIDⁱ	4522
KEGGⁱ	hsa:4522
UCSCⁱ	uc001xhb.4 human

Organism-specific databases

CTDⁱ	4522
DisGeNETⁱ	4522
EuPathDBⁱ	HostDB:ENSG00000100714.15
GeneCardsⁱ	MTHFD1
H-InvDBⁱ	HIX0011731
HGNCⁱ	HGNC:7432 MTHFD1
HPAⁱ	HPA000704 HPA001290 HPA015006 HPA050052
MalaCardsⁱ	MTHFD1
MIMⁱ	114500 phenotype 172460 gene+phenotype 601634 phenotype 617780 phenotype
neXtProtⁱ	NX_P11586
Orphanetⁱ	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
PharmGKBⁱ	PA31236
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG4230 Eukaryota COG0190 LUCA COG2759 LUCA
HOVERGENⁱ	HBG004916
InParanoidⁱ	P11586
KOⁱ	K00288
PhylomeDBⁱ	P11586
TreeFamⁱ	TF300623

Enzyme and pathway databases

UniPathwayⁱ	UPA00193
BioCycⁱ	MetaCyc:HS02138-MONOMER
BRENDAⁱ	1.5.1.5 2681 3.5.4.9 2681 6.3.4.3 2681
Reactomeⁱ	R-HSA-196757 Metabolism of folate and pterines

Miscellaneous databases

ChiTaRSⁱ	MTHFD1 human
EvolutionaryTraceⁱ	P11586
GeneWikiⁱ	MTHFD1
GenomeRNAiⁱ	4522
Protein Ontology More...PROⁱ	PR:P11586
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000100714 Expressed in 232 organ(s), highest expression level in right lobe of liver
CleanExⁱ	HS_MTHFD1
ExpressionAtlasⁱ	P11586 baseline and differential
Genevisibleⁱ	P11586 HS

Family and domain databases

CDDⁱ	cd00477 FTHFS, 1 hit
HAMAPⁱ	MF_01543 FTHFS, 1 hit MF_01576 THF_DHG_CYH, 1 hit
InterProⁱ	View protein in InterPro IPR000559 Formate_THF_ligase IPR020628 Formate_THF_ligase_CS IPR036291 NAD(P)-bd_dom_sf 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
Pfamⁱ	View protein in Pfam PF01268 FTHFS, 1 hit PF00763 THF_DHG_CYH, 1 hit PF02882 THF_DHG_CYH_C, 1 hit
PRINTSⁱ	PR00085 THFDHDRGNASE
SUPFAMⁱ	SSF51735 SSF51735, 1 hit SSF52540 SSF52540, 1 hit
PROSITEⁱ	View protein in 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
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	C1TC_HUMAN
Accessionⁱ	P11586Primary (citable) accession number: P11586 Secondary accession number(s): B2R5Y2 , G3V2B8, Q86VC9, Q9BVP5
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
	Last sequence update:	January 23, 2007
	Last modified:	November 7, 2018
	This is version 213 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PATHWAY comments
Index of metabolic and biosynthesis pathways
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM

UniProtKB

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UniProtKB - P11586 (C1TC_HUMAN)

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C-1-tetrahydrofolate synthase, cytoplasmic

MTHFD1

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: tetrahydrofolate interconversion

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Other locations

Cytosol

Extracellular region or secreted

Mitochondrion

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

2D gel databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

Pathwayⁱ: tetrahydrofolate interconversion

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ