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Protein

C-1-tetrahydrofolate synthase, cytoplasmic

Gene

MTHFD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<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 catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<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

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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei197NADP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi172 – 174NADP1 Publication3
Nucleotide bindingi380 – 387ATPBy similarity8

<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

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Ligase, Multifunctional enzyme, Oxidoreductase
Biological processAmino-acid biosynthesis, Histidine biosynthesis, Methionine biosynthesis, One-carbon metabolism, Purine biosynthesis
LigandATP-binding, NADP, Nucleotide-binding

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

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BioCyci
MetaCyc:HS02138-MONOMER

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
1.5.1.5 2681
3.5.4.9 2681
6.3.4.3 2681

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-196757 Metabolism of folate and pterines

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00193

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
C-1-tetrahydrofolate synthase, cytoplasmic
Short name:
C1-THF synthase
Cleaved into the following chain:
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)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MTHFD1
Synonyms:MTHFC, MTHFD
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 14

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...
EuPathDBi
HostDB:ENSG00000100714.15

Human Gene Nomenclature Database

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HGNCi
HGNC:7432 MTHFD1

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
172460 gene+phenotype

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P11586

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

<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

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
See also OMIM:601634
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_010241293R → H in NTDFS; associated with disease susceptibility. Corresponds to variant dbSNP:rs34181110EnsemblClinVar.1
Natural variantiVAR_010251653R → 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.
See also OMIM:114500
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.
See also OMIM:617780
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07407549S → F in CIMAH. 1 Publication1
Natural variantiVAR_08087351L → P in CIMAH. 1 Publication1
Natural variantiVAR_074076173R → C in CIMAH. 1 Publication1
Natural variantiVAR_080874225 – 935Missing in CIMAH. 1 PublicationAdd BLAST711
Natural variantiVAR_074077269T → I in CIMAH. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi49S → A: No effect on dehydrogenase and cyclohydrolase activity. Strong increase of Km for NADP. 1 Publication1
Mutagenesisi49S → Q: Reduces dehydrogenase by 75% and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication1
Mutagenesisi52Y → 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 Publication1
Mutagenesisi52Y → F: Slightly reduces dehydrogenase and cyclohydrolase activity. Increase of Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication1
Mutagenesisi56K → A, I, S or T: Decreases dehydrogenase activity over 90%. Loss of cyclohydrolase activity. 1 Publication1
Mutagenesisi56K → 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 Publication1
Mutagenesisi56K → R: Reduces dehydrogenase and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication1
Mutagenesisi147C → Q: Reduces dehydrogenase activity by 50% and cyclohydrolase activity by 87%. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
4522

MalaCards human disease database

More...
MalaCardsi
MTHFD1
MIMi114500 phenotype
172460 gene+phenotype
601634 phenotype
617780 phenotype

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
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

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA31236

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2541

Drug and drug target database

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

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
MTHFD1

Domain mapping of disease mutations (DMDM)

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DMDMi
115206

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004232801 – 935C-1-tetrahydrofolate synthase, cytoplasmicAdd BLAST935
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemoved; alternate3 Publications
ChainiPRO_00001993212 – 935C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processedAdd BLAST934

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1N-acetylmethionineCombined sources1
Modified residuei318PhosphoserineCombined sources1
Modified residuei413PhosphoserineCombined sources1
Modified residuei490PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
P11586

MaxQB - The MaxQuant DataBase

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MaxQBi
P11586

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P11586

PeptideAtlas

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PeptideAtlasi
P11586

PRoteomics IDEntifications database

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PRIDEi
P11586

ProteomicsDB human proteome resource

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ProteomicsDBi
52794

2D gel databases

REPRODUCTION-2DPAGE

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REPRODUCTION-2DPAGEi
IPI00218342

Two-dimensional polyacrylamide gel electrophoresis database from the Geneva University Hospital

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SWISS-2DPAGEi
P11586

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P11586

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P11586

SwissPalm database of S-palmitoylation events

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SwissPalmi
P11586

<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

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Ubiquitous.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000100714 Expressed in 232 organ(s), highest expression level in right lobe of liver

CleanEx database of gene expression profiles

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CleanExi
HS_MTHFD1

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P11586 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P11586 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA000704
HPA001290
HPA015006
HPA050052

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
Q9WMX23EBI-709638,EBI-710918From Hepatitis C virus genotype 1b (isolate Con1).

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
110622, 88 interactors

Database of interacting proteins

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DIPi
DIP-33682N

Protein interaction database and analysis system

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IntActi
P11586, 22 interactors

Molecular INTeraction database

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MINTi
P11586

STRING: functional protein association networks

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STRINGi
9606.ENSP00000450560

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P11586

<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

1935
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P11586

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P11586

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P11586

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni2 – 305Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd BLAST304
Regioni52 – 56Substrate binding5
Regioni99 – 101Substrate binding3
Regioni272 – 276Substrate binding5
Regioni306 – 935Formyltetrahydrofolate synthetaseAdd BLAST630

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>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.

<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

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

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG4230 Eukaryota
COG0190 LUCA
COG2759 LUCA

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG004916

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P11586

KEGG Orthology (KO)

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KOi
K00288

Database for complete collections of gene phylogenies

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PhylomeDBi
P11586

TreeFam database of animal gene trees

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TreeFami
TF300623

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00477 FTHFS, 1 hit

HAMAP database of protein families

More...
HAMAPi
MF_01543 FTHFS, 1 hit
MF_01576 THF_DHG_CYH, 1 hit

Integrated resource of protein families, domains and functional sites

More...
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

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00085 THFDHDRGNASE

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF51735 SSF51735, 1 hit
SSF52540 SSF52540, 1 hit

PROSITE; a protein domain and family database

More...
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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>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 allAlign All

P11586-1 [UniParc]FASTAAdd to basket
« Hide
        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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i29AE1C04B4922885
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H2F4F5H2F4_HUMAN
C-1-tetrahydrofolate synthase, cyto...
MTHFD1
1,020Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
V9GYY3V9GYY3_HUMAN
C-1-tetrahydrofolate synthase, cyto...
MTHFD1
107Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
V9GY75V9GY75_HUMAN
C-1-tetrahydrofolate synthase, cyto...
MTHFD1
68Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
V9GZ78V9GZ78_HUMAN
C-1-tetrahydrofolate synthase, cyto...
MTHFD1
25Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
V9GZ32V9GZ32_HUMAN
C-1-tetrahydrofolate synthase, cyto...
MTHFD1
23Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07407549S → F in CIMAH. 1 Publication1
Natural variantiVAR_08087351L → P in CIMAH. 1 Publication1
Natural variantiVAR_016232134R → K Associated with increased risk of colorectal cancer. Combined sources3 PublicationsCorresponds to variant dbSNP:rs1950902Ensembl.1
Natural variantiVAR_055458162P → L. Corresponds to variant dbSNP:rs4902283Ensembl.1
Natural variantiVAR_074076173R → C in CIMAH. 1 Publication1
Natural variantiVAR_080874225 – 935Missing in CIMAH. 1 PublicationAdd BLAST711
Natural variantiVAR_074077269T → I in CIMAH. 1 Publication1
Natural variantiVAR_010241293R → H in NTDFS; associated with disease susceptibility. Corresponds to variant dbSNP:rs34181110EnsemblClinVar.1
Natural variantiVAR_010251653R → 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_032789761T → M. Corresponds to variant dbSNP:rs10813Ensembl.1
Natural variantiVAR_032790769L → F1 PublicationCorresponds to variant dbSNP:rs17857382Ensembl.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
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

Protein sequence database of the Protein Information Resource

More...
PIRi
A31903

NCBI Reference Sequences

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RefSeqi
NP_005947.3, NM_005956.3

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.652308

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000216605; ENSP00000216605; ENSG00000100714
ENST00000555709; ENSP00000450560; ENSG00000100714

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
4522

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:4522

UCSC genome browser

More...
UCSCi
uc001xhb.4 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<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

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
CCDSiCCDS9763.1
PIRiA31903
RefSeqiNP_005947.3, NM_005956.3
UniGeneiHs.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 entryMethodResolution (Å)ChainPositionsPDBsum
1A4IX-ray1.50A/B1-301[»]
1DIAX-ray2.20A/B1-306[»]
1DIBX-ray2.70A/B1-306[»]
1DIGX-ray2.20A/B1-306[»]
ProteinModelPortaliP11586
SMRiP11586
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110622, 88 interactors
DIPiDIP-33682N
IntActiP11586, 22 interactors
MINTiP11586
STRINGi9606.ENSP00000450560

Chemistry databases

BindingDBiP11586
ChEMBLiCHEMBL2541
DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
DB04322 LY249543
DB02358 LY374571
DB00157 NADH
DB00116 Tetrahydrofolic acid

PTM databases

iPTMnetiP11586
PhosphoSitePlusiP11586
SwissPalmiP11586

Polymorphism and mutation databases

BioMutaiMTHFD1
DMDMi115206

2D gel databases

REPRODUCTION-2DPAGEiIPI00218342
SWISS-2DPAGEiP11586

Proteomic databases

EPDiP11586
MaxQBiP11586
PaxDbiP11586
PeptideAtlasiP11586
PRIDEiP11586
ProteomicsDBi52794

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
4522
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216605; ENSP00000216605; ENSG00000100714
ENST00000555709; ENSP00000450560; ENSG00000100714
GeneIDi4522
KEGGihsa:4522
UCSCiuc001xhb.4 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
4522
DisGeNETi4522
EuPathDBiHostDB:ENSG00000100714.15

GeneCards: human genes, protein and diseases

More...
GeneCardsi
MTHFD1

H-Invitational Database, human transcriptome db

More...
H-InvDBi
HIX0011731
HGNCiHGNC:7432 MTHFD1
HPAiHPA000704
HPA001290
HPA015006
HPA050052
MalaCardsiMTHFD1
MIMi114500 phenotype
172460 gene+phenotype
601634 phenotype
617780 phenotype
neXtProtiNX_P11586
Orphaneti268392 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
PharmGKBiPA31236

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4230 Eukaryota
COG0190 LUCA
COG2759 LUCA
HOVERGENiHBG004916
InParanoidiP11586
KOiK00288
PhylomeDBiP11586
TreeFamiTF300623

Enzyme and pathway databases

UniPathwayi
UPA00193

BioCyciMetaCyc:HS02138-MONOMER
BRENDAi1.5.1.5 2681
3.5.4.9 2681
6.3.4.3 2681
ReactomeiR-HSA-196757 Metabolism of folate and pterines

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
MTHFD1 human
EvolutionaryTraceiP11586

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
MTHFD1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
4522

Protein Ontology

More...
PROi
PR:P11586

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000100714 Expressed in 232 organ(s), highest expression level in right lobe of liver
CleanExiHS_MTHFD1
ExpressionAtlasiP11586 baseline and differential
GenevisibleiP11586 HS

Family and domain databases

CDDicd00477 FTHFS, 1 hit
HAMAPiMF_01543 FTHFS, 1 hit
MF_01576 THF_DHG_CYH, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF01268 FTHFS, 1 hit
PF00763 THF_DHG_CYH, 1 hit
PF02882 THF_DHG_CYH_C, 1 hit
PRINTSiPR00085 THFDHDRGNASE
SUPFAMiSSF51735 SSF51735, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView 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

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<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 subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiC1TC_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P11586
Secondary accession number(s): B2R5Y2
, G3V2B8, Q86VC9, Q9BVP5
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: December 5, 2018
This is version 214 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<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

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

Documents

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