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UniProtKB - P11586 (C1TC_HUMAN)

Entry version 234 (02 Jun 2021)
Sequence version 4 (02 Jun 2021)
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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%5Fsection">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%5Fsection">'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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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

More...BioCyci		MetaCyc:HS02138-MONOMER

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		1.5.1.5, 2681
3.5.4.9, 2681
6.3.3.2, 2681
6.3.4.3, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P11586

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%5Fand%5Ftaxonomy%5Fsection">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
Alternative name(s):
Epididymis secretory sperm binding protein1 Publication
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)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fmanual">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

Human Gene Nomenclature Database

More...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

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000100714.15

<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

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 variants affecting the gene represented in this entry.
Disease descriptionThe most common NTDs are open spina bifida (myelomeningocele) and anencephaly.
Related information in OMIM
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 variants affecting the gene represented in this entry. Susceptibility to colorectal cancer may be associated with the missense variant p.Arg134Lys, which has been observed in about 16% of the human population. The sequence shown in this entry represents the minor allele, as it is reported in the reference genome.1 Publication
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.
Related information in OMIM
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia (CIMAH)3 Publications
The disease is caused by variants 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07407549S → F in CIMAH. 1 PublicationCorresponds to variant dbSNP:rs370444838EnsemblClinVar.1
Natural variantiVAR_08087351L → P in CIMAH. 1 PublicationCorresponds to variant dbSNP:rs1555336810EnsemblClinVar.1
Natural variantiVAR_074076173R → C in CIMAH. 1 PublicationCorresponds to variant dbSNP:rs141210410EnsemblClinVar.1
Natural variantiVAR_080874225 – 935Missing in CIMAH. 1 PublicationAdd BLAST711
Natural variantiVAR_074077269T → I in CIMAH. 1 PublicationCorresponds to variant dbSNP:rs1555337681EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'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 variant

Organism-specific databases

DisGeNET

More...DisGeNETi		4522

MalaCards human disease database

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

Open Targets

More...OpenTargetsi		ENSG00000100714

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

More...PharmGKBi		PA31236

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P11586, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2541

Drug and drug target database

More...DrugBanki		DB04322, LY249543
DB02358, LY374571
DB00157, NADH
DB03461, Nicotinamide adenine dinucleotide phosphate
DB00116, Tetrahydrofolic acid

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		MTHFD1

Domain mapping of disease mutations (DMDM)

More...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 or proteolytic cleavage.<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%5Fprocessing%5Fsection">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

The CPTAC Assay portal

More...CPTACi		CPTAC-407
CPTAC-408

Encyclopedia of Proteome Dynamics

More...EPDi		P11586

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P11586

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P11586

MaxQB - The MaxQuant DataBase

More...MaxQBi		P11586

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

More...PaxDbi		P11586

PeptideAtlas

More...PeptideAtlasi		P11586

PRoteomics IDEntifications database

More...PRIDEi		P11586

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		32586
52794

2D gel databases

REPRODUCTION-2DPAGE

More...REPRODUCTION-2DPAGEi		IPI00218342

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

More...SWISS-2DPAGEi		P11586

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P11586

MetOSite database of methionine sulfoxide sites

More...MetOSitei		P11586

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

More...PhosphoSitePlusi		P11586

SwissPalm database of S-palmitoylation events

More...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 right lobe of liver and 244 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P11586, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P11586, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000100714, Tissue enriched (liver)

<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%5Fsection">'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%5Fsection">'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%5Fsection">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		110622, 145 interactors

Database of interacting proteins

More...DIPi		DIP-33682N

Protein interaction database and analysis system

More...IntActi		P11586, 40 interactors

Molecular INTeraction database

More...MINTi		P11586

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000216605

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P11586

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P11586, protein

<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

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

More...SMRi		P11586

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		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

Ensembl GeneTree

More...GeneTreei		ENSGT00940000154746

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_034045_3_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P11586

Identification of Orthologs from Complete Genome Data

More...OMAi		KVDTYTK

Database of Orthologous Groups

More...OrthoDBi		690393at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P11586

TreeFam database of animal gene trees

More...TreeFami		TF300623

Family and domain databases

Conserved Domains Database

More...CDDi		cd01080, NAD_bind_m-THF_DH_Cyclohyd, 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%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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 6 potential isoforms that are computationally mapped.Show allAlign All

P11586-1 [UniParc]FASTAAdd to basket
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MAPAEILNGK EISAQIRARL KNQVTQLKEQ VPGFTPRLAI LQVGNRDDSN 
        60         70         80         90        100
LYINVKLKAA EEIGIKATHI KLPRTTTESE VMKYITSLNE DSTVHGFLVQ 
       110        120        130        140        150
LPLDSENSIN TEEVINAIAP EKDVDGLTSI NAGKLARGDL 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):101,531
Last modified:June 2, 2021 - v4
<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:iB834DB504BC1869A
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 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H2F4F5H2F4_HUMAN
C-1-tetrahydrofolate synthase, cyto...
MTHFD1
964Annotation score:

Annotation score:4 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
922Annotation score:

Annotation score:3 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
854Annotation score:

Annotation score:3 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>
A0A494C1T2A0A494C1T2_HUMAN
C-1-tetrahydrofolate synthase, cyto...
MTHFD1
644Annotation score:

Annotation score:2 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>
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 PublicationCorresponds to variant dbSNP:rs370444838EnsemblClinVar.1
Natural variantiVAR_08087351L → P in CIMAH. 1 PublicationCorresponds to variant dbSNP:rs1555336810EnsemblClinVar.1
Natural variantiVAR_016232134K → R. Corresponds to variant dbSNP:rs1950902EnsemblClinVar.1
Natural variantiVAR_055458162P → L. Corresponds to variant dbSNP:rs4902283Ensembl.1
Natural variantiVAR_074076173R → C in CIMAH. 1 PublicationCorresponds to variant dbSNP:rs141210410EnsemblClinVar.1
Natural variantiVAR_080874225 – 935Missing in CIMAH. 1 PublicationAdd BLAST711
Natural variantiVAR_074077269T → I in CIMAH. 1 PublicationCorresponds to variant dbSNP:rs1555337681EnsemblClinVar.1
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:rs17857382EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
J04031 mRNA Translation: AAA59574.1
AK312361 mRNA Translation: BAG35279.1
GQ891332 mRNA Translation: ADO22194.1
AL122035 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW80857.1
CH471061 Genomic DNA Translation: EAW80858.1
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

More...RefSeqi		NP_005947.3, NM_005956.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		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

<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
GQ891332 mRNA Translation: ADO22194.1
AL122035 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW80857.1
CH471061 Genomic DNA Translation: EAW80858.1
BC001014 mRNA Translation: AAH01014.2
BC009806 mRNA Translation: AAH09806.1
BC050420 mRNA Translation: AAH50420.1
CCDSiCCDS9763.1
PIRiA31903
RefSeqiNP_005947.3, NM_005956.3

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[»]
6ECPX-ray2.20A/B1-306[»]
6ECQX-ray2.70A/B1-296[»]
6ECRX-ray2.20A/B1-296[»]
SMRiP11586
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi110622, 145 interactors
DIPiDIP-33682N
IntActiP11586, 40 interactors
MINTiP11586
STRINGi9606.ENSP00000216605

Chemistry databases

BindingDBiP11586
ChEMBLiCHEMBL2541
DrugBankiDB04322, LY249543
DB02358, LY374571
DB00157, NADH
DB03461, Nicotinamide adenine dinucleotide phosphate
DB00116, Tetrahydrofolic acid

PTM databases

iPTMnetiP11586
MetOSiteiP11586
PhosphoSitePlusiP11586
SwissPalmiP11586

Genetic variation databases

BioMutaiMTHFD1
DMDMi115206

2D gel databases

REPRODUCTION-2DPAGEiIPI00218342
SWISS-2DPAGEiP11586

Proteomic databases

CPTACiCPTAC-407
CPTAC-408
EPDiP11586
jPOSTiP11586
MassIVEiP11586
MaxQBiP11586
PaxDbiP11586
PeptideAtlasiP11586
PRIDEiP11586
ProteomicsDBi32586
52794

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		P11586, 1 sequenced antibody

Antibodypedia a portal for validated antibodies

More...Antibodypediai		52, 169 antibodies

The DNASU plasmid repository

More...DNASUi		4522

Genome annotation databases

EnsembliENST00000555709; ENSP00000450560; ENSG00000100714
GeneIDi4522
KEGGihsa:4522
UCSCiuc001xhb.4, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		4522
DisGeNETi4522

GeneCards: human genes, protein and diseases

More...GeneCardsi		MTHFD1
HGNCiHGNC:7432, MTHFD1
HPAiENSG00000100714, Tissue enriched (liver)
MalaCardsiMTHFD1
MIMi114500, phenotype
172460, gene+phenotype
601634, phenotype
617780, phenotype
neXtProtiNX_P11586
OpenTargetsiENSG00000100714
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
VEuPathDBiHostDB:ENSG00000100714.15

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG4230, Eukaryota
GeneTreeiENSGT00940000154746
HOGENOMiCLU_034045_3_0_1
InParanoidiP11586
OMAiKVDTYTK
OrthoDBi690393at2759
PhylomeDBiP11586
TreeFamiTF300623

Enzyme and pathway databases

UniPathwayiUPA00193
BioCyciMetaCyc:HS02138-MONOMER
BRENDAi1.5.1.5, 2681
3.5.4.9, 2681
6.3.3.2, 2681
6.3.4.3, 2681
PathwayCommonsiP11586
ReactomeiR-HSA-196757, Metabolism of folate and pterines

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		4522, 177 hits in 1006 CRISPR screens

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
PharosiP11586, Tbio

Protein Ontology

More...PROi		PR:P11586
RNActiP11586, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000100714, Expressed in right lobe of liver and 244 other tissues
ExpressionAtlasiP11586, baseline and differential
GenevisibleiP11586, HS

Family and domain databases

CDDicd01080, NAD_bind_m-THF_DH_Cyclohyd, 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

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		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): A0A024R652
, A0A384N5Y3, 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%5Fand%5Fisoforms">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: June 2, 2021
Last modified: June 2, 2021
This is version 234 of the entry and version 4 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, Direct protein sequencing, Reference proteome

Documents

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