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Protein

5-formyltetrahydrofolate cyclo-ligase

Gene

MTHFS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate.1 Publication

Catalytic activityi

ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate.1 Publication

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei14ATP1
Binding sitei56Substrate; via carbonyl oxygen1
Binding sitei61Substrate1
Metal bindingi154MagnesiumBy similarity1
Metal bindingi189MagnesiumBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 14ATP5
Nucleotide bindingi145 – 153ATP9

GO - Molecular functioni

  • 5-formyltetrahydrofolate cyclo-ligase activity Source: UniProtKB
  • ATP binding Source: BHF-UCL
  • folic acid binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • folic acid catabolic process Source: BHF-UCL
  • folic acid-containing compound biosynthetic process Source: GO_Central
  • folic acid metabolic process Source: Reactome
  • formate metabolic process Source: UniProtKB
  • glutamate metabolic process Source: BHF-UCL
  • tetrahydrofolate interconversion Source: BHF-UCL
  • tetrahydrofolate metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Ligandi

ATP-binding, Folate-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06152-MONOMER.
BRENDAi6.3.3.2. 2681.
ReactomeiR-HSA-196757. Metabolism of folate and pterines.

Names & Taxonomyi

Protein namesi
Recommended name:
5-formyltetrahydrofolate cyclo-ligase (EC:6.3.3.2)
Alternative name(s):
5,10-methenyl-tetrahydrofolate synthetase
Short name:
MTHFS
Short name:
Methenyl-THF synthetase
Gene namesi
Name:MTHFS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:7437. MTHFS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • mitochondrial matrix Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10K → A: Reduces activity by 93%. 1 Publication1
Mutagenesisi14R → A: Reduces activity by 87%. 1 Publication1
Mutagenesisi61E → A: Reduces activity by 94%. 1
Mutagenesisi145R → A: Reduces activity by 98%. 1 Publication1
Mutagenesisi153Y → A: Reduces activity by 97%. 1 Publication1
Mutagenesisi154D → A: Reduces activity by 99%. 1 Publication1

Organism-specific databases

DisGeNETi10588.
OpenTargetsiENSG00000136371.
ENSG00000259332.
PharmGKBiPA31239.

Polymorphism and mutation databases

BioMutaiMTHFS.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002002752 – 2035-formyltetrahydrofolate cyclo-ligaseAdd BLAST202

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP49914.
MaxQBiP49914.
PaxDbiP49914.
PeptideAtlasiP49914.
PRIDEiP49914.

PTM databases

iPTMnetiP49914.
PhosphoSitePlusiP49914.

Expressioni

Gene expression databases

BgeeiENSG00000136371.
CleanExiHS_MTHFS.
ExpressionAtlasiP49914. baseline and differential.
GenevisibleiP49914. HS.

Organism-specific databases

HPAiHPA008067.
HPA054177.

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi115837. 3 interactors.
IntActiP49914. 1 interactor.
STRINGi9606.ENSP00000258874.

Structurei

Secondary structure

1203
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 22Combined sources21
Helixi26 – 41Combined sources16
Helixi44 – 48Combined sources5
Beta strandi50 – 53Combined sources4
Helixi65 – 73Combined sources9
Beta strandi77 – 84Combined sources8
Turni85 – 88Combined sources4
Beta strandi89 – 95Combined sources7
Helixi98 – 101Combined sources4
Helixi123 – 125Combined sources3
Beta strandi130 – 134Combined sources5
Beta strandi137 – 139Combined sources3
Beta strandi148 – 150Combined sources3
Helixi152 – 160Combined sources9
Turni161 – 163Combined sources3
Beta strandi169 – 173Combined sources5
Helixi176 – 178Combined sources3
Beta strandi179 – 181Combined sources3
Beta strandi193 – 196Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3HXTX-ray1.90A1-203[»]
3HY3X-ray1.80A1-203[»]
3HY4X-ray2.80A1-203[»]
3HY6X-ray2.10A1-203[»]
ProteinModelPortaliP49914.
SMRiP49914.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49914.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni148 – 152Substrate binding5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3093. Eukaryota.
COG0212. LUCA.
GeneTreeiENSGT00390000017791.
HOGENOMiHOG000007299.
HOVERGENiHBG052525.
InParanoidiP49914.
KOiK01934.
OMAiKTSWNIP.
OrthoDBiEOG091G0Q5W.
PhylomeDBiP49914.
TreeFamiTF313668.

Family and domain databases

Gene3Di3.40.50.10420. 1 hit.
InterProiIPR002698. FTHF_cligase.
IPR024185. FTHF_cligase-like.
[Graphical view]
PANTHERiPTHR23407:SF1. PTHR23407:SF1. 1 hit.
PfamiPF01812. 5-FTHF_cyc-lig. 1 hit.
[Graphical view]
PIRSFiPIRSF006806. FTHF_cligase. 1 hit.
TIGRFAMsiTIGR02727. MTHFS_bact. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49914-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAAAVSSAK RSLRGELKQR LRAMSAEERL RQSRVLSQKV IAHSEYQKSK
60 70 80 90 100
RISIFLSMQD EIETEEIIKD IFQRGKICFI PRYRFQSNHM DMVRIESPEE
110 120 130 140 150
ISLLPKTSWN IPQPGEGDVR EEALSTGGLD LIFMPGLGFD KHGNRLGRGK
160 170 180 190 200
GYYDAYLKRC LQHQEVKPYT LALAFKEQIC LQVPVNENDM KVDEVLYEDS

STA
Length:203
Mass (Da):23,256
Last modified:January 23, 2007 - v2
Checksum:i658C4AE8FC7AB3F2
GO
Isoform 2 (identifier: P49914-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MAAAAVSSAKRSLRGELKQRLRAMSAEERLRQSRVLSQK → MARSRLTATSVSQVQ

Note: No experimental confirmation available.
Show »
Length:179
Mass (Da):20,519
Checksum:iDE1ACF55C16F8B49
GO

Sequence cautioni

The sequence CK002935 differs from that shown. Reason: Frameshift at positions 178 and 201.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti177E → D in CK002935 (PubMed:15489334).Curated1
Sequence conflicti203A → T in CK002935 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034115202T → A.Corresponds to variant rs8923dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0468631 – 39MAAAA…VLSQK → MARSRLTATSVSQVQ in isoform 2. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L38928 mRNA. Translation: AAC41945.1.
AC015871 Genomic DNA. No translation available.
AC021483 Genomic DNA. No translation available.
BC019921 mRNA. Translation: AAH19921.1.
CK002935 mRNA. No translation available.
CCDSiCCDS10311.1. [P49914-1]
PIRiJC4389.
RefSeqiNP_001186687.1. NM_001199758.1.
NP_006432.1. NM_006441.3. [P49914-1]
UniGeneiHs.194294.
Hs.459049.

Genome annotation databases

EnsembliENST00000258874; ENSP00000258874; ENSG00000136371. [P49914-1]
GeneIDi10588.
KEGGihsa:10588.
UCSCiuc002bex.5. human. [P49914-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L38928 mRNA. Translation: AAC41945.1.
AC015871 Genomic DNA. No translation available.
AC021483 Genomic DNA. No translation available.
BC019921 mRNA. Translation: AAH19921.1.
CK002935 mRNA. No translation available.
CCDSiCCDS10311.1. [P49914-1]
PIRiJC4389.
RefSeqiNP_001186687.1. NM_001199758.1.
NP_006432.1. NM_006441.3. [P49914-1]
UniGeneiHs.194294.
Hs.459049.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3HXTX-ray1.90A1-203[»]
3HY3X-ray1.80A1-203[»]
3HY4X-ray2.80A1-203[»]
3HY6X-ray2.10A1-203[»]
ProteinModelPortaliP49914.
SMRiP49914.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115837. 3 interactors.
IntActiP49914. 1 interactor.
STRINGi9606.ENSP00000258874.

PTM databases

iPTMnetiP49914.
PhosphoSitePlusiP49914.

Polymorphism and mutation databases

BioMutaiMTHFS.

Proteomic databases

EPDiP49914.
MaxQBiP49914.
PaxDbiP49914.
PeptideAtlasiP49914.
PRIDEiP49914.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258874; ENSP00000258874; ENSG00000136371. [P49914-1]
GeneIDi10588.
KEGGihsa:10588.
UCSCiuc002bex.5. human. [P49914-1]

Organism-specific databases

CTDi10588.
DisGeNETi10588.
GeneCardsiMTHFS.
HGNCiHGNC:7437. MTHFS.
HPAiHPA008067.
HPA054177.
MIMi604197. gene.
neXtProtiNX_P49914.
OpenTargetsiENSG00000136371.
ENSG00000259332.
PharmGKBiPA31239.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3093. Eukaryota.
COG0212. LUCA.
GeneTreeiENSGT00390000017791.
HOGENOMiHOG000007299.
HOVERGENiHBG052525.
InParanoidiP49914.
KOiK01934.
OMAiKTSWNIP.
OrthoDBiEOG091G0Q5W.
PhylomeDBiP49914.
TreeFamiTF313668.

Enzyme and pathway databases

BioCyciZFISH:HS06152-MONOMER.
BRENDAi6.3.3.2. 2681.
ReactomeiR-HSA-196757. Metabolism of folate and pterines.

Miscellaneous databases

ChiTaRSiMTHFS. human.
EvolutionaryTraceiP49914.
GenomeRNAii10588.
PROiP49914.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136371.
CleanExiHS_MTHFS.
ExpressionAtlasiP49914. baseline and differential.
GenevisibleiP49914. HS.

Family and domain databases

Gene3Di3.40.50.10420. 1 hit.
InterProiIPR002698. FTHF_cligase.
IPR024185. FTHF_cligase-like.
[Graphical view]
PANTHERiPTHR23407:SF1. PTHR23407:SF1. 1 hit.
PfamiPF01812. 5-FTHF_cyc-lig. 1 hit.
[Graphical view]
PIRSFiPIRSF006806. FTHF_cligase. 1 hit.
TIGRFAMsiTIGR02727. MTHFS_bact. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiMTHFS_HUMAN
AccessioniPrimary (citable) accession number: P49914
Secondary accession number(s): H3BQ75
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.