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Protein

5-formyltetrahydrofolate cyclo-ligase

Gene

MTHFS

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

Keywordsi

Molecular functionLigase
LigandATP-binding, Folate-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000136371.10
HGNCiHGNC:7437 MTHFS
MIMi604197 gene
neXtProtiNX_P49914

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

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
OMAiEMVACEY
OrthoDBiEOG091G0Q5W
PhylomeDBiP49914
TreeFamiTF313668

Family and domain databases

Gene3Di3.40.50.10420, 1 hit
InterProiView protein in InterPro
IPR002698 FTHF_cligase
IPR024185 FTHF_cligase-like_sf
IPR037171 NagB/RpiA_transferase-like
PANTHERiPTHR23407:SF1 PTHR23407:SF1, 1 hit
PfamiView protein in Pfam
PF01812 5-FTHF_cyc-lig, 1 hit
PIRSFiPIRSF006806 FTHF_cligase, 1 hit
SUPFAMiSSF100950 SSF100950, 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 dbSNP:rs8923Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiMTHFS_HUMAN
AccessioniPrimary (citable) accession number: P49914
Secondary accession number(s): H3BQ75
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 155 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health