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P49914 (MTHFS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended 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 names
Name:MTHFS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length203 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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

Cofactor

Magnesium.

Subunit structure

Monomer.

Subcellular location

Cytoplasm.

Sequence similarities

Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 2032035-formyltetrahydrofolate cyclo-ligase
PRO_0000200275

Regions

Nucleotide binding10 – 145ATP
Nucleotide binding147 – 1548ATP
Region148 – 1525Substrate binding

Sites

Binding site611Substrate
Binding site1091Substrate
Binding site1891ATP

Natural variations

Natural variant2021T → A.
Corresponds to variant rs8923 [ dbSNP | Ensembl ].
VAR_034115

Experimental info

Mutagenesis101K → A: Reduces activity by 93%. Ref.4
Mutagenesis141R → A: Reduces activity by 87%. Ref.4
Mutagenesis611E → A: Reduces activity by 94%.
Mutagenesis1451R → A: Reduces activity by 98%. Ref.4
Mutagenesis1531Y → A: Reduces activity by 97%. Ref.4
Mutagenesis1541D → A: Reduces activity by 99%. Ref.4

Secondary structure

1 ................................... 203
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P49914 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 658C4AE8FC7AB3F2

FASTA20323,256
        10         20         30         40         50         60 
MAAAAVSSAK RSLRGELKQR LRAMSAEERL RQSRVLSQKV IAHSEYQKSK RISIFLSMQD 

        70         80         90        100        110        120 
EIETEEIIKD IFQRGKICFI PRYRFQSNHM DMVRIESPEE ISLLPKTSWN IPQPGEGDVR 

       130        140        150        160        170        180 
EEALSTGGLD LIFMPGLGFD KHGNRLGRGK GYYDAYLKRC LQHQEVKPYT LALAFKEQIC 

       190        200 
LQVPVNENDM KVDEVLYEDS STA

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of the human 5,10-methenyltetrahydrofolate synthetase-encoding cDNA."
Dayan A., Bertrand R., Beauchemin M., Chahla D., Mamo A., Filion M., Skup D., Massie B., Jolivet J.
Gene 165:307-311(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[3]"Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates."
Bertrand R., MacKenzie R.E., Jolivet J.
Biochim. Biophys. Acta 911:154-161(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[4]"Structural basis for the inhibition of human 5,10-methenyltetrahydrofolate synthetase by N10-substituted folate analogues."
Wu D., Li Y., Song G., Cheng C., Zhang R., Joachimiak A., Shaw N., Liu Z.-J.
Cancer Res. 69:7294-7301(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE; PRODUCT; ADP AND MAGNESIUM IONS, MUTAGENESIS OF LYS-10; ARG-14; ARG-145; TYR-153 AND ASP-154.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		L38928 mRNA. Translation: AAC41945.1.
BC019921 mRNA. Translation: AAH19921.1.
IPIIPI00220567.
PIRJC4389.
RefSeqNP_001186687.1. NM_001199758.1.
NP_006432.1. NM_006441.3.
UniGeneHs.194294.
Hs.459049.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3HXTX-ray1.90A1-203[»]
3HY3X-ray1.80A1-203[»]
3HY4X-ray2.80A1-203[»]
3HY6X-ray2.10A1-203[»]
ProteinModelPortalP49914.
ModBaseSearch...

Protein-protein interaction databases

IntActP49914. 1 interaction.
STRING9606.ENSP00000258874.

PTM databases

PhosphoSiteP49914.

Polymorphism databases

DMDM1706921.

Proteomic databases

PaxDbP49914.
PRIDEP49914.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258874; ENSP00000258874; ENSG00000136371.
GeneID10588.
KEGGhsa:10588.
UCSCuc002bex.4. human.

Organism-specific databases

CTD10588.
GeneCardsGC15M080125.
HGNCHGNC:7437. MTHFS.
HPAHPA008067.
MIM604197. gene.
neXtProtNX_P49914.
PharmGKBPA31239.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0212.
HOGENOMHOG000007299.
HOVERGENHBG052525.
InParanoidP49914.
KOK01934.
OMANENDMKV.
OrthoDBEOG4BG8X3.
PhylomeDBP49914.

Gene expression databases

ArrayExpressP49914.
BgeeP49914.
CleanExHS_MTHFS.
GenevestigatorP49914.
GermOnlineENSG00000136371. Homo sapiens.

Family and domain databases

Gene3D3.40.50.10420. 1 hit.
InterProIPR002698. FTHF_cligase.
IPR024185. FTHF_cligase-like.
[Graphical view]
PANTHERPTHR23407:SF1. PTHR23407:SF1. 1 hit.
PfamPF01812. 5-FTHF_cyc-lig. 1 hit.
[Graphical view]
PIRSFPIRSF006806. FTHF_cligase. 1 hit.
TIGRFAMsTIGR02727. MTHFS_bact. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP49914.
GenomeRNAi10588.
NextBio40207.
SOURCESearch...

Entry information

Entry nameMTHFS_HUMAN
AccessionPrimary (citable) accession number: P49914
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents