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P49914 (MTHFS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

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 lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length203 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
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 caution

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

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49914-1)

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.
Isoform 2 (identifier: P49914-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MAAAAVSSAKRSLRGELKQRLRAMSAEERLRQSRVLSQK → MARSRLTATSVSQVQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 2032025-formyltetrahydrofolate cyclo-ligase
PRO_0000200275

Regions

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

Sites

Binding site611Substrate
Binding site1091Substrate
Binding site1891ATP

Amino acid modifications

Modified residue21N-acetylalanine Ref.5 Ref.7

Natural variations

Alternative sequence1 – 3939MAAAA…VLSQK → MARSRLTATSVSQVQ in isoform 2.
VSP_046863
Natural variant2021T → A.
Corresponds to variant rs8923 [ dbSNP | Ensembl ].
VAR_034115

Experimental info

Mutagenesis101K → A: Reduces activity by 93%. Ref.8
Mutagenesis141R → A: Reduces activity by 87%. Ref.8
Mutagenesis611E → A: Reduces activity by 94%.
Mutagenesis1451R → A: Reduces activity by 98%. Ref.8
Mutagenesis1531Y → A: Reduces activity by 97%. Ref.8
Mutagenesis1541D → A: Reduces activity by 99%. Ref.8
Sequence conflict1771E → D in CK002935. Ref.3
Sequence conflict2031A → T in CK002935. Ref.3

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [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

Isoform 2 [UniParc].

Checksum: DE1ACF55C16F8B49
Show »

FASTA17920,519

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] (ISOFORM 1).
Tissue: Liver.
[2]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] (ISOFORMS 1 AND 2).
Tissue: Brain cortex and Pancreas.
[4]"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.
[5]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"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.
AC015871 Genomic DNA. No translation available.
AC021483 Genomic DNA. No translation available.
BC019921 mRNA. Translation: AAH19921.1.
CK002935 mRNA. No translation available.
CCDSCCDS10311.1. [P49914-1]
PIRJC4389.
RefSeqNP_001186687.1. NM_001199758.1.
NP_001186689.1. NM_001199760.1. [P49914-2]
NP_006432.1. NM_006441.3. [P49914-1]
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.
SMRP49914. Positions 1-198.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115837. 2 interactions.
IntActP49914. 1 interaction.
STRING9606.ENSP00000258874.

PTM databases

PhosphoSiteP49914.

Proteomic databases

MaxQBP49914.
PaxDbP49914.
PRIDEP49914.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258874; ENSP00000258874; ENSG00000136371. [P49914-1]
GeneID100528021.
10588.
KEGGhsa:100528021.
hsa:10588.
UCSCuc002bex.4. human. [P49914-1]

Organism-specific databases

CTD100528021.
10588.
GeneCardsGC15M080125.
GC15M080140.
HGNCHGNC:7437. MTHFS.
HPAHPA008067.
HPA054177.
MIM604197. gene.
neXtProtNX_P49914.
PharmGKBPA31239.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0212.
HOGENOMHOG000007299.
HOVERGENHBG052525.
InParanoidP49914.
KOK01934.
OMAKTSWNIP.
OrthoDBEOG73806H.
PhylomeDBP49914.
TreeFamTF313668.

Gene expression databases

BgeeP49914.
CleanExHS_MTHFS.
GenevestigatorP49914.

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.
NextBio34054968.
PROP49914.
SOURCESearch...

Entry information

Entry nameMTHFS_HUMAN
AccessionPrimary (citable) accession number: P49914
Secondary accession number(s): H3BQ75
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 125 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

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