5-formyltetrahydrofolate cyclo-ligase

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P49914 (MTHFS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 101. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:

MTHFS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	203 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Folate-binding Magnesium Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	folic acid-containing compound biosynthetic process Inferred from electronic annotation. Source: InterPro formate metabolic process Non-traceable author statement Ref.1. Source: UniProtKB tetrahydrofolate metabolic process Inferred from direct assay Ref.6. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA cytosol Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA
Molecular function	5-formyltetrahydrofolate cyclo-ligase activity Inferred from direct assay Ref.6. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW folic acid binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed

Chain

2 – 203

202

5-formyltetrahydrofolate cyclo-ligase

PRO_0000200275

Regions

Nucleotide binding

10 – 14

ATP

Nucleotide binding

147 – 154

ATP

Region

148 – 152

Substrate binding

Sites

Binding site

Substrate

Binding site

109

Substrate

Binding site

189

ATP

Amino acid modifications

Modified residue

N-acetylalanine Ref.4

Natural variations

Natural variant

202

T → A.
Corresponds to variant rs8923 [ dbSNP | Ensembl ].

VAR_034115

Experimental info

Mutagenesis

K → A: Reduces activity by 93%. Ref.6

Mutagenesis

R → A: Reduces activity by 87%. Ref.6

Mutagenesis

E → A: Reduces activity by 94%.

Mutagenesis

145

R → A: Reduces activity by 98%. Ref.6

Mutagenesis

153

Y → A: Reduces activity by 97%. Ref.6

Mutagenesis

154

D → A: Reduces activity by 99%. Ref.6

Secondary structure

203

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P49914 [UniParc].

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

FASTA

203

23,256

        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' referencesShow '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: 8522195] [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: 15489334] [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: 3801490] [Abstract] Cited for: CHARACTERIZATION.
[4]	"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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[5]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]	"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: 19738041] [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.

IPI

IPI00220567.

PIR

JC4389.

RefSeq

NP_001186687.1. NM_001199758.1.
NP_006432.1. NM_006441.3.

UniGene

Hs.194294.
Hs.459049.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3HXT	X-ray	1.90	A	1-203	[»]
3HY3	X-ray	1.80	A	1-203	[»]
3HY4	X-ray	2.80	A	1-203	[»]
3HY6	X-ray	2.10	A	1-203	[»]

ProteinModelPortal

P49914.

SMR

P49914. Positions 1-198.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49914. 1 interaction.

STRING

P49914.

PTM databases

PhosphoSite

P49914.

Polymorphism databases

DMDM

1706921.

Proteomic databases

PRIDE

P49914.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258874; ENSP00000258874; ENSG00000136371.

GeneID

10588.

KEGG

hsa:10588.

UCSC

uc002bex.2. human.

Organism-specific databases

CTD

10588.

GeneCards

GC15M080137.

H-InvDB

HIX0012486.

HGNC

HGNC:7437. MTHFS.

HPA

HPA008067.

MIM

604197. gene.

neXtProt

NX_P49914.

PharmGKB

PA31239.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08884.

HOGENOM

HBG325345.

HOVERGEN

HBG052525.

InParanoid

P49914.

OMA

EYQKSKR.

OrthoDB

EOG4BG8X3.

PhylomeDB

P49914.

Gene expression databases

ArrayExpress

P49914.

Bgee

P49914.

CleanEx

HS_MTHFS.

Genevestigator

P49914.

GermOnline

ENSG00000136371. Homo sapiens.

Family and domain databases

InterPro

IPR002698. FTHF_cligase.
IPR024185. FTHF_cligase-like.
[Graphical view]

Gene3D

G3DSA:3.40.50.10420. FTHF_cligase. 1 hit.

K01934.

Pfam

PF01812. 5-FTHF_cyc-lig. 1 hit.
[Graphical view]

PIRSF

PIRSF006806. FTHF_cligase. 1 hit.

TIGRFAMs

TIGR02727. MTHFS_bact. 1 hit.

ProtoNet

Search...

Other

NextBio

40207.

SOURCE

Search...

Entry information

Entry name

MTHFS_HUMAN

Accession

Primary (citable) accession number: P49914

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents