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P49914

- MTHFS_HUMAN

UniProt

P49914 - MTHFS_HUMAN

Protein

5-formyltetrahydrofolate cyclo-ligase

Gene

MTHFS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
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    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

    Magnesium.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei14 – 141ATP
    Binding sitei56 – 561Substrate; via carbonyl oxygen
    Binding sitei61 – 611Substrate
    Metal bindingi154 – 1541MagnesiumBy similarity
    Metal bindingi189 – 1891MagnesiumBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi10 – 145ATP
    Nucleotide bindingi145 – 1539ATP

    GO - Molecular functioni

    1. 5-formyltetrahydrofolate cyclo-ligase activity Source: UniProtKB
    2. ATP binding Source: UniProtKB-KW
    3. folic acid binding Source: UniProtKB-KW

    GO - Biological processi

    1. folic acid-containing compound biosynthetic process Source: InterPro
    2. formate metabolic process Source: UniProtKB
    3. tetrahydrofolate metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Ligase

    Keywords - Ligandi

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

    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
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:7437. MTHFS.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: HPA

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi10 – 101K → A: Reduces activity by 93%. 1 Publication
    Mutagenesisi14 – 141R → A: Reduces activity by 87%. 1 Publication
    Mutagenesisi61 – 611E → A: Reduces activity by 94%.
    Mutagenesisi145 – 1451R → A: Reduces activity by 98%. 1 Publication
    Mutagenesisi153 – 1531Y → A: Reduces activity by 97%. 1 Publication
    Mutagenesisi154 – 1541D → A: Reduces activity by 99%. 1 Publication

    Organism-specific databases

    PharmGKBiPA31239.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 2032025-formyltetrahydrofolate cyclo-ligasePRO_0000200275Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine2 Publications

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP49914.
    PaxDbiP49914.
    PRIDEiP49914.

    PTM databases

    PhosphoSiteiP49914.

    Expressioni

    Gene expression databases

    BgeeiP49914.
    CleanExiHS_MTHFS.
    GenevestigatoriP49914.

    Organism-specific databases

    HPAiHPA008067.
    HPA054177.

    Interactioni

    Subunit structurei

    Monomer.

    Protein-protein interaction databases

    BioGridi115837. 2 interactions.
    IntActiP49914. 1 interaction.
    STRINGi9606.ENSP00000258874.

    Structurei

    Secondary structure

    1
    203
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi2 – 2221
    Helixi26 – 4116
    Helixi44 – 485
    Beta strandi50 – 534
    Helixi65 – 739
    Beta strandi77 – 848
    Turni85 – 884
    Beta strandi89 – 957
    Helixi98 – 1014
    Helixi123 – 1253
    Beta strandi130 – 1345
    Beta strandi137 – 1393
    Beta strandi148 – 1503
    Helixi152 – 1609
    Turni161 – 1633
    Beta strandi169 – 1735
    Helixi176 – 1783
    Beta strandi179 – 1813
    Beta strandi193 – 1964

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3HXTX-ray1.90A1-203[»]
    3HY3X-ray1.80A1-203[»]
    3HY4X-ray2.80A1-203[»]
    3HY6X-ray2.10A1-203[»]
    ProteinModelPortaliP49914.
    SMRiP49914. Positions 1-198.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP49914.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni148 – 1525Substrate binding

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0212.
    HOGENOMiHOG000007299.
    HOVERGENiHBG052525.
    InParanoidiP49914.
    KOiK01934.
    OMAiKTSWNIP.
    OrthoDBiEOG73806H.
    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. Align

    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

    MAAAAVSSAK RSLRGELKQR LRAMSAEERL RQSRVLSQKV IAHSEYQKSK    50
    RISIFLSMQD EIETEEIIKD IFQRGKICFI PRYRFQSNHM DMVRIESPEE 100
    ISLLPKTSWN IPQPGEGDVR EEALSTGGLD LIFMPGLGFD KHGNRLGRGK 150
    GYYDAYLKRC LQHQEVKPYT LALAFKEQIC LQVPVNENDM KVDEVLYEDS 200
    STA 203
    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti177 – 1771E → D in CK002935. (PubMed:15489334)Curated
    Sequence conflicti203 – 2031A → T in CK002935. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti202 – 2021T → A.
    Corresponds to variant rs8923 [ dbSNP | Ensembl ].
    VAR_034115

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3939MAAAA…VLSQK → MARSRLTATSVSQVQ in isoform 2. 1 PublicationVSP_046863Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_001186689.1. NM_001199760.1. [P49914-2]
    NP_006432.1. NM_006441.3. [P49914-1]
    UniGeneiHs.194294.
    Hs.459049.

    Genome annotation databases

    EnsembliENST00000258874; ENSP00000258874; ENSG00000136371. [P49914-1]
    GeneIDi100528021.
    10588.
    KEGGihsa:100528021.
    hsa:10588.
    UCSCiuc002bex.4. human. [P49914-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSi CCDS10311.1. [P49914-1 ]
    PIRi JC4389.
    RefSeqi NP_001186687.1. NM_001199758.1.
    NP_001186689.1. NM_001199760.1. [P49914-2 ]
    NP_006432.1. NM_006441.3. [P49914-1 ]
    UniGenei Hs.194294.
    Hs.459049.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali P49914.
    SMRi P49914. Positions 1-198.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115837. 2 interactions.
    IntActi P49914. 1 interaction.
    STRINGi 9606.ENSP00000258874.

    PTM databases

    PhosphoSitei P49914.

    Proteomic databases

    MaxQBi P49914.
    PaxDbi P49914.
    PRIDEi P49914.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000258874 ; ENSP00000258874 ; ENSG00000136371 . [P49914-1 ]
    GeneIDi 100528021.
    10588.
    KEGGi hsa:100528021.
    hsa:10588.
    UCSCi uc002bex.4. human. [P49914-1 ]

    Organism-specific databases

    CTDi 100528021.
    10588.
    GeneCardsi GC15M080125.
    GC15M080140.
    HGNCi HGNC:7437. MTHFS.
    HPAi HPA008067.
    HPA054177.
    MIMi 604197. gene.
    neXtProti NX_P49914.
    PharmGKBi PA31239.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0212.
    HOGENOMi HOG000007299.
    HOVERGENi HBG052525.
    InParanoidi P49914.
    KOi K01934.
    OMAi KTSWNIP.
    OrthoDBi EOG73806H.
    PhylomeDBi P49914.
    TreeFami TF313668.

    Miscellaneous databases

    EvolutionaryTracei P49914.
    NextBioi 34054968.
    PROi P49914.
    SOURCEi Search...

    Gene expression databases

    Bgeei P49914.
    CleanExi HS_MTHFS.
    Genevestigatori P49914.

    Family and domain databases

    Gene3Di 3.40.50.10420. 1 hit.
    InterProi IPR002698. FTHF_cligase.
    IPR024185. FTHF_cligase-like.
    [Graphical view ]
    PANTHERi PTHR23407:SF1. PTHR23407:SF1. 1 hit.
    Pfami PF01812. 5-FTHF_cyc-lig. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF006806. FTHF_cligase. 1 hit.
    TIGRFAMsi TIGR02727. MTHFS_bact. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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), FUNCTION, CATALYTIC ACTIVITY.
      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.
      , 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. 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.

    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: October 1, 2014
    This is version 127 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

    External Data

    Dasty 3