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Q922D8

- C1TC_MOUSE

UniProt

Q922D8 - C1TC_MOUSE

Protein

C-1-tetrahydrofolate synthase, cytoplasmic

Gene

Mthfd1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 4 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Catalytic activityi

    5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH.
    5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate.
    ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei197 – 1971NADPBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi172 – 1743NADPBy similarity
    Nucleotide bindingi380 – 3878ATPBy similarity

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. formate-tetrahydrofolate ligase activity Source: RefGenome
    3. methenyltetrahydrofolate cyclohydrolase activity Source: RefGenome
    4. methylenetetrahydrofolate dehydrogenase (NADP+) activity Source: RefGenome

    GO - Biological processi

    1. folic acid-containing compound biosynthetic process Source: InterPro
    2. histidine biosynthetic process Source: UniProtKB-KW
    3. methionine biosynthetic process Source: UniProtKB-KW
    4. one-carbon metabolic process Source: RefGenome
    5. purine nucleotide biosynthetic process Source: UniProtKB-KW
    6. tetrahydrofolate interconversion Source: UniProtKB-UniPathway

    Keywords - Molecular functioni

    Hydrolase, Ligase, Oxidoreductase

    Keywords - Biological processi

    Amino-acid biosynthesis, Histidine biosynthesis, Methionine biosynthesis, One-carbon metabolism, Purine biosynthesis

    Keywords - Ligandi

    ATP-binding, NADP, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_220137. Metabolism of folate and pterines.
    UniPathwayiUPA00193.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    C-1-tetrahydrofolate synthase, cytoplasmic
    Short name:
    C1-THF synthase
    Cleaved into the following chain:
    Including the following 3 domains:
    Methylenetetrahydrofolate dehydrogenase (EC:1.5.1.5)
    Methenyltetrahydrofolate cyclohydrolase (EC:3.5.4.9)
    Formyltetrahydrofolate synthetase (EC:6.3.4.3)
    Gene namesi
    Name:Mthfd1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:1342005. Mthfd1.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytosol Source: RefGenome
    2. mitochondrion Source: MGI

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Knockout mice have revealed Mthfd1l as a monofunctional enzyme having only formyltetrahydrofolate synthetase activity and lacking methenyl-THF dehydrogenase and cyclohydrolase activities.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 935935C-1-tetrahydrofolate synthase, cytoplasmicPRO_0000199322Add
    BLAST
    Initiator methioninei1 – 11Removed; alternateBy similarity
    Chaini2 – 935934C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processedPRO_0000423281Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ922D8.
    PaxDbiQ922D8.
    PRIDEiQ922D8.

    2D gel databases

    REPRODUCTION-2DPAGEQ922D8.

    PTM databases

    PhosphoSiteiQ922D8.

    Expressioni

    Gene expression databases

    ArrayExpressiQ922D8.
    BgeeiQ922D8.
    GenevestigatoriQ922D8.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi223871. 1 interaction.
    IntActiQ922D8. 5 interactions.
    MINTiMINT-1856310.

    Structurei

    3D structure databases

    ProteinModelPortaliQ922D8.
    SMRiQ922D8. Positions 2-296, 316-935.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 305305Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd
    BLAST
    Regioni52 – 565Substrate bindingBy similarity
    Regioni99 – 1013Substrate bindingBy similarity
    Regioni272 – 2765Substrate bindingBy similarity
    Regioni306 – 935630Formyltetrahydrofolate synthetaseAdd
    BLAST

    Domaini

    This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity.

    Sequence similaritiesi

    In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.Curated
    In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.Curated

    Phylogenomic databases

    eggNOGiCOG0190.
    GeneTreeiENSGT00750000117401.
    HOVERGENiHBG004916.
    InParanoidiQ8R013.
    KOiK00288.
    OMAiKWNISYT.
    OrthoDBiEOG76T9QN.
    TreeFamiTF300623.

    Family and domain databases

    Gene3Di3.40.50.300. 2 hits.
    3.40.50.720. 1 hit.
    HAMAPiMF_01543. FTHFS.
    MF_01576. THF_DHG_CYH.
    InterProiIPR000559. Formate_THF_ligase.
    IPR020628. Formate_THF_ligase_CS.
    IPR016040. NAD(P)-bd_dom.
    IPR027417. P-loop_NTPase.
    IPR000672. THF_DH/CycHdrlase.
    IPR020630. THF_DH/CycHdrlase_cat_dom.
    IPR020867. THF_DH/CycHdrlase_CS.
    IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
    [Graphical view]
    PfamiPF01268. FTHFS. 1 hit.
    PF00763. THF_DHG_CYH. 1 hit.
    PF02882. THF_DHG_CYH_C. 1 hit.
    [Graphical view]
    PRINTSiPR00085. THFDHDRGNASE.
    SUPFAMiSSF52540. SSF52540. 2 hits.
    PROSITEiPS00721. FTHFS_1. 1 hit.
    PS00722. FTHFS_2. 1 hit.
    PS00766. THF_DHG_CYH_1. 1 hit.
    PS00767. THF_DHG_CYH_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q922D8-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAPAGILNGK LVSAQIRDRL KNQVTRMQEQ VPGFTPGLAI LQVGDRDDSN    50
    LYINVKLKAA EEIGIKATHI KLPRTSTESE VLKYVISLNE DASVHGFIVQ 100
    LPLDSENSIN TEAVINAIAP EKDVDGLTSV SAGKLARGDL NDCFIPCTPK 150
    GCLELIKEAG VQIAGRHAVV VGRSKIVGAP MHDLLLWNNA TVTTCHSKTA 200
    NLDKEVNKGD ILVVATGQPE MVKGEWIKPG AVVIDCGINY VPDDTKPNGR 250
    KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AQRFLQKFKP 300
    GKWTIQYNKL NLKTPVPSDI AISRSCKPKL IGNLAREIGL LTEEVELYGE 350
    TKAKVLLSAL DRLKHQPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH 400
    LRQNVFACVR QPSQGPTFGI KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT 450
    AANNLVAAAI DARIFHELTQ TDKALFNRLV PSVNGIRKFS DIQIRRLRRL 500
    GIEKTDPTTL TDDEINRFAR LDIDPETITW QRVLDTNDRF LRKITIGQSP 550
    TEKGHTRTAQ FDISVASEIM AVLALTSSLE DMRERLGRMV VASSKKGEPI 600
    SCEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII 650
    ADRIALKLVG PEGFVVTEAG FGADIGMEKF FNIKCRYSGL QPHVVVLVAT 700
    VRALKMHGGG PTVTAGLPLP KAYTEEDLDL VEKGFSNLRK QIENARMFGV 750
    PVVVAVNVFK TDTDAELDLV SRLSREHGAF DAVKCTHWAE GGQGALALAQ 800
    AVQRASQAPS SFQLLYDLKL SIEDKIRIIA QRIYGADDIE LLPEAQNKAE 850
    IYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFVLPIRD IRASVGAGFL 900
    YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF 935
    Length:935
    Mass (Da):101,200
    Last modified:July 27, 2011 - v4
    Checksum:i0EB92D58C78DDEB5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti365 – 3651H → Y in AAH08523. (PubMed:15489334)Curated
    Sequence conflicti610 – 6101A → T in AAH08523. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF364579 mRNA. Translation: AAL99692.1.
    AF364591
    , AF364580, AF364581, AF364582, AF364583, AF364584, AF364585, AF364586, AF364587, AF364588, AF364589, AF364590 Genomic DNA. Translation: AAL99693.1.
    AK088700 mRNA. Translation: BAC40513.1.
    BC008523 mRNA. Translation: AAH08523.1.
    CCDSiCCDS25990.1.
    RefSeqiNP_620084.2. NM_138745.2.
    UniGeneiMm.29584.

    Genome annotation databases

    EnsembliENSMUST00000021443; ENSMUSP00000021443; ENSMUSG00000021048.
    GeneIDi108156.
    KEGGimmu:108156.
    UCSCiuc007nxz.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF364579 mRNA. Translation: AAL99692.1 .
    AF364591
    , AF364580 , AF364581 , AF364582 , AF364583 , AF364584 , AF364585 , AF364586 , AF364587 , AF364588 , AF364589 , AF364590 Genomic DNA. Translation: AAL99693.1 .
    AK088700 mRNA. Translation: BAC40513.1 .
    BC008523 mRNA. Translation: AAH08523.1 .
    CCDSi CCDS25990.1.
    RefSeqi NP_620084.2. NM_138745.2.
    UniGenei Mm.29584.

    3D structure databases

    ProteinModelPortali Q922D8.
    SMRi Q922D8. Positions 2-296, 316-935.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 223871. 1 interaction.
    IntActi Q922D8. 5 interactions.
    MINTi MINT-1856310.

    Chemistry

    ChEMBLi CHEMBL3137.

    PTM databases

    PhosphoSitei Q922D8.

    2D gel databases

    REPRODUCTION-2DPAGE Q922D8.

    Proteomic databases

    MaxQBi Q922D8.
    PaxDbi Q922D8.
    PRIDEi Q922D8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000021443 ; ENSMUSP00000021443 ; ENSMUSG00000021048 .
    GeneIDi 108156.
    KEGGi mmu:108156.
    UCSCi uc007nxz.2. mouse.

    Organism-specific databases

    CTDi 4522.
    MGIi MGI:1342005. Mthfd1.

    Phylogenomic databases

    eggNOGi COG0190.
    GeneTreei ENSGT00750000117401.
    HOVERGENi HBG004916.
    InParanoidi Q8R013.
    KOi K00288.
    OMAi KWNISYT.
    OrthoDBi EOG76T9QN.
    TreeFami TF300623.

    Enzyme and pathway databases

    UniPathwayi UPA00193 .
    Reactomei REACT_220137. Metabolism of folate and pterines.

    Miscellaneous databases

    ChiTaRSi MTHFD1. mouse.
    NextBioi 360186.
    PROi Q922D8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q922D8.
    Bgeei Q922D8.
    Genevestigatori Q922D8.

    Family and domain databases

    Gene3Di 3.40.50.300. 2 hits.
    3.40.50.720. 1 hit.
    HAMAPi MF_01543. FTHFS.
    MF_01576. THF_DHG_CYH.
    InterProi IPR000559. Formate_THF_ligase.
    IPR020628. Formate_THF_ligase_CS.
    IPR016040. NAD(P)-bd_dom.
    IPR027417. P-loop_NTPase.
    IPR000672. THF_DH/CycHdrlase.
    IPR020630. THF_DH/CycHdrlase_cat_dom.
    IPR020867. THF_DH/CycHdrlase_CS.
    IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
    [Graphical view ]
    Pfami PF01268. FTHFS. 1 hit.
    PF00763. THF_DHG_CYH. 1 hit.
    PF02882. THF_DHG_CYH_C. 1 hit.
    [Graphical view ]
    PRINTSi PR00085. THFDHDRGNASE.
    SUPFAMi SSF52540. SSF52540. 2 hits.
    PROSITEi PS00721. FTHFS_1. 1 hit.
    PS00722. FTHFS_2. 1 hit.
    PS00766. THF_DHG_CYH_1. 1 hit.
    PS00767. THF_DHG_CYH_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase derived from a trifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase."
      Patel H., Christensen K.E., Mejia N., MacKenzie R.E.
      Arch. Biochem. Biophys. 403:145-148(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
      Strain: 129/SvJ.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: NOD.
      Tissue: Thymus.
    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].
    4. Lubec G., Sunyer B., Chen W.-Q.
      Submitted (JAN-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-17; 27-56; 59-66; 75-83; 123-134; 138-173; 176-198; 205-223; 251-262; 314-324; 330-352; 355-362; 371-402; 464-473; 488-495; 505-517; 521-532; 543-553; 658-679; 687-702; 706-733; 747-772; 776-784; 805-819; 833-848 AND 855-889, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: OF1.
      Tissue: Hippocampus.
    5. "Disruption of the mthfd1 gene reveals a monofunctional 10-formyltetrahydrofolate synthetase in mammalian mitochondria."
      Christensen K.E., Patel H., Kuzmanov U., Mejia N.R., MacKenzie R.E.
      J. Biol. Chem. 280:7597-7602(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiC1TC_MOUSE
    AccessioniPrimary (citable) accession number: Q922D8
    Secondary accession number(s): Q8R013
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 19, 2003
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 110 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3