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P11586

- C1TC_HUMAN

UniProt

P11586 - C1TC_HUMAN

Protein

C-1-tetrahydrofolate synthase, cytoplasmic

Gene

MTHFD1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 169 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      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 – 1971NADP1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi172 – 1743NADP1 Publication
    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
    5. methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity Source: Reactome

    GO - Biological processi

    1. folic acid-containing compound biosynthetic process Source: InterPro
    2. folic acid metabolic process Source: Reactome
    3. histidine biosynthetic process Source: UniProtKB-KW
    4. methionine biosynthetic process Source: UniProtKB-KW
    5. one-carbon metabolic process Source: RefGenome
    6. purine nucleotide biosynthetic process Source: UniProtKB-KW
    7. small molecule metabolic process Source: Reactome
    8. tetrahydrofolate interconversion Source: UniProtKB-UniPathway
    9. vitamin metabolic process Source: Reactome
    10. water-soluble vitamin metabolic process Source: Reactome

    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

    BioCyciMetaCyc:HS02138-MONOMER.
    BRENDAi6.3.4.3. 2681.
    ReactomeiREACT_11167. 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
    Synonyms:MTHFC, MTHFD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:7432. MTHFD1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: RefGenome
    2. extracellular vesicular exosome Source: UniProt
    3. membrane Source: UniProtKB
    4. mitochondrion Source: ProtInc

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly.3 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti293 – 2931R → H Associated with susceptibility to FS-NTD.
    Corresponds to variant rs34181110 [ dbSNP | Ensembl ].
    VAR_010241
    Natural varianti653 – 6531R → Q May be associated with susceptibility to FS-NTD; decreases enzyme stability and increases risk for congenital heart defects. 4 Publications
    Corresponds to variant rs2236225 [ dbSNP | Ensembl ].
    VAR_010251
    Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
    Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi49 – 491S → A: No effect on dehydrogenase and cyclohydrolase activity. Strong increase of Km for NADP. 1 Publication
    Mutagenesisi49 – 491S → Q: Reduces dehydrogenase by 75% and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication
    Mutagenesisi52 – 521Y → A or S: Reduces dehydrogenase activity by 99%. Reduces cyclohydrolase activity by 70%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication
    Mutagenesisi52 – 521Y → F: Slightly reduces dehydrogenase and cyclohydrolase activity. Increase of Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication
    Mutagenesisi56 – 561K → A, I, S or T: Decreases dehydrogenase activity over 90%. Loss of cyclohydrolase activity. 1 Publication
    Mutagenesisi56 – 561K → E, M or Q: Moderate decrease of dehydrogenase activity. Loss of cyclohydrolase activity. Strong increase of Km for NADP. Decrease of Km for 5,10-methenyltetrahydrofolate. 1 Publication
    Mutagenesisi56 – 561K → R: Reduces dehydrogenase and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate. 1 Publication
    Mutagenesisi147 – 1471C → Q: Reduces dehydrogenase activity by 50% and cyclohydrolase activity by 87%. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi114500. phenotype.
    172460. gene+phenotype.
    601634. phenotype.
    Orphaneti268392. Cervical spina bifida aperta.
    268762. Cervical spina bifida cystica.
    268397. Cervicothoracic spina bifida aperta.
    268766. Cervicothoracic spina bifida cystica.
    268388. Lumbosacral spina bifida aperta.
    268758. Lumbosacral spina bifida cystica.
    268384. Thoracolumbosacral spina bifida aperta.
    268752. Thoracolumbosacral spina bifida cystica.
    268377. Total spina bifida aperta.
    268748. Total spina bifida cystica.
    268740. Upper thoracic spina bifida aperta.
    268770. Upper thoracic spina bifida cystica.
    PharmGKBiPA31236.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 935935C-1-tetrahydrofolate synthase, cytoplasmicPRO_0000423280Add
    BLAST
    Initiator methioninei1 – 11Removed; alternate3 Publications
    Chaini2 – 935934C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processedPRO_0000199321Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine3 Publications

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP11586.
    PaxDbiP11586.
    PRIDEiP11586.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00218342.
    SWISS-2DPAGEP11586.

    PTM databases

    PhosphoSiteiP11586.

    Expressioni

    Tissue specificityi

    Ubiquitous.

    Gene expression databases

    ArrayExpressiP11586.
    BgeeiP11586.
    CleanExiHS_MTHFD1.
    GenevestigatoriP11586.

    Organism-specific databases

    HPAiHPA000704.
    HPA001290.
    HPA015006.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MCCP235081EBI-709638,EBI-307531
    TRAF6Q9Y4K31EBI-709638,EBI-359276
    WDR8Q9P2S51EBI-709638,EBI-1054904

    Protein-protein interaction databases

    BioGridi110622. 50 interactions.
    IntActiP11586. 7 interactions.
    MINTiMINT-5000922.
    STRINGi9606.ENSP00000216605.

    Structurei

    Secondary structure

    1
    935
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi9 – 3022
    Beta strandi37 – 448
    Helixi47 – 6317
    Beta strandi66 – 727
    Helixi78 – 9013
    Beta strandi96 – 994
    Helixi111 – 1166
    Helixi120 – 1223
    Helixi129 – 1368
    Helixi147 – 15711
    Turni158 – 1603
    Beta strandi167 – 1715
    Turni175 – 1773
    Helixi178 – 18710
    Beta strandi191 – 1955
    Helixi202 – 2065
    Beta strandi210 – 2145
    Helixi224 – 2263
    Beta strandi232 – 2354
    Helixi258 – 2614
    Turni262 – 2643
    Beta strandi266 – 2683
    Beta strandi271 – 2744
    Helixi275 – 29521

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1A4IX-ray1.50A/B1-301[»]
    1DIAX-ray2.20A/B1-306[»]
    1DIBX-ray2.70A/B1-306[»]
    1DIGX-ray2.20A/B1-306[»]
    ProteinModelPortaliP11586.
    SMRiP11586. Positions 2-296, 317-935.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11586.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 305304Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd
    BLAST
    Regioni52 – 565Substrate binding
    Regioni99 – 1013Substrate binding
    Regioni272 – 2765Substrate binding
    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.
    HOVERGENiHBG004916.
    InParanoidiP11586.
    KOiK00288.
    PhylomeDBiP11586.
    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.

    P11586-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAPAEILNGK EISAQIRARL KNQVTQLKEQ VPGFTPRLAI LQVGNRDDSN    50
    LYINVKLKAA EEIGIKATHI KLPRTTTESE VMKYITSLNE DSTVHGFLVQ 100
    LPLDSENSIN TEEVINAIAP EKDVDGLTSI NAGRLARGDL NDCFIPCTPK 150
    GCLELIKETG VPIAGRHAVV VGRSKIVGAP MHDLLLWNNA TVTTCHSKTA 200
    HLDEEVNKGD ILVVATGQPE MVKGEWIKPG AIVIDCGINY VPDDKKPNGR 250
    KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP 300
    GKWMIQYNNL NLKTPVPSDI DISRSCKPKP IGKLAREIGL LSEEVELYGE 350
    TKAKVLLSAL ERLKHRPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH 400
    LYQNVFACVR QPSQGPTFGI KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT 450
    AANNLVAAAI DARIFHELTQ TDKALFNRLV PSVNGVRRFS DIQIRRLKRL 500
    GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF LRKITIGQAP 550
    TEKGHTRTAQ FDISVASEIM AVLALTTSLE DMRERLGKMV VASSKKGEPV 600
    SAEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII 650
    ADRIALKLVG PEGFVVTEAG FGADIGMEKF FNIKCRYSGL CPHVVVLVAT 700
    VRALKMHGGG PTVTAGLPLP KAYIQENLEL VEKGFSNLKK QIENARMFGI 750
    PVVVAVNAFK TDTESELDLI SRLSREHGAF DAVKCTHWAE GGKGALALAQ 800
    AVQRAAQAPS SFQLLYDLKL PVEDKIRIIA QKIYGADDIE LLPEAQHKAE 850
    VYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFILPIRD IRASVGAGFL 900
    YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF 935
    Length:935
    Mass (Da):101,559
    Last modified:January 23, 2007 - v3
    Checksum:i29AE1C04B4922885
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti134 – 1341R → K Associated with increased risk of colorectal cancer. 3 Publications
    Corresponds to variant rs1950902 [ dbSNP | Ensembl ].
    VAR_016232
    Natural varianti162 – 1621P → L.
    Corresponds to variant rs4902283 [ dbSNP | Ensembl ].
    VAR_055458
    Natural varianti293 – 2931R → H Associated with susceptibility to FS-NTD.
    Corresponds to variant rs34181110 [ dbSNP | Ensembl ].
    VAR_010241
    Natural varianti653 – 6531R → Q May be associated with susceptibility to FS-NTD; decreases enzyme stability and increases risk for congenital heart defects. 4 Publications
    Corresponds to variant rs2236225 [ dbSNP | Ensembl ].
    VAR_010251
    Natural varianti761 – 7611T → M.
    Corresponds to variant rs10813 [ dbSNP | Ensembl ].
    VAR_032789
    Natural varianti769 – 7691L → F.1 Publication
    Corresponds to variant rs17857382 [ dbSNP | Ensembl ].
    VAR_032790

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04031 mRNA. Translation: AAA59574.1.
    AK312361 mRNA. Translation: BAG35279.1.
    AL122035 Genomic DNA. No translation available.
    CH471061 Genomic DNA. Translation: EAW80857.1.
    BC001014 mRNA. Translation: AAH01014.2.
    BC009806 mRNA. Translation: AAH09806.1.
    BC050420 mRNA. Translation: AAH50420.1.
    CCDSiCCDS9763.1.
    PIRiA31903.
    RefSeqiNP_005947.3. NM_005956.3.
    UniGeneiHs.652308.

    Genome annotation databases

    EnsembliENST00000216605; ENSP00000216605; ENSG00000100714.
    ENST00000555709; ENSP00000450560; ENSG00000100714.
    GeneIDi4522.
    KEGGihsa:4522.

    Polymorphism databases

    DMDMi115206.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04031 mRNA. Translation: AAA59574.1 .
    AK312361 mRNA. Translation: BAG35279.1 .
    AL122035 Genomic DNA. No translation available.
    CH471061 Genomic DNA. Translation: EAW80857.1 .
    BC001014 mRNA. Translation: AAH01014.2 .
    BC009806 mRNA. Translation: AAH09806.1 .
    BC050420 mRNA. Translation: AAH50420.1 .
    CCDSi CCDS9763.1.
    PIRi A31903.
    RefSeqi NP_005947.3. NM_005956.3.
    UniGenei Hs.652308.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1A4I X-ray 1.50 A/B 1-301 [» ]
    1DIA X-ray 2.20 A/B 1-306 [» ]
    1DIB X-ray 2.70 A/B 1-306 [» ]
    1DIG X-ray 2.20 A/B 1-306 [» ]
    ProteinModelPortali P11586.
    SMRi P11586. Positions 2-296, 317-935.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110622. 50 interactions.
    IntActi P11586. 7 interactions.
    MINTi MINT-5000922.
    STRINGi 9606.ENSP00000216605.

    Chemistry

    BindingDBi P11586.
    ChEMBLi CHEMBL2541.
    DrugBanki DB00157. NADH.
    DB00116. Tetrahydrofolic acid.

    PTM databases

    PhosphoSitei P11586.

    Polymorphism databases

    DMDMi 115206.

    2D gel databases

    REPRODUCTION-2DPAGE IPI00218342.
    SWISS-2DPAGE P11586.

    Proteomic databases

    MaxQBi P11586.
    PaxDbi P11586.
    PRIDEi P11586.

    Protocols and materials databases

    DNASUi 4522.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000216605 ; ENSP00000216605 ; ENSG00000100714 .
    ENST00000555709 ; ENSP00000450560 ; ENSG00000100714 .
    GeneIDi 4522.
    KEGGi hsa:4522.

    Organism-specific databases

    CTDi 4522.
    GeneCardsi GC14P064854.
    H-InvDB HIX0011731.
    HGNCi HGNC:7432. MTHFD1.
    HPAi HPA000704.
    HPA001290.
    HPA015006.
    MIMi 114500. phenotype.
    172460. gene+phenotype.
    601634. phenotype.
    neXtProti NX_P11586.
    Orphaneti 268392. Cervical spina bifida aperta.
    268762. Cervical spina bifida cystica.
    268397. Cervicothoracic spina bifida aperta.
    268766. Cervicothoracic spina bifida cystica.
    268388. Lumbosacral spina bifida aperta.
    268758. Lumbosacral spina bifida cystica.
    268384. Thoracolumbosacral spina bifida aperta.
    268752. Thoracolumbosacral spina bifida cystica.
    268377. Total spina bifida aperta.
    268748. Total spina bifida cystica.
    268740. Upper thoracic spina bifida aperta.
    268770. Upper thoracic spina bifida cystica.
    PharmGKBi PA31236.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0190.
    HOVERGENi HBG004916.
    InParanoidi P11586.
    KOi K00288.
    PhylomeDBi P11586.
    TreeFami TF300623.

    Enzyme and pathway databases

    UniPathwayi UPA00193 .
    BioCyci MetaCyc:HS02138-MONOMER.
    BRENDAi 6.3.4.3. 2681.
    Reactomei REACT_11167. Metabolism of folate and pterines.

    Miscellaneous databases

    ChiTaRSi MTHFD1. human.
    EvolutionaryTracei P11586.
    GeneWikii MTHFD1.
    GenomeRNAii 4522.
    NextBioi 17468.
    PROi P11586.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P11586.
    Bgeei P11586.
    CleanExi HS_MTHFD1.
    Genevestigatori P11586.

    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. "Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase."
      Hum D.W., Bell A.W., Rozen R., Mackenzie R.E.
      J. Biol. Chem. 263:15946-15950(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-31.
      Tissue: Liver.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-653.
      Tissue: Amygdala.
    3. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLN-653.
    5. "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], VARIANTS GLN-653 AND PHE-769.
      Tissue: Brain, Eye and Lymph.
    6. "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
      Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
      Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-17.
      Tissue: Platelet.
    7. Bienvenut W.V., Gao M., Leug H., Campbell A., Ozanne B.W.
      Submitted (JUL-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-17; 251-264; 314-324; 355-362; 596-616 AND 722-733, CLEAVAGE OF INITIATOR METHIONINE, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Foreskin fibroblast and Prostatic carcinoma.
    8. "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 MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. "The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5-A resolution."
      Allaire M., Li Y., Mackenzie R.E., Cygler M.
      Structure 6:173-182(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-302.
    13. "Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase."
      Schmidt A., Wu H., MacKenzie R.E., Chen V.J., Bewly J.R., Ray J.E., Toth J.E., Cygler M.
      Biochemistry 39:6325-6335(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-306 IN COMPLEX WITH NADP AND SUBSTRATE ANALOGS, SUBUNIT, MUTAGENESIS OF SER-49; TYR-52; LYS-56 AND CYS-147.
    14. "Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects."
      Hol F.A., van der Put N.M.J., Geurds M.P.A., Heil S.G., Trijbels F.J.M., Hamel B.C.J., Mariman E.C.M., Blom H.J.
      Clin. Genet. 53:119-125(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION OF VARIANT HIS-293 WITH SUSCEPTIBILITY TO FS-NTD, VARIANT GLN-653.
    15. "A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group."
      Brody L.C., Conley M., Cox C., Kirke P.N., McKeever M.P., Mills J.L., Molloy A.M., O'Leary V.B., Parle-McDermott A., Scott J.M., Swanson D.A.
      Am. J. Hum. Genet. 71:1207-1215(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION OF VARIANT GLN-653 WITH SUSCEPTIBILITY TO FS-NTD, VARIANT LYS-134.
    16. "Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population."
      Parle-McDermott A., Kirke P.N., Mills J.L., Molloy A.M., Cox C., O'Leary V.B., Pangilinan F., Conley M., Cleary L., Brody L.C., Scott J.M.
      Eur. J. Hum. Genet. 14:768-772(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION OF VARIANT GLN-653 WITH SUSCEPTIBILITY TO FS-NTD, VARIANT LYS-134.
    17. "Search for low penetrance alleles for colorectal cancer through a scan of 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort analysis of 14 704 first-degree relatives."
      Webb E.L., Rudd M.F., Sellick G.S., El Galta R., Bethke L., Wood W., Fletcher O., Penegar S., Withey L., Qureshi M., Johnson N., Tomlinson I., Gray R., Peto J., Houlston R.S.
      Hum. Mol. Genet. 15:3263-3271(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LYS-134, ASSOCIATION WITH COLORECTAL CANCER SUSCEPTIBILITY.
    18. "The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects."
      Christensen K.E., Rohlicek C.V., Andelfinger G.U., Michaud J., Bigras J.-L., Richter A., Mackenzie R.E., Rozen R.
      Hum. Mutat. 30:212-220(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT GLN-653, ASSOCIATION WITH RISK OF CONGENITAL HEART DEFECTS.

    Entry informationi

    Entry nameiC1TC_HUMAN
    AccessioniPrimary (citable) accession number: P11586
    Secondary accession number(s): B2R5Y2
    , G3V2B8, Q86VC9, Q9BVP5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 169 of the entry and version 3 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, Direct protein sequencing, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3