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P61457

- PHS_HUMAN

UniProt

P61457 - PHS_HUMAN

Protein

Pterin-4-alpha-carbinolamine dehydratase

Gene

PCBD1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity.

    Catalytic activityi

    (6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin = (6R)-6-(L-erythro-1,2-dihydroxypropyl)-7,8-dihydro-6H-pterin + H2O.

    GO - Molecular functioni

    1. 4-alpha-hydroxytetrahydrobiopterin dehydratase activity Source: Reactome
    2. identical protein binding Source: IntAct
    3. phenylalanine 4-monooxygenase activity Source: Ensembl
    4. protein binding Source: IntAct
    5. transcription coactivator activity Source: ProtInc

    GO - Biological processi

    1. cellular nitrogen compound metabolic process Source: Reactome
    2. L-phenylalanine catabolic process Source: Reactome
    3. positive regulation of transcription, DNA-templated Source: Ensembl
    4. protein heterooligomerization Source: Ensembl
    5. protein homotetramerization Source: Ensembl
    6. regulation of protein homodimerization activity Source: Ensembl
    7. small molecule metabolic process Source: Reactome
    8. tetrahydrobiopterin biosynthetic process Source: UniProtKB-KW
    9. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Lyase

    Keywords - Biological processi

    Tetrahydrobiopterin biosynthesis, Transcription, Transcription regulation

    Enzyme and pathway databases

    BioCyciMetaCyc:HS09360-MONOMER.
    ReactomeiREACT_1786. Phenylalanine and tyrosine catabolism.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pterin-4-alpha-carbinolamine dehydratase (EC:4.2.1.96)
    Short name:
    PHS
    Alternative name(s):
    4-alpha-hydroxy-tetrahydropterin dehydratase
    Dimerization cofactor of hepatocyte nuclear factor 1-alpha
    Short name:
    DCoH
    Short name:
    Dimerization cofactor of HNF1
    Phenylalanine hydroxylase-stimulating protein
    Pterin carbinolamine dehydratase
    Short name:
    PCD
    Gene namesi
    Name:PCBD1
    Synonyms:DCOH, PCBD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:8646. PCBD1.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Cytoplasmic and/or nuclear.

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. cytosol Source: Reactome
    3. extracellular vesicular exosome Source: UniProt
    4. nucleus Source: HPA

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Hyperphenylalaninemia, BH4-deficient, D (HPABH4D) [MIM:264070]: An autosomal recessive disease characterized by primapterinuria, a variant form of hyperphenylalaninemia defined by increased excretion of 7-substituted pterins in the urine. Patients with primapterinuria show an increased ratio of neopterin to biopterin in the urine, excretion of subnormal levels of biopterins, and normal levels of biogenic amines in cerebrospinal fluid. Neurologic signs are mild, present in the neonatal period only, and include hypotonia, delayed motor development and tremor.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti82 – 821C → R in HPABH4D; mild form. 1 Publication
    VAR_005528
    Natural varianti88 – 881R → Q in HPABH4D. 1 Publication
    Corresponds to variant rs115117837 [ dbSNP | Ensembl ].
    VAR_005529
    Natural varianti97 – 971E → K in HPABH4D; mild form. 1 Publication
    VAR_005530

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi264070. phenotype.
    Orphaneti1578. Dehydratase deficiency.
    PharmGKBiPA32985.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 104103Pterin-4-alpha-carbinolamine dehydratasePRO_0000063052Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP61457.
    PaxDbiP61457.
    PeptideAtlasiP61457.
    PRIDEiP61457.

    2D gel databases

    UCD-2DPAGEP61457.

    PTM databases

    PhosphoSiteiP61457.

    Expressioni

    Gene expression databases

    ArrayExpressiP61457.
    BgeeiP61457.
    CleanExiHS_PCBD1.
    GenevestigatoriP61457.

    Organism-specific databases

    HPAiHPA037575.

    Interactioni

    Subunit structurei

    Homotetramer and homodimer. Heterotetramer with HNF1A; formed by a dimer of dimers By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-740475,EBI-740475
    ACIN1Q9UKV32EBI-740475,EBI-396258
    APPP050672EBI-740475,EBI-77613

    Protein-protein interaction databases

    BioGridi111125. 58 interactions.
    IntActiP61457. 40 interactions.
    MINTiMINT-1436903.
    STRINGi9606.ENSP00000299299.

    Structurei

    3D structure databases

    ProteinModelPortaliP61457.
    SMRiP61457. Positions 6-104.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni61 – 633Substrate bindingBy similarity
    Regioni78 – 814Substrate bindingBy similarity

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG2154.
    HOGENOMiHOG000007680.
    HOVERGENiHBG000259.
    InParanoidiP61457.
    KOiK01724.
    OMAiDDEERNA.
    OrthoDBiEOG7034K1.
    PhylomeDBiP61457.
    TreeFamiTF300188.

    Family and domain databases

    Gene3Di3.30.1360.20. 1 hit.
    HAMAPiMF_00434. Pterin_4_alpha.
    InterProiIPR001533. Trans/pterin_deHydtase.
    [Graphical view]
    PANTHERiPTHR12599. PTHR12599. 1 hit.
    PfamiPF01329. Pterin_4a. 1 hit.
    [Graphical view]
    SUPFAMiSSF55248. SSF55248. 1 hit.

    Sequencei

    Sequence statusi: Complete.

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

    P61457-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAGKAHRLSA EERDQLLPNL RAVGWNELEG RDAIFKQFHF KDFNRAFGFM    50
    TRVALQAEKL DHHPEWFNVY NKVHITLSTH ECAGLSERDI NLASFIEQVA 100
    VSMT 104
    Length:104
    Mass (Da):12,000
    Last modified:January 23, 2007 - v2
    Checksum:i997DF8C2417FE5F5
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti79 – 791T → I in hyperphenylalaninemia.
    VAR_005527
    Natural varianti82 – 821C → R in HPABH4D; mild form. 1 Publication
    VAR_005528
    Natural varianti88 – 881R → Q in HPABH4D. 1 Publication
    Corresponds to variant rs115117837 [ dbSNP | Ensembl ].
    VAR_005529
    Natural varianti97 – 971E → K in HPABH4D; mild form. 1 Publication
    VAR_005530

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M83742 mRNA. No translation available.
    L41560 Genomic DNA. Translation: AAA69662.1.
    L41559 mRNA. Translation: AAA69663.1.
    AF082858 mRNA. Translation: AAD25732.1.
    BC006324 mRNA. Translation: AAH06324.1.
    CCDSiCCDS31217.1.
    PIRiA47010.
    RefSeqiNP_000272.1. NM_000281.3.
    NP_001276726.1. NM_001289797.1.
    UniGeneiHs.3192.

    Genome annotation databases

    EnsembliENST00000299299; ENSP00000299299; ENSG00000166228.
    GeneIDi5092.
    KEGGihsa:5092.
    UCSCiuc001jrn.1. human.

    Polymorphism databases

    DMDMi47606444.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M83742 mRNA. No translation available.
    L41560 Genomic DNA. Translation: AAA69662.1 .
    L41559 mRNA. Translation: AAA69663.1 .
    AF082858 mRNA. Translation: AAD25732.1 .
    BC006324 mRNA. Translation: AAH06324.1 .
    CCDSi CCDS31217.1.
    PIRi A47010.
    RefSeqi NP_000272.1. NM_000281.3.
    NP_001276726.1. NM_001289797.1.
    UniGenei Hs.3192.

    3D structure databases

    ProteinModelPortali P61457.
    SMRi P61457. Positions 6-104.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111125. 58 interactions.
    IntActi P61457. 40 interactions.
    MINTi MINT-1436903.
    STRINGi 9606.ENSP00000299299.

    PTM databases

    PhosphoSitei P61457.

    Polymorphism databases

    DMDMi 47606444.

    2D gel databases

    UCD-2DPAGE P61457.

    Proteomic databases

    MaxQBi P61457.
    PaxDbi P61457.
    PeptideAtlasi P61457.
    PRIDEi P61457.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000299299 ; ENSP00000299299 ; ENSG00000166228 .
    GeneIDi 5092.
    KEGGi hsa:5092.
    UCSCi uc001jrn.1. human.

    Organism-specific databases

    CTDi 5092.
    GeneCardsi GC10M072642.
    HGNCi HGNC:8646. PCBD1.
    HPAi HPA037575.
    MIMi 126090. gene.
    264070. phenotype.
    neXtProti NX_P61457.
    Orphaneti 1578. Dehydratase deficiency.
    PharmGKBi PA32985.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2154.
    HOGENOMi HOG000007680.
    HOVERGENi HBG000259.
    InParanoidi P61457.
    KOi K01724.
    OMAi DDEERNA.
    OrthoDBi EOG7034K1.
    PhylomeDBi P61457.
    TreeFami TF300188.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS09360-MONOMER.
    Reactomei REACT_1786. Phenylalanine and tyrosine catabolism.

    Miscellaneous databases

    GeneWikii PCBD1.
    GenomeRNAii 5092.
    NextBioi 19640.
    PROi P61457.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P61457.
    Bgeei P61457.
    CleanExi HS_PCBD1.
    Genevestigatori P61457.

    Family and domain databases

    Gene3Di 3.30.1360.20. 1 hit.
    HAMAPi MF_00434. Pterin_4_alpha.
    InterProi IPR001533. Trans/pterin_deHydtase.
    [Graphical view ]
    PANTHERi PTHR12599. PTHR12599. 1 hit.
    Pfami PF01329. Pterin_4a. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55248. SSF55248. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein."
      Mendel D.B., Khavari P.A., Conley P.B., Graves M.K., Hansen L.P., Admon A., Crabtree G.R.
      Science 254:1762-1767(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Liver.
    2. "Characterization of the human PCBD gene encoding the bifunctional protein pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor for the transcription factor HNF-1 alpha."
      Thoeny B., Neuheiser F., Blau N., Heizmann C.W.
      Biochem. Biophys. Res. Commun. 210:966-973(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    3. "Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1."
      Lei X.D., Kaufman S.
      DNA Cell Biol. 18:243-252(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "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].
      Tissue: Muscle.
    5. "Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine dehydratase from rat and human liver. Purification, characterization, and complete amino acid sequence."
      Hauer C.R., Rebrin I., Thoeny B., Neuheiser F., Curtius H.-C., Hunziker P., Blau N., Ghisla S., Heizmann C.W.
      J. Biol. Chem. 268:4828-4831(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-104, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2.
      Tissue: Liver.
    6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. "Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism."
      Citron B.A., Kaufman S., Milstien S., Naylor E.W., Greene C.L., Davis M.D.
      Am. J. Hum. Genet. 53:768-774(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HPABH4D ARG-82.
    8. "Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia."
      Thoeny B., Neuheiser F., Kierat L., Rolland M.O., Guibaud P., Schlueter T., Germann R., Heidenreich R.A., Duran M., de Klerk J.B.C., Ayling J.E., Blau N.
      Hum. Genet. 103:162-167(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HPABH4D GLN-88 AND LYS-97.

    Entry informationi

    Entry nameiPHS_HUMAN
    AccessioniPrimary (citable) accession number: P61457
    Secondary accession number(s): P70519, P80095, Q9D930
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 24, 2004
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 112 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

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3