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Protein

Pterin-4-alpha-carbinolamine dehydratase

Gene

PCBD1

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

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. 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
Complete GO annotation...

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: UniProtKB
  4. nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Hyperphenylalaninemia, BH4-deficient, D2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn 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.

See also OMIM:264070
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

BgeeiP61457.
CleanExiHS_PCBD1.
ExpressionAtlasiP61457. baseline and differential.
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. 59 interactions.
IntActiP61457. 41 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.
GeneTreeiENSGT00390000007221.
HOGENOMiHOG000007680.
HOVERGENiHBG000259.
InParanoidiP61457.
KOiK01724.
OMAiEWRNVYK.
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

        10         20         30         40         50
MAGKAHRLSA EERDQLLPNL RAVGWNELEG RDAIFKQFHF KDFNRAFGFM
60 70 80 90 100
TRVALQAEKL DHHPEWFNVY NKVHITLSTH ECAGLSERDI NLASFIEQVA

VSMT
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi111125. 59 interactions.
IntActiP61457. 41 interactions.
MINTiMINT-1436903.
STRINGi9606.ENSP00000299299.

PTM databases

PhosphoSiteiP61457.

Polymorphism databases

DMDMi47606444.

2D gel databases

UCD-2DPAGEP61457.

Proteomic databases

MaxQBiP61457.
PaxDbiP61457.
PeptideAtlasiP61457.
PRIDEiP61457.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5092.
GeneCardsiGC10M072642.
HGNCiHGNC:8646. PCBD1.
HPAiHPA037575.
MIMi126090. gene.
264070. phenotype.
neXtProtiNX_P61457.
Orphaneti1578. Dehydratase deficiency.
PharmGKBiPA32985.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2154.
GeneTreeiENSGT00390000007221.
HOGENOMiHOG000007680.
HOVERGENiHBG000259.
InParanoidiP61457.
KOiK01724.
OMAiEWRNVYK.
OrthoDBiEOG7034K1.
PhylomeDBiP61457.
TreeFamiTF300188.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiPCBD1.
GenomeRNAii5092.
NextBioi19640.
PROiP61457.
SOURCEiSearch...

Gene expression databases

BgeeiP61457.
CleanExiHS_PCBD1.
ExpressionAtlasiP61457. baseline and differential.
GenevestigatoriP61457.

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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: February 4, 2015
This is version 115 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.