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P61457 (PHS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pterin-4-alpha-carbinolamine dehydratase

Short name=PHS
EC=4.2.1.96
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 names
Name:PCBD1
Synonyms:DCOH, PCBD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length104 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. HAMAP-Rule MF_00434

Catalytic activity

(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. HAMAP-Rule MF_00434

Subunit structure

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

Subcellular location

Cytoplasm. Nucleus. Note: Cytoplasmic and/or nuclear. HAMAP-Rule MF_00434

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8

Sequence similarities

Belongs to the pterin-4-alpha-carbinolamine dehydratase family.

Ontologies

Keywords
   Biological processTetrahydrobiopterin biosynthesis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DiseaseDisease mutation
   Molecular functionActivator
Lyase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processL-phenylalanine catabolic process

Traceable author statement. Source: Reactome

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

positive regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein homotetramerization

Inferred from electronic annotation. Source: Ensembl

regulation of protein homodimerization activity

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

tetrahydrobiopterin biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

nucleus

Inferred from direct assay. Source: HPA

   Molecular_function4-alpha-hydroxytetrahydrobiopterin dehydratase activity

Inferred from experiment. Source: Reactome

identical protein binding

Inferred from physical interaction PubMed 16189514PubMed 21516116. Source: IntAct

phenylalanine 4-monooxygenase activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 20195357. Source: IntAct

transcription coactivator activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 104103Pterin-4-alpha-carbinolamine dehydratase HAMAP-Rule MF_00434
PRO_0000063052

Regions

Region61 – 633Substrate binding By similarity
Region78 – 814Substrate binding By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.5

Natural variations

Natural variant791T → I in hyperphenylalaninemia.
VAR_005527
Natural variant821C → R in HPABH4D; mild form. Ref.7
VAR_005528
Natural variant881R → Q in HPABH4D. Ref.8
Corresponds to variant rs115117837 [ dbSNP | Ensembl ].
VAR_005529
Natural variant971E → K in HPABH4D; mild form. Ref.8
VAR_005530

Sequences

Sequence LengthMass (Da)Tools
P61457 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 997DF8C2417FE5F5

FASTA10412,000
        10         20         30         40         50         60 
MAGKAHRLSA EERDQLLPNL RAVGWNELEG RDAIFKQFHF KDFNRAFGFM TRVALQAEKL 

        70         80         90        100 
DHHPEWFNVY NKVHITLSTH ECAGLSERDI NLASFIEQVA VSMT 

« Hide

References

« Hide 'large scale' references
[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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

BIOMDB

Db of mutations causing tetrahydrobiopterin deficiencies

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS31217.1.
PIRA47010.
RefSeqNP_000272.1. NM_000281.3.
NP_001276726.1. NM_001289797.1.
UniGeneHs.3192.

3D structure databases

ProteinModelPortalP61457.
SMRP61457. Positions 6-104.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111125. 58 interactions.
IntActP61457. 40 interactions.
MINTMINT-1436903.
STRING9606.ENSP00000299299.

PTM databases

PhosphoSiteP61457.

Polymorphism databases

DMDM47606444.

2D gel databases

UCD-2DPAGEP61457.

Proteomic databases

MaxQBP61457.
PaxDbP61457.
PeptideAtlasP61457.
PRIDEP61457.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299299; ENSP00000299299; ENSG00000166228.
GeneID5092.
KEGGhsa:5092.
UCSCuc001jrn.1. human.

Organism-specific databases

CTD5092.
GeneCardsGC10M072642.
HGNCHGNC:8646. PCBD1.
HPAHPA037575.
MIM126090. gene.
264070. phenotype.
neXtProtNX_P61457.
Orphanet1578. Dehydratase deficiency.
PharmGKBPA32985.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2154.
HOGENOMHOG000007680.
HOVERGENHBG000259.
InParanoidP61457.
KOK01724.
OMADDEERNA.
OrthoDBEOG7034K1.
PhylomeDBP61457.
TreeFamTF300188.

Enzyme and pathway databases

BioCycMetaCyc:HS09360-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP61457.
BgeeP61457.
CleanExHS_PCBD1.
GenevestigatorP61457.

Family and domain databases

Gene3D3.30.1360.20. 1 hit.
HAMAPMF_00434. Pterin_4_alpha.
InterProIPR001533. Trans/pterin_deHydtase.
[Graphical view]
PANTHERPTHR12599. PTHR12599. 1 hit.
PfamPF01329. Pterin_4a. 1 hit.
[Graphical view]
SUPFAMSSF55248. SSF55248. 1 hit.
ProtoNetSearch...

Other

GeneWikiPCBD1.
GenomeRNAi5092.
NextBio19640.
PROP61457.
SOURCESearch...

Entry information

Entry namePHS_HUMAN
AccessionPrimary (citable) accession number: P61457
Secondary accession number(s): P70519, P80095, Q9D930
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM