P61457 (PHS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	104 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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.
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.
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 process	Tetrahydrobiopterin biosynthesis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Disease	Disease mutation
Molecular function	Activator Lyase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	L-phenylalanine catabolic process Traceable author statement. Source: Reactome cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara protein heterooligomerization Inferred from electronic annotation. Source: Compara protein homotetramerization Inferred from electronic annotation. Source: Compara regulation of protein homodimerization activity Inferred from electronic annotation. Source: Compara tetrahydrobiopterin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular_function	4-alpha-hydroxytetrahydrobiopterin dehydratase activity Inferred from experiment. Source: Reactome phenylalanine 4-monooxygenase activity Inferred from electronic annotation. Source: Compara transcription coactivator activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-740475,EBI-740475
ACIN1	Q9UKV3	2	EBI-740475,EBI-396258
APP	P05067	2	EBI-740475,EBI-77613

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.5
	Chain	2 – 104	103	Pterin-4-alpha-carbinolamine dehydratase		PRO_0000063052
Regions
	Region	61 – 63	3	Substrate binding By similarity
	Region	78 – 81	4	Substrate binding By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine
Natural variations
	Natural variant	79	1	T → I in hyperphenylalaninemia.		VAR_005527
	Natural variant	82	1	C → R in HPABH4D; mild form. Ref.7		VAR_005528
	Natural variant	88	1	R → Q in HPABH4D. Ref.8		VAR_005529
	Natural variant	97	1	E → K in HPABH4D; mild form. Ref.8		VAR_005530

Sequences

	Sequence		Length	Mass (Da)
	P61457 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 997DF8C2417FE5F5	FASTA	104	12,000
	10 20 30 40 50 60 MAGKAHRLSA EERDQLLPNL RAVGWNELEG RDAIFKQFHF KDFNRAFGFM TRVALQAEKL 70 80 90 100 DHHPEWFNVY NKVHITLSTH ECAGLSERDI NLASFIEQVA VSMT

References

	« Hide 'large scale' referencesShow '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. 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

GeneReviews

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.
IPI	IPI00218568.
PIR	A47010.
RefSeq	NP_000272.1. NM_000281.2.
UniGene	Hs.3192.
3D structure databases
ProteinModelPortal	P61457.
ModBase	Search...
Protein-protein interaction databases
IntAct	P61457. 40 interactions.
MINT	MINT-1436903.
STRING	9606.ENSP00000299299.
PTM databases
PhosphoSite	P61457.
Polymorphism databases
DMDM	47606444.
2D gel databases
UCD-2DPAGE	P61457.
Proteomic databases
PaxDb	P61457.
PeptideAtlas	P61457.
PRIDE	P61457.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299299; ENSP00000299299; ENSG00000166228.
GeneID	5092.
KEGG	hsa:5092.
UCSC	uc001jrn.1. human.
Organism-specific databases
CTD	5092.
GeneCards	GC10M072642.
HGNC	HGNC:8646. PCBD1.
HPA	HPA037575.
MIM	126090. gene. 264070. phenotype.
neXtProt	NX_P61457.
Orphanet	1578. Dehydratase deficiency.
PharmGKB	PA32985.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2154.
HOGENOM	HOG000007680.
HOVERGEN	HBG000259.
InParanoid	P61457.
KO	K01724.
OMA	EWRNVYK.
OrthoDB	EOG4QNMXP.
PhylomeDB	P61457.
Enzyme and pathway databases
BioCyc	MetaCyc:HS09360-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P61457.
Bgee	P61457.
CleanEx	HS_PCBD1.
Genevestigator	P61457.
GermOnline	ENSG00000166228. Homo sapiens.
Family and domain databases
Gene3D	3.30.1360.20. 1 hit.
InterPro	IPR001533. Trans/pterin_deHydtase. [Graphical view]
PANTHER	PTHR12599. PTHR12599. 1 hit.
Pfam	PF01329. Pterin_4a. 1 hit. [Graphical view]
SUPFAM	SSF55248. Trans_pterinDh. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	5092.
NextBio	19640.
SOURCE	Search...

Entry information

Entry name

PHS_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.