PHS_RAT
ID PHS_RAT Reviewed; 104 AA.
AC P61459; P70519; P80095; Q9D930;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Pterin-4-alpha-carbinolamine dehydratase;
DE Short=PHS;
DE EC=4.2.1.96 {ECO:0000269|PubMed:1465414, ECO:0000269|PubMed:8444860, ECO:0000269|PubMed:8618906};
DE AltName: Full=4-alpha-hydroxy-tetrahydropterin dehydratase;
DE AltName: Full=Dimerization cofactor of hepatocyte nuclear factor 1-alpha;
DE Short=DCoH;
DE Short=Dimerization cofactor of HNF1;
DE AltName: Full=Phenylalanine hydroxylase-stimulating protein;
DE AltName: Full=Pterin carbinolamine dehydratase;
DE Short=PCD;
GN Name=Pcbd1; Synonyms=Dcoh, Pcbd;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP SUBUNIT.
RC TISSUE=Liver;
RX PubMed=1763325; DOI=10.1126/science.1763325;
RA Mendel D.B., Khavari P.A., Conley P.B., Graves M.K., Hansen L.P., Admon A.,
RA Crabtree G.R.;
RT "Characterization of a cofactor that regulates dimerization of a mammalian
RT homeodomain protein.";
RL Science 254:1762-1767(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9865610;
RA Bossow S., Riepl S., Igo-Kemenes T.;
RT "Characterization of the chicken and rat DCoH gene domains using an
RT improved ligation-mediated PCR method.";
RL Biol. Chem. 379:1359-1365(1998).
RN [3]
RP PROTEIN SEQUENCE OF 2-104, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=8444860; DOI=10.1016/s0021-9258(18)53471-2;
RA Hauer C.R., Rebrin I., Thoeny B., Neuheiser F., Curtius H.-C., Hunziker P.,
RA Blau N., Ghisla S., Heizmann C.W.;
RT "Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine
RT dehydratase from rat and human liver. Purification, characterization, and
RT complete amino acid sequence.";
RL J. Biol. Chem. 268:4828-4831(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-45, AND CATALYTIC ACTIVITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1465414; DOI=10.1073/pnas.89.24.11891;
RA Citron B.A., Davis M.D., Milstien S., Gutierrez J., Mendel D.B.,
RA Crabtree G.R., Kaufman S.;
RT "Identity of 4a-carbinolamine dehydratase, a component of the phenylalanine
RT hydroxylation system, and DCoH, a transregulator of homeodomain proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:11891-11894(1992).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-82.
RX PubMed=8618906; DOI=10.1073/pnas.92.26.12384;
RA Johnen G., Kowlessur D., Citron B.A., Kaufman S.;
RT "Characterization of the wild-type form of 4a-carbinolamine dehydratase and
RT two naturally occurring mutants associated with hyperphenylalaninemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:12384-12388(1995).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), AND SUBUNIT.
RX PubMed=7744010; DOI=10.1002/j.1460-2075.1995.tb07195.x;
RA Ficner R., Sauer U.H., Stier G., Suck D.;
RT "Three-dimensional structure of the bifunctional protein PCD/DCoH, a
RT cytoplasmic enzyme interacting with transcription factor HNF1.";
RL EMBO J. 14:2034-2042(1995).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH 7,8-DIHYDROBIOPTERIN,
RP AND SUBUNIT.
RX PubMed=8897596; DOI=10.1002/pro.5560051002;
RA Cronk J.D., Endrizzi J.A., Alber T.;
RT "High-resolution structures of the bifunctional enzyme and transcriptional
RT coactivator DCoH and its complex with a product analogue.";
RL Protein Sci. 5:1963-1972(1996).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), INTERACTION WITH HNF1A, AND SUBUNIT.
RX PubMed=10966642; DOI=10.1038/78966;
RA Rose R.B., Bayle J.H., Endrizzi J.A., Cronk J.D., Crabtree G.R., Alber T.;
RT "Structural basis of dimerization, coactivator recognition and MODY3
RT mutations in HNF-1alpha.";
RL Nat. Struct. Biol. 7:744-748(2000).
CC -!- FUNCTION: Involved in tetrahydrobiopterin biosynthesis (PubMed:8444860,
CC PubMed:8618906). Seems to both prevent the formation of 7-pterins and
CC accelerate the formation of quinonoid-BH2 (PubMed:8444860). Coactivator
CC for HNF1A-dependent transcription (PubMed:1763325). Regulates the
CC dimerization of homeodomain protein HNF1A and enhances its
CC transcriptional activity (PubMed:1763325). Also acts as a coactivator
CC for HNF1B-dependent transcription (By similarity).
CC {ECO:0000250|UniProtKB:P61457, ECO:0000269|PubMed:1763325,
CC ECO:0000269|PubMed:8444860, ECO:0000269|PubMed:8618906}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin =
CC (6R)-L-erythro-6,7-dihydrobiopterin + H2O; Xref=Rhea:RHEA:11920,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15642, ChEBI:CHEBI:43120; EC=4.2.1.96;
CC Evidence={ECO:0000269|PubMed:1465414, ECO:0000269|PubMed:8444860,
CC ECO:0000269|PubMed:8618906};
CC -!- SUBUNIT: Homotetramer and homodimer (PubMed:1763325, PubMed:8444860,
CC PubMed:10966642, PubMed:7744010, PubMed:8897596). Heterotetramer with
CC HNF1A; formed by a dimer of dimers (PubMed:10966642). Interacts with
CC HNF1B (via HNF-p1 domain); the interaction increases HNF1B
CC transactivation activity (By similarity).
CC {ECO:0000250|UniProtKB:P35680, ECO:0000269|PubMed:10966642,
CC ECO:0000269|PubMed:1763325, ECO:0000269|PubMed:7744010,
CC ECO:0000269|PubMed:8444860, ECO:0000269|PubMed:8897596}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8444860}. Nucleus
CC {ECO:0000269|PubMed:8444860}. Note=Recruited to the nucleus through the
CC interaction with HNF1B. {ECO:0000250|UniProtKB:P35680}.
CC -!- SIMILARITY: Belongs to the pterin-4-alpha-carbinolamine dehydratase
CC family. {ECO:0000305}.
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DR EMBL; M83740; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AJ005542; CAA06587.1; -; Genomic_DNA.
DR EMBL; L04537; AAA40609.1; -; mRNA.
DR PIR; A47189; A47189.
DR RefSeq; NP_001007602.1; NM_001007601.2.
DR RefSeq; XP_006256476.1; XM_006256414.1.
DR PDB; 1DCH; X-ray; 3.00 A; A/B/C/D/E/F/G/H=1-104.
DR PDB; 1DCO; X-ray; 2.30 A; A/B/C/D/E/F/G/H=1-104.
DR PDB; 1DCP; X-ray; 2.30 A; A/B/C/D/E/F/G/H=1-104.
DR PDB; 1F93; X-ray; 2.60 A; A/B/C/D=1-104.
DR PDB; 3HXA; X-ray; 1.80 A; A/B/C/D/E/F/G/H=1-104.
DR PDBsum; 1DCH; -.
DR PDBsum; 1DCO; -.
DR PDBsum; 1DCP; -.
DR PDBsum; 1F93; -.
DR PDBsum; 3HXA; -.
DR AlphaFoldDB; P61459; -.
DR SMR; P61459; -.
DR STRING; 10116.ENSRNOP00000000687; -.
DR MoonProt; P61459; -.
DR iPTMnet; P61459; -.
DR PhosphoSitePlus; P61459; -.
DR jPOST; P61459; -.
DR PaxDb; P61459; -.
DR PRIDE; P61459; -.
DR Ensembl; ENSRNOT00000115927; ENSRNOP00000080781; ENSRNOG00000067614.
DR Ensembl; ENSRNOT00000120036; ENSRNOP00000085944; ENSRNOG00000000566.
DR GeneID; 29700; -.
DR KEGG; rno:29700; -.
DR UCSC; RGD:3263; rat.
DR CTD; 5092; -.
DR RGD; 3263; Pcbd1.
DR eggNOG; KOG4073; Eukaryota.
DR GeneTree; ENSGT00390000007221; -.
DR HOGENOM; CLU_081974_3_2_1; -.
DR InParanoid; P61459; -.
DR OMA; WAEKWNH; -.
DR OrthoDB; 1588292at2759; -.
DR PhylomeDB; P61459; -.
DR TreeFam; TF300188; -.
DR BRENDA; 4.2.1.96; 5301.
DR Reactome; R-RNO-8964208; Phenylalanine metabolism.
DR EvolutionaryTrace; P61459; -.
DR PRO; PR:P61459; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000566; Expressed in liver and 20 other tissues.
DR Genevisible; P61459; RN.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IPI:MGI.
DR GO; GO:0008124; F:4-alpha-hydroxytetrahydrobiopterin dehydratase activity; IDA:CAFA.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:MGI.
DR GO; GO:0006558; P:L-phenylalanine metabolic process; IDA:CAFA.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0043393; P:regulation of protein binding; IDA:MGI.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1360.20; -; 1.
DR HAMAP; MF_00434; Pterin_4_alpha; 1.
DR InterPro; IPR036428; PCD_sf.
DR InterPro; IPR001533; Pterin_deHydtase.
DR PANTHER; PTHR12599; PTHR12599; 1.
DR Pfam; PF01329; Pterin_4a; 1.
DR SUPFAM; SSF55248; SSF55248; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Cytoplasm; Direct protein sequencing;
KW Lyase; Nucleus; Reference proteome; Tetrahydrobiopterin biosynthesis;
KW Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8444860"
FT CHAIN 2..104
FT /note="Pterin-4-alpha-carbinolamine dehydratase"
FT /id="PRO_0000063054"
FT BINDING 61..63
FT /ligand="substrate"
FT BINDING 78..81
FT /ligand="substrate"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:8444860"
FT MUTAGEN 82
FT /note="C->R: Reduced dehydratase activity. No impact on
FT hydroxytetrahydrobiopterin-binding."
FT /evidence="ECO:0000269|PubMed:8618906"
FT HELIX 10..16
FT /evidence="ECO:0007829|PDB:3HXA"
FT HELIX 18..21
FT /evidence="ECO:0007829|PDB:3HXA"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:3HXA"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:3HXA"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:3HXA"
FT HELIX 43..60
FT /evidence="ECO:0007829|PDB:3HXA"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:3HXA"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:3HXA"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:3HXA"
FT HELIX 87..102
FT /evidence="ECO:0007829|PDB:3HXA"
SQ SEQUENCE 104 AA; 12000 MW; 997DF8C2417FE5F5 CRC64;
MAGKAHRLSA EERDQLLPNL RAVGWNELEG RDAIFKQFHF KDFNRAFGFM TRVALQAEKL
DHHPEWFNVY NKVHITLSTH ECAGLSERDI NLASFIEQVA VSMT
