PHS2_HUMAN
ID PHS2_HUMAN Reviewed; 130 AA.
AC Q9H0N5; Q8TD40;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 4.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Pterin-4-alpha-carbinolamine dehydratase 2;
DE Short=PHS 2;
DE EC=4.2.1.96;
DE AltName: Full=4-alpha-hydroxy-tetrahydropterin dehydratase 2;
DE AltName: Full=DcoH-like protein DCoHm;
DE AltName: Full=Dimerization cofactor of hepatocyte nuclear factor 1 from muscle;
DE AltName: Full=HNF-1-alpha dimerization cofactor;
GN Name=PCBD2; Synonyms=DCOH2, DCOHM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-130, FUNCTION IN HNF-1-ALPHA REGULATION,
RP AND INTERACTION WITH DYRK1B.
RC TISSUE=Skeletal muscle;
RX PubMed=11980910; DOI=10.1074/jbc.m203257200;
RA Lim S., Jin K., Friedman E.;
RT "Mirk protein kinase is activated by MKK3 and functions as a
RT transcriptional activator of HNF1alpha.";
RL J. Biol. Chem. 277:25040-25046(2002).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Involved in tetrahydrobiopterin biosynthesis. Seems to both
CC prevent the formation of 7-pterins and accelerate the formation of
CC quinonoid-BH2 (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Regulates the dimerization of homeodomain protein HNF-1-alpha
CC and enhances its transcriptional activity.
CC {ECO:0000269|PubMed:11980910}.
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 -!- SUBUNIT: Homotetramer. Interacts with DYRK1B.
CC {ECO:0000269|PubMed:11980910}.
CC -!- INTERACTION:
CC Q9H0N5; O75934: BCAS2; NbExp=3; IntAct=EBI-634289, EBI-1050106;
CC Q9H0N5; Q8IU89: CERS3; NbExp=3; IntAct=EBI-634289, EBI-18202821;
CC Q9H0N5; Q9Y463: DYRK1B; NbExp=2; IntAct=EBI-634289, EBI-634187;
CC Q9H0N5; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-634289, EBI-11978177;
CC Q9H0N5; Q6P597-3: KLC3; NbExp=3; IntAct=EBI-634289, EBI-12076930;
CC Q9H0N5; Q8TCE9: LGALS14; NbExp=3; IntAct=EBI-634289, EBI-10274069;
CC Q9H0N5; P43364: MAGEA11; NbExp=3; IntAct=EBI-634289, EBI-739552;
CC Q9H0N5; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-634289, EBI-10178634;
CC Q9H0N5; P43360: MAGEA6; NbExp=3; IntAct=EBI-634289, EBI-1045155;
CC Q9H0N5; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-634289, EBI-995714;
CC Q9H0N5; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-634289, EBI-742688;
CC -!- SIMILARITY: Belongs to the pterin-4-alpha-carbinolamine dehydratase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM18136.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL136721; CAB66655.1; -; mRNA.
DR EMBL; AC006077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008670; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC054021; AAH54021.1; -; mRNA.
DR EMBL; AF499009; AAM18136.1; ALT_INIT; mRNA.
DR CCDS; CCDS43364.1; -.
DR RefSeq; NP_115527.3; NM_032151.4.
DR PDB; 4C45; X-ray; 1.45 A; A=28-130.
DR PDBsum; 4C45; -.
DR AlphaFoldDB; Q9H0N5; -.
DR SMR; Q9H0N5; -.
DR BioGRID; 123893; 44.
DR IntAct; Q9H0N5; 40.
DR STRING; 9606.ENSP00000421544; -.
DR iPTMnet; Q9H0N5; -.
DR PhosphoSitePlus; Q9H0N5; -.
DR BioMuta; PCBD2; -.
DR DMDM; 239938927; -.
DR EPD; Q9H0N5; -.
DR jPOST; Q9H0N5; -.
DR MassIVE; Q9H0N5; -.
DR MaxQB; Q9H0N5; -.
DR PaxDb; Q9H0N5; -.
DR PeptideAtlas; Q9H0N5; -.
DR PRIDE; Q9H0N5; -.
DR ProteomicsDB; 80304; -.
DR Antibodypedia; 26376; 63 antibodies from 18 providers.
DR DNASU; 84105; -.
DR Ensembl; ENST00000254908.11; ENSP00000254908.6; ENSG00000132570.15.
DR Ensembl; ENST00000512783.5; ENSP00000421544.1; ENSG00000132570.15.
DR GeneID; 84105; -.
DR KEGG; hsa:84105; -.
DR MANE-Select; ENST00000254908.11; ENSP00000254908.6; NM_032151.5; NP_115527.3.
DR UCSC; uc010jdz.4; human.
DR CTD; 84105; -.
DR DisGeNET; 84105; -.
DR GeneCards; PCBD2; -.
DR HGNC; HGNC:24474; PCBD2.
DR HPA; ENSG00000132570; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 609836; gene.
DR neXtProt; NX_Q9H0N5; -.
DR OpenTargets; ENSG00000132570; -.
DR PharmGKB; PA142671197; -.
DR VEuPathDB; HostDB:ENSG00000132570; -.
DR eggNOG; KOG4073; Eukaryota.
DR GeneTree; ENSGT00390000007221; -.
DR InParanoid; Q9H0N5; -.
DR OMA; MSSQSHW; -.
DR OrthoDB; 1588292at2759; -.
DR PhylomeDB; Q9H0N5; -.
DR TreeFam; TF300188; -.
DR BioCyc; MetaCyc:HS13433-MON; -.
DR BRENDA; 4.2.1.96; 2681.
DR PathwayCommons; Q9H0N5; -.
DR SignaLink; Q9H0N5; -.
DR BioGRID-ORCS; 84105; 22 hits in 1082 CRISPR screens.
DR ChiTaRS; PCBD2; human.
DR GeneWiki; PCBD2; -.
DR GenomeRNAi; 84105; -.
DR Pharos; Q9H0N5; Tbio.
DR PRO; PR:Q9H0N5; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9H0N5; protein.
DR Bgee; ENSG00000132570; Expressed in tibialis anterior and 168 other tissues.
DR ExpressionAtlas; Q9H0N5; baseline and differential.
DR Genevisible; Q9H0N5; HS.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0008124; F:4-alpha-hydroxytetrahydrobiopterin dehydratase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
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; Lyase; Reference proteome;
KW Tetrahydrobiopterin biosynthesis.
FT CHAIN 1..130
FT /note="Pterin-4-alpha-carbinolamine dehydratase 2"
FT /id="PRO_0000063057"
FT MOD_RES 114
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZL5"
FT MOD_RES 114
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZL5"
FT MOD_RES 118
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZL5"
FT MOD_RES 118
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZL5"
FT MOD_RES 125
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZL5"
FT MOD_RES 125
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CZL5"
FT CONFLICT 36
FT /note="T -> I (in Ref. 1; CAB66655)"
FT /evidence="ECO:0000305"
FT HELIX 37..49
FT /evidence="ECO:0007829|PDB:4C45"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:4C45"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:4C45"
FT HELIX 70..87
FT /evidence="ECO:0007829|PDB:4C45"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:4C45"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:4C45"
FT TURN 107..110
FT /evidence="ECO:0007829|PDB:4C45"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:4C45"
SQ SEQUENCE 130 AA; 14365 MW; 7B834F95D7ACD1EE CRC64;
MAAVLGALGA TRRLLAALRG QSLGLAAMSS GTHRLTAEER NQAILDLKAA GWSELSERDA
IYKEFSFHNF NQAFGFMSRV ALQAEKMNHH PEWFNVYNKV QITLTSHDCG ELTKKDVKLA
KFIEKAAASV
