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   24-JAN-2024, entry version 173.
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};
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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; 46.
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; 9606-ENSP00000421544; -.
DR   PeptideAtlas; Q9H0N5; -.
DR   ProteomicsDB; 80304; -.
DR   Pumba; Q9H0N5; -.
DR   Antibodypedia; 26376; 77 antibodies from 19 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   AGR; HGNC:24474; -.
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; SHDCGGV; -.
DR   OrthoDB; 117067at2759; -.
DR   PhylomeDB; Q9H0N5; -.
DR   TreeFam; TF300188; -.
DR   BioCyc; MetaCyc:HS13433-MONOMER; -.
DR   BRENDA; 4.2.1.96; 2681.
DR   PathwayCommons; Q9H0N5; -.
DR   SignaLink; Q9H0N5; -.
DR   BioGRID-ORCS; 84105; 22 hits in 1163 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 170 other cell types or tissues.
DR   ExpressionAtlas; Q9H0N5; baseline and differential.
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 DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IEA:UniProtKB-KW.
DR   CDD; cd00914; PCD_DCoH_subfamily_b; 1.
DR   Gene3D; 3.30.1360.20; Transcriptional coactivator/pterin dehydratase; 1.
DR   HAMAP; MF_00434; Pterin_4_alpha; 1.
DR   InterPro; IPR036428; PCD_sf.
DR   InterPro; IPR001533; Pterin_deHydtase.
DR   PANTHER; PTHR12599; PTERIN-4-ALPHA-CARBINOLAMINE DEHYDRATASE; 1.
DR   PANTHER; PTHR12599:SF15; PTERIN-4-ALPHA-CARBINOLAMINE DEHYDRATASE 2; 1.
DR   Pfam; PF01329; Pterin_4a; 1.
DR   SUPFAM; SSF55248; PCD-like; 1.
DR   Genevisible; Q9H0N5; HS.
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
//