PTPS_HUMAN
ID PTPS_HUMAN Reviewed; 145 AA.
AC Q03393; B0YJ87; Q8WVG8;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=6-pyruvoyl tetrahydrobiopterin synthase;
DE Short=PTP synthase;
DE Short=PTPS;
DE EC=4.2.3.12;
GN Name=PTS;
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 [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=1282802; DOI=10.1016/0006-291x(92)90235-d;
RA Thoeny B., Leimbacher W., Buergisser D., Heizmann C.W.;
RT "Human 6-pyruvoyltetrahydropterin synthase: cDNA cloning and heterologous
RT expression of the recombinant enzyme.";
RL Biochem. Biophys. Res. Commun. 189:1437-1443(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8216273; DOI=10.1006/bbrc.1993.2197;
RA Ashida A., Hatakeyama K., Kagamiyama H.;
RT "cDNA cloning, expression in Escherichia coli and purification of human 6-
RT pyruvoyl-tetrahydropterin synthase.";
RL Biochem. Biophys. Res. Commun. 195:1386-1393(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HPABH4A VAL-114.
RX PubMed=7698774; DOI=10.1006/geno.1994.1642;
RA Ashida A., Owada M., Hatakeyama K.;
RT "A missense mutation (A to G) of 6-pyruvoyltetrahydropterin synthase in
RT tetrahydrobiopterin-deficient form of hyperphenylalaninemia.";
RL Genomics 24:408-410(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8841415; DOI=10.1111/j.1432-1033.1996.0477h.x;
RA Kluge C., Brecevic L., Heizmann C.W., Blau N., Thoeny B.;
RT "Chromosomal localization, genomic structure and characterization of the
RT human gene and a retropseudogene for 6-pyruvoyltetrahydropterin synthase.";
RL Eur. J. Biochem. 240:477-484(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Liu T.T., Lu S.F., Hsiao K.J.;
RT "Genomic structure of 6-pyruvoyl-tetrahydropterin synthase gene and a T/C
RT polymorphism detected in Chinese.";
RL J. Biomed. Lab. Sci. 10:39-47(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Hsiao K.-J., Liu T.-T., Chang Y.-H., Chiu Y.-H., Chiang S.-H., Chang H.-M.,
RA Chen C.-Y., Tsai S.-F.;
RT "Isolation and sequencing of human 6-pyruvoyl-tetrahydropterin synthase
RT gene containing BAC clone 321H15.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Pancreas;
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND TYR-128, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP CHARACTERIZATION OF VARIANTS HPABH4A CYS-16 AND GLN-25, KINETIC PARAMETERS,
RP PHOSPHORYLATION AT SER-19, AND MUTAGENESIS OF SER-19.
RX PubMed=10531334; DOI=10.1074/jbc.274.44.31341;
RA Scherer-Oppliger T., Leimbacher W., Blau N., Thoeny B.;
RT "Serine 19 of human 6-pyruvoyltetrahydropterin synthase is phosphorylated
RT by cGMP protein kinase II.";
RL J. Biol. Chem. 274:31341-31348(1999).
RN [15]
RP REVIEW ON VARIANTS.
RX PubMed=9222755;
RX DOI=10.1002/(sici)1098-1004(1997)10:1<11::aid-humu2>3.0.co;2-p;
RA Thoeny B., Blau N.;
RT "Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin
RT synthase genes.";
RL Hum. Mutat. 10:11-20(1997).
RN [16]
RP VARIANTS HPABH4A CYS-16 AND GLN-25.
RX PubMed=8178819;
RA Thoeny B., Leimbacher W., Blau N., Harvie A., Heizmann C.W.;
RT "Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism:
RT molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin
RT synthase.";
RL Am. J. Hum. Genet. 54:782-792(1994).
RN [17]
RP CHARACTERIZATION OF VARIANTS HPABH4A CYS-16; GLN-25; VAL-57 DEL AND LEU-87.
RX PubMed=7493990; DOI=10.1074/jbc.270.49.29498;
RA Oppliger T., Thoeny B., Nar H., Buergisser D., Huber R., Heizmann C.W.,
RA Blau N.;
RT "Structural and functional consequences of mutations in 6-
RT pyruvoyltetrahydropterin synthase causing hyperphenylalaninemia in humans.
RT Phosphorylation is a requirement for in vivo activity.";
RL J. Biol. Chem. 270:29498-29506(1995).
RN [18]
RP VARIANTS HPABH4A SER-52 AND SER-87.
RX PubMed=8707300; DOI=10.1007/s004390050213;
RA Liu T.T., Hsiao K.J.;
RT "Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation
RT at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin
RT synthesis deficiency.";
RL Hum. Genet. 98:313-316(1996).
RN [19]
RP VARIANTS HPABH4A VAL-57 DEL; MET-67; GLU-129 AND VAL-136.
RX PubMed=9222757;
RX DOI=10.1002/(sici)1098-1004(1997)10:1<25::aid-humu4>3.0.co;2-l;
RA Oppliger T., Thoeny B., Kluge C., Matasovic A., Heizmann C.W., Ponzone A.,
RA Spada M., Blau N.;
RT "Identification of mutations causing 6-pyruvoyl-tetrahydropterin synthase
RT deficiency in four Italian families.";
RL Hum. Mutat. 10:25-35(1997).
RN [20]
RP VARIANT HPABH4A VAL-114.
RX PubMed=9159737; DOI=10.1002/mds.870120321;
RA Hanihara T., Inoue K., Kawanishi C., Sugiyama N., Miyakawa T., Onishi H.,
RA Yamada Y., Osaka H., Kosaka K., Iwabuchi K., Owada M.;
RT "6-pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia
RT and diurnal fluctuation of symptoms: a clinical and molecular study.";
RL Mov. Disord. 12:408-411(1997).
RN [21]
RP VARIANTS HPABH4A GLY-25; SER-52; MET-56; ASP-70; SER-87; ASN-96 AND
RP MET-106.
RX PubMed=9450907;
RX DOI=10.1002/(sici)1098-1004(1998)11:1<76::aid-humu12>3.0.co;2-w;
RA Liu T.-T., Hsiao K.-J., Lu S.-F., Wu S.-J., Wu K.-F., Chiang S.-H.,
RA Liu X.-Q., Chen R.-G., Yu W.-M.;
RT "Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in
RT Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis
RT deficiency.";
RL Hum. Mutat. 11:76-83(1998).
RN [22]
RP VARIANTS HPABH4A VAL-57 DEL AND MET-97.
RX PubMed=10585341;
RA Romstad A., Guldberg P., Blau N., Guettler F.;
RT "Single-step mutation scanning of the 6-pyruvoyltetrahydropterin synthase
RT gene in patients with hyperphenylalaninemia.";
RL Clin. Chem. 45:2102-2108(1999).
RN [23]
RP VARIANTS HPABH4A ASP-47 AND GLY-116.
RX PubMed=10220141;
RX DOI=10.1002/(sici)1098-1004(1999)13:4<286::aid-humu4>3.0.co;2-c;
RA Scherer-Oppliger T., Matasovic A., Laufs S., Levy H.L., Quackenbush E.J.,
RA Blau N., Thoeny B.;
RT "Dominant negative allele (N47D) in a compound heterozygote for a variant
RT of 6-pyruvoyltetrahydropterin synthase deficiency causing transient
RT hyperphenylalaninemia.";
RL Hum. Mutat. 13:286-289(1999).
RN [24]
RP VARIANT HPABH4A CYS-99.
RX PubMed=10874306;
RX DOI=10.1002/1098-1004(200007)16:1<54::aid-humu10>3.0.co;2-c;
RA Blau N., Scherer-Oppliger T., Baumer A., Riegel M., Matasovic A.,
RA Schinzel A., Jaeken J., Thoeny B.;
RT "Isolated central form of tetrahydrobiopterin deficiency associated with
RT hemizygosity on chromosome 11q and a mutant allele of PTPS.";
RL Hum. Mutat. 16:54-60(2000).
RN [25]
RP VARIANTS HPABH4A PHE-26; MET-67; LEU-87; LEU-124; GLY-136 AND VAL-136.
RX PubMed=11388593; DOI=10.1007/s004310000722;
RA Dudesek A., Roeschinger W., Muntau A.C., Seidel J., Leupold D., Thoeny B.,
RA Blau N.;
RT "Molecular analysis and long-term follow-up of patients with different
RT forms of 6-pyruvoyl-tetrahydropterin synthase deficiency.";
RL Eur. J. Pediatr. 160:267-276(2001).
CC -!- FUNCTION: Involved in the biosynthesis of tetrahydrobiopterin, an
CC essential cofactor of aromatic amino acid hydroxylases. Catalyzes the
CC transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl
CC tetrahydropterin. {ECO:0000269|PubMed:1282802}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8-
CC tetrahydropterin + H(+) + triphosphate; Xref=Rhea:RHEA:22048,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18036, ChEBI:CHEBI:58462,
CC ChEBI:CHEBI:136564; EC=4.2.3.12;
CC Evidence={ECO:0000269|PubMed:1282802};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.1 uM for 7,8-dihydroneopterin triphosphate
CC {ECO:0000269|PubMed:10531334};
CC Vmax=120 nmol/min/mg enzyme {ECO:0000269|PubMed:10531334};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrobiopterin biosynthesis;
CC tetrahydrobiopterin from 7,8-dihydroneopterin triphosphate: step 1/3.
CC -!- SUBUNIT: Homohexamer formed of two homotrimers in a head to head
CC fashion.
CC -!- INTERACTION:
CC Q03393; Q96CW1: AP2M1; NbExp=3; IntAct=EBI-712344, EBI-297683;
CC Q03393; P38432: COIL; NbExp=3; IntAct=EBI-712344, EBI-945751;
CC Q03393; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-712344, EBI-742054;
CC Q03393; P51116: FXR2; NbExp=4; IntAct=EBI-712344, EBI-740459;
CC Q03393; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-712344, EBI-739832;
CC Q03393; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-712344, EBI-741158;
CC Q03393; Q03393: PTS; NbExp=16; IntAct=EBI-712344, EBI-712344;
CC Q03393; O00560: SDCBP; NbExp=4; IntAct=EBI-712344, EBI-727004;
CC Q03393; Q9P2Z0: THAP10; NbExp=3; IntAct=EBI-712344, EBI-745404;
CC -!- PTM: Phosphorylation of Ser-19 is required for maximal enzyme activity.
CC {ECO:0000269|PubMed:10531334}.
CC -!- DISEASE: Hyperphenylalaninemia, BH4-deficient, A (HPABH4A)
CC [MIM:261640]: An autosomal recessive disorder characterized by
CC hyperphenylalaninemia, depletion of the neurotransmitters dopamine and
CC serotonin, and progressive cognitive and motor deficits. Neurological
CC symptoms are unresponsive to the classic phenylalanine-low diet.
CC {ECO:0000269|PubMed:10220141, ECO:0000269|PubMed:10531334,
CC ECO:0000269|PubMed:10585341, ECO:0000269|PubMed:10874306,
CC ECO:0000269|PubMed:11388593, ECO:0000269|PubMed:7493990,
CC ECO:0000269|PubMed:7698774, ECO:0000269|PubMed:8178819,
CC ECO:0000269|PubMed:8707300, ECO:0000269|PubMed:9159737,
CC ECO:0000269|PubMed:9222757, ECO:0000269|PubMed:9450907}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: The active site is at the interface between 2 subunits.
CC The proton acceptor Cys is on one subunit, and the charge relay system
CC is on the other subunit.
CC -!- SIMILARITY: Belongs to the PTPS family. {ECO:0000305}.
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DR EMBL; M97655; AAA51541.1; -; mRNA.
DR EMBL; D17400; BAA04224.1; -; mRNA.
DR EMBL; D25234; BAA04959.1; -; Genomic_DNA.
DR EMBL; L76259; AAB64229.1; -; Genomic_DNA.
DR EMBL; U63383; AAC16970.1; -; Genomic_DNA.
DR EMBL; U63380; AAC16970.1; JOINED; Genomic_DNA.
DR EMBL; U63381; AAC16970.1; JOINED; Genomic_DNA.
DR EMBL; U63382; AAC16970.1; JOINED; Genomic_DNA.
DR EMBL; AB042297; BAA95486.1; -; Genomic_DNA.
DR EMBL; EF445018; ACA06065.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67195.1; -; Genomic_DNA.
DR EMBL; BC009686; AAH09686.1; -; mRNA.
DR EMBL; BC018029; AAH18029.1; -; mRNA.
DR CCDS; CCDS8359.1; -.
DR PIR; JC1405; JC1405.
DR RefSeq; NP_000308.1; NM_000317.2.
DR PDB; 3I2B; X-ray; 2.30 A; A/B/C/D/E/F/G/H/I/J/K/L=7-145.
DR PDBsum; 3I2B; -.
DR AlphaFoldDB; Q03393; -.
DR SMR; Q03393; -.
DR BioGRID; 111769; 44.
DR IntAct; Q03393; 20.
DR MINT; Q03393; -.
DR STRING; 9606.ENSP00000280362; -.
DR BindingDB; Q03393; -.
DR ChEMBL; CHEMBL4630823; -.
DR DrugBank; DB03886; Biopterin.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR iPTMnet; Q03393; -.
DR PhosphoSitePlus; Q03393; -.
DR BioMuta; PTS; -.
DR EPD; Q03393; -.
DR jPOST; Q03393; -.
DR MassIVE; Q03393; -.
DR MaxQB; Q03393; -.
DR PaxDb; Q03393; -.
DR PeptideAtlas; Q03393; -.
DR PRIDE; Q03393; -.
DR ProteomicsDB; 58205; -.
DR TopDownProteomics; Q03393; -.
DR Antibodypedia; 780; 209 antibodies from 27 providers.
DR DNASU; 5805; -.
DR Ensembl; ENST00000280362.8; ENSP00000280362.3; ENSG00000150787.8.
DR GeneID; 5805; -.
DR KEGG; hsa:5805; -.
DR MANE-Select; ENST00000280362.8; ENSP00000280362.3; NM_000317.3; NP_000308.1.
DR UCSC; uc001pnj.5; human.
DR CTD; 5805; -.
DR DisGeNET; 5805; -.
DR GeneCards; PTS; -.
DR HGNC; HGNC:9689; PTS.
DR HPA; ENSG00000150787; Low tissue specificity.
DR MalaCards; PTS; -.
DR MIM; 261640; phenotype.
DR MIM; 612719; gene.
DR neXtProt; NX_Q03393; -.
DR OpenTargets; ENSG00000150787; -.
DR Orphanet; 13; 6-pyruvoyl-tetrahydropterin synthase deficiency.
DR PharmGKB; PA34032; -.
DR VEuPathDB; HostDB:ENSG00000150787; -.
DR eggNOG; KOG4105; Eukaryota.
DR GeneTree; ENSGT00390000002752; -.
DR HOGENOM; CLU_111016_2_0_1; -.
DR InParanoid; Q03393; -.
DR OMA; NVAIFIW; -.
DR OrthoDB; 1502673at2759; -.
DR PhylomeDB; Q03393; -.
DR TreeFam; TF105796; -.
DR BioCyc; MetaCyc:HS07692-MON; -.
DR BRENDA; 4.2.3.12; 2681.
DR PathwayCommons; Q03393; -.
DR Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR SABIO-RK; Q03393; -.
DR SignaLink; Q03393; -.
DR SIGNOR; Q03393; -.
DR UniPathway; UPA00849; UER00819.
DR BioGRID-ORCS; 5805; 10 hits in 1083 CRISPR screens.
DR ChiTaRS; PTS; human.
DR EvolutionaryTrace; Q03393; -.
DR GeneWiki; PTS_(gene); -.
DR GenomeRNAi; 5805; -.
DR Pharos; Q03393; Tbio.
DR PRO; PR:Q03393; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q03393; protein.
DR Bgee; ENSG00000150787; Expressed in adrenal tissue and 206 other tissues.
DR ExpressionAtlas; Q03393; baseline and differential.
DR Genevisible; Q03393; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:LIFEdb.
DR GO; GO:0003874; F:6-pyruvoyltetrahydropterin synthase activity; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006520; P:cellular amino acid metabolic process; TAS:ProtInc.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; TAS:ProtInc.
DR Gene3D; 3.30.479.10; -; 1.
DR InterPro; IPR007115; 6-PTP_synth/QueD.
DR InterPro; IPR038418; 6-PTP_synth/QueD_sf.
DR InterPro; IPR022470; PTPS_Cys_AS.
DR InterPro; IPR022469; PTPS_His_AS.
DR PANTHER; PTHR12589; PTHR12589; 1.
DR Pfam; PF01242; PTPS; 1.
DR PIRSF; PIRSF006113; PTP_synth; 1.
DR TIGRFAMs; TIGR00039; 6PTHBS; 1.
DR PROSITE; PS00987; PTPS_1; 1.
DR PROSITE; PS00988; PTPS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Lyase; Metal-binding; Phenylketonuria;
KW Phosphoprotein; Reference proteome; Tetrahydrobiopterin biosynthesis; Zinc.
FT CHAIN 1..145
FT /note="6-pyruvoyl tetrahydrobiopterin synthase"
FT /id="PRO_0000057914"
FT ACT_SITE 43
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT ACT_SITE 90
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10124"
FT ACT_SITE 134
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10124"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT BINDING 49
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT BINDING 51
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT MOD_RES 19
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000269|PubMed:10531334,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1Z7"
FT MOD_RES 128
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 16
FT /note="R -> C (in HPABH4A; severe decrease in activity;
FT diminishes phosphorylation by PKG; dbSNP:rs104894274)"
FT /evidence="ECO:0000269|PubMed:10531334,
FT ECO:0000269|PubMed:7493990, ECO:0000269|PubMed:8178819"
FT /id="VAR_006816"
FT VARIANT 25
FT /note="R -> G (in HPABH4A; severe form;
FT dbSNP:rs1167104933)"
FT /evidence="ECO:0000269|PubMed:9450907"
FT /id="VAR_006817"
FT VARIANT 25
FT /note="R -> Q (in HPABH4A; abolishes activity; no effect on
FT phosphorylation by PKG; dbSNP:rs104894273)"
FT /evidence="ECO:0000269|PubMed:10531334,
FT ECO:0000269|PubMed:7493990, ECO:0000269|PubMed:8178819"
FT /id="VAR_006818"
FT VARIANT 26
FT /note="L -> F (in HPABH4A; dbSNP:rs1317230624)"
FT /evidence="ECO:0000269|PubMed:11388593"
FT /id="VAR_058265"
FT VARIANT 35
FT /note="E -> G (in HPABH4A; dbSNP:rs1328320990)"
FT /id="VAR_006819"
FT VARIANT 36
FT /note="N -> K (in HPABH4A; dbSNP:rs1449216377)"
FT /id="VAR_006820"
FT VARIANT 47
FT /note="N -> D (in HPABH4A; transient phenotype due to
FT partial PTS deficiency; total loss of activity;
FT dbSNP:rs104894278)"
FT /evidence="ECO:0000269|PubMed:10220141"
FT /id="VAR_008040"
FT VARIANT 52
FT /note="N -> S (in HPABH4A; severe form; dbSNP:rs104894275)"
FT /evidence="ECO:0000269|PubMed:8707300,
FT ECO:0000269|PubMed:9450907"
FT /id="VAR_006821"
FT VARIANT 56
FT /note="V -> M (in HPABH4A; mild form; dbSNP:rs104894277)"
FT /evidence="ECO:0000269|PubMed:9450907"
FT /id="VAR_006822"
FT VARIANT 57
FT /note="Missing (in HPABH4A; dbSNP:rs770387277)"
FT /evidence="ECO:0000269|PubMed:10585341,
FT ECO:0000269|PubMed:7493990, ECO:0000269|PubMed:9222757"
FT /id="VAR_006823"
FT VARIANT 67
FT /note="T -> M (in HPABH4A; dbSNP:rs370340361)"
FT /evidence="ECO:0000269|PubMed:11388593,
FT ECO:0000269|PubMed:9222757"
FT /id="VAR_006824"
FT VARIANT 70
FT /note="V -> D (in HPABH4A; dbSNP:rs1592880489)"
FT /evidence="ECO:0000269|PubMed:9450907"
FT /id="VAR_006825"
FT VARIANT 87
FT /note="P -> L (in HPABH4A; dbSNP:rs765406631)"
FT /evidence="ECO:0000269|PubMed:11388593,
FT ECO:0000269|PubMed:7493990"
FT /id="VAR_006826"
FT VARIANT 87
FT /note="P -> S (in HPABH4A; severe form; dbSNP:rs104894276)"
FT /evidence="ECO:0000269|PubMed:8707300,
FT ECO:0000269|PubMed:9450907"
FT /id="VAR_006827"
FT VARIANT 96
FT /note="D -> N (in HPABH4A; severe form; dbSNP:rs104894280)"
FT /evidence="ECO:0000269|PubMed:9450907"
FT /id="VAR_006828"
FT VARIANT 97
FT /note="V -> M (in HPABH4A; dbSNP:rs750455879)"
FT /evidence="ECO:0000269|PubMed:10585341"
FT /id="VAR_058266"
FT VARIANT 99
FT /note="Y -> C (in HPABH4A; dbSNP:rs1555198458)"
FT /evidence="ECO:0000269|PubMed:10874306"
FT /id="VAR_058267"
FT VARIANT 100
FT /note="F -> V (in HPABH4A)"
FT /id="VAR_006829"
FT VARIANT 106
FT /note="T -> M (in HPABH4A; dbSNP:rs200712908)"
FT /evidence="ECO:0000269|PubMed:9450907"
FT /id="VAR_006830"
FT VARIANT 114
FT /note="I -> V (in HPABH4A; dbSNP:rs1555198495)"
FT /evidence="ECO:0000269|PubMed:7698774,
FT ECO:0000269|PubMed:9159737"
FT /id="VAR_006831"
FT VARIANT 116
FT /note="D -> G (in HPABH4A; transient phenotype due to
FT partial PTS deficiency; mild decrease of activity;
FT dbSNP:rs104894279)"
FT /evidence="ECO:0000269|PubMed:10220141"
FT /id="VAR_008041"
FT VARIANT 124
FT /note="V -> L (in HPABH4A; dbSNP:rs150726932)"
FT /evidence="ECO:0000269|PubMed:11388593"
FT /id="VAR_058268"
FT VARIANT 129
FT /note="K -> E (in HPABH4A; dbSNP:rs1040441824)"
FT /evidence="ECO:0000269|PubMed:9222757"
FT /id="VAR_006832"
FT VARIANT 136
FT /note="D -> G (in HPABH4A)"
FT /evidence="ECO:0000269|PubMed:11388593"
FT /id="VAR_058269"
FT VARIANT 136
FT /note="D -> V (in HPABH4A)"
FT /evidence="ECO:0000269|PubMed:11388593,
FT ECO:0000269|PubMed:9222757"
FT /id="VAR_006833"
FT MUTAGEN 19
FT /note="S->A: Decrease in activity; abolishes
FT phosphorylation by PKG."
FT /evidence="ECO:0000269|PubMed:10531334"
FT CONFLICT 114
FT /note="I -> M (in Ref. 9; AAH18029)"
FT /evidence="ECO:0000305"
FT STRAND 11..24
FT /evidence="ECO:0007829|PDB:3I2B"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:3I2B"
FT HELIX 33..40
FT /evidence="ECO:0007829|PDB:3I2B"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:3I2B"
FT STRAND 49..62
FT /evidence="ECO:0007829|PDB:3I2B"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:3I2B"
FT HELIX 73..83
FT /evidence="ECO:0007829|PDB:3I2B"
FT HELIX 85..88
FT /evidence="ECO:0007829|PDB:3I2B"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:3I2B"
FT HELIX 98..101
FT /evidence="ECO:0007829|PDB:3I2B"
FT HELIX 107..119
FT /evidence="ECO:0007829|PDB:3I2B"
FT STRAND 127..135
FT /evidence="ECO:0007829|PDB:3I2B"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:3I2B"
SQ SEQUENCE 145 AA; 16386 MW; A1CD0DC2F83187E0 CRC64;
MSTEGGGRRC QAQVSRRISF SASHRLYSKF LSDEENLKLF GKCNNPNGHG HNYKVVVTVH
GEIDPATGMV MNLADLKKYM EEAIMQPLDH KNLDMDVPYF ADVVSTTENV AVYIWDNLQK
VLPVGVLYKV KVYETDNNIV VYKGE
