ID:PTPS_HUMAN DESCRIPTION: RecName: Full=6-pyruvoyl tetrahydrobiopterin synthase; Short=PTP synthase; Short=PTPS; EC=4.2.3.12; FUNCTION: Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6- pyruvoyl tetrahydropterin. CATALYTIC ACTIVITY: 7,8-dihydroneopterin 3'-triphosphate = 6- pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate. COFACTOR: Binds 1 zinc ion per subunit (By similarity). BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=8.1 uM for 7,8-dihydroneopterin triphosphate; Vmax=120 nmol/min/mg enzyme; PATHWAY: Cofactor biosynthesis; tetrahydrobiopterin biosynthesis; tetrahydrobiopterin from 7,8-dihydroneopterin triphosphate: step 1/3. SUBUNIT: Homohexamer formed of two homotrimers in a head to head fashion. INTERACTION: Self; NbExp=3; IntAct=EBI-712344, EBI-712344; PTM: Phosphorylation of Ser-19 is required for maximal enzyme activity. DISEASE: Defects in PTS are the cause of BH4-deficient hyperphenylalaninemia type A (HPABH4A) [MIM:261640]; also called 6-pyruvoyl-tetrahydropterin synthase deficiency (PTS deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to PTS deficiency. HPABH4A is an autosomal recessive disorder characterized by depletion of the neurotransmitters dopamine and serotonin, and clinically by severe neurological symptoms unresponsive to the classic phenylalanine-low diet. MISCELLANEOUS: The active site is at the interface between 2 subunits. The proton acceptor Cys is on one subunit, and the charge relay system is on the other subunit. SIMILARITY: Belongs to the PTPS family. WEB RESOURCE: Name=BIOMDB; Note=Db of mutations causing tetrahydrobiopterin deficiencies; URL="http://www.bh4.org/biodef1.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PTS";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q03393
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006520 cellular amino acid metabolic process GO:0006729 tetrahydrobiopterin biosynthetic process GO:0007417 central nervous system development GO:0051186 cofactor metabolic process
LF208478 - JP 2014500723-A/15981: Polycomb-Associated Non-Coding RNAs. BC018029 - Homo sapiens 6-pyruvoyltetrahydropterin synthase, mRNA (cDNA clone MGC:26099 IMAGE:4819386), complete cds. D17400 - Homo sapiens PTPS mRNA for 6-pyruvoyl-tetrahydropterin synthase, complete cds. AK310768 - Homo sapiens cDNA, FLJ17810. BC009686 - Homo sapiens 6-pyruvoyltetrahydropterin synthase, mRNA (cDNA clone MGC:9027 IMAGE:3901665), complete cds. AK307133 - Homo sapiens cDNA, FLJ97081. JD139975 - Sequence 120999 from Patent EP1572962. JD063969 - Sequence 44993 from Patent EP1572962. M97655 - Human 6-pyruvoyltetrahydropterin synthase (PTS) mRNA, complete cds. AM392676 - Synthetic construct Homo sapiens clone IMAGE:100002110 for hypothetical protein (PTS gene). AM393300 - Synthetic construct Homo sapiens clone IMAGE:100002111 for hypothetical protein (PTS gene). AM393668 - Synthetic construct Homo sapiens clone IMAGE:100002112 for hypothetical protein (PTS gene). DQ894133 - Synthetic construct Homo sapiens clone IMAGE:100008593; FLH168027.01L; RZPDo839B0491D 6-pyruvoyltetrahydropterin synthase (PTS) gene, encodes complete protein. KJ897426 - Synthetic construct Homo sapiens clone ccsbBroadEn_06820 PTS gene, encodes complete protein. KJ897427 - Synthetic construct Homo sapiens clone ccsbBroadEn_06821 PTS gene, encodes complete protein. KR709470 - Synthetic construct Homo sapiens clone CCSBHm_00002488 PTS (PTS) mRNA, encodes complete protein. KR709471 - Synthetic construct Homo sapiens clone CCSBHm_00002495 PTS (PTS) mRNA, encodes complete protein. KR709472 - Synthetic construct Homo sapiens clone CCSBHm_00002505 PTS (PTS) mRNA, encodes complete protein. KR709473 - Synthetic construct Homo sapiens clone CCSBHm_00002520 PTS (PTS) mRNA, encodes complete protein. DQ890961 - Synthetic construct clone IMAGE:100003591; FLH168031.01X; RZPDo839B0492D 6-pyruvoyltetrahydropterin synthase (PTS) gene, encodes complete protein. JD294692 - Sequence 275716 from Patent EP1572962. MA444055 - JP 2018138019-A/15981: Polycomb-Associated Non-Coding RNAs. MH373432 - Homo sapiens pop variant Case 1 truncated 6-pyruvoyltetrahydropterin synthase (PTPS) mRNA, complete cds. MH373433 - Homo sapiens pop variant Case 2 truncated 6-pyruvoyltetrahydropterin synthase (PTPS) mRNA, complete cds. MH373434 - Homo sapiens pop variant Case 3 truncated 6-pyruvoyltetrahydropterin synthase (PTPS) mRNA, complete cds. MH373435 - Homo sapiens pop variant Case 4 truncated 6-pyruvoyltetrahydropterin synthase (PTPS) mRNA, complete cds.
Biochemical and Signaling Pathways
BioCyc Knowledge Library PWY-5663 - tetrahydrobiopterin de novo biosynthesis
Reactome (by CSHL, EBI, and GO)
Protein Q03393 (Reactome details) participates in the following event(s):
R-HSA-1475422 PTPS is phosphorylated by cGMP-dependant protein kinase II R-HSA-1474184 DHNTP is dephosphorylated by PTPS to PTHP R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation R-HSA-8978934 Metabolism of cofactors R-HSA-196854 Metabolism of vitamins and cofactors R-HSA-1430728 Metabolism