PTPS_RAT
ID PTPS_RAT Reviewed; 144 AA.
AC P27213;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=6-pyruvoyl tetrahydrobiopterin synthase;
DE Short=PTP synthase;
DE Short=PTPS;
DE EC=4.2.3.12 {ECO:0000269|PubMed:1939130};
DE Flags: Precursor;
GN Name=Pts;
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, AND CATALYTIC
RP ACTIVITY.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=1939130; DOI=10.1016/s0021-9258(18)54778-5;
RA Inoue Y., Kawasaki Y., Harada T., Hatakeyama K., Kagamiyama H.;
RT "Purification and cDNA cloning of rat 6-pyruvoyl-tetrahydropterin
RT synthase.";
RL J. Biol. Chem. 266:20791-20796(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
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 [3]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=8137809; DOI=10.1002/j.1460-2075.1994.tb06377.x;
RA Nar H., Huber R., Heizmann C.W., Thoeny B., Buergisser D.;
RT "Three-dimensional structure of 6-pyruvoyl tetrahydropterin synthase, an
RT enzyme involved in tetrahydrobiopterin biosynthesis.";
RL EMBO J. 13:1255-1262(1994).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=10024455; DOI=10.1006/jmbi.1998.2511;
RA Ploom T., Thoeny B., Yim J., Lee S., Nar H., Leimbacher W., Richardson J.,
RA Huber R., Auerbach G.;
RT "Crystallographic and kinetic investigations on the mechanism of 6-pyruvoyl
RT tetrahydropterin synthase.";
RL J. Mol. Biol. 286:851-860(1999).
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.
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:0000305|PubMed:1939130};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22049;
CC Evidence={ECO:0000305|PubMed:1939130};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
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 -!- PTM: Phosphorylation of Ser-18 is required for maximal enzyme activity.
CC {ECO:0000250}.
CC -!- DISEASE: Note=Deficiency leads to phenylketonuria.
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; M77850; AAA40625.1; -; mRNA.
DR EMBL; BC059140; AAH59140.1; -; mRNA.
DR PIR; A39499; A39499.
DR RefSeq; NP_058916.1; NM_017220.1.
DR PDB; 1B66; X-ray; 1.90 A; A/B=5-144.
DR PDB; 1B6Z; X-ray; 2.00 A; A/B=5-144.
DR PDB; 1GTQ; X-ray; 2.30 A; A/B=5-144.
DR PDBsum; 1B66; -.
DR PDBsum; 1B6Z; -.
DR PDBsum; 1GTQ; -.
DR AlphaFoldDB; P27213; -.
DR SMR; P27213; -.
DR STRING; 10116.ENSRNOP00000012434; -.
DR iPTMnet; P27213; -.
DR PhosphoSitePlus; P27213; -.
DR jPOST; P27213; -.
DR PaxDb; P27213; -.
DR Ensembl; ENSRNOT00000012434; ENSRNOP00000012434; ENSRNOG00000009250.
DR GeneID; 29498; -.
DR KEGG; rno:29498; -.
DR UCSC; RGD:68367; rat.
DR CTD; 5805; -.
DR RGD; 68367; Pts.
DR eggNOG; KOG4105; Eukaryota.
DR GeneTree; ENSGT00390000002752; -.
DR HOGENOM; CLU_111016_2_0_1; -.
DR InParanoid; P27213; -.
DR OMA; NVAIFIW; -.
DR OrthoDB; 1502673at2759; -.
DR PhylomeDB; P27213; -.
DR TreeFam; TF105796; -.
DR BRENDA; 4.2.3.12; 5301.
DR Reactome; R-RNO-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR UniPathway; UPA00849; UER00819.
DR EvolutionaryTrace; P27213; -.
DR PRO; PR:P27213; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000009250; Expressed in kidney and 20 other tissues.
DR Genevisible; P27213; RN.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0003874; F:6-pyruvoyltetrahydropterin synthase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; ISO:RGD.
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; Direct protein sequencing; Lyase; Metal-binding;
KW Phenylketonuria; Phosphoprotein; Reference proteome;
KW Tetrahydrobiopterin biosynthesis; Zinc.
FT PROPEP 1..4
FT /id="PRO_0000029868"
FT CHAIN 5..144
FT /note="6-pyruvoyl tetrahydrobiopterin synthase"
FT /id="PRO_0000029869"
FT ACT_SITE 42
FT /note="Proton acceptor"
FT ACT_SITE 89
FT /note="Charge relay system"
FT ACT_SITE 133
FT /note="Charge relay system"
FT BINDING 23
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 48
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03393"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1Z7"
FT MOD_RES 127
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q03393"
FT STRAND 10..23
FT /evidence="ECO:0007829|PDB:1B66"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:1B66"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:1B66"
FT STRAND 48..61
FT /evidence="ECO:0007829|PDB:1B66"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:1B66"
FT HELIX 72..82
FT /evidence="ECO:0007829|PDB:1B66"
FT HELIX 84..87
FT /evidence="ECO:0007829|PDB:1B66"
FT HELIX 92..95
FT /evidence="ECO:0007829|PDB:1B66"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:1B66"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:1B66"
FT HELIX 106..120
FT /evidence="ECO:0007829|PDB:1B66"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:1GTQ"
FT STRAND 126..134
FT /evidence="ECO:0007829|PDB:1B66"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:1B66"
SQ SEQUENCE 144 AA; 16241 MW; 0657C78F87C6FC3B CRC64;
MNAAVGLRRR ARLSRLVSFS ASHRLHSPSL SAEENLKVFG KCNNPNGHGH NYKVVVTIHG
EIDPVTGMVM NLTDLKEYME EAIMKPLDHK NLDLDVPYFA DVVSTTENVA VYIWENLQRL
LPVGALYKVK VYETDNNIVV YKGE
