PTPS_MOUSE
ID PTPS_MOUSE Reviewed; 144 AA.
AC Q9R1Z7; Q3UIB6; Q9Z2N2;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=6-pyruvoyl tetrahydrobiopterin synthase;
DE Short=PTP synthase;
DE Short=PTPS;
DE EC=4.2.3.12 {ECO:0000305|PubMed:9894812};
GN Name=Pts {ECO:0000312|MGI:MGI:1338783};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC STRAIN=129/Ola;
RX PubMed=9894812; DOI=10.1515/bchm.1998.379.12.1441;
RA Turri M.O., Ilg E.C., Thony B., Blau N.;
RT "Structure, genomic localization and recombinant expression of the mouse 6-
RT pyruvoyl-tetrahydropterin synthase gene.";
RL Biol. Chem. 379:1441-1447(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=C57BL/6J; TISSUE=Placenta;
RA Thony B., Turri M., Blau N.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:0000305|PubMed:9894812}.
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:9894812};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22049;
CC Evidence={ECO:0000305|PubMed:9894812};
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=10.6 uM for dihydroneopterin triphosphate
CC {ECO:0000269|PubMed:9894812};
CC Note=kcat is 0.27 (-1) with dihydroneopterin triphosphate as
CC substrate. {ECO:0000269|PubMed:9894812};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrobiopterin biosynthesis;
CC tetrahydrobiopterin from 7,8-dihydroneopterin triphosphate: step 1/3.
CC -!- SUBUNIT: Homodimer (PubMed:9894812). Homohexamer formed of two
CC homotrimers in a head to head fashion. {ECO:0000250,
CC ECO:0000269|PubMed:9894812}.
CC -!- PTM: Phosphorylation of Ser-18 is required for maximal enzyme activity.
CC {ECO:0000250}.
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; AF061880; AAD15827.1; -; Genomic_DNA.
DR EMBL; AF061878; AAD15827.1; JOINED; Genomic_DNA.
DR EMBL; AF061879; AAD15827.1; JOINED; Genomic_DNA.
DR EMBL; AF043225; AAD02249.1; -; mRNA.
DR EMBL; AK002614; BAB22231.1; -; mRNA.
DR EMBL; AK146987; BAE27590.1; -; mRNA.
DR EMBL; BC029013; AAH29013.1; -; mRNA.
DR CCDS; CCDS23164.1; -.
DR RefSeq; NP_035350.1; NM_011220.2.
DR AlphaFoldDB; Q9R1Z7; -.
DR SMR; Q9R1Z7; -.
DR BioGRID; 202512; 4.
DR IntAct; Q9R1Z7; 4.
DR MINT; Q9R1Z7; -.
DR STRING; 10090.ENSMUSP00000034570; -.
DR iPTMnet; Q9R1Z7; -.
DR PhosphoSitePlus; Q9R1Z7; -.
DR EPD; Q9R1Z7; -.
DR jPOST; Q9R1Z7; -.
DR MaxQB; Q9R1Z7; -.
DR PaxDb; Q9R1Z7; -.
DR PeptideAtlas; Q9R1Z7; -.
DR PRIDE; Q9R1Z7; -.
DR ProteomicsDB; 301953; -.
DR Antibodypedia; 780; 209 antibodies from 27 providers.
DR DNASU; 19286; -.
DR Ensembl; ENSMUST00000034570; ENSMUSP00000034570; ENSMUSG00000032067.
DR GeneID; 19286; -.
DR KEGG; mmu:19286; -.
DR UCSC; uc009pjp.1; mouse.
DR CTD; 5805; -.
DR MGI; MGI:1338783; Pts.
DR VEuPathDB; HostDB:ENSMUSG00000032067; -.
DR eggNOG; KOG4105; Eukaryota.
DR GeneTree; ENSGT00390000002752; -.
DR HOGENOM; CLU_111016_2_0_1; -.
DR InParanoid; Q9R1Z7; -.
DR OMA; NVAIFIW; -.
DR OrthoDB; 1502673at2759; -.
DR PhylomeDB; Q9R1Z7; -.
DR TreeFam; TF105796; -.
DR Reactome; R-MMU-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR UniPathway; UPA00849; UER00819.
DR BioGRID-ORCS; 19286; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Pts; mouse.
DR PRO; PR:Q9R1Z7; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9R1Z7; protein.
DR Bgee; ENSMUSG00000032067; Expressed in right kidney and 258 other tissues.
DR ExpressionAtlas; Q9R1Z7; baseline and differential.
DR Genevisible; Q9R1Z7; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0003874; F:6-pyruvoyltetrahydropterin synthase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IDA:MGI.
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 Lyase; Metal-binding; Phosphoprotein; Reference proteome;
KW Tetrahydrobiopterin biosynthesis; Zinc.
FT CHAIN 1..144
FT /note="6-pyruvoyl tetrahydrobiopterin synthase"
FT /id="PRO_0000057915"
FT ACT_SITE 42
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT ACT_SITE 89
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10124"
FT ACT_SITE 133
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10124"
FT BINDING 23
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT BINDING 48
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10123"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03393"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 127
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q03393"
FT CONFLICT 6
FT /note="D -> G (in Ref. 1; AAD15827)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 144 AA; 16188 MW; AAB034E27ED7A9E3 CRC64;
MSAAGDLRRR ARLSRLVSFS ASHRLHSPSL SDEENLRVFG KCNNPNGHGH NYKVVVTVHG
EIDPVTGMVM NLTDLKEYME EAIMKPLDHK NLDLDVPYFA DAVSTTENVA VYIWESLQKL
LPVGALYKVK VFETDNNIVV YKGE
