ID HPRT_YEAST Reviewed; 221 AA. AC Q04178; D6VT32; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 161. DE RecName: Full=Hypoxanthine-guanine phosphoribosyltransferase; DE Short=HGPRT; DE Short=HGPRTase; DE EC=2.4.2.8 {ECO:0000269|PubMed:18245832}; DE AltName: Full=Bypass of repression by adenine protein 6; GN Name=HPT1; Synonyms=BRA6; OrderedLocusNames=YDR399W; GN ORFNames=D9509.18; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169867; RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., RA Mewes H.-W., Zollner A., Zaccaria P.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."; RL Nature 387:75-78(1997). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [3] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=371963; DOI=10.1111/j.1432-1033.1979.tb12830.x; RA Schmidt R., Wiegand H., Reichert U.; RT "Purification and characterization of the hypoxanthine-guanine RT phosphoribosyltransferase from Saccharomyces cerevisiae."; RL Eur. J. Biochem. 93:355-361(1979). RN [4] RP FUNCTION, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=6170313; DOI=10.1021/bi00519a011; RA Nussbaum R.L., Caskey C.T.; RT "Purification and characterization of hypoxanthine-guanine RT phosphoribosyltransferase from Saccharomyces cerevisiae."; RL Biochemistry 20:4584-4590(1981). RN [5] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=7035445; DOI=10.1016/s0021-9258(19)68166-4; RA Ali L.Z., Sloan D.L.; RT "Studies of the kinetic mechanism of hypoxanthine-guanine RT phosphoribosyltransferase from yeast."; RL J. Biol. Chem. 257:1149-1155(1982). RN [6] RP FUNCTION. RX PubMed=6392474; DOI=10.1099/00221287-130-10-2629; RA Woods R.A., Roberts D.G., Stein D.S., Filpula D.; RT "Adenine phosphoribosyltransferase mutants in Saccharomyces cerevisiae."; RL J. Gen. Microbiol. 130:2629-2637(1984). RN [7] RP FUNCTION. RX PubMed=9335580; DOI=10.1093/genetics/147.2.383; RA Guetsova M.L., Lecoq K., Daignan-Fornier B.; RT "The isolation and characterization of Saccharomyces cerevisiae mutants RT that constitutively express purine biosynthetic genes."; RL Genetics 147:383-397(1997). RN [8] RP FUNCTION. RX PubMed=11035032; DOI=10.1074/jbc.m007926200; RA Escobar-Henriques M., Daignan-Fornier B.; RT "Transcriptional regulation of the yeast gmp synthesis pathway by its end RT products."; RL J. Biol. Chem. 276:1523-1530(2001). RN [9] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [10] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND GMP, RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=18245832; DOI=10.1534/genetics.107.083295; RA Breton A., Pinson B., Coulpier F., Giraud M.F., Dautant A., RA Daignan-Fornier B.; RT "Lethal accumulation of guanylic nucleotides in Saccharomyces cerevisiae RT HPT1-deregulated mutants."; RL Genetics 178:815-824(2008). CC -!- FUNCTION: Converts guanine to guanosine monophosphate, and hypoxanthine CC to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5- CC phosphoribosylpyrophosphate onto the purine. Plays a central role in CC the generation of purine nucleotides through the purine salvage CC pathway. {ECO:0000269|PubMed:11035032, ECO:0000269|PubMed:18245832, CC ECO:0000269|PubMed:371963, ECO:0000269|PubMed:6170313, CC ECO:0000269|PubMed:6392474, ECO:0000269|PubMed:7035445, CC ECO:0000269|PubMed:9335580}. CC -!- CATALYTIC ACTIVITY: CC Reaction=diphosphate + IMP = 5-phospho-alpha-D-ribose 1-diphosphate + CC hypoxanthine; Xref=Rhea:RHEA:17973, ChEBI:CHEBI:17368, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58053; EC=2.4.2.8; CC Evidence={ECO:0000269|PubMed:18245832}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17975; CC Evidence={ECO:0000269|PubMed:18245832}; CC -!- CATALYTIC ACTIVITY: CC Reaction=diphosphate + GMP = 5-phospho-alpha-D-ribose 1-diphosphate + CC guanine; Xref=Rhea:RHEA:25424, ChEBI:CHEBI:16235, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:58017, ChEBI:CHEBI:58115; EC=2.4.2.8; CC Evidence={ECO:0000269|PubMed:18245832}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25426; CC Evidence={ECO:0000269|PubMed:18245832}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=The magnesium ions are essentially bound to the substrate and have CC few direct interactions with the protein.; CC -!- ACTIVITY REGULATION: Subject to feedback inhibition by GMP. CC {ECO:0000269|PubMed:18245832}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=23 uM for hypoxanthine {ECO:0000269|PubMed:371963, CC ECO:0000269|PubMed:6170313, ECO:0000269|PubMed:7035445}; CC KM=18 uM for guanine {ECO:0000269|PubMed:371963, CC ECO:0000269|PubMed:6170313, ECO:0000269|PubMed:7035445}; CC KM=50 uM for phosphoribosylpyrophosphate {ECO:0000269|PubMed:371963, CC ECO:0000269|PubMed:6170313, ECO:0000269|PubMed:7035445}; CC pH dependence: CC Optimum pH is 8.5. {ECO:0000269|PubMed:371963, CC ECO:0000269|PubMed:6170313, ECO:0000269|PubMed:7035445}; CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP CC from hypoxanthine: step 1/1. CC -!- SUBUNIT: Dimer. {ECO:0000269|PubMed:18245832, CC ECO:0000269|PubMed:6170313}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus CC {ECO:0000269|PubMed:14562095}. CC -!- MISCELLANEOUS: Present with 36500 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U32274; AAB64840.1; -; Genomic_DNA. DR EMBL; BK006938; DAA12242.1; -; Genomic_DNA. DR PIR; S69682; S69682. DR RefSeq; NP_010687.3; NM_001180707.3. DR PDB; 2JKY; X-ray; 2.30 A; A/B=2-214. DR PDB; 2JKZ; X-ray; 3.45 A; A/B/C/D=2-221. DR PDB; 2XBU; X-ray; 1.80 A; A/B=1-221. DR PDBsum; 2JKY; -. DR PDBsum; 2JKZ; -. DR PDBsum; 2XBU; -. DR AlphaFoldDB; Q04178; -. DR SMR; Q04178; -. DR BioGRID; 32460; 242. DR DIP; DIP-4318N; -. DR IntAct; Q04178; 5. DR STRING; 4932.YDR399W; -. DR iPTMnet; Q04178; -. DR MaxQB; Q04178; -. DR PaxDb; 4932-YDR399W; -. DR PeptideAtlas; Q04178; -. DR EnsemblFungi; YDR399W_mRNA; YDR399W; YDR399W. DR GeneID; 852008; -. DR KEGG; sce:YDR399W; -. DR AGR; SGD:S000002807; -. DR SGD; S000002807; HPT1. DR VEuPathDB; FungiDB:YDR399W; -. DR eggNOG; ENOG502QRN9; Eukaryota. DR GeneTree; ENSGT00940000176607; -. DR HOGENOM; CLU_092544_0_0_1; -. DR InParanoid; Q04178; -. DR OMA; IMKTGNY; -. DR OrthoDB; 102665at2759; -. DR BioCyc; MetaCyc:YDR399W-MONOMER; -. DR BioCyc; YEAST:YDR399W-MONOMER; -. DR SABIO-RK; Q04178; -. DR UniPathway; UPA00591; UER00648. DR BioGRID-ORCS; 852008; 1 hit in 10 CRISPR screens. DR EvolutionaryTrace; Q04178; -. DR PRO; PR:Q04178; -. DR Proteomes; UP000002311; Chromosome IV. DR RNAct; Q04178; Protein. DR GO; GO:0005737; C:cytoplasm; HDA:SGD. DR GO; GO:0005634; C:nucleus; HDA:SGD. DR GO; GO:0052657; F:guanine phosphoribosyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0004422; F:hypoxanthine phosphoribosyltransferase activity; IDA:SGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW. DR GO; GO:0032263; P:GMP salvage; IDA:SGD. DR GO; GO:0046100; P:hypoxanthine metabolic process; IBA:GO_Central. DR GO; GO:0032264; P:IMP salvage; IDA:SGD. DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW. DR GO; GO:0032265; P:XMP salvage; IBA:GO_Central. DR CDD; cd06223; PRTases_typeI; 1. DR Gene3D; 3.40.50.2020; -; 1. DR InterPro; IPR000836; PRibTrfase_dom. DR InterPro; IPR029057; PRTase-like. DR PANTHER; PTHR43363; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; 1. DR PANTHER; PTHR43363:SF1; HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; 1. DR Pfam; PF00156; Pribosyltran; 1. DR SUPFAM; SSF53271; PRTase-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Glycosyltransferase; Magnesium; KW Metal-binding; Nucleotide-binding; Nucleus; Purine salvage; KW Reference proteome; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..221 FT /note="Hypoxanthine-guanine phosphoribosyltransferase" FT /id="PRO_0000257807" FT ACT_SITE 114 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 85 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:18245832" FT BINDING 110..118 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:18245832" FT BINDING 159 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:18245832" FT BINDING 188..194 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:18245832" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:22814378" FT STRAND 6..8 FT /evidence="ECO:0007829|PDB:2JKY" FT HELIX 11..25 FT /evidence="ECO:0007829|PDB:2XBU" FT TURN 26..28 FT /evidence="ECO:0007829|PDB:2XBU" FT STRAND 31..36 FT /evidence="ECO:0007829|PDB:2XBU" FT HELIX 37..51 FT /evidence="ECO:0007829|PDB:2XBU" FT STRAND 60..69 FT /evidence="ECO:0007829|PDB:2XBU" FT STRAND 85..90 FT /evidence="ECO:0007829|PDB:2XBU" FT HELIX 94..97 FT /evidence="ECO:0007829|PDB:2XBU" FT STRAND 105..116 FT /evidence="ECO:0007829|PDB:2XBU" FT HELIX 117..136 FT /evidence="ECO:0007829|PDB:2XBU" FT TURN 141..143 FT /evidence="ECO:0007829|PDB:2XBU" FT HELIX 145..147 FT /evidence="ECO:0007829|PDB:2XBU" FT STRAND 150..159 FT /evidence="ECO:0007829|PDB:2XBU" FT HELIX 169..172 FT /evidence="ECO:0007829|PDB:2XBU" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:2XBU" FT STRAND 178..184 FT /evidence="ECO:0007829|PDB:2XBU" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:2JKY" FT HELIX 192..194 FT /evidence="ECO:0007829|PDB:2XBU" FT HELIX 198..208 FT /evidence="ECO:0007829|PDB:2XBU" SQ SEQUENCE 221 AA; 25191 MW; 0D18A02BAF8F5390 CRC64; MSANDKQYIS YNNVHQLCQV SAERIKNFKP DLIIAIGGGG FIPARILRTF LKEPGVPTIR IFAIILSLYE DLNSVGSEVE EVGVKVSRTQ WIDYEQCKLD LVGKNVLIVD EVDDTRTTLH YALSELEKDA AEQAKAKGID TEKSPEMKTN FGIFVLHDKQ KPKKADLPAE MLNDKNRYFA AKTVPDKWYA YPWESTDIVF HTRMAIEQGN DIFIPEQEHK Q //