HPRT_YEAST
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 03-AUG-2022, entry version 155.
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; 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}.
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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; 241.
DR DIP; DIP-4318N; -.
DR IntAct; Q04178; 5.
DR STRING; 4932.YDR399W; -.
DR iPTMnet; Q04178; -.
DR MaxQB; Q04178; -.
DR PaxDb; Q04178; -.
DR PRIDE; Q04178; -.
DR EnsemblFungi; YDR399W_mRNA; YDR399W; YDR399W.
DR GeneID; 852008; -.
DR KEGG; sce:YDR399W; -.
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 BioCyc; MetaCyc:YDR399W-MON; -.
DR BioCyc; YEAST:YDR399W-MON; -.
DR SABIO-RK; Q04178; -.
DR UniPathway; UPA00591; UER00648.
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:0004615; F:phosphomannomutase activity; IBA:GO_Central.
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 Pfam; PF00156; Pribosyltran; 1.
DR SUPFAM; SSF53271; SSF53271; 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
