ID HPRT_HUMAN Reviewed; 218 AA. AC P00492; A6NHF0; B2R8M9; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 241. DE RecName: Full=Hypoxanthine-guanine phosphoribosyltransferase; DE Short=HGPRT; DE Short=HGPRTase; DE EC=2.4.2.8 {ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031}; GN Name=HPRT1; Synonyms=HPRT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6300847; DOI=10.1073/pnas.80.2.477; RA Jolly D.J., Okayama H., Berg P., Esty A.C., Filpula D., Bohlen P., RA Johnson G.G., Shively J.E., Hunkapillar T., Friedmann T.; RT "Isolation and characterization of a full-length expressible cDNA for human RT hypoxanthine phosphoribosyl transferase."; RL Proc. Natl. Acad. Sci. U.S.A. 80:477-481(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2341149; DOI=10.1016/0888-7543(90)90493-e; RA Edwards A., Voss H., Rice P., Civitello A., Stegemann J., Schwager C., RA Zimmermann J., Erfle H., Caskey C.T., Ansorge W.; RT "Automated DNA sequencing of the human HPRT locus."; RL Genomics 6:593-608(1990). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [9] RP PROTEIN SEQUENCE OF 2-218, CLEAVAGE OF INITIATOR METHIONINE, AND RP ACETYLATION AT ALA-2. RX PubMed=7107641; DOI=10.1016/s0021-9258(18)33920-6; RA Wilson J.M., Tarr G.E., Mahoney W.C., Kelley W.N.; RT "Human hypoxanthine-guanine phosphoribosyltransferase. Complete amino acid RT sequence of the erythrocyte enzyme."; RL J. Biol. Chem. 257:10978-10985(1982). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9. RX PubMed=3023844; DOI=10.1128/mcb.6.2.393-403.1986; RA Patel P.I., Framson P.E., Caskey C.T., Chinault A.C.; RT "Fine structure of the human hypoxanthine phosphoribosyltransferase gene."; RL Mol. Cell. Biol. 6:393-403(1986). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-115, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-115, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) IN COMPLEX WITH GMP. RX PubMed=8044844; DOI=10.1016/0092-8674(94)90301-8; RA Eads J.C., Scapin G., Xu Y., Grubmeyer C., Sacchettini J.C.; RT "The crystal structure of human hypoxanthine-guanine RT phosphoribosyltransferase with bound GMP."; RL Cell 78:325-334(1994). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH A TRANSITION-STATE RP ANALOG. RX PubMed=10360366; DOI=10.1038/9376; RA Shi W., Li C.M., Tyler P.C., Furneaux R.H., Grubmeyer C., Schramm V.L., RA Almo S.C.; RT "The 2.0 A structure of human hypoxanthine-guanine RT phosphoribosyltransferase in complex with a transition-state analog RT inhibitor."; RL Nat. Struct. Biol. 6:588-593(1999). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF MUTANT ALA-69 IN COMPLEX WITH RP PHOSPHORIBOSYLPYROPHOSPHATE; MAGNESIUM IONS AND HYPOXANTHINE ANALOG HPP, RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-69, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=10338013; DOI=10.1110/ps.8.5.1023; RA Balendiran G.K., Molina J.A., Xu Y., Torres-Martinez J., Stevens R., RA Focia P.J., Eakin A.E., Sacchettini J.C., Craig S.P. III; RT "Ternary complex structure of human HGPRTase, PRPP, Mg2+, and the inhibitor RT HPP reveals the involvement of the flexible loop in substrate binding."; RL Protein Sci. 8:1023-1031(1999). RN [19] RP REVIEW ON VARIANTS. RX PubMed=1487231; DOI=10.1007/bf00220062; RA Sculley D.G., Dawson P.A., Emmerson B.T., Gordon R.B.; RT "A review of the molecular basis of hypoxanthine-guanine RT phosphoribosyltransferase (HPRT) deficiency."; RL Hum. Genet. 90:195-207(1992). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF APOPROTEIN, AND SUBUNIT. RX PubMed=15990111; DOI=10.1016/j.jmb.2005.05.061; RA Keough D.T., Brereton I.M., de Jersey J., Guddat L.W.; RT "The crystal structure of free human hypoxanthine-guanine RT phosphoribosyltransferase reveals extensive conformational plasticity RT throughout the catalytic cycle."; RL J. Mol. Biol. 351:170-181(2005). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEXES WITH ACYCLIC NUCLEOSIDE RP PHOSPHONATES, AND CATALYTIC ACTIVITY. RX PubMed=19527031; DOI=10.1021/jm900267n; RA Keough D.T., Hockova D., Holy A., Naesens L.M., Skinner-Adams T.S., RA Jersey J., Guddat L.W.; RT "Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic RT nucleoside phosphonates: a new class of antimalarial therapeutics."; RL J. Med. Chem. 52:4391-4399(2009). RN [22] RP VARIANT HRH TORONTO GLY-51. RX PubMed=6853490; DOI=10.1016/s0021-9258(18)32432-3; RA Wilson J.M., Kobayashi R., Fox I.H., Kelley W.N.; RT "Human hypoxanthine-guanine phosphoribosyltransferase."; RL J. Biol. Chem. 258:6458-6460(1983). RN [23] RP VARIANT LNS KINSTON ASN-194. RX PubMed=6853716; DOI=10.1172/jci110884; RA Wilson J.M., Kelley W.N.; RT "Molecular basis of hypoxanthine-guanine phosphoribosyltransferase RT deficiency in a patient with the Lesch-Nyhan syndrome."; RL J. Clin. Invest. 71:1331-1335(1983). RN [24] RP VARIANT HRH LONDON LEU-110. RX PubMed=6572373; DOI=10.1073/pnas.80.3.870; RA Wilson J.M., Tarr G.E., Kelley W.N.; RT "Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid RT substitution in a mutant form of the enzyme isolated from a patient with RT gout."; RL Proc. Natl. Acad. Sci. U.S.A. 80:870-873(1983). RN [25] RP VARIANT HRH MUNICH ARG-104. RX PubMed=6706936; DOI=10.1016/s0021-9258(17)43616-7; RA Wilson J.M., Kelley W.N.; RT "Human hypoxanthine-guanine phosphoribosyltransferase. Structural RT alteration in a dysfunctional enzyme variant (HPRTMunich) isolated from a RT patient with gout."; RL J. Biol. Chem. 259:27-30(1984). RN [26] RP VARIANT HRH MUNICH ARG-104. RX PubMed=3358423; RA Cariello N.F., Scott J.K., Kat A.G., Thilly W.G., Keohavong P.; RT "Resolution of a missense mutant in human genomic DNA by denaturing RT gradient gel electrophoresis and direct sequencing using in vitro DNA RT amplification: HPRT Munich."; RL Am. J. Hum. Genet. 42:726-734(1988). RN [27] RP VARIANT LNS FLINT LEU-74. RX PubMed=3384338; DOI=10.1016/0378-1119(88)90536-7; RA Davidson B.L., Pashmforoush M., Kelly W.N., Palella T.D.; RT "Genetic basis of hypoxanthine guanine phosphoribosyltransferase deficiency RT in a patient with the Lesch-Nyhan syndrome (HPRTFlint)."; RL Gene 63:331-336(1988). RN [28] RP VARIANT LNS MIDLAND ASP-130. RX PubMed=3265398; DOI=10.1016/0378-1119(88)90601-4; RA Davidson B.L., Palella T.D., Kelly W.N.; RT "Human hypoxanthine-guanine phosphoribosyltransferase: a single nucleotide RT substitution in cDNA clones isolated from a patient with Lesch-Nyhan RT syndrome (HPRTMidland)."; RL Gene 68:85-91(1988). RN [29] RP VARIANT HRH MET-132. RX PubMed=2896620; DOI=10.1007/bf00291707; RA Fujimori S., Hidaka Y., Davidson B.L., Palella T.D., Kelley W.N.; RT "Identification of a single nucleotide change in a mutant gene for RT hypoxanthine-guanine phosphoribosyltransferase (HPRT Ann Arbor)."; RL Hum. Genet. 79:39-43(1988). RN [30] RP VARIANT HRH LONDON LEU-110. RX PubMed=3198771; DOI=10.1172/jci113839; RA Davidson B.L., Chin S.J., Wilson J.M., Kelley W.N., Palella T.D.; RT "Hypoxanthine-guanine phosphoribosyltransferase. Genetic evidence for RT identical mutations in two partially deficient subjects."; RL J. Clin. Invest. 82:2164-2167(1988). RN [31] RP VARIANTS DIRRANBANDI AND YERONGA. RX PubMed=3148064; DOI=10.1007/bf01800364; RA Keough D.T., Gordon R.B., Dejersey J., Emmerson B.T.; RT "Biochemical basis of hypoxanthine-guanine phosphoribosyltransferase RT deficiency in nine families."; RL J. Inherit. Metab. Dis. 11:229-238(1988). RN [32] RP VARIANTS LNS LEU-54 AND 179-VAL-GLY-180 DELINS GLY-ARG. RX PubMed=2572141; DOI=10.1111/j.1442-200x.1989.tb01306.x; RA Igarashi T., Minami M., Nishida Y.; RT "Molecular analysis of hypoxanthine-guanine phosphoribosyltransferase RT mutations in five unrelated Japanese patients."; RL Acta Paediatr. Jpn. Overseas Ed. 31:303-313(1989). RN [33] RP VARIANT HRH ASHVILLE GLY-201. RX PubMed=2909537; DOI=10.1016/s0021-9258(17)31289-9; RA Davidson B.L., Pashmforoush M., Kelly W.N., Palella T.D.; RT "Human hypoxanthine-guanine phosphoribosyltransferase deficiency. The RT molecular defect in a patient with gout (HPRTAshville)."; RL J. Biol. Chem. 264:520-525(1989). RN [34] RP VARIANT LNS YALE ARG-71. RX PubMed=2910902; DOI=10.1172/jci113846; RA Fujimori S., Davidson B.L., Kelley W.N., Palella T.D.; RT "Identification of a single nucleotide change in the hypoxanthine-guanine RT phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan RT syndrome."; RL J. Clin. Invest. 83:11-13(1989). RN [35] RP VARIANTS ARLINGEN; DETROIT; NEW BRITON AND NEW HAVEN. RX PubMed=2738157; DOI=10.1172/jci114160; RA Davidson B.L., Tarle S.A., Palella T.D., Kelley W.N.; RT "Molecular basis of hypoxanthine-guanine phosphoribosyltransferase RT deficiency in ten subjects determined by direct sequencing of amplified RT transcripts."; RL J. Clin. Invest. 84:342-346(1989). RN [36] RP VARIANTS RKJ. RX PubMed=2928313; DOI=10.1073/pnas.86.6.1919; RA Gibbs R.A., Nguyen P.N., McBride L.J., Koepf S.M., Caskey C.T.; RT "Identification of mutations leading to the Lesch-Nyhan syndrome by RT automated direct DNA sequencing of in vitro amplified cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 86:1919-1923(1989). RN [37] RP VARIANTS LNS RJK LYS-45; LEU-74; ASP-130; SER-131; LYS-143; SER-161; RP TYR-177; ASN-194; VAL-199; ASP-204 AND TYR-206. RX PubMed=2347587; DOI=10.1016/0888-7543(90)90545-6; RA Gibbs R.A., Nguyen P.N., Edwards A., Civitello A.B., Caskey C.T.; RT "Multiplex DNA deletion detection and exon sequencing of the hypoxanthine RT phosphoribosyltransferase gene in Lesch-Nyhan families."; RL Genomics 7:235-244(1990). RN [38] RP VARIANT LNS MONTREAL THR-57. RX PubMed=2358296; DOI=10.1007/bf00276334; RA Skopek T.R., Recio L., Simpson D., Dallaire L., Melancon S.B., Ogier H., RA O'Neill J.P., Falta M.T., Nicklas J.A., Albertini R.J.; RT "Molecular analyses of a Lesch-Nyhan syndrome mutation (hprtMontreal) by RT use of T-lymphocyte cultures."; RL Hum. Genet. 85:111-116(1990). RN [39] RP VARIANT LNS BRISBANE ILE-168. RX PubMed=2246854; DOI=10.1007/bf01799570; RA Gordon R.B., Sculley D.G., Dawson P.A., Beacham I.R., Emmerson B.T.; RT "Identification of a single nucleotide substitution in the coding sequence RT of in vitro amplified cDNA from a patient with partial HPRT deficiency RT (HPRTBRISBANE)."; RL J. Inherit. Metab. Dis. 13:692-700(1990). RN [40] RP VARIANTS GRAVESEND; MASHAD; HEAPEY; BANBURY; RUNCORN; FARNHAM; MARLOW AND RP READING. RX PubMed=2018042; RA Davidson B.L., Tarle S.A., van Antwerp M., Gibbs D.A., Watts R.W.E., RA Kelley W.N., Palella T.D.; RT "Identification of 17 independent mutations responsible for human RT hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency."; RL Am. J. Hum. Genet. 48:951-958(1991). RN [41] RP VARIANTS LNS TYR-28 DEL; VAL-50; GLU-70; LEU-74; THR-183 AND ARG-204. RX PubMed=2071157; DOI=10.1016/0888-7543(91)90341-b; RA Tarle S.A., Davidson B.L., Wu V.C., Zidar F.J., Seegmiller J.E., RA Kelley W.N., Palella T.D.; RT "Determination of the mutations responsible for the Lesch-Nyhan syndrome in RT 17 subjects."; RL Genomics 10:499-501(1991). RN [42] RP VARIANTS PERTH; SWAN; TOOWONG AND URANGAN. RX PubMed=1937471; DOI=10.1007/bf00201727; RA Sculley D.G., Dawson P.A., Beacham I.R., Emmerson B.T., Gordon R.B.; RT "Hypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of RT HPRT mutations by direct sequencing and allele-specific amplification."; RL Hum. Genet. 87:688-692(1991). RN [43] RP VARIANT ALA-188, AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 183-193. RX PubMed=1840476; DOI=10.1007/978-1-4615-7703-4_27; RA Yamada Y., Goto H., Ogasawara N.; RT "Identification of two independent Japanese mutant HPRT genes using the PCR RT technique."; RL Adv. Exp. Med. Biol. 309B:121-124(1991). RN [44] RP VARIANT EDINBURGH GLY-52, AND NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1551676; DOI=10.1007/bf02265300; RA Lightfoot T., Joshi R., Nuki G., Snyder F.F.; RT "The point mutation of hypoxanthine-guanine phosphoribosyltransferase RT (HPRTEdinburgh) and detection by allele-specific polymerase chain RT reaction."; RL Hum. Genet. 88:695-696(1992). RN [45] RP VARIANTS, AND NUCLEOTIDE SEQUENCE [MRNA] OF 35-50. RX PubMed=1301916; DOI=10.1093/hmg/1.6.427; RA Sege-Paterson K., Chambers J., Page T., Jones O.W., Nyhan W.L.; RT "Characterization of mutations in phenotypic variants of hypoxanthine RT phosphoribosyltransferase deficiency."; RL Hum. Mol. Genet. 1:427-432(1992). RN [46] RP VARIANT HRH MOOSE JAW GLU-194, AND NUCLEOTIDE SEQUENCE. RX PubMed=7987318; DOI=10.1093/hmg/3.8.1377; RA Lightfoot T., Lewkonia R.M., Snyder F.F.; RT "Sequence, expression and characterization of HPRTMoose Jaw: a point RT mutation resulting in cooperativity and decreased substrate affinities."; RL Hum. Mol. Genet. 3:1377-1381(1994). RN [47] RP VARIANT LNS ISAR PHE-42. RX PubMed=7627191; DOI=10.1002/humu.1380050413; RA Burgemeister R., Roetzer E., Gutensohn W., Gehrke M., Schiel W.; RT "Identification of a new missense mutation in exon 2 of the human RT hypoxanthine phosphoribosyltransferase gene (HPRTIsar): a further example RT of clinical heterogeneity in HPRT deficiencies."; RL Hum. Mutat. 5:341-344(1995). RN [48] RP VARIANT ARG-61. RX PubMed=9003484; DOI=10.1007/s004390050300; RA Fujimori S., Sakuma R., Yamaoka N., Hakoda M., Yamanaka H., Kamatani N.; RT "An asymptomatic germline missense base substitution in the hypoxanthine RT phosphoribosyltransferase (HPRT) gene that reduces the amount of enzyme in RT humans."; RL Hum. Genet. 99:8-10(1997). RN [49] RP VARIANT LNS ROANNE VAL-177. RX PubMed=9452051; DOI=10.1002/humu.1380110130; RA Liu G., Aral B., Zabot M.-T., Kamoun P., Ceballos-Picot I.; RT "The molecular basis of hypoxanthine-guanine phosphoribosyltransferase RT deficiency in French families; report of two novel mutations."; RL Hum. Mutat. Suppl. 1:S88-S90(1998). RN [50] RP VARIANTS LNS PRO-64; PRO-65; GLU-70; CYS-72; GLN-78; PRO-147; GLU-159 AND RP 107-ASN--SER-110 DEL, AND VARIANTS HRH ALA-188; VAL-192 AND CYS-195. RX PubMed=15571223; DOI=10.1081/ncn-200027439; RA Yamada Y., Yamada K., Sonta S., Wakamatsu N., Ogasawara N.; RT "Mutations in the hypoxanthine guanine phosphoribosyltransferase gene RT (HPRT1) in Asian HPRT deficient families."; RL Nucleosides Nucleotides Nucleic Acids 23:1169-1172(2004). RN [51] RP VARIANTS LNS VAL-8 DEL; TYR-28 DEL; PRO-64; PRO-65; GLU-70; CYS-72; GLN-78; RP PRO-147; GLU-159; VAL-159 INS AND ALA-188, AND VARIANTS HRH PRO-124; RP GLY-185; VAL-192 AND CYS-195. RX PubMed=17027311; DOI=10.1016/j.ymgme.2006.08.013; RA Yamada Y., Nomura N., Yamada K., Wakamatsu N.; RT "Molecular analysis of HPRT deficiencies: an update of the spectrum of RT Asian mutations with novel mutations."; RL Mol. Genet. Metab. 90:70-76(2007). RN [52] RP VARIANTS LNS TYR-44 AND LEU-74. RX PubMed=20544509; DOI=10.1080/15257771003738691; RA Yamada Y., Yamada K., Nomura N., Yamano A., Kimura R., Tomida S., Naiki M., RA Wakamatsu N.; RT "Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked RT inborn errors of purine metabolism."; RL Nucleosides Nucleotides Nucleic Acids 29:291-294(2010). RN [53] RP INVOLVEMENT IN LNS, INVOLVEMENT IN HRH, VARIANTS HRH VAL-20; PHE-23 AND RP ARG-60, AND CHARACTERIZATION OF VARIANTS HRH VAL-20; PHE-23 AND ARG-60. RX PubMed=24940672; DOI=10.1080/15257770.2013.865743; RA Yamada Y., Nomura N., Yamada K., Kimura R., Fukushi D., Wakamatsu N., RA Matsuda Y., Yamauchi T., Ueda T., Hasegawa H., Nakamura M., Ichida K., RA Kaneko K., Fujimori S.; RT "Hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiencies: HPRT1 RT mutations in new Japanese families and PRPP concentration."; RL Nucleosides Nucleotides Nucleic Acids 33:218-222(2014). 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. 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:10338013, ECO:0000269|PubMed:19527031}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17975; CC Evidence={ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031}; 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:10338013, ECO:0000269|PubMed:19527031}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25426; CC Evidence={ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=Binds 2 magnesium ions per subunit. The magnesium ions are CC essentially bound to the substrate and have few direct interactions CC with the protein.; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=5.4 uM for IMP {ECO:0000269|PubMed:10338013}; CC KM=0.45 uM for hypoxanthine {ECO:0000269|PubMed:10338013}; CC KM=25 uM for pyrophosphate {ECO:0000269|PubMed:10338013}; CC KM=31 uM for phosphoribosylpyrophosphate CC {ECO:0000269|PubMed:10338013}; CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP CC from hypoxanthine: step 1/1. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10338013, CC ECO:0000269|PubMed:10360366, ECO:0000269|PubMed:15990111, CC ECO:0000269|PubMed:8044844}. CC -!- INTERACTION: CC P00492; Q96G04: EEF2KMT; NbExp=3; IntAct=EBI-748210, EBI-747840; CC P00492; Q8N7B9-2: EFCAB3; NbExp=3; IntAct=EBI-748210, EBI-11958551; CC P00492; Q14749: GNMT; NbExp=3; IntAct=EBI-748210, EBI-744239; CC P00492; P00492: HPRT1; NbExp=6; IntAct=EBI-748210, EBI-748210; CC P00492; P42858: HTT; NbExp=15; IntAct=EBI-748210, EBI-466029; CC P00492; Q9H1K1: ISCU; NbExp=4; IntAct=EBI-748210, EBI-1047335; CC P00492; Q96HA8: NTAQ1; NbExp=10; IntAct=EBI-748210, EBI-741158; CC P00492; Q9NRG1: PRTFDC1; NbExp=11; IntAct=EBI-748210, EBI-739759; CC P00492; O00560: SDCBP; NbExp=7; IntAct=EBI-748210, EBI-727004; CC P00492; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-748210, EBI-742688; CC P00492; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-748210, EBI-5235340; CC P00492; Q8N9Q2: SREK1IP1; NbExp=3; IntAct=EBI-748210, EBI-10268630; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- DISEASE: Lesch-Nyhan syndrome (LNS) [MIM:300322]: Characterized by CC complete lack of enzymatic activity that results in hyperuricemia, CC choreoathetosis, intellectual disability, and compulsive self- CC mutilation. {ECO:0000269|PubMed:15571223, ECO:0000269|PubMed:17027311, CC ECO:0000269|PubMed:20544509, ECO:0000269|PubMed:2071157, CC ECO:0000269|PubMed:2246854, ECO:0000269|PubMed:2347587, CC ECO:0000269|PubMed:2358296, ECO:0000269|PubMed:24940672, CC ECO:0000269|PubMed:2572141, ECO:0000269|PubMed:2910902, CC ECO:0000269|PubMed:3265398, ECO:0000269|PubMed:3384338, CC ECO:0000269|PubMed:6853716, ECO:0000269|PubMed:7627191, CC ECO:0000269|PubMed:9452051}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hyperuricemia, HPRT-related (HRH) [MIM:300323]: An X-linked CC metabolic disorder characterized by uric acid excess in the blood, CC renal stones, uric acid nephropathy, and renal obstruction. After CC puberty, the hyperuricemia may cause gout. CC {ECO:0000269|PubMed:15571223, ECO:0000269|PubMed:17027311, CC ECO:0000269|PubMed:20544509, ECO:0000269|PubMed:24940672, CC ECO:0000269|PubMed:2896620, ECO:0000269|PubMed:2909537, CC ECO:0000269|PubMed:3198771, ECO:0000269|PubMed:3358423, CC ECO:0000269|PubMed:6572373, ECO:0000269|PubMed:6706936, CC ECO:0000269|PubMed:6853490, ECO:0000269|PubMed:7987318}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase CC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/hprt1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Hypoxanthine-guanine CC phosphoribosyltransferase entry; CC URL="https://en.wikipedia.org/wiki/Hypoxanthine-guanine_phosphoribosyltransferase"; 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; M31642; AAA52690.1; -; mRNA. DR EMBL; M26434; AAA36012.1; -; Genomic_DNA. DR EMBL; AK313435; BAG36226.1; -; mRNA. DR EMBL; BT019350; AAV38157.1; -; mRNA. DR EMBL; AY780550; AAV31777.1; -; Genomic_DNA. DR EMBL; AC004383; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471107; EAX11761.1; -; Genomic_DNA. DR EMBL; BC000578; AAH00578.1; -; mRNA. DR EMBL; M12452; AAA52691.1; -; Genomic_DNA. DR EMBL; S79313; AAB21289.1; -; Genomic_DNA. DR EMBL; L29383; AAB59391.1; -; mRNA. DR EMBL; L29382; AAB59392.1; -; mRNA. DR EMBL; S60300; AAC60591.2; -; mRNA. DR CCDS; CCDS14641.1; -. DR PIR; A32728; RTHUG. DR RefSeq; NP_000185.1; NM_000194.2. DR PDB; 1BZY; X-ray; 2.00 A; A/B/C/D=2-218. DR PDB; 1D6N; X-ray; 2.70 A; A/B=5-218. DR PDB; 1HMP; X-ray; 2.50 A; A/B=2-218. DR PDB; 1Z7G; X-ray; 1.90 A; A/B/C/D=2-218. DR PDB; 2VFA; X-ray; 2.80 A; A/B=49-160. DR PDB; 3GEP; X-ray; 2.60 A; A/B=2-218. DR PDB; 3GGC; X-ray; 2.78 A; A/B=2-218. DR PDB; 3GGJ; X-ray; 2.60 A; A/B=2-218. DR PDB; 4IJQ; X-ray; 2.00 A; A/B/C/D=2-218. DR PDB; 4KN6; X-ray; 2.73 A; A=3-218. DR PDB; 4RAB; X-ray; 2.26 A; A/B/C/D=2-218. DR PDB; 4RAC; X-ray; 2.05 A; A/B/C/D=2-218. DR PDB; 4RAD; X-ray; 2.00 A; A/B/C/D/E/F/G/H=2-218. DR PDB; 4RAN; X-ray; 2.55 A; A/B/C/D=2-218. DR PDB; 4RAO; X-ray; 1.87 A; A/B/C/D=2-218. DR PDB; 4RAQ; X-ray; 2.53 A; A/B/C/D=2-218. DR PDB; 5BRN; X-ray; 2.30 A; A/B/C/D=1-218. DR PDB; 5BSK; X-ray; 2.61 A; A/B/C/D=1-218. DR PDB; 5HIA; X-ray; 1.77 A; A/B/C/D=1-218. DR PDB; 5W8V; X-ray; 2.35 A; A/B/C/D=5-218. DR PDB; 6BNJ; X-ray; 1.91 A; A/B/C/D=1-218. DR PDB; 7SAN; X-ray; 2.58 A; A/B/C/D=2-218. DR PDBsum; 1BZY; -. DR PDBsum; 1D6N; -. DR PDBsum; 1HMP; -. DR PDBsum; 1Z7G; -. DR PDBsum; 2VFA; -. DR PDBsum; 3GEP; -. DR PDBsum; 3GGC; -. DR PDBsum; 3GGJ; -. DR PDBsum; 4IJQ; -. DR PDBsum; 4KN6; -. DR PDBsum; 4RAB; -. DR PDBsum; 4RAC; -. DR PDBsum; 4RAD; -. DR PDBsum; 4RAN; -. DR PDBsum; 4RAO; -. DR PDBsum; 4RAQ; -. DR PDBsum; 5BRN; -. DR PDBsum; 5BSK; -. DR PDBsum; 5HIA; -. DR PDBsum; 5W8V; -. DR PDBsum; 6BNJ; -. DR PDBsum; 7SAN; -. DR AlphaFoldDB; P00492; -. DR SMR; P00492; -. DR BioGRID; 109488; 115. DR IntAct; P00492; 38. DR MINT; P00492; -. DR STRING; 9606.ENSP00000298556; -. DR BindingDB; P00492; -. DR ChEMBL; CHEMBL2360; -. DR DrugBank; DB03153; 3H-pyrazolo[4,3-d]pyrimidin-7-ol. DR DrugBank; DB02309; 5-monophosphate-9-beta-D-ribofuranosyl xanthine. DR DrugBank; DB01632; 5-O-phosphono-alpha-D-ribofuranosyl diphosphate. DR DrugBank; DB04356; 9-Deazaguanine. DR DrugBank; DB00993; Azathioprine. DR DrugBank; DB01033; Mercaptopurine. DR DrugBank; DB00352; Tioguanine. DR DrugCentral; P00492; -. DR GlyGen; P00492; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P00492; -. DR MetOSite; P00492; -. DR PhosphoSitePlus; P00492; -. DR SwissPalm; P00492; -. DR BioMuta; HPRT1; -. DR DMDM; 123497; -. DR OGP; P00492; -. DR REPRODUCTION-2DPAGE; IPI00218493; -. DR CPTAC; CPTAC-216; -. DR EPD; P00492; -. DR jPOST; P00492; -. DR MassIVE; P00492; -. DR MaxQB; P00492; -. DR PaxDb; 9606-ENSP00000298556; -. DR PeptideAtlas; P00492; -. DR ProteomicsDB; 51257; -. DR Pumba; P00492; -. DR TopDownProteomics; P00492; -. DR Antibodypedia; 1912; 685 antibodies from 37 providers. DR DNASU; 3251; -. DR Ensembl; ENST00000298556.8; ENSP00000298556.7; ENSG00000165704.15. DR GeneID; 3251; -. DR KEGG; hsa:3251; -. DR MANE-Select; ENST00000298556.8; ENSP00000298556.7; NM_000194.3; NP_000185.1. DR UCSC; uc004exl.5; human. DR AGR; HGNC:5157; -. DR CTD; 3251; -. DR DisGeNET; 3251; -. DR GeneCards; HPRT1; -. DR GeneReviews; HPRT1; -. DR HGNC; HGNC:5157; HPRT1. DR HPA; ENSG00000165704; Low tissue specificity. DR MalaCards; HPRT1; -. DR MIM; 300322; phenotype. DR MIM; 300323; phenotype. DR MIM; 308000; gene. DR neXtProt; NX_P00492; -. DR OpenTargets; ENSG00000165704; -. DR Orphanet; 79233; Hypoxanthine guanine phosphoribosyltransferase partial deficiency. DR Orphanet; 510; Lesch-Nyhan syndrome. DR PharmGKB; PA29427; -. DR VEuPathDB; HostDB:ENSG00000165704; -. DR eggNOG; KOG3367; Eukaryota. DR GeneTree; ENSGT00940000155028; -. DR HOGENOM; CLU_073615_3_0_1; -. DR InParanoid; P00492; -. DR OMA; MQWRVAP; -. DR OrthoDB; 4216383at2759; -. DR PhylomeDB; P00492; -. DR TreeFam; TF313367; -. DR BioCyc; MetaCyc:HS09275-MONOMER; -. DR BRENDA; 2.4.2.8; 2681. DR PathwayCommons; P00492; -. DR Reactome; R-HSA-74217; Purine salvage. DR Reactome; R-HSA-9734281; Defective HPRT1 disrupts guanine and hypoxanthine salvage. DR Reactome; R-HSA-9748787; Azathioprine ADME. DR SABIO-RK; P00492; -. DR SignaLink; P00492; -. DR UniPathway; UPA00591; UER00648. DR BioGRID-ORCS; 3251; 20 hits in 790 CRISPR screens. DR ChiTaRS; HPRT1; human. DR EvolutionaryTrace; P00492; -. DR GeneWiki; Hypoxanthine-guanine_phosphoribosyltransferase; -. DR GenomeRNAi; 3251; -. DR Pharos; P00492; Tchem. DR PRO; PR:P00492; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P00492; Protein. DR Bgee; ENSG00000165704; Expressed in oocyte and 209 other cell types or tissues. DR ExpressionAtlas; P00492; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0052657; F:guanine phosphoribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0004422; F:hypoxanthine phosphoribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW. DR GO; GO:0046083; P:adenine metabolic process; IEA:Ensembl. DR GO; GO:0044209; P:AMP salvage; IEA:Ensembl. DR GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl. DR GO; GO:0021895; P:cerebral cortex neuron differentiation; IEA:Ensembl. DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0042417; P:dopamine metabolic process; IEA:Ensembl. DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl. DR GO; GO:0046038; P:GMP catabolic process; IDA:UniProtKB. DR GO; GO:0032263; P:GMP salvage; IDA:MGI. DR GO; GO:0007625; P:grooming behavior; IEA:Ensembl. DR GO; GO:0006178; P:guanine salvage; IDA:UniProtKB. DR GO; GO:0046100; P:hypoxanthine metabolic process; IMP:UniProtKB. DR GO; GO:0043103; P:hypoxanthine salvage; IDA:UniProtKB. DR GO; GO:0046040; P:IMP metabolic process; IDA:UniProtKB. DR GO; GO:0032264; P:IMP salvage; IBA:GO_Central. DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl. DR GO; GO:0046651; P:lymphocyte proliferation; IEA:Ensembl. DR GO; GO:0045964; P:positive regulation of dopamine metabolic process; IMP:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IPI:UniProtKB. DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IMP:UniProtKB. DR GO; GO:0006166; P:purine ribonucleoside salvage; IMP:UniProtKB. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR GO; GO:0021756; P:striatum development; IEA:Ensembl. DR GO; GO:0001913; P:T cell mediated cytotoxicity; IEA:Ensembl. DR CDD; cd06223; PRTases_typeI; 1. DR Gene3D; 3.40.50.2020; -; 1. DR InterPro; IPR005904; Hxn_phspho_trans. DR InterPro; IPR000836; PRibTrfase_dom. DR InterPro; IPR029057; PRTase-like. DR NCBIfam; TIGR01203; HGPRTase; 1. DR PANTHER; PTHR43340; HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; 1. DR PANTHER; PTHR43340:SF6; HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; 1. DR Pfam; PF00156; Pribosyltran; 1. DR SUPFAM; SSF53271; PRTase-like; 1. DR PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1. DR Genevisible; P00492; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; KW Disease variant; Glycosyltransferase; Gout; Isopeptide bond; Magnesium; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Purine salvage; KW Reference proteome; Transferase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:7107641" FT CHAIN 2..218 FT /note="Hypoxanthine-guanine phosphoribosyltransferase" FT /id="PRO_0000139585" FT ACT_SITE 138 FT /note="Proton acceptor" FT /evidence="ECO:0000305" FT BINDING 69 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:8044844" FT BINDING 134..142 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:8044844" FT BINDING 166 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:8044844" FT BINDING 186..188 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:8044844" FT BINDING 194 FT /ligand="GMP" FT /ligand_id="ChEBI:CHEBI:58115" FT /evidence="ECO:0000269|PubMed:8044844" FT BINDING 194 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|PubMed:7107641" FT MOD_RES 103 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P00493" FT MOD_RES 142 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P27605" FT CROSSLNK 115 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 115 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 7 FT /note="G -> D (in HRH; Gravesend)" FT /id="VAR_006750" FT VARIANT 8 FT /note="V -> G (in LNS; HB)" FT /id="VAR_006751" FT VARIANT 8 FT /note="Missing (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:17027311" FT /id="VAR_071609" FT VARIANT 16 FT /note="G -> D (in LNS; FG)" FT /id="VAR_006752" FT VARIANT 16 FT /note="G -> S (in HRH; Urangan; dbSNP:rs137852499)" FT /id="VAR_006753" FT VARIANT 20 FT /note="D -> V (in HRH; Mashad; strongly reduces enzymatic FT activity)" FT /evidence="ECO:0000269|PubMed:24940672" FT /id="VAR_006754" FT VARIANT 23 FT /note="C -> F (in HRH; Reduces enzymatic activity)" FT /evidence="ECO:0000269|PubMed:24940672" FT /id="VAR_071610" FT VARIANT 23 FT /note="C -> W (in HRH; JS)" FT /id="VAR_006755" FT VARIANT 28 FT /note="Missing (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:17027311, FT ECO:0000269|PubMed:2071157" FT /id="VAR_012312" FT VARIANT 41 FT /note="L -> P (in LNS; Detroit; dbSNP:rs137852480)" FT /id="VAR_006756" FT VARIANT 42 FT /note="I -> F (in LNS; Isar)" FT /evidence="ECO:0000269|PubMed:7627191" FT /id="VAR_006757" FT VARIANT 42 FT /note="I -> T (in LNS; Heapey)" FT /id="VAR_006758" FT VARIANT 43..44 FT /note="MD -> RN (in LNS; Salamanca)" FT /id="VAR_006759" FT VARIANT 44 FT /note="D -> Y (in LNS; Japan)" FT /evidence="ECO:0000269|PubMed:20544509" FT /id="VAR_071611" FT VARIANT 45 FT /note="R -> K (in LNS; RJK 2163; dbSNP:rs137852491)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006760" FT VARIANT 48 FT /note="R -> H (in HRH; AD and DD; dbSNP:rs387906725)" FT /id="VAR_006761" FT VARIANT 50 FT /note="A -> P (in LNS; LW; dbSNP:rs1556026984)" FT /id="VAR_006763" FT VARIANT 50 FT /note="A -> V (in LNS; 1265)" FT /evidence="ECO:0000269|PubMed:2071157" FT /id="VAR_006762" FT VARIANT 51 FT /note="R -> G (in HRH; Toronto; dbSNP:rs137852494)" FT /evidence="ECO:0000269|PubMed:6853490" FT /id="VAR_006764" FT VARIANT 51 FT /note="R -> P (in LNS; Banbury)" FT /id="VAR_006765" FT VARIANT 52 FT /note="D -> G (in Edinburgh; dbSNP:rs137852502)" FT /evidence="ECO:0000269|PubMed:1551676" FT /id="VAR_006766" FT VARIANT 53 FT /note="V -> A (in HRH; MG)" FT /id="VAR_006767" FT VARIANT 53 FT /note="V -> M (in HRH; TE)" FT /id="VAR_006768" FT VARIANT 54 FT /note="M -> L (in LNS; Japan-1)" FT /evidence="ECO:0000269|PubMed:2572141" FT /id="VAR_006769" FT VARIANT 57 FT /note="M -> T (in LNS; Montreal; dbSNP:rs137852495)" FT /evidence="ECO:0000269|PubMed:2358296" FT /id="VAR_006770" FT VARIANT 58 FT /note="G -> R (in HRH; Toowong; dbSNP:rs137852500)" FT /id="VAR_006771" FT VARIANT 60 FT /note="H -> R (in HRH; Reduces enzymatic activity; FT dbSNP:rs1228634091)" FT /evidence="ECO:0000269|PubMed:24940672" FT /id="VAR_071612" FT VARIANT 61 FT /note="H -> R (enzyme activity 37% of normal; FT asymptomatic)" FT /evidence="ECO:0000269|PubMed:9003484" FT /id="VAR_006772" FT VARIANT 64 FT /note="A -> P (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_071613" FT VARIANT 65 FT /note="L -> P (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_071614" FT VARIANT 70 FT /note="G -> E (in LNS; New Haven/1510, Asia; FT dbSNP:rs137852487)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311, ECO:0000269|PubMed:2071157" FT /id="VAR_006773" FT VARIANT 71 FT /note="G -> R (in LNS; Yale; dbSNP:rs137852488)" FT /evidence="ECO:0000269|PubMed:2910902" FT /id="VAR_006774" FT VARIANT 72 FT /note="Y -> C (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_071615" FT VARIANT 74 FT /note="F -> L (in LNS; Flint/RJK 892/DW/Perth/1522, Japan; FT dbSNP:rs137852481)" FT /evidence="ECO:0000269|PubMed:20544509, FT ECO:0000269|PubMed:2071157, ECO:0000269|PubMed:2347587, FT ECO:0000269|PubMed:3384338" FT /id="VAR_006775" FT VARIANT 78 FT /note="L -> Q (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_071616" FT VARIANT 78 FT /note="L -> V (in HRH; Swan; dbSNP:rs137852501)" FT /id="VAR_006776" FT VARIANT 80 FT /note="D -> V (in HRH; Arlington; dbSNP:rs137852478)" FT /id="VAR_006777" FT VARIANT 104 FT /note="S -> R (in HRH; Munich; dbSNP:rs137852485)" FT /evidence="ECO:0000269|PubMed:3358423, FT ECO:0000269|PubMed:6706936" FT /id="VAR_006778" FT VARIANT 107..110 FT /note="Missing (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223" FT /id="VAR_071617" FT VARIANT 110 FT /note="S -> L (in HRH; London; dbSNP:rs137852482)" FT /evidence="ECO:0000269|PubMed:3198771, FT ECO:0000269|PubMed:6572373" FT /id="VAR_006779" FT VARIANT 124 FT /note="T -> P (in HRH; Asia)" FT /evidence="ECO:0000269|PubMed:17027311" FT /id="VAR_071618" FT VARIANT 130 FT /note="V -> D (in LNS; Midland/RJK 896; dbSNP:rs137852483)" FT /evidence="ECO:0000269|PubMed:2347587, FT ECO:0000269|PubMed:3265398" FT /id="VAR_006780" FT VARIANT 131 FT /note="L -> S (in LNS; RJK 1784)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006781" FT VARIANT 132 FT /note="I -> M (in HRH; Ann-Arbor; dbSNP:rs137852477)" FT /evidence="ECO:0000269|PubMed:2896620" FT /id="VAR_006782" FT VARIANT 132 FT /note="I -> T (in LNS; Runcorn)" FT /id="VAR_006783" FT VARIANT 135 FT /note="D -> G (in HRH; Yeronga)" FT /id="VAR_006784" FT VARIANT 143 FT /note="M -> K (in LNS; RJK 1210; dbSNP:rs137852496)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006785" FT VARIANT 143 FT /note="M -> MA (in LNS; RW)" FT /id="VAR_006786" FT VARIANT 147 FT /note="L -> P (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_071619" FT VARIANT 159 FT /note="K -> E (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_071620" FT VARIANT 159 FT /note="K -> KV (in LNS; Asia)" FT /evidence="ECO:0000269|PubMed:17027311" FT /id="VAR_071621" FT VARIANT 161 FT /note="A -> S (in HRH; Milwaukee/RJK 949; FT dbSNP:rs137852484)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006787" FT VARIANT 162 FT /note="S -> R (in LNS; Farnham)" FT /id="VAR_006788" FT VARIANT 168 FT /note="T -> I (in HRH; Brisbane; dbSNP:rs137852498)" FT /evidence="ECO:0000269|PubMed:2246854" FT /id="VAR_006789" FT VARIANT 176 FT /note="P -> L (in LNS; Marlow; dbSNP:rs137852493)" FT /id="VAR_006790" FT VARIANT 177 FT /note="D -> V (in LNS; Roanne)" FT /evidence="ECO:0000269|PubMed:9452051" FT /id="VAR_006791" FT VARIANT 177 FT /note="D -> Y (in LNS; RJK 2185; dbSNP:rs137852492)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006792" FT VARIANT 179..180 FT /note="VG -> GR (in HRH; Japan-2)" FT /evidence="ECO:0000269|PubMed:2572141" FT /id="VAR_006794" FT VARIANT 179 FT /note="Missing (in LNS; Michigan)" FT /id="VAR_006793" FT VARIANT 183 FT /note="I -> T (in HRH; JF)" FT /evidence="ECO:0000269|PubMed:2071157" FT /id="VAR_006796" FT VARIANT 185 FT /note="D -> G (in HRH; Asia)" FT /evidence="ECO:0000269|PubMed:17027311" FT /id="VAR_071622" FT VARIANT 188 FT /note="V -> A (in HRH and LNS; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311, ECO:0000269|PubMed:1840476" FT /id="VAR_006795" FT VARIANT 192 FT /note="A -> V (in HRH; Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_071623" FT VARIANT 194 FT /note="D -> E (in HRH; Moose-Jaw; results in cooperativity FT and decreased substrate affinities; dbSNP:rs137852504)" FT /evidence="ECO:0000269|PubMed:7987318" FT /id="VAR_006797" FT VARIANT 194 FT /note="D -> N (in LNS; Kinston/RJK 2188; FT dbSNP:rs267606863)" FT /evidence="ECO:0000269|PubMed:2347587, FT ECO:0000269|PubMed:6853716" FT /id="VAR_006798" FT VARIANT 195 FT /note="Y -> C (in HRH; Dirranbandi, Asia)" FT /evidence="ECO:0000269|PubMed:15571223, FT ECO:0000269|PubMed:17027311" FT /id="VAR_006799" FT VARIANT 199 FT /note="F -> V (in LNS; New Briton/RJK 950; FT dbSNP:rs137852486)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006800" FT VARIANT 201 FT /note="D -> G (in HRH; Ashville; dbSNP:rs137852479)" FT /evidence="ECO:0000269|PubMed:2909537" FT /id="VAR_006801" FT VARIANT 201 FT /note="D -> N (in HRH; RB)" FT /id="VAR_006802" FT VARIANT 201 FT /note="D -> Y (in LNS; GM)" FT /id="VAR_006803" FT VARIANT 204 FT /note="H -> D (in LNS; RJK 1874; dbSNP:rs137852490)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006804" FT VARIANT 204 FT /note="H -> R (in LNS; 779)" FT /evidence="ECO:0000269|PubMed:2071157" FT /id="VAR_006805" FT VARIANT 206 FT /note="C -> Y (in LNS; Reading/RJK 1727)" FT /evidence="ECO:0000269|PubMed:2347587" FT /id="VAR_006806" FT MUTAGEN 69 FT /note="K->A: Reduced affinity for hypoxanthine, FT phosphoribosylpyrophosphate and IMP. Reduced catalytic FT activity." FT /evidence="ECO:0000269|PubMed:10338013" FT STRAND 7..9 FT /evidence="ECO:0007829|PDB:1HMP" FT STRAND 12..14 FT /evidence="ECO:0007829|PDB:7SAN" FT HELIX 19..21 FT /evidence="ECO:0007829|PDB:5HIA" FT HELIX 26..28 FT /evidence="ECO:0007829|PDB:5HIA" FT TURN 29..31 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 32..37 FT /evidence="ECO:0007829|PDB:5HIA" FT HELIX 39..57 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 62..68 FT /evidence="ECO:0007829|PDB:5HIA" FT TURN 69..71 FT /evidence="ECO:0007829|PDB:5HIA" FT HELIX 72..87 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 88..90 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 95..101 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:1D6N" FT STRAND 115..118 FT /evidence="ECO:0007829|PDB:6BNJ" FT HELIX 119..121 FT /evidence="ECO:0007829|PDB:4RAC" FT HELIX 123..125 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 128..140 FT /evidence="ECO:0007829|PDB:5HIA" FT HELIX 141..150 FT /evidence="ECO:0007829|PDB:5HIA" FT HELIX 151..153 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 156..166 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 169..171 FT /evidence="ECO:0007829|PDB:1Z7G" FT STRAND 177..183 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:5HIA" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:5BSK" FT STRAND 198..201 FT /evidence="ECO:0007829|PDB:1BZY" FT STRAND 203..208 FT /evidence="ECO:0007829|PDB:5HIA" FT HELIX 210..215 FT /evidence="ECO:0007829|PDB:5HIA" SQ SEQUENCE 218 AA; 24579 MW; 1928EE69517CCB40 CRC64; MATRSPGVVI SDDEPGYDLD LFCIPNHYAE DLERVFIPHG LIMDRTERLA RDVMKEMGGH HIVALCVLKG GYKFFADLLD YIKALNRNSD RSIPMTVDFI RLKSYCNDQS TGDIKVIGGD DLSTLTGKNV LIVEDIIDTG KTMQTLLSLV RQYNPKMVKV ASLLVKRTPR SVGYKPDFVG FEIPDKFVVG YALDYNEYFR DLNHVCVISE TGKAKYKA //