HPRT_HUMAN
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 03-AUG-2022, entry version 232.
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-GLY-ARG-180.
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";
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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 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 AlphaFoldDB; P00492; -.
DR SMR; P00492; -.
DR BioGRID; 109488; 84.
DR IntAct; P00492; 34.
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; P00492; -.
DR PeptideAtlas; P00492; -.
DR PRIDE; P00492; -.
DR ProteomicsDB; 51257; -.
DR TopDownProteomics; P00492; -.
DR Antibodypedia; 1912; 613 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 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; TMDWMAV; -.
DR OrthoDB; 1537610at2759; -.
DR PhylomeDB; P00492; -.
DR TreeFam; TF313367; -.
DR BioCyc; MetaCyc:HS09275-MON; -.
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; 18 hits in 708 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 207 other tissues.
DR ExpressionAtlas; P00492; baseline and differential.
DR Genevisible; P00492; HS.
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 Pfam; PF00156; Pribosyltran; 1.
DR SUPFAM; SSF53271; SSF53271; 1.
DR TIGRFAMs; TIGR01203; HGPRTase; 1.
DR PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1.
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 /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:3GEP"
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
