P00492 (HPRT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hypoxanthine-guanine phosphoribosyltransferase
Short name=HGPRT
Short name=HGPRTase
EC=2.4.2.8

Gene names

Name:	HPRT1
Synonyms:	HPRT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	218 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
Catalytic activity	IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate. Ref.14 Ref.17 GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-diphosphate. Ref.14 Ref.17
Cofactor	Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein.
Pathway	Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1.
Subunit structure	Homotetramer. Ref.16
Subcellular location	Cytoplasm.
Involvement in disease	Lesch-Nyhan syndrome (LNS) [MIM:300322]: Characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, mental retardation, and compulsive self-mutilation. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.23 Ref.24 Ref.30 Ref.33 Ref.34 Ref.35 Ref.37 Ref.43 Ref.45 Gout HPRT-related (GOUT-HPRT) [MIM:300323]: Characterized by partial enzyme activity and hyperuricemia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.20 Ref.21 Ref.22 Ref.26 Ref.29 Ref.42
Sequence similarities	Belongs to the purine/pyrimidine phosphoribosyltransferase family.
Biophysicochemical properties	Kinetic parameters: KM=5.4 µM for IMP Ref.14 KM=0.45 µM for hypoxanthine KM=25 µM for pyrophosphate KM=31 µM for phosphoribosylpyrophosphate

Ontologies

Keywords
Biological process	Purine salvage
Cellular component	Cytoplasm
Disease	Disease mutation Gout
Ligand	Magnesium Metal-binding Nucleotide-binding
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	GMP catabolic process Inferred from direct assay Ref.17. Source: UniProtKB GMP salvage Inferred from Biological aspect of Ancestor. Source: RefGenome IMP salvage Inferred from Biological aspect of Ancestor. Source: RefGenome adenine salvage Inferred from Biological aspect of Ancestor. Source: RefGenome behavior Inferred from mutant phenotype PubMed 16138897. Source: UniProtKB central nervous system neuron development Inferred from electronic annotation. Source: Compara cerebral cortex neuron differentiation Inferred from electronic annotation. Source: Compara cytolysis Inferred from electronic annotation. Source: Compara dendrite morphogenesis Inferred from electronic annotation. Source: Compara dopamine metabolic process Inferred from electronic annotation. Source: Compara grooming behavior Inferred from electronic annotation. Source: Compara guanine salvage Inferred from direct assay Ref.17. Source: UniProtKB hypoxanthine salvage Inferred from direct assay Ref.17. Source: UniProtKB lymphocyte proliferation Inferred from electronic annotation. Source: Compara positive regulation of dopamine metabolic process Inferred from mutant phenotype PubMed 8643611. Source: UniProtKB protein homotetramerization Inferred from direct assay PubMed 9521733. Source: UniProtKB purine ribonucleoside salvage Inferred from mutant phenotype PubMed 9824441. Source: UniProtKB response to amphetamine Inferred from electronic annotation. Source: Compara striatum development Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	guanine phosphoribosyltransferase activity Inferred from direct assay Ref.17. Source: UniProtKB hypoxanthine phosphoribosyltransferase activity Inferred from direct assay Ref.17Ref.1PubMed 9521733. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.13. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
WDYHV1	Q96HA8	3	EBI-748210,EBI-741158

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.9

Chain

2 – 218

217

Hypoxanthine-guanine phosphoribosyltransferase

PRO_0000139585

Regions

Nucleotide binding

134 – 142

9

GMP

Nucleotide binding

186 – 188

3

GMP

Sites

Active site

138

1

Proton acceptor Probable

Metal binding

194

1

Magnesium

Binding site

69

1

GMP

Binding site

166

1

GMP

Binding site

194

1

GMP; via carbonyl oxygen

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Natural variations

Natural variant

7

1

G → D in GOUT-HPRT; Gravesend.

VAR_006750

Natural variant

8

1

V → G in LNS; HB.

VAR_006751

Natural variant

16

1

G → D in LNS; FG.

VAR_006752

Natural variant

16

1

G → S in GOUT-HPRT; Urangan.

VAR_006753

Natural variant

20

1

D → V in GOUT-HPRT; Mashad.

VAR_006754

Natural variant

23

1

C → W in GOUT-HPRT; JS.

VAR_006755

Natural variant

28

1

Missing in LNS. Ref.37

VAR_012312

Natural variant

41

1

L → P in LNS; Detroit.

VAR_006756

Natural variant

42

1

I → F in LNS; Isar. Ref.43

VAR_006757

Natural variant

42

1

I → T in LNS; Heapey.

VAR_006758

Natural variant

43 – 44

2

MD → RN in LNS; Salamanca.

VAR_006759

Natural variant

45

1

R → K in LNS; RJK 2163. Ref.33

VAR_006760

Natural variant

48

1

R → H in GOUT-HPRT; AD and DD.

VAR_006761

Natural variant

50

1

A → P in LNS; LW.

VAR_006763

Natural variant

50

1

A → V in LNS; 1265. Ref.37

VAR_006762

Natural variant

51

1

R → G in GOUT-HPRT; Toronto. Ref.18

VAR_006764

Natural variant

51

1

R → P in LNS; Banbury.

VAR_006765

Natural variant

52

1

D → G in Edinburgh. Ref.40

VAR_006766

Natural variant

53

1

V → A in GOUT-HPRT; MG.

VAR_006767

Natural variant

53

1

V → M in GOUT-HPRT; TE.

VAR_006768

Natural variant

54

1

M → L in LNS; Japan-1.

VAR_006769

Natural variant

57

1

M → T in LNS; Montreal. Ref.34

VAR_006770

Natural variant

58

1

G → R in GOUT-HPRT; Toowong.

VAR_006771

Natural variant

61

1

H → R Enzyme activity 37% of normal; asymptomatic. Ref.44

VAR_006772

Natural variant

70

1

G → E in LNS; New Haven/1510. Ref.37

VAR_006773

Natural variant

71

1

G → R in LNS; Yale. Ref.30

VAR_006774

Natural variant

74

1

F → L in LNS; Flint/RJK 892/DW/Perth/1522. Ref.23 Ref.33 Ref.37

VAR_006775

Natural variant

78

1

L → V in GOUT-HPRT; Swan.

VAR_006776

Natural variant

80

1

D → V in GOUT-HPRT; Arlington.

VAR_006777

Natural variant

104

1

S → R in GOUT-HPRT; Munich. Ref.21 Ref.22

VAR_006778

Natural variant

110

1

S → L in GOUT-HPRT; London. Ref.20 Ref.26

VAR_006779

Natural variant

130

1

V → D in LNS; Midland/RJK 896. Ref.24 Ref.33

VAR_006780

Natural variant

131

1

L → S in LNS; RJK 1784. Ref.33

VAR_006781

Natural variant

132

1

I → M in GOUT-HPRT; Ann-Arbor.

VAR_006782

Natural variant

132

1

I → T in LNS; Runcorn.

VAR_006783

Natural variant

135

1

D → G in GOUT-HPRT; Yeronga.

VAR_006784

Natural variant

143

1

M → K in LNS; RJK 1210. Ref.33

VAR_006785

Natural variant

143

1

M → MA in LNS; RW.

VAR_006786

Natural variant

161

1

A → S in GOUT-HPRT; Milwaukee/RJK 949. Ref.33

VAR_006787

Natural variant

162

1

S → R in LNS; Farnham.

VAR_006788

Natural variant

168

1

T → I in GOUT-HPRT; Brisbane. Ref.35

VAR_006789

Natural variant

176

1

P → L in LNS; Marlow.

VAR_006790

Natural variant

177

1

D → V in LNS; Roanne. Ref.45

VAR_006791

Natural variant

177

1

D → Y in LNS; RJK 2185. Ref.33

VAR_006792

Natural variant

179 – 180

2

VG → GR in GOUT-HPRT; Japan-2.

VAR_006794

Natural variant

179

1

Missing in LNS; Michigan.

VAR_006793

Natural variant

183

1

I → T in GOUT-HPRT; JF. Ref.37

VAR_006796

Natural variant

188

1

V → A in Japan. Ref.39

VAR_006795

Natural variant

194

1

D → E in GOUT-HPRT; Moose-Jaw; results in cooperativity and decreased substrate affinities. Ref.42

VAR_006797

Natural variant

194

1

D → N in LNS; Kinston/RJK 2188. Ref.19 Ref.33

VAR_006798

Natural variant

195

1

Y → C in GOUT-HPRT; Dirranbandi.

VAR_006799

Natural variant

199

1

F → V in LNS; New Briton/RJK 950. Ref.33

VAR_006800

Natural variant

201

1

D → G in GOUT-HPRT; Ashville. Ref.29

VAR_006801

Natural variant

201

1

D → N in GOUT-HPRT; RB.

VAR_006802

Natural variant

201

1

D → Y in LNS; GM.

VAR_006803

Natural variant

204

1

H → D in LNS; RJK 1874. Ref.33

VAR_006804

Natural variant

204

1

H → R in LNS; 779. Ref.37

VAR_006805

Natural variant

206

1

C → Y in LNS; Reading/RJK 1727. Ref.33

VAR_006806

Experimental info

Mutagenesis

69

1

K → A: Reduced affinity for hypoxanthine, phosphoribosylpyrophosphate and IMP. Reduced catalytic activity. Ref.14

Secondary structure

1

.

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218

Helix Strand Turn

Details...

Beta strand

7 – 9

3

Beta strand

12 – 14

3

Helix

19 – 21

3

Helix

26 – 28

3

Turn

29 – 31

3

Beta strand

32 – 37

6

Helix

39 – 57

19

Beta strand

62 – 67

6

Turn

69 – 71

3

Helix

73 – 86

14

Beta strand

88 – 90

3

Beta strand

95 – 100

6

Beta strand

109 – 118

10

Helix

122 – 125

4

Beta strand

128 – 136

9

Helix

140 – 151

12

Beta strand

156 – 166

11

Beta strand

177 – 183

7

Beta strand

188 – 190

3

Beta strand

198 – 201

4

Beta strand

204 – 208

5

Helix

210 – 216

7

Sequences

	Sequence		Length	Mass (Da)
	P00492 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 1928EE69517CCB40	FASTA	218	24,579
	10 20 30 40 50 60 MATRSPGVVI SDDEPGYDLD LFCIPNHYAE DLERVFIPHG LIMDRTERLA RDVMKEMGGH 70 80 90 100 110 120 HIVALCVLKG GYKFFADLLD YIKALNRNSD RSIPMTVDFI RLKSYCNDQS TGDIKVIGGD 130 140 150 160 170 180 DLSTLTGKNV LIVEDIIDTG KTMQTLLSLV RQYNPKMVKV ASLLVKRTPR SVGYKPDFVG 190 200 210 FEIPDKFVVG YALDYNEYFR DLNHVCVISE TGKAKYKA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase." Jolly D.J., Okayama H., Berg P., Esty A.C., Filpula D., Bohlen P., Johnson G.G., Shively J.E., Hunkapillar T., Friedmann T. Proc. Natl. Acad. Sci. U.S.A. 80:477-481(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Automated DNA sequencing of the human HPRT locus." Edwards A., Voss H., Rice P., Civitello A., Stegemann J., Schwager C., Zimmermann J., Erfle H., Caskey C.T., Ansorge W. Genomics 6:593-608(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[9]	"Human hypoxanthine-guanine phosphoribosyltransferase. Complete amino acid sequence of the erythrocyte enzyme." Wilson J.M., Tarr G.E., Mahoney W.C., Kelley W.N. J. Biol. Chem. 257:10978-10985(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-218.
[10]	"Fine structure of the human hypoxanthine phosphoribosyltransferase gene." Patel P.I., Framson P.E., Caskey C.T., Chinault A.C. Mol. Cell. Biol. 6:393-403(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP." Eads J.C., Scapin G., Xu Y., Grubmeyer C., Sacchettini J.C. Cell 78:325-334(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) IN COMPLEX WITH GMP.
[13]	"The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor." Shi W., Li C.M., Tyler P.C., Furneaux R.H., Grubmeyer C., Schramm V.L., Almo S.C. Nat. Struct. Biol. 6:588-593(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH A TRANSITION-STATE ANALOG.
[14]	"Ternary complex structure of human HGPRTase, PRPP, Mg2+, and the inhibitor HPP reveals the involvement of the flexible loop in substrate binding." Balendiran G.K., Molina J.A., Xu Y., Torres-Martinez J., Stevens R., Focia P.J., Eakin A.E., Sacchettini J.C., Craig S.P. III Protein Sci. 8:1023-1031(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF MUTANT ALA-69 IN COMPLEX WITH PHOSPHORIBOSYLPYROPHOSPHATE; MAGNESIUM IONS AND HYPOXANTHINE ANALOG HPP, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, MUTAGENESIS OF LYS-69.
[15]	"A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency." Sculley D.G., Dawson P.A., Emmerson B.T., Gordon R.B. Hum. Genet. 90:195-207(1992) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[16]	"The crystal structure of free human hypoxanthine-guanine phosphoribosyltransferase reveals extensive conformational plasticity throughout the catalytic cycle." Keough D.T., Brereton I.M., de Jersey J., Guddat L.W. J. Mol. Biol. 351:170-181(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF APOPROTEIN, SUBUNIT.
[17]	"Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic nucleoside phosphonates: a new class of antimalarial therapeutics." Keough D.T., Hockova D., Holy A., Naesens L.M., Skinner-Adams T.S., Jersey J., Guddat L.W. J. Med. Chem. 52:4391-4399(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEXES WITH ACYCLIC NUCLEOSIDE PHOSPHONATES, CATALYTIC ACTIVITY.
[18]	"Human hypoxanthine-guanine phosphoribosyltransferase." Wilson J.M., Kobayashi R., Fox I.H., Kelley W.N. J. Biol. Chem. 258:6458-6460(1983) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GOUT-HPRT TORONTO GLY-51.
[19]	"Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome." Wilson J.M., Kelley W.N. J. Clin. Invest. 71:1331-1335(1983) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS KINSTON ASN-194.
[20]	"Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid substitution in a mutant form of the enzyme isolated from a patient with gout." Wilson J.M., Tarr G.E., Kelley W.N. Proc. Natl. Acad. Sci. U.S.A. 80:870-873(1983) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GOUT-HPRT LONDON LEU-110.
[21]	"Human hypoxanthine-guanine phosphoribosyltransferase. Structural alteration in a dysfunctional enzyme variant (HPRTMunich) isolated from a patient with gout." Wilson J.M., Kelley W.N. J. Biol. Chem. 259:27-30(1984) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GOUT-HPRT MUNICH ARG-104.
[22]	"Resolution of a missense mutant in human genomic DNA by denaturing gradient gel electrophoresis and direct sequencing using in vitro DNA amplification: HPRT Munich." Cariello N.F., Scott J.K., Kat A.G., Thilly W.G., Keohavong P. Am. J. Hum. Genet. 42:726-734(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GOUT-HPRT MUNICH ARG-104.
[23]	"Genetic basis of hypoxanthine guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome (HPRTFlint)." Davidson B.L., Pashmforoush M., Kelly W.N., Palella T.D. Gene 63:331-336(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS FLINT LEU-74.
[24]	"Human hypoxanthine-guanine phosphoribosyltransferase: a single nucleotide substitution in cDNA clones isolated from a patient with Lesch-Nyhan syndrome (HPRTMidland)." Davidson B.L., Palella T.D., Kelly W.N. Gene 68:85-91(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS MIDLAND ASP-130.
[25]	"Identification of a single nucleotide change in a mutant gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT Ann Arbor)." Fujimori S., Hidaka Y., Davidson B.L., Palella T.D., Kelley W.N. Hum. Genet. 79:39-43(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ANN ARBOR.
[26]	"Hypoxanthine-guanine phosphoribosyltransferase. Genetic evidence for identical mutations in two partially deficient subjects." Davidson B.L., Chin S.J., Wilson J.M., Kelley W.N., Palella T.D. J. Clin. Invest. 82:2164-2167(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GOUT-HPRT LONDON LEU-110.
[27]	"Biochemical basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in nine families." Keough D.T., Gordon R.B., Dejersey J., Emmerson B.T. J. Inherit. Metab. Dis. 11:229-238(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DIRRANBANDI AND YERONGA.
[28]	"Molecular analysis of hypoxanthine-guanine phosphoribosyltransferase mutations in five unrelated Japanese patients." Igarashi T., Minami M., Nishida Y. Acta Paediatr. Jpn. Overseas Ed. 31:303-313(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS JAPAN-1 AND JAPAN-2.
[29]	"Human hypoxanthine-guanine phosphoribosyltransferase deficiency. The molecular defect in a patient with gout (HPRTAshville)." Davidson B.L., Pashmforoush M., Kelly W.N., Palella T.D. J. Biol. Chem. 264:520-525(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GOUT-HPRT ASHVILLE GLY-201.
[30]	"Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome." Fujimori S., Davidson B.L., Kelley W.N., Palella T.D. J. Clin. Invest. 83:11-13(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS YALE ARG-71.
[31]	"Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts." Davidson B.L., Tarle S.A., Palella T.D., Kelley W.N. J. Clin. Invest. 84:342-346(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARLINGEN; DETROIT; NEW BRITON AND NEW HAVEN.
[32]	"Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA." Gibbs R.A., Nguyen P.N., McBride L.J., Koepf S.M., Caskey C.T. Proc. Natl. Acad. Sci. U.S.A. 86:1919-1923(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RKJ.
[33]	"Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families." Gibbs R.A., Nguyen P.N., Edwards A., Civitello A.B., Caskey C.T. Genomics 7:235-244(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LNS RJK LYS-45; LEU-74; ASP-130; SER-131; LYS-143; SER-161; TYR-177; ASN-194; VAL-199; ASP-204 AND TYR-206.
[34]	"Molecular analyses of a Lesch-Nyhan syndrome mutation (hprtMontreal) by use of T-lymphocyte cultures." Skopek T.R., Recio L., Simpson D., Dallaire L., Melancon S.B., Ogier H., O'Neill J.P., Falta M.T., Nicklas J.A., Albertini R.J. Hum. Genet. 85:111-116(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS MONTREAL THR-57.
[35]	"Identification of a single nucleotide substitution in the coding sequence of in vitro amplified cDNA from a patient with partial HPRT deficiency (HPRTBRISBANE)." Gordon R.B., Sculley D.G., Dawson P.A., Beacham I.R., Emmerson B.T. J. Inherit. Metab. Dis. 13:692-700(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS BRISBANE ILE-168.
[36]	"Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency." Davidson B.L., Tarle S.A., van Antwerp M., Gibbs D.A., Watts R.W.E., Kelley W.N., Palella T.D. Am. J. Hum. Genet. 48:951-958(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GRAVESEND; MASHAD; HEAPEY; BANBURY; RUNCORN; FARNHAM; MARLOW AND READING.
[37]	"Determination of the mutations responsible for the Lesch-Nyhan syndrome in 17 subjects." Tarle S.A., Davidson B.L., Wu V.C., Zidar F.J., Seegmiller J.E., Kelley W.N., Palella T.D. Genomics 10:499-501(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LNS TYR-28 DEL; VAL-50; GLU-70; LEU-74; THR-183 AND ARG-204.
[38]	"Hypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of HPRT mutations by direct sequencing and allele-specific amplification." Sculley D.G., Dawson P.A., Beacham I.R., Emmerson B.T., Gordon R.B. Hum. Genet. 87:688-692(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PERTH; SWAN; TOOWONG AND URANGAN.
[39]	"Identification of two independent Japanese mutant HPRT genes using the PCR technique." Yamada Y., Goto H., Ogasawara N. Adv. Exp. Med. Biol. 309B:121-124(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ALA-188, NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 183-193.
[40]	"The point mutation of hypoxanthine-guanine phosphoribosyltransferase (HPRTEdinburgh) and detection by allele-specific polymerase chain reaction." Lightfoot T., Joshi R., Nuki G., Snyder F.F. Hum. Genet. 88:695-696(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EDINBURGH GLY-52, NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[41]	"Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency." Sege-Paterson K., Chambers J., Page T., Jones O.W., Nyhan W.L. Hum. Mol. Genet. 1:427-432(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS, NUCLEOTIDE SEQUENCE [MRNA] OF 35-50.
[42]	Lightfoot T., Snyder F.F. Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases Cited for: VARIANT GOUT-HPRT MOOSE JAW GLU-194, NUCLEOTIDE SEQUENCE.
[43]	"Identification of a new missense mutation in exon 2 of the human hypoxanthine phosphoribosyltransferase gene (HPRTIsar): a further example of clinical heterogeneity in HPRT deficiencies." Burgemeister R., Roetzer E., Gutensohn W., Gehrke M., Schiel W. Hum. Mutat. 5:341-344(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS ISAR PHE-42.
[44]	"An asymptomatic germline missense base substitution in the hypoxanthine phosphoribosyltransferase (HPRT) gene that reduces the amount of enzyme in humans." Fujimori S., Sakuma R., Yamaoka N., Hakoda M., Yamanaka H., Kamatani N. Hum. Genet. 99:8-10(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-61.
[45]	"The molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in French families; report of two novel mutations." Liu G., Aral B., Zabot M.-T., Kamoun P., Ceballos-Picot I. Hum. Mutat. Suppl. 1:S88-S90(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LNS ROANNE VAL-177.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Wikipedia

Hypoxanthine-guanine phosphoribosyltransferase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M31642 mRNA. Translation: AAA52690.1.
M26434 Genomic DNA. Translation: AAA36012.1.
AK313435 mRNA. Translation: BAG36226.1.
BT019350 mRNA. Translation: AAV38157.1.
AY780550 Genomic DNA. Translation: AAV31777.1.
AC004383 Genomic DNA. No translation available.
CH471107 Genomic DNA. Translation: EAX11761.1.
BC000578 mRNA. Translation: AAH00578.1.
M12452 Genomic DNA. Translation: AAA52691.1.
S79313 Genomic DNA. Translation: AAB21289.1.
L29383 mRNA. Translation: AAB59391.1.
L29382 mRNA. Translation: AAB59392.1.
S60300 mRNA. Translation: AAC60591.2.

IPI

IPI00218493.

PIR

RTHUG. A32728.

RefSeq

NP_000185.1. NM_000194.2.

UniGene

Hs.412707.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BZY	X-ray	2.00	A/B/C/D	2-218	[»]
1D6N	X-ray	2.70	A/B	5-218	[»]
1HMP	X-ray	2.50	A/B	2-218	[»]
1Z7G	X-ray	1.90	A/B/C/D	2-217	[»]
2VFA	X-ray	2.80	A/B	49-160	[»]
3GEP	X-ray	2.60	A/B	2-218	[»]
3GGC	X-ray	2.78	A/B	2-218	[»]
3GGJ	X-ray	2.60	A/B	2-218	[»]

ProteinModelPortal

P00492.

ModBase

Search...

Protein-protein interaction databases

IntAct

P00492. 4 interactions.

MINT

MINT-1443310.

STRING

9606.ENSP00000298556.

PTM databases

PhosphoSite

P00492.

Polymorphism databases

DMDM

123497.

2D gel databases

OGP

P00492.

REPRODUCTION-2DPAGE

IPI00218493.

Proteomic databases

PaxDb

P00492.

PeptideAtlas

P00492.

PRIDE

P00492.

Protocols and materials databases

DNASU

3251.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000298556; ENSP00000298556; ENSG00000165704.

GeneID

3251.

KEGG

hsa:3251.

UCSC

uc004exl.4. human.

Organism-specific databases

CTD

3251.

GeneCards

GC0XP133594.

HGNC

HGNC:5157. HPRT1.

HPA

CAB012200.
HPA006360.

MIM

300322. phenotype.
300323. phenotype.
308000. gene.

neXtProt

NX_P00492.

Orphanet

79233. Kelley-Seegmiller syndrome.
510. Lesch-Nyhan syndrome.

PharmGKB

PA29427.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0634.

HOGENOM

HOG000236521.

HOVERGEN

HBG000242.

KO

K00760.

OMA

MGAKRFL.

OrthoDB

EOG4H72CM.

PhylomeDB

P00492.

Enzyme and pathway databases

BioCyc

MetaCyc:HS09275-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P00492.

UniPathway

UPA00591; UER00648.

Gene expression databases

Bgee

P00492.

CleanEx

HS_HPRT1.

Genevestigator

P00492.

GermOnline

ENSG00000165704. Homo sapiens.

Family and domain databases

InterPro

IPR005904. Hxn_phspho_trans.
IPR000836. PRibTrfase_dom.
[Graphical view]

Pfam

PF00156. Pribosyltran. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01203. HGPRTase. 1 hit.

PROSITE

PS00103. PUR_PYR_PR_TRANSFER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00492.

ChEMBL

CHEMBL2360.

ChiTaRS

HPRT1. human.

DrugBank

DB01033. Mercaptopurine.
DB00352. Thioguanine.

EvolutionaryTrace

P00492.

GenomeRNAi

3251.

NextBio

12927.

SOURCE

Search...

Entry information

Entry name

HPRT_HUMAN

Accession

Primary (citable) accession number: P00492
Secondary accession number(s): A6NHF0, B2R8M9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 155 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.