Reviewed, UniProtKB/Swiss-Prot P00492 (HPRT_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	HPRT1
Synonyms:	HPRT

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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)

Catalytic activity	IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate. GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-diphosphate.
Cofactor	Binds 2 magnesium ions per subunit. One of the ions does not make direct protein contacts.
Pathway	Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1.
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm.
Involvement in disease	Defects in HPRT1 are the cause of Lesch-Nyhan syndrome (LNS) [MIM:300322]. LNS is characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, mental retardation, and compulsive self-mutilation. Ref.17 Ref.21 Ref.22 Ref.28 Ref.31 Ref.32 Ref.33 Ref.35 Ref.41 Ref.43 Defects in HPRT1 are the cause of gout [MIM:300323]; also known as HPRT-related gout or Kelley-Seegmiller syndrome. Gout is characterized by partial enzyme activity and hyperuricemia. Ref.16 Ref.18 Ref.19 Ref.20 Ref.24 Ref.27 Ref.40
Sequence similarities	Belongs to the purine/pyrimidine phosphoribosyltransferase family.

Ontologies

Keywords
Biological process	Purine salvage
Cellular component	Cytoplasm
Disease	Disease mutation Gout
Ligand	Magnesium Metal-binding
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	hypoxanthine metabolic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of dopamine metabolic process Inferred from mutant phenotype. Source: UniProtKB protein homotetramerization Inferred from direct assay. Source: UniProtKB purine nucleotide biosynthetic process Inferred from mutant phenotype. Source: UniProtKB purine ribonucleoside salvage Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	hypoxanthine phosphoribosyltransferase activity Ref.1 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.13 Inferred from direct assay. Source: UniProtKB protein homodimerization activity Ref.12 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF1B	O60739	1	EBI-748210,EBI-1043343
HUS1	O60921	1	EBI-748210,EBI-1056174
MCC	P23508	1	EBI-748210,EBI-307531

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

Sites

Metal binding

194

1

Magnesium 1

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Natural variations

Natural variant

7

1

G → D in gout; 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; Urangan.

VAR_006753

Natural variant

20

1

D → V in gout; Mashad.

VAR_006754

Natural variant

23

1

C → W in gout JS.

VAR_006755

Natural variant

28

1

Missing in LNS. Ref.35

VAR_012312

Natural variant

41

1

L → P in LNS; Detroit.

VAR_006756

Natural variant

42

1

I → F in LNS; Isar. Ref.41

VAR_006757

Natural variant

42

1

I → T in LNS; Heapey. Ref.41

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.31

VAR_006760

Natural variant

48

1

R → H in gout; AD and DD.

VAR_006761

Natural variant

50

1

A → P in LNS; LW. Ref.35

VAR_006763

Natural variant

50

1

A → V in LNS; 1265. Ref.35

VAR_006762

Natural variant

51

1

R → G in gout; Toronto. Ref.16

VAR_006764

Natural variant

51

1

R → P in LNS; Banbury.

VAR_006765

Natural variant

52

1

D → G in Edinburgh.

VAR_006766

Natural variant

53

1

V → A in gout; MG.

VAR_006767

Natural variant

53

1

V → M in gout; 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.32

VAR_006770

Natural variant

58

1

G → R in gout; Toowong.

VAR_006771

Natural variant

61

1

H → R Enzyme activity 37% of normal; asymptomatic. Ref.42

VAR_006772

Natural variant

70

1

G → E in LNS; New Haven/1510. Ref.35

VAR_006773

Natural variant

71

1

G → R in LNS; Yale. Ref.28

VAR_006774

Natural variant

74

1

F → L in LNS; Flint/RJK 892/DW/Perth/1522. Ref.21 Ref.31 Ref.35

VAR_006775

Natural variant

78

1

L → V in gout; Swan.

VAR_006776

Natural variant

80

1

D → V in gout; Arlington.

VAR_006777

Natural variant

104

1

S → R in gout; Munich. Ref.19 Ref.20

VAR_006778

Natural variant

110

1

S → L in gout; London. Ref.18 Ref.24

VAR_006779

Natural variant

130

1

V → D in LNS; Midland/RJK 896. Ref.22 Ref.31

VAR_006780

Natural variant

131

1

L → S in LNS; RJK 1784. Ref.31

VAR_006781

Natural variant

132

1

I → M in gout; Ann-Arbor.

VAR_006782

Natural variant

132

1

I → T in LNS; Runcorn.

VAR_006783

Natural variant

135

1

D → G in gout; Yeronga.

VAR_006784

Natural variant

143

1

M → K in LNS; RJK 1210. Ref.31

VAR_006785

Natural variant

143

1

M → MA in LNS; RW. Ref.31

VAR_006786

Natural variant

161

1

A → S in gout; Milwaukee/RJK 949. Ref.31

VAR_006787

Natural variant

162

1

S → R in LNS; Farnham.

VAR_006788

Natural variant

168

1

T → I in gout; Brisbane. Ref.33

VAR_006789

Natural variant

176

1

P → L in LNS; Marlow.

VAR_006790

Natural variant

177

1

D → V in LNS; Roanne. Ref.31 Ref.43

VAR_006791

Natural variant

177

1

D → Y in LNS; RJK 2185. Ref.31 Ref.43

VAR_006792

Natural variant

179 – 180

2

VG → GR in gout; Japan-2.

VAR_006794

Natural variant

179

1

Missing in LNS; Michigan.

VAR_006793

Natural variant

183

1

I → T in gout; JF. Ref.35

VAR_006796

Natural variant

188

1

V → A in Japan.

VAR_006795

Natural variant

194

1

D → E in gout; Moose-Jaw; results in cooperativity and decreased substrate affinities. Ref.17 Ref.31 Ref.40

VAR_006797

Natural variant

194

1

D → N in LNS; Kinston/RJK 2188. Ref.17 Ref.31

VAR_006798

Natural variant

195

1

Y → C in gout; Dirranbandi.

VAR_006799

Natural variant

199

1

F → V in LNS; New Briton/RJK 950. Ref.31

VAR_006800

Natural variant

201

1

D → G in gout; Ashville. Ref.27

VAR_006801

Natural variant

201

1

D → N in gout; RB. Ref.27

VAR_006802

Natural variant

201

1

D → Y in LNS; GM.

VAR_006803

Natural variant

204

1

H → D in LNS; RJK 1874. Ref.31 Ref.35

VAR_006804

Natural variant

204

1

H → R in LNS; 779. Ref.31 Ref.35

VAR_006805

Natural variant

206

1

C → Y in LNS; Reading/RJK 1727. Ref.31

VAR_006806

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

218

Helix Strand Turn

Details...

Helix

19 – 21

3

Helix

26 – 28

3

Turn

29 – 31

3

Beta strand

32 – 37

6

Helix

39 – 57

19

Beta strand

62 – 68

7

Turn

69 – 71

3

Helix

72 – 86

15

Beta strand

95 – 106

12

Beta strand

109 – 118

10

Helix

120 – 125

6

Beta strand

129 – 140

12

Helix

141 – 151

11

Beta strand

156 – 166

11

Beta strand

177 – 183

7

Beta strand

188 – 190

3

Beta strand

198 – 201

4

Beta strand

203 – 208

6

Helix

210 – 216

7

Sequences

	Sequence		Length	Mass (Da)
	P00492-1 [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: 6300847] [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: 2341149] [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: 14702039] [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: 15772651] [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: 15489334] [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: 7107641] [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: 3023844] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 8044844] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS).
[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: 10360366] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[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: 10338013] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[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: 1487231] [Abstract] Cited for: REVIEW ON VARIANTS.
[16]	"Human hypoxanthine-guanine phosphoribosyltransferase." Wilson J.M., Kobayashi R., Fox I.H., Kelley W.N. J. Biol. Chem. 258:6458-6460(1983) [PubMed: 6853490] [Abstract] Cited for: VARIANT GOUT TORONTO GLY-51.
[17]	"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: 6853716] [Abstract] Cited for: VARIANT LNS KINSTON ASN-194.
[18]	"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: 6572373] [Abstract] Cited for: VARIANT GOUT LONDON LEU-110.
[19]	"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: 6706936] [Abstract] Cited for: VARIANT GOUT MUNICH ARG-104.
[20]	"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: 3358423] [Abstract] Cited for: VARIANT GOUT MUNICH ARG-104.
[21]	"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: 3384338] [Abstract] Cited for: VARIANT LNS FLINT LEU-74.
[22]	"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: 3265398] [Abstract] Cited for: VARIANT LNS MIDLAND ASP-130.
[23]	"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: 2896620] [Abstract] Cited for: VARIANT ANN ARBOR.
[24]	"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: 3198771] [Abstract] Cited for: VARIANT GOUT LONDON LEU-110.
[25]	"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: 3148064] [Abstract] Cited for: VARIANTS DIRRANBANDI AND YERONGA.
[26]	"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: 2572141] [Abstract] Cited for: VARIANTS JAPAN-1 AND JAPAN-2.
[27]	"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: 2909537] [Abstract] Cited for: VARIANT GOUT ASHVILLE GLY-201.
[28]	"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: 2910902] [Abstract] Cited for: VARIANT LNS YALE ARG-71.
[29]	"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: 2738157] [Abstract] Cited for: VARIANTS ARLINGEN; DETROIT; NEW BRITON AND NEW HAVEN.
[30]	"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: 2928313] [Abstract] Cited for: VARIANTS RKJ.
[31]	"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: 2347587] [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.
[32]	"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: 2358296] [Abstract] Cited for: VARIANT LNS MONTREAL THR-57.
[33]	"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: 2246854] [Abstract] Cited for: VARIANT LNS BRISBANE ILE-168.
[34]	"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: 2018042] [Abstract] Cited for: VARIANTS GRAVESEND; MASHAD; HEAPEY; BANBURY; RUNCORN; FARNHAM; MARLOW AND READING.
[35]	"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: 2071157] [Abstract] Cited for: VARIANTS LNS TYR-28 DEL; VAL-50; GLU-70; LEU-74; THR-183 AND ARG-204.
[36]	"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: 1937471] [Abstract] Cited for: VARIANTS PERTH; SWAN; TOOWONG AND URANGAN.
[37]	"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: 1840476] [Abstract] Cited for: VARIANT ALA-188, NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 183-193.
[38]	"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: 1551676] [Abstract] Cited for: VARIANT EDINBURGH GLY-52, NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[39]	"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: 1301916] [Abstract] Cited for: VARIANTS, NUCLEOTIDE SEQUENCE [MRNA] OF 35-50.
[40]	Lightfoot T., Snyder F.F. Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases Cited for: VARIANT GOUT MOOSE JAW GLU-194, NUCLEOTIDE SEQUENCE.
[41]	"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: 7627191] [Abstract] Cited for: VARIANT LNS ISAR PHE-42.
[42]	"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: 9003484] [Abstract] Cited for: VARIANT ARG-61.
[43]	"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: 9452051] [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

EMBLGenBankDDBJ

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.

UniGene

Hs.412707

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P00492. 15 interactions.

2-D gel databases

OGP

P00492.

REPRODUCTION-2DPAGE

IPI00218493.

Proteomic databases

PeptideAtlas

P00492.

PRIDE

P00492.

Genome annotation databases

Ensembl

ENSG00000165704. Homo sapiens. [Contig view]

GeneID

3251.

KEGG

hsa:3251.

UCSC

uc004exl.2. human.

Organism-specific databases

GeneCards

GC0XP133421.

H-InvDB

HIX0017063.

HGNC

HGNC:5157. HPRT1.

HPA

CAB012200.
HPA006360.

MIM

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

Orphanet

510. Lesch-Nyhan syndrome.

PharmGKB

PA29427.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P00492.

HOVERGEN

P00492.

Enzyme and pathway databases

BRENDA

2.4.2.8. 247.

Reactome

REACT_1698. Metablism of nucleotides.

Gene expression databases

ArrayExpress

P00492.

Bgee

P00492.

CleanEx

HS_HPRT1.

GermOnline

ENSG00000165704. Homo sapiens.

Family and domain databases

InterPro

IPR005904. Hxn_phspho_trans.
IPR002375. Pr/py_Pribosyl_transf_CS.
IPR000836. PRibTrfase.
[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 Resources

DrugBank

DB01033. Mercaptopurine.
DB00352. Thioguanine.

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:	July 7, 2009
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)