Q9UBQ7 (GRHPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glyoxylate reductase/hydroxypyruvate reductase
EC=1.1.1.79
EC=1.1.1.81

Gene names

Name:	GRHPR
Synonyms:	GLXR
ORF Names:	MSTP035

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	328 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate.
Catalytic activity	Glycolate + NADP+ = glyoxylate + NADPH. D-glycerate + NAD(P)+ = hydroxypyruvate + NAD(P)H.
Subunit structure	Homodimer. Ref.1 Ref.10
Tissue specificity	Ubiquitous. Most abundantly expressed in the liver. Ref.8
Involvement in disease	Hyperoxaluria primary 2 (HP2) [MIM:260000]: A disorder characterized by elevated urinary excretion of oxalate and L-glycerate, progressive tissue accumulation of insoluble calcium oxalate, nephrolithiasis, nephrocalcinosis, and end-stage renal disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2
Sequence similarities	Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.
Sequence caution	The sequence AAD54066.1 differs from that shown. Reason: Frameshift at positions 109 and 137. The sequence AAG39286.1 differs from that shown. Reason: Frameshift at position 237.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome excretion Inferred from mutant phenotype Ref.2. Source: UniProtKB glyoxylate metabolic process Traceable author statement. Source: Reactome protein oligomerization Inferred from direct assay Ref.10. Source: UniProtKB
Cellular_component	peroxisomal matrix Traceable author statement. Source: Reactome
Molecular_function	NAD binding Traceable author statement Ref.2. Source: UniProtKB NADPH binding Inferred from direct assay Ref.10. Source: UniProtKB glycerate dehydrogenase activity Inferred from direct assay Ref.2. Source: UniProtKB glyoxylate reductase (NADP) activity Inferred from direct assay Ref.2. Source: UniProtKB hydroxypyruvate reductase activity Inferred from direct assay Ref.2PubMed 17510093. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 328

328

Glyoxylate reductase/hydroxypyruvate reductase

PRO_0000075944

Regions

Nucleotide binding

162 – 164

3

NADP

Nucleotide binding

185 – 188

4

NADP

Region

83 – 84

2

Substrate binding

Region

293 – 296

4

Substrate binding

Sites

Active site

293

1

Proton donor

Binding site

217

1

NADP

Binding site

243

1

NADP; via carbonyl oxygen

Binding site

245

1

Substrate

Binding site

269

1

Substrate

Binding site

295

1

NADP; via amide nitrogen

Site

274

1

Raises pKa of active site His

Natural variations

Natural variant

170

1

R → Q.
Corresponds to variant rs12002324 [ dbSNP | Ensembl ].

VAR_032762

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

328

Helix Strand Turn

Details...

Beta strand

7 – 13

7

Helix

17 – 25

9

Beta strand

29 – 33

5

Beta strand

36 – 38

3

Helix

42 – 49

8

Beta strand

53 – 57

5

Helix

65 – 71

7

Beta strand

77 – 83

7

Helix

90 – 95

6

Beta strand

99 – 101

3

Helix

108 – 123

16

Helix

126 – 134

9

Beta strand

143 – 146

4

Beta strand

155 – 159

5

Helix

163 – 172

10

Helix

173 – 175

3

Beta strand

179 – 186

8

Helix

189 – 193

5

Turn

194 – 196

3

Beta strand

197 – 199

3

Helix

202 – 208

7

Beta strand

210 – 214

5

Turn

220 – 224

5

Helix

228 – 233

6

Beta strand

239 – 242

4

Helix

246 – 248

3

Helix

251 – 259

9

Beta strand

262 – 269

8

Beta strand

272 – 275

4

Helix

281 – 284

4

Beta strand

288 – 290

3

Helix

299 – 318

20

Sequences

	Sequence		Length	Mass (Da)
	Q9UBQ7 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 68A0E311AA4E5650	FASTA	328	35,668
	10 20 30 40 50 60 MRPVRLMKVF VTRRIPAEGR VALARAADCE VEQWDSDEPI PAKELERGVA GAHGLLCLLS 70 80 90 100 110 120 DHVDKRILDA AGANLKVIST MSVGIDHLAL DEIKKRGIRV GYTPDVLTDT TAELAVSLLL 130 140 150 160 170 180 TTCRRLPEAI EEVKNGGWTS WKPLWLCGYG LTQSTVGIIG LGRIGQAIAR RLKPFGVQRF 190 200 210 220 230 240 LYTGRQPRPE EAAEFQAEFV STPELAAQSD FIVVACSLTP ATEGLCNKDF FQKMKETAVF 250 260 270 280 290 300 INISRGDVVN QDDLYQALAS GKIAAAGLDV TSPEPLPTNH PLLTLKNCVI LPHIGSATHR 310 320 TRNTMSLLAA NNLLAGLRGE PMPSELKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and expression of a cDNA for human hydroxypyruvate/glyoxylate reductase." Rumsby G., Cregeen D.P. Biochim. Biophys. Acta 1446:383-388(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT. Tissue: Liver.
[2]	"The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II." Cramer S.D., Ferree P.M., Lin K., Milliner D.S., Holmes R.P. Hum. Mol. Genet. 8:2063-2069(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INVOLVEMENT IN HP2. Tissue: Liver.
[3]	Liu B., Liu Y.Q., Wang X.Y., Zhao B., Sheng H., Zhao X.W., Liu S., Xu Y.Y., Ye J., Song L., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Cao H.Q., Zhao Y., Liu L.S., Ding J.F. , Gao R.L., Wu Q.Y., Qiang B.Q., Yuan J.G., Liew C.C., Zhao M.S., Hui R.T. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Aorta.
[4]	"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]. Tissue: Testis.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton 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].
[7]	"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: Kidney.
[8]	"Cloning and characterization of a putative human D-2-hydroxyacid dehydrogenase in chromosome 9q." Huang T., Yang W., Pereira A.C., Craigen W.J., Shih V.E. Biochem. Biophys. Res. Commun. 268:298-301(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 45-328, TISSUE SPECIFICITY.
[9]	"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].
[10]	"Structural basis of substrate specificity in human glyoxylate reductase/hydroxypyruvate reductase." Booth M.P.S., Conners R., Rumsby G., Brady R.L. J. Mol. Biol. 360:178-189(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NADP AND SUBSTRATE, SUBUNIT.
[11]	"Crystal structure of a glyoxylate/hydroxypyruvate reductase from Homo sapiens." Center for eukaryotic structural genomics (CESG) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 2-328.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF134895 mRNA. Translation: AAF00111.1.
AF146018 mRNA. Translation: AAD45886.1.
AF146689 Genomic DNA. Translation: AAD46517.1.
AF113215 mRNA. Translation: AAG39286.1. Frameshift.
AK315690 mRNA. Translation: BAG38053.1.
AL158155 Genomic DNA. Translation: CAI13848.1.
CH471071 Genomic DNA. Translation: EAW58284.1.
BC000605 mRNA. Translation: AAH00605.1.
AF113251 mRNA. Translation: AAD54066.1. Frameshift.

IPI

IPI00037448.

PIR

JC7190.

RefSeq

NP_036335.1. NM_012203.1.

UniGene

Hs.731459.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GCG	X-ray	2.20	A/B/C/D	1-328	[»]
2H1S	X-ray	2.45	A/B/C/D	2-328	[»]
2Q50	X-ray	2.45	A/B/C/D	2-328	[»]
2WWR	X-ray	2.82	A/B/C/D	1-328	[»]

ProteinModelPortal

Q9UBQ7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBQ7. 5 interactions.

STRING

9606.ENSP00000313432.

PTM databases

PhosphoSite

Q9UBQ7.

Polymorphism databases

DMDM

47116943.

2D gel databases

REPRODUCTION-2DPAGE

IPI00037448.

UCD-2DPAGE

Q9UBQ7.

Proteomic databases

PaxDb

Q9UBQ7.

PRIDE

Q9UBQ7.

Protocols and materials databases

DNASU

9380.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000318158; ENSP00000313432; ENSG00000137106.

GeneID

9380.

KEGG

hsa:9380.

UCSC

uc003zzt.1. human.

Organism-specific databases

CTD

9380.

GeneCards

GC09P037412.

HGNC

HGNC:4570. GRHPR.

HPA

HPA022971.

MIM

260000. phenotype.
604296. gene.

neXtProt

NX_Q9UBQ7.

Orphanet

93599. D-glycerate dehydrogenase deficiency.

PharmGKB

PA28965.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1052.

HOVERGEN

HBG051838.

KO

K00049.

OMA

IGSATHR.

OrthoDB

EOG4GHZPX.

PhylomeDB

Q9UBQ7.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q9UBQ7.

Gene expression databases

ArrayExpress

Q9UBQ7.

Bgee

Q9UBQ7.

CleanEx

HS_GRHPR.

Genevestigator

Q9UBQ7.

GermOnline

ENSG00000137106. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 2 hits.

InterPro

IPR006139. D-isomer_2_OHA_DH_cat_dom.
IPR006140. D-isomer_2_OHA_DH_NAD-bd.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Pfam

PF00389. 2-Hacid_dh. 1 hit.
PF02826. 2-Hacid_dh_C. 1 hit.
[Graphical view]

PROSITE

PS00065. D_2_HYDROXYACID_DH_1. False negative.
PS00670. D_2_HYDROXYACID_DH_2. False negative.
PS00671. D_2_HYDROXYACID_DH_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

GRHPR. human.

EvolutionaryTrace

Q9UBQ7.

GenomeRNAi

9380.

NextBio

35148.

SOURCE

Search...

Entry information

Entry name

GRHPR_HUMAN

Accession

Primary (citable) accession number: Q9UBQ7
Secondary accession number(s): Q5T945, Q9H3E9, Q9UKX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 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.