Q9P2T1 (GMPR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GMP reductase 2
EC=1.7.1.7

Alternative name(s):
Guanosine 5'-monophosphate oxidoreductase 2
Short name=Guanosine monophosphate reductase 2

Gene names

Name:

GMPR2

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

General annotation (Comments)

Function	Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides. Plays a role in modulating cellular differentiation. Ref.1 Ref.2
Catalytic activity	Inosine 5'-phosphate + NH3 + NADP+ = guanosine 5'-phosphate + NADPH.
Tissue specificity	Highly expressed in heart, skeletal muscle, kidney, brain, liver, prostate, spleen, placenta, testis and ovary. Low expression in colon, thymus and peripheral blood leukocytes. Ref.1 Ref.2
Sequence similarities	Belongs to the IMPDH/GMPR family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding NADP Potassium
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nucleotide metabolic process Inferred from electronic annotation. Source: InterPro purine nucleobase metabolic process Traceable author statement. Source: Reactome purine-containing compound salvage Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	GMP reductase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9P2T1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9P2T1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MTSCLPALRFIATPRLSAM

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 348

348

GMP reductase 2

PRO_0000093726

Regions

Nucleotide binding

108 – 131

24

NADP By similarity

Sites

Active site

186

1

Thioimidate intermediate By similarity

Metal binding

181

1

Potassium; via carbonyl oxygen By similarity

Metal binding

183

1

Potassium; via carbonyl oxygen By similarity

Binding site

219

1

NADP By similarity

Amino acid modifications

Modified residue

291

1

N6-acetyllysine Ref.8

Natural variations

Alternative sequence

1

1

M → MTSCLPALRFIATPRLSAM in isoform 2.

VSP_041459

Natural variant

242

1

G → D.
Corresponds to variant rs34354104 [ dbSNP | Ensembl ].

VAR_049602

Experimental info

Sequence conflict

91

1

Q → R in CAG33437. Ref.5

Sequence conflict

200

1

S → G in CAG33437. Ref.5

Sequence conflict

223

1

S → N in CAG33437. Ref.5

Secondary structure

1

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348

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Helix

12 – 14

3

Beta strand

15 – 17

3

Helix

27 – 29

3

Beta strand

34 – 37

4

Turn

39 – 41

3

Beta strand

44 – 47

4

Beta strand

50 – 52

3

Turn

56 – 58

3

Helix

61 – 69

9

Beta strand

73 – 75

3

Helix

82 – 91

10

Helix

93 – 95

3

Beta strand

99 – 103

5

Helix

107 – 119

13

Beta strand

125 – 129

5

Helix

136 – 148

13

Beta strand

152 – 159

8

Helix

162 – 170

9

Beta strand

174 – 178

5

Helix

188 – 192

5

Helix

198 – 211

14

Beta strand

215 – 220

6

Helix

225 – 233

9

Beta strand

237 – 242

6

Turn

243 – 247

5

Beta strand

248 – 251

4

Beta strand

255 – 258

4

Beta strand

261 – 267

7

Beta strand

269 – 271

3

Helix

272 – 278

7

Beta strand

279 – 281

3

Turn

283 – 285

3

Beta strand

286 – 288

3

Beta strand

292 – 296

5

Helix

301 – 319

19

Helix

324 – 326

3

Helix

327 – 330

4

Beta strand

333 – 335

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: E7812A754C433E51	FASTA	348	37,874
	10 20 30 40 50 60 MPHIDNDVKL DFKDVLLRPK RSTLKSRSEV DLTRSFSFRN SKQTYSGVPI IAANMDTVGT 70 80 90 100 110 120 FEMAKVLCKF SLFTAVHKHY SLVQWQEFAG QNPDCLEHLA ASSGTGSSDF EQLEQILEAI 130 140 150 160 170 180 PQVKYICLDV ANGYSEHFVE FVKDVRKRFP QHTIMAGNVV TGEMVEELIL SGADIIKVGI 190 200 210 220 230 240 GPGSVCTTRK KTGVGYPQLS AVMECADAAH GLKGHIISDG GCSCPGDVAK AFGAGADFVM 250 260 270 280 290 300 LGGMLAGHSE SGGELIERDG KKYKLFYGMS SEMAMKKYAG GVAEYRASEG KTVEVPFKGD 310 320 330 340 VEHTIRDILG GIRSTCTYVG AAKLKELSRR TTFIRVTQQV NPIFSEAC
	Isoform 2 [UniParc]. Checksum: 009CF162967F2112	FASTA	366	39,805
	10 20 30 40 50 60 MTSCLPALRF IATPRLSAMP HIDNDVKLDF KDVLLRPKRS TLKSRSEVDL TRSFSFRNSK 70 80 90 100 110 120 QTYSGVPIIA ANMDTVGTFE MAKVLCKFSL FTAVHKHYSL VQWQEFAGQN PDCLEHLAAS 130 140 150 160 170 180 SGTGSSDFEQ LEQILEAIPQ VKYICLDVAN GYSEHFVEFV KDVRKRFPQH TIMAGNVVTG 190 200 210 220 230 240 EMVEELILSG ADIIKVGIGP GSVCTTRKKT GVGYPQLSAV MECADAAHGL KGHIISDGGC 250 260 270 280 290 300 SCPGDVAKAF GAGADFVMLG GMLAGHSESG GELIERDGKK YKLFYGMSSE MAMKKYAGGV 310 320 330 340 350 360 AEYRASEGKT VEVPFKGDVE HTIRDILGGI RSTCTYVGAA KLKELSRRTT FIRVTQQVNP IFSEAC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression, purification, and kinetic properties." Deng Y., Wang Z., Ying K., Gu S., Ji C., Huang Y., Gu X., Wang Y., Xu Y., Li Y., Xie Y., Mao Y. Int. J. Biochem. Cell Biol. 34:1035-1050(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[2]	"Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells." Zhang J., Zhang W., Zou D., Chen G., Wan T., Zhang M., Cao X. J. Cancer Res. Clin. Oncol. 129:76-83(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[3]	"A novel protein related to guanosine monophosphate reductase." Okaze H., Hayashi A., Kozuma S., Saito T. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	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].
[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] (ISOFORMS 1 AND 2). Tissue: Lung and Placenta.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-291, MASS SPECTROMETRY.
[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].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF419346 mRNA. Translation: AAN32701.1.
AF135159 mRNA. Translation: AAG09132.1.
AB032903 mRNA. Translation: BAA93080.1.
BX161436 mRNA. Translation: CAD61908.1.
CR457156 mRNA. Translation: CAG33437.1.
CH471078 Genomic DNA. Translation: EAW66051.1.
CH471078 Genomic DNA. Translation: EAW66053.1.
CH471078 Genomic DNA. Translation: EAW66054.1.
CH471078 Genomic DNA. Translation: EAW66057.1.
BC008021 mRNA. Translation: AAH08021.2.
BC009832 mRNA. Translation: AAH09832.1.
BC093039 mRNA. Translation: AAH93039.1.

IPI

IPI00009844.
IPI00433025.

RefSeq

NP_001002000.1. NM_001002000.1.
NP_001002001.1. NM_001002001.1.
NP_001002002.1. NM_001002002.1.
NP_057660.2. NM_016576.3.

UniGene

Hs.368855.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A7R	X-ray	3.00	A/B/C/D	1-348	[»]
2BZN	X-ray	2.15	A/B/C/D/E/F/G/H	10-341	[»]
2C6Q	X-ray	1.70	A/B/C/D/E/F/G/H	10-341	[»]

ProteinModelPortal

Q9P2T1.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P2T1. 1 interaction.

STRING

9606.ENSP00000392859.

PTM databases

PhosphoSite

Q9P2T1.

Polymorphism databases

DMDM

25008511.

Proteomic databases

PaxDb

Q9P2T1.

PRIDE

Q9P2T1.

Protocols and materials databases

DNASU

51292.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355299; ENSP00000347449; ENSG00000100938.
ENST00000399440; ENSP00000382369; ENSG00000100938.
ENST00000420554; ENSP00000392859; ENSG00000100938.
ENST00000559836; ENSP00000453299; ENSG00000100938.

GeneID

51292.

KEGG

hsa:51292.

UCSC

uc001wnr.3. human.
uc001wnx.3. human.

Organism-specific databases

CTD

51292.

GeneCards

GC14P024701.

HGNC

HGNC:4377. GMPR2.

HPA

HPA000904.

MIM

610781. gene.

neXtProt

NX_Q9P2T1.

PharmGKB

PA28762.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0516.

HOGENOM

HOG000165756.

HOVERGEN

HBG051744.

InParanoid

Q9P2T1.

KO

K00364.

OrthoDB

EOG4FXR7V.

PhylomeDB

Q9P2T1.

Enzyme and pathway databases

BRENDA

1.7.1.7. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9P2T1.

Bgee

Q9P2T1.

CleanEx

HS_GMPR2.

Genevestigator

Q9P2T1.

Family and domain databases

Gene3D

3.20.20.70. 1 hit.

InterPro

IPR013785. Aldolase_TIM.
IPR005993. GMP_reduct1.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]

Pfam

PF00478. IMPDH. 1 hit.
[Graphical view]

PIRSF

PIRSF000235. GMP_reductase. 1 hit.

TIGRFAMs

TIGR01305. GMP_reduct_1. 1 hit.

PROSITE

PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

GMPR2. human.

EvolutionaryTrace

Q9P2T1.

GenomeRNAi

51292.

NextBio

54555.

SOURCE

Search...

Entry information

Entry name

GMPR2_HUMAN

Accession

Primary (citable) accession number: Q9P2T1
Secondary accession number(s): D3DS66, Q567T0, Q6IAJ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 112 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.