GMPR1_HUMAN
ID GMPR1_HUMAN Reviewed; 345 AA.
AC P36959; Q96HQ6;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=GMP reductase 1 {ECO:0000255|HAMAP-Rule:MF_03195};
DE Short=GMPR 1 {ECO:0000255|HAMAP-Rule:MF_03195};
DE EC=1.7.1.7 {ECO:0000255|HAMAP-Rule:MF_03195};
DE AltName: Full=Guanosine 5'-monophosphate oxidoreductase 1 {ECO:0000255|HAMAP-Rule:MF_03195};
DE Short=Guanosine monophosphate reductase 1 {ECO:0000255|HAMAP-Rule:MF_03195};
GN Name=GMPR; Synonyms=GMPR1 {ECO:0000255|HAMAP-Rule:MF_03195};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=2758468; DOI=10.1016/0092-8674(89)90440-6;
RA Kanno H., Huang I.Y., Kan Y.W., Yoshida A.;
RT "Two structural genes on different chromosomes are required for encoding
RT the major subunit of human red cell glucose-6-phosphate dehydrogenase.";
RL Cell 58:595-606(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1661705; DOI=10.1007/bf00206076;
RA Kondoh T., Kanno H., Chang L., Yoshida A.;
RT "Genomic structure and expression of human guanosine monophosphate
RT reductase.";
RL Hum. Genet. 88:219-224(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-256.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SIMILARITY TO GMP REDUCTASE.
RX PubMed=2570640; DOI=10.1016/0092-8674(89)90498-4;
RA Henikoff S., Smith J.M.;
RT "The human mRNA that provides the N-terminus of chimeric G6PD encodes GMP
RT reductase.";
RL Cell 58:1021-1022(1989).
RN [6]
RP LACK OF ROLE IN G6PD.
RX PubMed=1694726; DOI=10.1016/0092-8674(90)90233-5;
RA Yoshida A., Kan Y.W.;
RT "Origin of 'fused' glucose-6-phosphate dehydrogenase.";
RL Cell 62:11-12(1990).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH GMP AND POTASSIUM
RP IONS.
RG Structural genomics consortium (SGC);
RT "Structure of human guanosine monophosphate reductase GMPR1 in complex with
RT GMP.";
RL Submitted (JUL-2005) to the PDB data bank.
RN [9]
RP VARIANTS THR-234 AND ILE-256.
RX PubMed=1757097; DOI=10.1007/bf00206077;
RA Kondoh T., Kanno H., Chang L., Yoshida A.;
RT "Identification of common variant alleles of the human guanosine
RT monophosphate reductase gene.";
RL Hum. Genet. 88:225-227(1991).
CC -!- FUNCTION: Catalyzes the irreversible NADPH-dependent deamination of GMP
CC to IMP. It functions in the conversion of nucleobase, nucleoside and
CC nucleotide derivatives of G to A nucleotides, and in maintaining the
CC intracellular balance of A and G nucleotides. {ECO:0000255|HAMAP-
CC Rule:MF_03195}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=IMP + NADP(+) + NH4(+) = GMP + 2 H(+) + NADPH;
CC Xref=Rhea:RHEA:17185, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58053, ChEBI:CHEBI:58115,
CC ChEBI:CHEBI:58349; EC=1.7.1.7; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03195};
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_03195,
CC ECO:0000269|Ref.8}.
CC -!- POLYMORPHISM: At least two different alleles are known.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03195}.
CC -!- CAUTION: The N-terminus was initially (PubMed:2758468) thought to be
CC fused with glucose-6-phosphate-dehydrogenase (G6PD) protein in vivo.
CC However, PubMed:2570640 showed that it encodes a GMP reductase, and
CC PubMed:1694726 showed that the chimeric protein is an artifact.
CC {ECO:0000305|PubMed:2758468}.
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DR EMBL; L35304; AAA52503.1; -; Genomic_DNA.
DR EMBL; M27941; AAA53106.1; -; Genomic_DNA.
DR EMBL; M24470; AAA52498.1; -; mRNA.
DR EMBL; AL009031; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008281; AAH08281.1; -; mRNA.
DR CCDS; CCDS4537.1; -.
DR PIR; B32902; B32902.
DR RefSeq; NP_006868.3; NM_006877.3.
DR PDB; 2BLE; X-ray; 1.90 A; A=1-345.
DR PDB; 2BWG; X-ray; 2.40 A; A/B/C/D=1-345.
DR PDBsum; 2BLE; -.
DR PDBsum; 2BWG; -.
DR AlphaFoldDB; P36959; -.
DR SMR; P36959; -.
DR BioGRID; 109028; 5.
DR IntAct; P36959; 1.
DR STRING; 9606.ENSP00000259727; -.
DR DrugBank; DB01972; Guanosine-5'-Monophosphate.
DR iPTMnet; P36959; -.
DR PhosphoSitePlus; P36959; -.
DR BioMuta; GMPR; -.
DR DMDM; 544455; -.
DR jPOST; P36959; -.
DR MassIVE; P36959; -.
DR MaxQB; P36959; -.
DR PaxDb; P36959; -.
DR PeptideAtlas; P36959; -.
DR PRIDE; P36959; -.
DR ProteomicsDB; 55249; -.
DR Antibodypedia; 10292; 168 antibodies from 22 providers.
DR DNASU; 2766; -.
DR Ensembl; ENST00000259727.5; ENSP00000259727.4; ENSG00000137198.10.
DR GeneID; 2766; -.
DR KEGG; hsa:2766; -.
DR MANE-Select; ENST00000259727.5; ENSP00000259727.4; NM_006877.4; NP_006868.3.
DR UCSC; uc003nbs.3; human.
DR CTD; 2766; -.
DR DisGeNET; 2766; -.
DR GeneCards; GMPR; -.
DR HGNC; HGNC:4376; GMPR.
DR HPA; ENSG00000137198; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 139265; gene.
DR neXtProt; NX_P36959; -.
DR OpenTargets; ENSG00000137198; -.
DR PharmGKB; PA28761; -.
DR VEuPathDB; HostDB:ENSG00000137198; -.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000156595; -.
DR HOGENOM; CLU_022552_5_3_1; -.
DR InParanoid; P36959; -.
DR OMA; AYKEYFG; -.
DR OrthoDB; 618077at2759; -.
DR PhylomeDB; P36959; -.
DR TreeFam; TF300378; -.
DR BRENDA; 1.7.1.7; 2681.
DR PathwayCommons; P36959; -.
DR Reactome; R-HSA-74217; Purine salvage.
DR SignaLink; P36959; -.
DR BioGRID-ORCS; 2766; 6 hits in 1081 CRISPR screens.
DR ChiTaRS; GMPR; human.
DR EvolutionaryTrace; P36959; -.
DR GenomeRNAi; 2766; -.
DR Pharos; P36959; Tbio.
DR PRO; PR:P36959; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P36959; protein.
DR Bgee; ENSG00000137198; Expressed in gastrocnemius and 169 other tissues.
DR Genevisible; P36959; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1902560; C:GMP reductase complex; IEA:InterPro.
DR GO; GO:0003920; F:GMP reductase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006144; P:purine nucleobase metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006163; P:purine nucleotide metabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009409; P:response to cold; TAS:ProtInc.
DR CDD; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00596; GMP_reduct_type1; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005993; GMPR.
DR InterPro; IPR015875; IMP_DH/GMP_Rdtase_CS.
DR InterPro; IPR001093; IMP_DH_GMPRt.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000235; GMP_reductase; 1.
DR TIGRFAMs; TIGR01305; GMP_reduct_1; 1.
DR PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Metal-binding; NADP; Oxidoreductase; Potassium;
KW Purine metabolism; Reference proteome.
FT CHAIN 1..345
FT /note="GMP reductase 1"
FT /id="PRO_0000093723"
FT ACT_SITE 186
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT ACT_SITE 188
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 26..27
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 78
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 129..131
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 180..181
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 181
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 183
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 186
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 189
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 219..221
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 242..243
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 268..270
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 269
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 285..286
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 286..290
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195,
FT ECO:0000269|Ref.8"
FT BINDING 314..317
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT VARIANT 234
FT /note="A -> T (in dbSNP:rs760571328)"
FT /evidence="ECO:0000269|PubMed:1757097"
FT /id="VAR_003969"
FT VARIANT 256
FT /note="F -> I (in dbSNP:rs1042391)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1757097"
FT /id="VAR_003970"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:2BWG"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2BLE"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:2BLE"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 61..67
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 82..91
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 93..98
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 107..119
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 136..148
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 162..170
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 198..210
FT /evidence="ECO:0007829|PDB:2BLE"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 225..234
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 272..277
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 285..288
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 292..296
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 301..319
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:2BLE"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:2BLE"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:2BLE"
SQ SEQUENCE 345 AA; 37419 MW; 217E1A5A599CA510 CRC64;
MPRIDADLKL DFKDVLLRPK RSSLKSRAEV DLERTFTFRN SKQTYSGIPI IVANMDTVGT
FEMAAVMSQH SMFTAIHKHY SLDDWKLFAT NHPECLQNVA VSSGSGQNDL EKMTSILEAV
PQVKFICLDV ANGYSEHFVE FVKLVRAKFP EHTIMAGNVV TGEMVEELIL SGADIIKVGV
GPGSVCTTRT KTGVGYPQLS AVIECADSAH GLKGHIISDG GCTCPGDVAK AFGAGADFVM
LGGMFSGHTE CAGEVFERNG RKLKLFYGMS SDTAMNKHAG GVAEYRASEG KTVEVPYKGD
VENTILDILG GLRSTCTYVG AAKLKELSRR ATFIRVTQQH NTVFS
