ID GUAA_MOUSE Reviewed; 693 AA.
AC Q3THK7; Q3TFR6; Q3TIH1; Q3UJ21; Q3V343; Q66JZ6;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 27-MAR-2024, entry version 145.
DE RecName: Full=GMP synthase [glutamine-hydrolyzing];
DE EC=6.3.5.2 {ECO:0000269|PubMed:240826};
DE AltName: Full=GMP synthetase;
DE AltName: Full=Glutamine amidotransferase;
GN Name=Gmps;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=BALB/cJ, C57BL/6J, DBA/2J, and NOD;
RC TISSUE=Eye, Heart, Kidney, Spinal cord, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 217-693.
RC TISSUE=Limb;
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 [3]
RP PROTEIN SEQUENCE OF 536-548 AND 570-589, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=240826; DOI=10.1016/s0021-9258(19)40954-x;
RA Spector T.;
RT "Studies with GMP synthetase from Ehrlich ascites cells. Purification,
RT properties, and interactions with nucleotide analogs.";
RL J. Biol. Chem. 250:7372-7376(1975).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the conversion of xanthine monophosphate (XMP) to
CC GMP in the presence of glutamine and ATP through an adenyl-XMP
CC intermediate. {ECO:0000269|PubMed:240826}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-glutamine + XMP = AMP + diphosphate + GMP + 2
CC H(+) + L-glutamate; Xref=Rhea:RHEA:11680, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57464, ChEBI:CHEBI:58115,
CC ChEBI:CHEBI:58359, ChEBI:CHEBI:456215; EC=6.3.5.2;
CC Evidence={ECO:0000269|PubMed:240826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11681;
CC Evidence={ECO:0000305|PubMed:240826};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q4V7C6};
CC -!- ACTIVITY REGULATION: Stimulated by dithiothreitol and inhibited by 2-
CC mercaptoethanol, p-chloromercuribenzoate and hydroxylamine.
CC {ECO:0000269|PubMed:240826}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.0036 mM for XMP {ECO:0000269|PubMed:240826};
CC KM=0.28 mM for ATP {ECO:0000269|PubMed:240826};
CC KM=0.68 mM for glutamine {ECO:0000269|PubMed:240826};
CC Vmax=1.0 nmol/min/mg enzyme for XMP {ECO:0000269|PubMed:240826};
CC Vmax=1.1 nmol/min/mg enzyme for ATP {ECO:0000269|PubMed:240826};
CC Vmax=1.37 nmol/min/mg enzyme for glutamine
CC {ECO:0000269|PubMed:240826};
CC pH dependence:
CC Optimum pH is 7.6. {ECO:0000269|PubMed:240826};
CC -!- PATHWAY: Purine metabolism; GMP biosynthesis; GMP from XMP (L-Gln
CC route): step 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P49915}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P49915}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE20667.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK049755; BAE20667.1; ALT_FRAME; mRNA.
DR EMBL; AK143197; BAE25299.1; -; mRNA.
DR EMBL; AK146654; BAE27334.1; -; mRNA.
DR EMBL; AK167857; BAE39875.1; -; mRNA.
DR EMBL; AK168239; BAE40189.1; -; mRNA.
DR EMBL; AK169043; BAE40832.1; -; mRNA.
DR EMBL; AK169701; BAE41314.1; -; mRNA.
DR EMBL; BC080685; AAH80685.1; -; mRNA.
DR CCDS; CCDS17383.1; -.
DR RefSeq; NP_001028472.2; NM_001033300.2.
DR AlphaFoldDB; Q3THK7; -.
DR SMR; Q3THK7; -.
DR BioGRID; 230837; 22.
DR STRING; 10090.ENSMUSP00000029405; -.
DR BindingDB; Q3THK7; -.
DR ChEMBL; CHEMBL2765; -.
DR MEROPS; C26.950; -.
DR GlyGen; Q3THK7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q3THK7; -.
DR PhosphoSitePlus; Q3THK7; -.
DR SwissPalm; Q3THK7; -.
DR REPRODUCTION-2DPAGE; IPI00351252; -.
DR EPD; Q3THK7; -.
DR jPOST; Q3THK7; -.
DR MaxQB; Q3THK7; -.
DR PaxDb; 10090-ENSMUSP00000029405; -.
DR ProteomicsDB; 270905; -.
DR Pumba; Q3THK7; -.
DR Antibodypedia; 33632; 285 antibodies from 33 providers.
DR Ensembl; ENSMUST00000029405.8; ENSMUSP00000029405.8; ENSMUSG00000027823.10.
DR GeneID; 229363; -.
DR KEGG; mmu:229363; -.
DR UCSC; uc008pke.1; mouse.
DR AGR; MGI:2448526; -.
DR CTD; 8833; -.
DR MGI; MGI:2448526; Gmps.
DR VEuPathDB; HostDB:ENSMUSG00000027823; -.
DR eggNOG; KOG1622; Eukaryota.
DR GeneTree; ENSGT00390000006591; -.
DR HOGENOM; CLU_014340_0_2_1; -.
DR InParanoid; Q3THK7; -.
DR OMA; IWQSFAV; -.
DR OrthoDB; 6206at2759; -.
DR PhylomeDB; Q3THK7; -.
DR TreeFam; TF106132; -.
DR Reactome; R-MMU-73817; Purine ribonucleoside monophosphate biosynthesis.
DR Reactome; R-MMU-9748787; Azathioprine ADME.
DR UniPathway; UPA00189; UER00296.
DR BioGRID-ORCS; 229363; 23 hits in 80 CRISPR screens.
DR ChiTaRS; Gmps; mouse.
DR PRO; PR:Q3THK7; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q3THK7; Protein.
DR Bgee; ENSMUSG00000027823; Expressed in ear vesicle and 238 other cell types or tissues.
DR ExpressionAtlas; Q3THK7; baseline and differential.
DR Genevisible; Q3THK7; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003922; F:GMP synthase (glutamine-hydrolyzing) activity; IDA:MGI.
DR GO; GO:0003921; F:GMP synthase activity; ISO:MGI.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006177; P:GMP biosynthetic process; IDA:MGI.
DR GO; GO:0032263; P:GMP salvage; ISO:MGI.
DR CDD; cd01742; GATase1_GMP_Synthase; 1.
DR CDD; cd01997; GMP_synthase_C; 1.
DR Gene3D; 3.30.300.10; -; 2.
DR Gene3D; 3.40.50.880; -; 1.
DR Gene3D; 3.40.50.620; HUPs; 1.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR017926; GATASE.
DR InterPro; IPR001674; GMP_synth_C.
DR InterPro; IPR004739; GMP_synth_GATase.
DR InterPro; IPR025777; GMPS_ATP_PPase_dom.
DR InterPro; IPR022310; NAD/GMP_synthase.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR NCBIfam; TIGR00888; guaA_Nterm; 1.
DR PANTHER; PTHR11922:SF2; GMP SYNTHASE [GLUTAMINE-HYDROLYZING]; 1.
DR PANTHER; PTHR11922; GMP SYNTHASE-RELATED; 1.
DR Pfam; PF00117; GATase; 1.
DR Pfam; PF00958; GMP_synt_C; 1.
DR Pfam; PF02540; NAD_synthase; 1.
DR PRINTS; PR00097; ANTSNTHASEII.
DR PRINTS; PR00096; GATASE.
DR SUPFAM; SSF52402; Adenine nucleotide alpha hydrolases-like; 1.
DR SUPFAM; SSF52317; Class I glutamine amidotransferase-like; 1.
DR SUPFAM; SSF54810; GMP synthetase C-terminal dimerisation domain; 2.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
DR PROSITE; PS51553; GMPS_ATP_PPASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cytoplasm; Direct protein sequencing;
KW Glutamine amidotransferase; GMP biosynthesis; Ligase; Nucleotide-binding;
KW Phosphoprotein; Purine biosynthesis; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT CHAIN 2..693
FT /note="GMP synthase [glutamine-hydrolyzing]"
FT /id="PRO_0000284365"
FT DOMAIN 27..216
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT DOMAIN 217..435
FT /note="GMPS ATP-PPase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00886"
FT ACT_SITE 104
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 190
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 192
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT BINDING 244..250
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00886"
FT BINDING 337
FT /ligand="XMP"
FT /ligand_id="ChEBI:CHEBI:57464"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT BINDING 522
FT /ligand="XMP"
FT /ligand_id="ChEBI:CHEBI:57464"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT BINDING 610
FT /ligand="XMP"
FT /ligand_id="ChEBI:CHEBI:57464"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT BINDING 685
FT /ligand="XMP"
FT /ligand_id="ChEBI:CHEBI:57464"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT BINDING 691
FT /ligand="XMP"
FT /ligand_id="ChEBI:CHEBI:57464"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT MOD_RES 9
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT MOD_RES 318
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49915"
FT CONFLICT 201
FT /note="V -> I (in Ref. 1; BAE39875)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="N -> Y (in Ref. 1; BAE39875)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="V -> D (in Ref. 1; BAE39875)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="S -> G (in Ref. 1; BAE40189)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="P -> H (in Ref. 1; BAE40189)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="P -> R (in Ref. 1; BAE39875)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="Missing (in Ref. 1; BAE39875)"
FT /evidence="ECO:0000305"
FT CONFLICT 511..512
FT /note="LL -> CC (in Ref. 1; BAE27334)"
FT /evidence="ECO:0000305"
FT CONFLICT 586
FT /note="S -> G (in Ref. 1; BAE39875)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 693 AA; 76723 MW; 854DBAD6A9C75A12 CRC64;
MALCNGDSKP ENAGGDLKDG SHHYEGAVVI LDAGAQYGKV IDRRVRELFV QSEIFPLETP
AFAIKEQGFR AIIISGGPNS VYAEDAPWFD PAIFTIGKPI LGICYGMQMM NKVFGGTVHK
KSVREDGVFN ISMDNTCSLF RGLQKEEIVL LTHGDSVDKV ADGFKVVARS GNIVAGIANE
SKKLYGVQFH PEVGLTENGK VILKNFLYDI AGCSGNFTVQ NRELECIREI KEKVGTSKVL
VLLSGGVDST VCTALLNRAL NQDQVIAVHI DNGFMRKRES QSVEEALKKL GIQVKVINAA
HSFYNGTTTL PISDEDRTPR KRISKTLNMT TSPEEKRKII GDTFVKIANE VIGEMSLKPE
EVFLAQGTLR PDLIESASLV ASGKAELIKT HHNDTELIRK LREEGKVIEP LKDFHKDEVR
ILGRELDLPE ELVSRHPFPG PGLAIRVICA EEPYICKDFP ETNNILKIVA DFSASVKKPH
TLLQRVKACT TEEDQEKLMQ ITSLHSLNAF LLPIKTVGVQ GDCRSYSYVC GISSKDEPDW
ESLIFLARLI PRMCHNINRV VYIFGPPVKE PPTDVTPTFL TTGVLSTLRQ ADFEAHNILR
ESGFAGKISQ MPVILTPLHF DRDPLQKQPS CQRSVVIRTF ITSDFMTGVP ATPGNEIPVE
VVLKMVTEIK KIPGISRIMY DLTSKPPGTT EWE
//
