PURA2_MOUSE
ID PURA2_MOUSE Reviewed; 456 AA.
AC P46664; Q9CQL9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Adenylosuccinate synthetase isozyme 2 {ECO:0000255|HAMAP-Rule:MF_03127};
DE Short=AMPSase 2 {ECO:0000255|HAMAP-Rule:MF_03127};
DE Short=AdSS 2 {ECO:0000255|HAMAP-Rule:MF_03127};
DE EC=6.3.4.4 {ECO:0000255|HAMAP-Rule:MF_03127, ECO:0000269|PubMed:12482871};
DE AltName: Full=Adenylosuccinate synthetase, acidic isozyme {ECO:0000255|HAMAP-Rule:MF_03127};
DE AltName: Full=Adenylosuccinate synthetase, liver isozyme {ECO:0000255|HAMAP-Rule:MF_03127};
DE Short=L-type adenylosuccinate synthetase {ECO:0000255|HAMAP-Rule:MF_03127};
DE AltName: Full=IMP--aspartate ligase 2 {ECO:0000255|HAMAP-Rule:MF_03127};
GN Name=Adss2; Synonyms=Adss {ECO:0000312|MGI:MGI:87948};
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 [MRNA].
RC STRAIN=129/Sv; TISSUE=Kidney;
RX PubMed=8308018; DOI=10.1016/s0021-9258(17)41805-9;
RA Guicherit O.M., Cooper B.F., Rudolph F.B., Kellems R.E.;
RT "Amplification of an adenylosuccinate synthetase gene in alanosine-
RT resistant murine T-lymphoma cells. Molecular cloning of a cDNA encoding the
RT 'non-muscle' isozyme.";
RL J. Biol. Chem. 269:4488-4496(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=12482871; DOI=10.1074/jbc.m210838200;
RA Borza T., Iancu C.V., Pike E., Honzatko R.B., Fromm H.J.;
RT "Variations in the response of mouse isozymes of adenylosuccinate
RT synthetase to inhibitors of physiological relevance.";
RL J. Biol. Chem. 278:6673-6679(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Cerebellum, and Liver;
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 [4]
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: Plays an important role in the de novo pathway and in the
CC salvage pathway of purine nucleotide biosynthesis. Catalyzes the first
CC committed step in the biosynthesis of AMP from IMP.
CC {ECO:0000269|PubMed:12482871}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + IMP + L-aspartate = GDP + 2 H(+) + N(6)-(1,2-
CC dicarboxyethyl)-AMP + phosphate; Xref=Rhea:RHEA:15753,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29991, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57567, ChEBI:CHEBI:58053,
CC ChEBI:CHEBI:58189; EC=6.3.4.4; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03127, ECO:0000269|PubMed:12482871};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03127};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03127};
CC -!- ACTIVITY REGULATION: Inhibited competitively by AMP and IMP and non-
CC competitively by fructose 1,6-bisphosphate.
CC {ECO:0000269|PubMed:12482871}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15 uM for GTP {ECO:0000269|PubMed:12482871};
CC KM=12 uM for IMP {ECO:0000269|PubMed:12482871};
CC KM=950 uM for L-aspartate {ECO:0000269|PubMed:12482871};
CC pH dependence:
CC Optimum pH is 6.6-6.9. {ECO:0000269|PubMed:12482871};
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via de novo pathway; AMP
CC from IMP: step 1/2. {ECO:0000255|HAMAP-Rule:MF_03127}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03127}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03127}.
CC Mitochondrion {ECO:0000250|UniProtKB:A4Z6H1}.
CC -!- SIMILARITY: Belongs to the adenylosuccinate synthetase family.
CC {ECO:0000255|HAMAP-Rule:MF_03127}.
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DR EMBL; L24554; AAA19727.1; -; mRNA.
DR EMBL; AK004877; BAB23635.1; -; mRNA.
DR EMBL; AK010263; BAB26805.1; -; mRNA.
DR EMBL; AK028060; BAC25730.1; -; mRNA.
DR EMBL; AK148420; BAE28543.1; -; mRNA.
DR EMBL; AK170279; BAE41682.1; -; mRNA.
DR CCDS; CCDS15555.1; -.
DR PIR; A53162; A53162.
DR RefSeq; NP_031448.2; NM_007422.3.
DR AlphaFoldDB; P46664; -.
DR SMR; P46664; -.
DR BioGRID; 198011; 12.
DR STRING; 10090.ENSMUSP00000016105; -.
DR iPTMnet; P46664; -.
DR PhosphoSitePlus; P46664; -.
DR SwissPalm; P46664; -.
DR REPRODUCTION-2DPAGE; P46664; -.
DR REPRODUCTION-2DPAGE; Q9CQL9; -.
DR EPD; P46664; -.
DR jPOST; P46664; -.
DR MaxQB; P46664; -.
DR PaxDb; P46664; -.
DR PRIDE; P46664; -.
DR ProteomicsDB; 301889; -.
DR Antibodypedia; 20829; 154 antibodies from 23 providers.
DR DNASU; 11566; -.
DR Ensembl; ENSMUST00000016105; ENSMUSP00000016105; ENSMUSG00000015961.
DR GeneID; 11566; -.
DR KEGG; mmu:11566; -.
DR UCSC; uc007dut.1; mouse.
DR CTD; 11566; -.
DR MGI; MGI:87948; Adss.
DR VEuPathDB; HostDB:ENSMUSG00000015961; -.
DR eggNOG; KOG1355; Eukaryota.
DR GeneTree; ENSGT00390000015553; -.
DR HOGENOM; CLU_029848_3_2_1; -.
DR InParanoid; P46664; -.
DR OMA; FHHAKPI; -.
DR OrthoDB; 1276527at2759; -.
DR PhylomeDB; P46664; -.
DR TreeFam; TF300486; -.
DR Reactome; R-MMU-73817; Purine ribonucleoside monophosphate biosynthesis.
DR UniPathway; UPA00075; UER00335.
DR BioGRID-ORCS; 11566; 11 hits in 74 CRISPR screens.
DR ChiTaRS; Adss; mouse.
DR PRO; PR:P46664; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P46664; protein.
DR Bgee; ENSMUSG00000015961; Expressed in animal zygote and 262 other tissues.
DR ExpressionAtlas; P46664; baseline and differential.
DR Genevisible; P46664; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0004019; F:adenylosuccinate synthase activity; IDA:MGI.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IMP:MGI.
DR GO; GO:0006167; P:AMP biosynthetic process; IDA:MGI.
DR GO; GO:0044209; P:AMP salvage; TAS:MGI.
DR GO; GO:0006531; P:aspartate metabolic process; ISO:MGI.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0046040; P:IMP metabolic process; ISO:MGI.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IDA:MGI.
DR GO; GO:0060359; P:response to ammonium ion; IEA:Ensembl.
DR GO; GO:0014074; P:response to purine-containing compound; IEA:Ensembl.
DR CDD; cd03108; AdSS; 1.
DR Gene3D; 1.10.300.10; -; 1.
DR Gene3D; 3.40.440.10; -; 1.
DR Gene3D; 3.90.170.10; -; 1.
DR HAMAP; MF_00011; Adenylosucc_synth; 1.
DR HAMAP; MF_03127; Adenylosucc_synth_vert_acid; 1.
DR InterPro; IPR018220; Adenylosuccin_syn_GTP-bd.
DR InterPro; IPR033128; Adenylosuccin_syn_Lys_AS.
DR InterPro; IPR042109; Adenylosuccinate_synth_dom1.
DR InterPro; IPR042110; Adenylosuccinate_synth_dom2.
DR InterPro; IPR042111; Adenylosuccinate_synth_dom3.
DR InterPro; IPR001114; Adenylosuccinate_synthetase.
DR InterPro; IPR027529; AdSS_2_vert.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11846; PTHR11846; 1.
DR Pfam; PF00709; Adenylsucc_synt; 1.
DR SMART; SM00788; Adenylsucc_synt; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00184; purA; 1.
DR PROSITE; PS01266; ADENYLOSUCCIN_SYN_1; 1.
DR PROSITE; PS00513; ADENYLOSUCCIN_SYN_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; GTP-binding; Ligase; Magnesium; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Purine biosynthesis; Reference proteome.
FT CHAIN 1..456
FT /note="Adenylosuccinate synthetase isozyme 2"
FT /id="PRO_0000095131"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 40
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT ACT_SITE 68
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 39..45
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 40..43
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 40
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 40
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 65..68
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 67..69
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 67
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 162
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 176
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 255
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 270
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 330..336
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 334
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 336
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 362..364
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT BINDING 444..447
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03127"
FT CONFLICT 167
FT /note="G -> R (in Ref. 1; AAA19727)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="A -> T (in Ref. 1; AAA19727)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 456 AA; 50021 MW; 7825B758BC6CDA38 CRC64;
MSISESSPAA TSLPNGDCGR PRARSGGNRV TVVLGAQWGD EGKGKVVDLL AQDADIVCRC
QGGNNAGHTV VVDSVEYDFH LLPSGIINPN VTAFIGNGVV IHLPGLFEEA EKNVQKGKGL
DGWEKRLIIS DRAHIVFDFH QAADGIQEQQ RQEQAGKNLG TTKKGIGPVY SSKAARSGLR
MCDLVSDFDG FSERFKVLAN QYKSIYPTLE IDIEGELQQL KGYMERIKPM VKDGVYFLYE
ALHGPPKKIL VEGANAALLD IDFGTYPFVT SSNCTVGGVC TGLGMPPQNV GEVYGVVKAY
TTRVGIGAFP TEQDNEIGEL LQTRGREFGV TTGRKRRCGW LDLVSLKYAH MINGFTALAL
TKLDILDMFT EIKVGVAYKL DGETIPHFPA NQEVLNKVEV QYKTLPGWNT DISNARTFKE
LPVNAQNYVR FIEDELQIPV KWIGVGKSRE SMIQLF
