ID PURA1_MOUSE Reviewed; 457 AA. AC P28650; Q8CHQ1; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 2. DT 02-OCT-2024, entry version 194. DE RecName: Full=Adenylosuccinate synthetase isozyme 1 {ECO:0000255|HAMAP-Rule:MF_03126}; DE Short=AMPSase 1 {ECO:0000255|HAMAP-Rule:MF_03126}; DE Short=AdSS 1 {ECO:0000255|HAMAP-Rule:MF_03126}; DE EC=6.3.4.4 {ECO:0000255|HAMAP-Rule:MF_03126}; DE AltName: Full=Adenylosuccinate synthetase like 1 {ECO:0000312|MGI:MGI:87947}; DE AltName: Full=Adenylosuccinate synthetase, basic isozyme {ECO:0000255|HAMAP-Rule:MF_03126}; DE AltName: Full=Adenylosuccinate synthetase, muscle isozyme {ECO:0000255|HAMAP-Rule:MF_03126, ECO:0000303|PubMed:11560929, ECO:0000303|PubMed:12482871}; DE Short=M-type adenylosuccinate synthetase {ECO:0000255|HAMAP-Rule:MF_03126}; DE AltName: Full=IMP--aspartate ligase 1 {ECO:0000255|HAMAP-Rule:MF_03126}; GN Name=Adss1; Synonyms=Adssl1 {ECO:0000312|MGI:MGI:87947}; 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] (ISOFORM 1). RC TISSUE=Muscle; RX PubMed=1939273; DOI=10.1016/s0021-9258(18)54611-1; RA Guicherit O.M., Rudolph F.B., Kellems R.E., Cooper B.F.; RT "Molecular cloning and expression of a mouse muscle cDNA encoding RT adenylosuccinate synthetase."; RL J. Biol. Chem. 266:22582-22587(1991). RN [2] RP SEQUENCE REVISION. 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=Czech II; TISSUE=Mammary tumor; 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 [4] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. 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 [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen; 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). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS). RX PubMed=11560929; DOI=10.1074/jbc.m106294200; RA Iancu C.V., Borza T., Choe J.Y., Fromm H.J., Honzatko R.B.; RT "Recombinant mouse muscle adenylosuccinate synthetase: overexpression, RT kinetics, and crystal structure."; RL J. Biol. Chem. 276:42146-42152(2001). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH IMP AND GTP. RX PubMed=12004071; DOI=10.1074/jbc.m203730200; RA Iancu C.V., Borza T., Fromm H.J., Honzatko R.B.; RT "IMP, GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle RT adenylosuccinate synthetase."; RL J. Biol. Chem. 277:26779-26787(2002). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS). RX PubMed=12186864; DOI=10.1074/jbc.m204952200; RA Iancu C.V., Borza T., Fromm H.J., Honzatko R.B.; RT "Feedback inhibition and product complexes of recombinant mouse muscle RT adenylosuccinate synthetase."; RL J. Biol. Chem. 277:40536-40543(2002). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS). RX PubMed=16981730; DOI=10.1021/bi0607498; RA Iancu C.V., Zhou Y., Borza T., Fromm H.J., Honzatko R.B.; RT "Cavitation as a mechanism of substrate discrimination by adenylosuccinate RT synthetases."; RL Biochemistry 45:11703-11711(2006). CC -!- FUNCTION: Component of the purine nucleotide cycle (PNC), which CC interconverts IMP and AMP to regulate the nucleotide levels in various CC tissues, and which contributes to glycolysis and ammoniagenesis. CC Catalyzes the first 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_03126}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=Binds 1 Mg(2+) ion per subunit.; CC -!- ACTIVITY REGULATION: Weakly inhibited by AMP non-competitively to all CC substrates. Inhibited by IMP non-competitively with respect to GTP. CC Inhibited by fructose 1,6-bisphosphate competitively with respect to CC IMP. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=12 uM for GTP {ECO:0000269|PubMed:12482871}; CC KM=45 uM for IMP {ECO:0000269|PubMed:12482871}; CC KM=140 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_03126}. CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03126, CC ECO:0000269|PubMed:12004071}. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. CC Note=Partially associated with particulate fractions. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P28650-1; Sequence=Displayed; CC Name=2; CC IsoId=P28650-2; Sequence=VSP_008422; CC -!- TISSUE SPECIFICITY: High levels in muscle. CC -!- SIMILARITY: Belongs to the adenylosuccinate synthetase family. CC {ECO:0000255|HAMAP-Rule:MF_03126}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M74495; AAA82870.1; -; mRNA. DR EMBL; BC039943; AAH39943.1; -; mRNA. DR CCDS; CCDS26192.1; -. [P28650-1] DR PIR; A39317; AJMSDS. DR RefSeq; NP_031447.1; NM_007421.2. [P28650-1] DR PDB; 1IWE; X-ray; 2.10 A; A/B=1-457. DR PDB; 1J4B; X-ray; 2.50 A; A=1-457. DR PDB; 1LNY; X-ray; 2.20 A; A/B=1-457. DR PDB; 1LON; X-ray; 2.10 A; A=1-457. DR PDB; 1LOO; X-ray; 2.20 A; A=1-457. DR PDB; 1MEZ; X-ray; 2.40 A; A=1-457. DR PDB; 1MF0; X-ray; 2.50 A; A=1-457. DR PDB; 1MF1; X-ray; 2.70 A; A=1-457. DR PDB; 2DGN; X-ray; 2.40 A; A=1-457. DR PDBsum; 1IWE; -. DR PDBsum; 1J4B; -. DR PDBsum; 1LNY; -. DR PDBsum; 1LON; -. DR PDBsum; 1LOO; -. DR PDBsum; 1MEZ; -. DR PDBsum; 1MF0; -. DR PDBsum; 1MF1; -. DR PDBsum; 2DGN; -. DR AlphaFoldDB; P28650; -. DR SMR; P28650; -. DR BioGRID; 198010; 6. DR STRING; 10090.ENSMUSP00000021726; -. DR iPTMnet; P28650; -. DR PhosphoSitePlus; P28650; -. DR SwissPalm; P28650; -. DR jPOST; P28650; -. DR PaxDb; 10090-ENSMUSP00000136572; -. DR PeptideAtlas; P28650; -. DR ProteomicsDB; 302033; -. [P28650-1] DR ProteomicsDB; 302034; -. [P28650-2] DR Antibodypedia; 28209; 108 antibodies from 18 providers. DR DNASU; 11565; -. DR Ensembl; ENSMUST00000021726.8; ENSMUSP00000021726.7; ENSMUSG00000011148.15. [P28650-1] DR GeneID; 11565; -. DR KEGG; mmu:11565; -. DR UCSC; uc007peu.2; mouse. [P28650-1] DR AGR; MGI:87947; -. DR CTD; 122622; -. DR MGI; MGI:87947; Adss1. DR VEuPathDB; HostDB:ENSMUSG00000011148; -. DR eggNOG; KOG1355; Eukaryota. DR GeneTree; ENSGT00390000015553; -. DR HOGENOM; CLU_029848_0_0_1; -. DR InParanoid; P28650; -. DR OMA; TNARKWE; -. DR OrthoDB; 122722at2759; -. DR PhylomeDB; P28650; -. DR BRENDA; 6.3.4.4; 3474. DR Reactome; R-MMU-73817; Purine ribonucleoside monophosphate biosynthesis. DR UniPathway; UPA00075; UER00335. DR BioGRID-ORCS; 11565; 3 hits in 78 CRISPR screens. DR ChiTaRS; Adssl1; mouse. DR EvolutionaryTrace; P28650; -. DR PRO; PR:P28650; -. DR Proteomes; UP000000589; Chromosome 12. DR RNAct; P28650; protein. DR Bgee; ENSMUSG00000011148; Expressed in triceps brachii and 215 other cell types or tissues. DR ExpressionAtlas; P28650; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0051015; F:actin filament binding; ISO:MGI. DR GO; GO:0004019; F:adenylosuccinate synthase activity; IDA:MGI. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule. DR GO; GO:0003924; F:GTPase activity; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IBA:GO_Central. DR GO; GO:0044209; P:AMP salvage; IDA:MGI. DR GO; GO:0006531; P:aspartate metabolic process; ISO:MGI. DR GO; GO:0046040; P:IMP metabolic process; ISO:MGI. DR GO; GO:0006163; P:purine nucleotide metabolic process; IDA:MGI. DR CDD; cd03108; AdSS; 1. DR Gene3D; 3.40.440.10; Adenylosuccinate Synthetase, subunit A, domain 1; 1. DR Gene3D; 1.10.300.10; Adenylosuccinate Synthetase, subunit A, domain 2; 1. DR Gene3D; 3.90.170.10; Adenylosuccinate Synthetase, subunit A, domain 3; 1. DR HAMAP; MF_00011; Adenylosucc_synth; 1. DR HAMAP; MF_03126; Adenylosucc_synth_vert_basic; 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; IPR027509; AdSS_1_vert. DR InterPro; IPR027417; P-loop_NTPase. DR NCBIfam; TIGR00184; purA; 1. DR PANTHER; PTHR11846; ADENYLOSUCCINATE SYNTHETASE; 1. DR PANTHER; PTHR11846:SF2; ADENYLOSUCCINATE SYNTHETASE ISOZYME 1; 1. DR Pfam; PF00709; Adenylsucc_synt; 1. DR SMART; SM00788; Adenylsucc_synt; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS01266; ADENYLOSUCCIN_SYN_1; 1. DR PROSITE; PS00513; ADENYLOSUCCIN_SYN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; GTP-binding; Ligase; KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; KW Purine biosynthesis; Reference proteome. FT CHAIN 1..457 FT /note="Adenylosuccinate synthetase isozyme 1" FT /id="PRO_0000095133" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 43 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126" FT ACT_SITE 71 FT /note="Proton donor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126" FT BINDING 42..48 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 43..46 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT BINDING 43 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 43 FT /ligand="substrate" FT BINDING 68..71 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT BINDING 70..72 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 70 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 163 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_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 177 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 256 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_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 271 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_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 331..337 FT /ligand="substrate" FT BINDING 335 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_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 337 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 363..365 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126, FT ECO:0000269|PubMed:12004071" FT BINDING 445..448 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03126, FT ECO:0000269|PubMed:12004071" FT VAR_SEQ 136 FT /note="L -> LENEVPHEPLPSASLLPMCWLLAP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_008422" FT TURN 27..29 FT /evidence="ECO:0007829|PDB:1J4B" FT STRAND 33..42 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 46..54 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 58..62 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 71..74 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 79..85 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 87..90 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 94..98 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 102..104 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 106..117 FT /evidence="ECO:0007829|PDB:1IWE" FT TURN 118..120 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 127..131 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 139..155 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 164..166 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 167..175 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 182..185 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 189..205 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 214..228 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 229..231 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 235..244 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 250..253 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 258..260 FT /evidence="ECO:0007829|PDB:1IWE" FT TURN 262..264 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 278..284 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 288..290 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 291..304 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 306..308 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 317..325 FT /evidence="ECO:0007829|PDB:1IWE" FT TURN 331..333 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 344..354 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 357..362 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 364..367 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 371..381 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 384..388 FT /evidence="ECO:0007829|PDB:1LOO" FT HELIX 395..398 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 400..407 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 419..421 FT /evidence="ECO:0007829|PDB:1IWE" FT HELIX 424..437 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 441..445 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 447..449 FT /evidence="ECO:0007829|PDB:1IWE" FT TURN 450..452 FT /evidence="ECO:0007829|PDB:1IWE" FT STRAND 453..455 FT /evidence="ECO:0007829|PDB:1IWE" SQ SEQUENCE 457 AA; 50254 MW; EBEC85BF907B7FED CRC64; MSGTRASNDR PPGTGGVKRG RLQQEAAATG SRVTVVLGAQ WGDEGKGKVV DLLATDADIV SRCQGGNNAG HTVVVDGKEY DFHLLPSGII NTKAVSFIGN GVVIHLPGLF EEAEKNEKKG LKDWEKRLII SDRAHLVFDF HQAVDGLQEV QRQAQEGKNI GTTKKGIGPT YSSKAARTGL RICDLLSDFD EFSARFKNLA HQHQSMFPTL EIDVEGQLKR LKGFAERIRP MVRDGVYFMY EALHGPPKKV LVEGANAALL DIDFGTYPFV TSSNCTVGGV CTGLGIPPQN IGDVYGVVKA YTTRVGIGAF PTEQINEIGD LLQNRGHEWG VTTGRKRRCG WLDLMILRYA HMVNGFTALA LTKLDILDVL SEIKVGISYK LNGKRIPYFP ANQEILQKVE VEYETLPGWK ADTTGARKWE DLPPQAQSYV RFVENHMGVA VKWVGVGKSR ESMIQLF //