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 31-MAY-2011, entry version 109. DE RecName: Full=Adenylosuccinate synthetase isozyme 1; DE Short=AMPSase 1; DE Short=AdSS 1; DE EC=6.3.4.4; DE AltName: Full=Adenylosuccinate synthetase, basic isozyme; DE AltName: Full=Adenylosuccinate synthetase, muscle isozyme; DE Short=M-type adenylosuccinate synthetase; DE AltName: Full=IMP--aspartate ligase 1; GN Name=Adssl1; Synonyms=Adss1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Muscle; RX MEDLINE=92042206; PubMed=1939273; 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 MEDLINE=94140883; PubMed=8308018; 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 RT encoding the '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 RT project: 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 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 [6] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH IMP AND GTP. RX MEDLINE=22128853; 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 [7] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS). RX MEDLINE=22287400; 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 [8] 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 RT adenylosuccinate 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 CC various tissues, and which contributes to glycolysis and CC ammoniagenesis. Catalyzes the first commited step in the CC biosynthesis of AMP from IMP. CC -!- CATALYTIC ACTIVITY: GTP + IMP + L-aspartate = GDP + phosphate + CC N(6)-(1,2-dicarboxyethyl)-AMP. CC -!- COFACTOR: Binds 1 magnesium ion per subunit. CC -!- ENZYME REGULATION: Weakly inhibited by AMP non-competitively to CC all substrates. Inhibited by IMP non-competitively with respect to CC GTP. Inhibited by fructose 1,6-bisphosphate competitively with CC respect to IMP. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=12 uM for GTP; CC KM=45 uM for IMP; CC KM=140 uM for L-aspartate; CC pH dependence: CC Optimum pH is 6.6-6.9; CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via de novo pathway; CC AMP from IMP: step 1/2. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane CC protein. 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 Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: High levels in muscle. CC -!- SIMILARITY: Belongs to the adenylosuccinate synthetase family. 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 IPI; IPI00123190; -. DR IPI; IPI00229690; -. DR PIR; A39317; AJMSDS. DR RefSeq; NP_031447.1; NM_007421.2. DR UniGene; Mm.3440; -. 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 ProteinModelPortal; P28650; -. DR SMR; P28650; 27-457. DR STRING; P28650; -. DR PhosphoSite; P28650; -. DR PRIDE; P28650; -. DR Ensembl; ENSMUST00000021726; ENSMUSP00000021726; ENSMUSG00000011148. DR GeneID; 11565; -. DR KEGG; mmu:11565; -. DR UCSC; uc007peu.1; mouse. DR CTD; 11565; -. DR MGI; MGI:87947; Adssl1. DR eggNOG; roNOG05223; -. DR GeneTree; ENSGT00390000015553; -. DR HOVERGEN; HBG053768; -. DR OrthoDB; EOG4P5K90; -. DR PhylomeDB; P28650; -. DR DrugBank; DB00131; Adenosine monophosphate. DR NextBio; 279066; -. DR ArrayExpress; P28650; -. DR Bgee; P28650; -. DR CleanEx; MM_ADSSL1; -. DR Genevestigator; P28650; -. DR GermOnline; ENSMUSG00000011148; Mus musculus. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004019; F:adenylosuccinate synthase activity; IDA:MGI. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0005515; F:protein binding; IPI:MGI. DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW. DR InterPro; IPR018220; Adenylosuccinate_synthase_AS. DR InterPro; IPR001114; Adenylosuccinate_synthetase. DR PANTHER; PTHR11846; Asucc_synthtase; 1. DR Pfam; PF00709; Adenylsucc_synt; 1. DR SMART; SM00788; Adenylsucc_synt; 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 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; KW GTP-binding; Ligase; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Purine biosynthesis. FT CHAIN 1 457 Adenylosuccinate synthetase isozyme 1. FT /FTId=PRO_0000095133. FT NP_BIND 42 48 GTP. FT NP_BIND 70 72 GTP. FT NP_BIND 363 365 GTP. FT NP_BIND 445 448 GTP. FT REGION 43 46 IMP binding. FT REGION 68 71 IMP binding. FT REGION 331 337 Substrate binding. FT ACT_SITE 43 43 Proton acceptor (By similarity). FT ACT_SITE 71 71 Proton donor (By similarity). FT METAL 43 43 Magnesium. FT METAL 70 70 Magnesium; via carbonyl oxygen. FT BINDING 43 43 Substrate. FT BINDING 163 163 IMP. FT BINDING 177 177 IMP; shared with dimeric partner. FT BINDING 256 256 IMP. FT BINDING 271 271 IMP. FT BINDING 335 335 IMP. FT BINDING 337 337 GTP. FT MOD_RES 388 388 Phosphotyrosine (By similarity). FT VAR_SEQ 136 136 L -> LENEVPHEPLPSASLLPMCWLLAP (in isoform FT 2). FT /FTId=VSP_008422. FT STRAND 33 42 FT HELIX 46 54 FT STRAND 58 62 FT STRAND 71 74 FT STRAND 79 85 FT HELIX 87 90 FT STRAND 94 98 FT STRAND 102 104 FT HELIX 106 117 FT TURN 118 120 FT HELIX 124 126 FT STRAND 127 131 FT HELIX 139 155 FT STRAND 164 166 FT HELIX 167 175 FT HELIX 182 185 FT HELIX 189 205 FT HELIX 214 228 FT HELIX 229 231 FT HELIX 235 244 FT STRAND 250 253 FT HELIX 258 260 FT TURN 262 264 FT HELIX 278 284 FT HELIX 288 290 FT STRAND 291 304 FT STRAND 306 308 FT HELIX 317 325 FT TURN 331 333 FT STRAND 338 340 FT HELIX 344 354 FT STRAND 357 362 FT HELIX 364 367 FT STRAND 371 381 FT HELIX 395 398 FT STRAND 400 407 FT HELIX 419 421 FT HELIX 424 437 FT STRAND 441 445 FT STRAND 447 449 FT TURN 450 452 FT STRAND 453 455 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 //