ID   PURA_YEAST              Reviewed;         433 AA.
AC   P80210; D6W0X0;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   04-NOV-2026, entry version 205.
DE   RecName: Full=Adenylosuccinate synthetase {ECO:0000255|HAMAP-Rule:MF_03125};
DE            Short=AMPSase {ECO:0000255|HAMAP-Rule:MF_03125};
DE            Short=AS-synthetase;
DE            Short=AdSS {ECO:0000255|HAMAP-Rule:MF_03125};
DE            EC=6.3.4.4 {ECO:0000255|HAMAP-Rule:MF_03125};
DE   AltName: Full=IMP--aspartate ligase {ECO:0000255|HAMAP-Rule:MF_03125};
GN   Name=ADE12 {ECO:0000255|HAMAP-Rule:MF_03125};
GN   OrderedLocusNames=YNL220W; ORFNames=N1290;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7603488;
RA   Andreichuk I.V., Shabes A.V., Ryzhova T.A., Kotova I.A., Domkin V.D.;
RT   "Saccharomyces cerevisiae ADE12 gene, coding for adenylosuccinate
RT   synthetase (EC 6.3.4.4). Cloning, sequencing, expression, and
RT   superproduction.";
RL   Mol. Genet. Mikrobiol. Virusol. 1:21-28(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], INHIBITION BY SS-DNA, AND SUBUNIT.
RX   PubMed=8706758; DOI=10.1111/j.1432-1033.1996.0487u.x;
RA   Gallert K.C., Ohanjan T., Daignan-Fornier B., Lottspeich F., Krauss G.;
RT   "Enzymatic properties and inhibition by single-stranded autonomously
RT   replicating sequences of adenylosuccinate synthase from Saccharomyces
RT   cerevisiae.";
RL   Eur. J. Biochem. 239:487-493(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169873; DOI=10.1038/387s093;
RA   Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA   Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA   Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA   Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA   Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA   Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA   Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA   Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA   Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA   Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA   Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA   Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA   Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA   Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA   Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA   Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA   Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT   evolutionary implications.";
RL   Nature 387:93-98(1997).
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [5]
RP   PROTEIN SEQUENCE OF 2-23 AND 234-245.
RX   PubMed=8376380; DOI=10.1016/s0021-9258(20)80713-3;
RA   Zeidler R., Hobert O., Johannes L., Faulhammer H., Krauss G.;
RT   "Characterization of two novel single-stranded DNA-specific autonomously
RT   replicating sequence-binding proteins from Saccharomyces cerevisiae, one of
RT   which is adenylosuccinate synthetase.";
RL   J. Biol. Chem. 268:20191-20197(1993).
RN   [6]
RP   PROTEIN SEQUENCE OF 2-6, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP   AND ACTIVITY REGULATION.
RX   PubMed=10417315; DOI=10.1042/bj3410537;
RA   Lipps G., Krauss G.;
RT   "Adenylosuccinate synthase from Saccharomyces cerevisiae: homologous
RT   overexpression, purification and characterization of the recombinant
RT   protein.";
RL   Biochem. J. 341:537-543(1999).
RN   [7]
RP   FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX   PubMed=9668204;
RA   Ryzhova T.A., Andreichuk Y.V., Domkin V.D.;
RT   "Adenylosuccinate synthetase of the yeast Saccharomyces cerevisiae:
RT   purification and properties.";
RL   Biochemistry (Mosc.) 63:650-656(1998).
RN   [8]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [9]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
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:10417315, ECO:0000269|PubMed:9668204}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=IMP + L-aspartate + GTP = N(6)-(1,2-dicarboxyethyl)-AMP + GDP
CC         + phosphate + 2 H(+); Xref=Rhea:RHEA:15753, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:29991, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57567, ChEBI:CHEBI:58053, ChEBI:CHEBI:58189; EC=6.3.4.4;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03125};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03125};
CC       Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03125};
CC   -!- ACTIVITY REGULATION: Inhibited by GMP. Inhibited by chloride. Inhibited
CC       in a highly specific manner by the binding of a 44-base DNA
CC       oligonucleotide carrying the ARS core consensus sequence.
CC       {ECO:0000269|PubMed:10417315}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1650 uM for L-aspartate {ECO:0000269|PubMed:10417315,
CC         ECO:0000269|PubMed:9668204};
CC         KM=200 uM for IMP {ECO:0000269|PubMed:10417315,
CC         ECO:0000269|PubMed:9668204};
CC         KM=1650 uM for GTP {ECO:0000269|PubMed:10417315,
CC         ECO:0000269|PubMed:9668204};
CC       pH dependence:
CC         Optimum pH is 8.0. {ECO:0000269|PubMed:10417315,
CC         ECO:0000269|PubMed:9668204};
CC       Temperature dependence:
CC         Optimum temperature is 35 degrees Celsius.
CC         {ECO:0000269|PubMed:10417315, ECO:0000269|PubMed:9668204};
CC   -!- PATHWAY: Purine metabolism; AMP biosynthesis via de novo pathway; AMP
CC       from IMP: step 1/2. {ECO:0000255|HAMAP-Rule:MF_03125}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03125,
CC       ECO:0000269|PubMed:10417315, ECO:0000269|PubMed:8706758,
CC       ECO:0000269|PubMed:9668204}.
CC   -!- INTERACTION:
CC       P80210; P33203: PRP40; NbExp=2; IntAct=EBI-14267, EBI-701;
CC       P80210; P39940: RSP5; NbExp=2; IntAct=EBI-14267, EBI-16219;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03125,
CC       ECO:0000269|PubMed:14562095}.
CC   -!- MISCELLANEOUS: Present with 56800 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the adenylosuccinate synthetase family.
CC       {ECO:0000255|HAMAP-Rule:MF_03125}.
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DR   EMBL; L22185; AAA91338.1; -; Genomic_DNA.
DR   EMBL; Z48671; CAA88590.1; -; Genomic_DNA.
DR   EMBL; Z71496; CAA96123.1; -; Genomic_DNA.
DR   EMBL; BK006947; DAA10336.1; -; Genomic_DNA.
DR   PIR; S48515; S48515.
DR   RefSeq; NP_014179.1; NM_001183058.1.
DR   AlphaFoldDB; P80210; -.
DR   SMR; P80210; -.
DR   BioGRID; 35616; 166.
DR   DIP; DIP-4286N; -.
DR   FunCoup; P80210; 1051.
DR   IntAct; P80210; 16.
DR   STRING; 4932.YNL220W; -.
DR   GlyGen; P80210; 1 site.
DR   iPTMnet; P80210; -.
DR   PaxDb; 4932-YNL220W; -.
DR   PeptideAtlas; P80210; -.
DR   EnsemblFungi; YNL220W_mRNA; YNL220W; YNL220W.
DR   GeneID; 855501; -.
DR   KEGG; sce:YNL220W; -.
DR   AGR; SGD:S000005164; -.
DR   SGD; S000005164; ADE12.
DR   VEuPathDB; FungiDB:YNL220W; -.
DR   eggNOG; KOG1355; Eukaryota.
DR   HOGENOM; CLU_029848_3_2_1; -.
DR   InParanoid; P80210; -.
DR   OMA; AAAMHCV; -.
DR   OrthoDB; 10265645at2759; -.
DR   BioCyc; MetaCyc:YNL220W-MONOMER; -.
DR   BioCyc; YEAST:YNL220W-MONOMER; -.
DR   Reactome; R-SCE-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   UniPathway; UPA00075; UER00335.
DR   BioGRID-ORCS; 855501; 8 hits in 10 CRISPR screens.
DR   PRO; PR:P80210; -.
DR   Proteomes; UP000002311; Chromosome XIV.
DR   RNAct; P80210; protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0004019; F:adenylosuccinate synthase activity; IDA:SGD.
DR   GO; GO:0003688; F:DNA replication origin binding; IDA:SGD.
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; IBA:GO_Central.
DR   GO; GO:0046040; P:IMP metabolic process; IBA:GO_Central.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IMP:SGD.
DR   CDD; cd03108; AdSS; 1.
DR   FunFam; 3.90.170.10:FF:000001; Adenylosuccinate synthetase; 1.
DR   FunFam; 1.10.300.10:FF:000002; Adenylosuccinate synthetase, chloroplastic; 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   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; IPR027417; P-loop_NTPase.
DR   NCBIfam; NF002223; PRK01117.1; 1.
DR   NCBIfam; TIGR00184; purA; 1.
DR   PANTHER; PTHR11846; ADENYLOSUCCINATE SYNTHETASE; 1.
DR   PANTHER; PTHR11846:SF0; ADENYLOSUCCINATE SYNTHETASE; 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   Cytoplasm; Direct protein sequencing; GTP-binding; Ligase; Magnesium;
KW   Metal-binding; Nucleotide-binding; Purine biosynthesis; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:10417315,
FT                   ECO:0000269|PubMed:8376380"
FT   CHAIN           2..433
FT                   /note="Adenylosuccinate synthetase"
FT                   /id="PRO_0000095138"
FT   ACT_SITE        12
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   ACT_SITE        40
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         11..17
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         12..15
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_03125"
FT   BINDING         12
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         37..40
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_03125"
FT   BINDING         39..41
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         39
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         134
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_03125"
FT   BINDING         148
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         230
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_03125"
FT   BINDING         245
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_03125"
FT   BINDING         305..311
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         309
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_03125"
FT   BINDING         311
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         337..339
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   BINDING         419..421
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT   CONFLICT        237
FT                   /note="D -> G (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   433 AA;  48279 MW;  800E0F4062D9856F CRC64;
     MVNVVLGSQW GDEGKGKLVD LLVGKYDIVA RCAGGNNAGH TIVVDGVKYD FHMLPSGLVN
     PNCQNLLGNG VVIHVPSFFK ELETLEAKGL KNARSRLFVS SRAHLVFDFH QVTDKLRELE
     LSGRSKDGKN IGTTGKGIGP TYSTKASRSG LRVHHLVNDQ PGAWEEFVAR YKRLLETRRQ
     RYGDFEYDFE AKLAEYKKLR EQLKPFVVDS VVFMHNAIEA KKKILVEGAN ALMLDIDFGT
     YPYVTSSNTG IGGVLTGLGI PPRTIDEIYG VVKAYTTRVG EGPFPTEQLN ENGEKLQTIG
     AEFGVTTGRK RRCGWLDLVV LKYSTLINGY TSLNITKLDV LDTFKEIPVG ISYSIQGKKL
     DLFPEDLNIL GKVEVEYKVL PGWDQDITKI TKYEDLPENA KKYLKYIEDF VGVPVEWVGT
     GPARESMLHK EIK
//