ID   PUR6_MOUSE              Reviewed;         425 AA.
AC   Q9DCL9; Q9CQ38;
DT   14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 4.
DT   02-SEP-2026, entry version 180.
DE   RecName: Full=Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase {ECO:0000250|UniProtKB:P22234};
DE            Short=PAICS {ECO:0000250|UniProtKB:P22234};
DE   Includes:
DE     RecName: Full=Phosphoribosylaminoimidazole carboxylase {ECO:0000250|UniProtKB:P22234};
DE              EC=4.1.1.21 {ECO:0000250|UniProtKB:P22234};
DE     AltName: Full=AIR carboxylase {ECO:0000250|UniProtKB:P22234};
DE              Short=AIRC {ECO:0000250|UniProtKB:P22234};
DE   Includes:
DE     RecName: Full=Phosphoribosylaminoimidazole succinocarboxamide synthetase {ECO:0000250|UniProtKB:P22234};
DE              EC=6.3.2.6 {ECO:0000250|UniProtKB:P22234};
DE     AltName: Full=SAICAR synthetase {ECO:0000250|UniProtKB:P22234};
GN   Name=Paics {ECO:0000312|MGI:MGI:1914304};
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=C57BL/6J; TISSUE=Heart, Kidney, and Mammary gland;
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 GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and Czech II; TISSUE=Brain;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-22, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA   Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT   "Large scale localization of protein phosphorylation by use of electron
RT   capture dissociation mass spectrometry.";
RL   Mol. Cell. Proteomics 8:904-912(2009).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, 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).
RN   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-36, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Bifunctional phosphoribosylaminoimidazole carboxylase and
CC       phosphoribosylaminoimidazole succinocarboxamide synthetase catalyzing
CC       two reactions of the de novo purine biosynthetic pathway.
CC       {ECO:0000250|UniProtKB:P22234}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-
CC         aspartate + ATP = (2S)-2-[5-amino-1-(5-phospho-beta-D-
CC         ribosyl)imidazole-4-carboxamido]succinate + ADP + phosphate + 2 H(+);
CC         Xref=Rhea:RHEA:22628, ChEBI:CHEBI:15378, ChEBI:CHEBI:29991,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58443,
CC         ChEBI:CHEBI:77657, ChEBI:CHEBI:456216; EC=6.3.2.6;
CC         Evidence={ECO:0000250|UniProtKB:P22234};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22629;
CC         Evidence={ECO:0000250|UniProtKB:P22234};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + H(+)
CC         = 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + CO2;
CC         Xref=Rhea:RHEA:10792, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:77657, ChEBI:CHEBI:137981; EC=4.1.1.21;
CC         Evidence={ECO:0000250|UniProtKB:P22234};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10794;
CC         Evidence={ECO:0000250|UniProtKB:P22234};
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC       amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-
CC       phospho-D-ribosyl)imidazole-4-carboxylate: step 1/2.
CC       {ECO:0000250|UniProtKB:P22234}.
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC       amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate from 5-amino-1-(5-
CC       phospho-D-ribosyl)imidazole (carboxylase route): step 1/1.
CC       {ECO:0000250|UniProtKB:P22234}.
CC   -!- SUBUNIT: Homooctamer. {ECO:0000250|UniProtKB:P22234}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the SAICAR synthetase
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the AIR carboxylase
CC       family. Class II subfamily. {ECO:0000305}.
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DR   EMBL; AK002669; BAB22273.1; -; mRNA.
DR   EMBL; AK010462; BAB26957.1; -; mRNA.
DR   EMBL; AK012118; BAB28044.1; -; mRNA.
DR   EMBL; AK146722; BAE27385.1; -; mRNA.
DR   EMBL; AK159398; BAE35051.1; -; mRNA.
DR   EMBL; AK166264; BAE38669.1; -; mRNA.
DR   EMBL; CH466524; EDL37918.1; -; Genomic_DNA.
DR   EMBL; BC018153; AAH18153.1; -; mRNA.
DR   EMBL; BC052691; AAH52691.1; -; mRNA.
DR   CCDS; CCDS19367.1; -.
DR   RefSeq; NP_001343900.1; NM_001356971.1.
DR   RefSeq; NP_001343901.1; NM_001356972.1.
DR   RefSeq; NP_001343902.1; NM_001356973.1.
DR   RefSeq; NP_080215.1; NM_025939.3.
DR   RefSeq; XP_006535246.1; XM_006535183.4.
DR   AlphaFoldDB; Q9DCL9; -.
DR   SMR; Q9DCL9; -.
DR   BioGRID; 211906; 32.
DR   FunCoup; Q9DCL9; 2037.
DR   IntAct; Q9DCL9; 3.
DR   STRING; 10090.ENSMUSP00000031160; -.
DR   GlyGen; Q9DCL9; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; Q9DCL9; -.
DR   PhosphoSitePlus; Q9DCL9; -.
DR   SwissPalm; Q9DCL9; -.
DR   CPTAC; non-CPTAC-3741; -.
DR   jPOST; Q9DCL9; -.
DR   PaxDb; 10090-ENSMUSP00000031160; -.
DR   PeptideAtlas; Q9DCL9; -.
DR   ProteomicsDB; 302032; -.
DR   Pumba; Q9DCL9; -.
DR   Antibodypedia; 24027; 351 antibodies from 32 providers.
DR   DNASU; 67054; -.
DR   Ensembl; ENSMUST00000031160.16; ENSMUSP00000031160.10; ENSMUSG00000029247.18.
DR   Ensembl; ENSMUST00000117536.8; ENSMUSP00000112879.2; ENSMUSG00000029247.18.
DR   Ensembl; ENSMUST00000120912.8; ENSMUSP00000113483.2; ENSMUSG00000029247.18.
DR   GeneID; 67054; -.
DR   KEGG; mmu:67054; -.
DR   UCSC; uc008xvn.2; mouse.
DR   AGR; MGI:1914304; -.
DR   CTD; 10606; -.
DR   MGI; MGI:1914304; Paics.
DR   VEuPathDB; HostDB:ENSMUSG00000029247; -.
DR   eggNOG; KOG2835; Eukaryota.
DR   GeneTree; ENSGT00390000010172; -.
DR   HOGENOM; CLU_061495_1_0_1; -.
DR   InParanoid; Q9DCL9; -.
DR   OMA; WSDEQII; -.
DR   OrthoDB; 9991235at2759; -.
DR   PhylomeDB; Q9DCL9; -.
DR   Reactome; R-MMU-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   UniPathway; UPA00074; UER00130.
DR   UniPathway; UPA00074; UER00131.
DR   BioGRID-ORCS; 67054; 25 hits in 82 CRISPR screens.
DR   CD-CODE; CE726F99; Postsynaptic density.
DR   PRO; PR:Q9DCL9; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q9DCL9; protein.
DR   Bgee; ENSMUSG00000029247; Expressed in gonadal ridge and 268 other cell types or tissues.
DR   ExpressionAtlas; Q9DCL9; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:GO_Central.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; ISO:GO_Central.
DR   GO; GO:0004638; F:phosphoribosylaminoimidazole carboxylase activity; ISS:UniProtKB.
DR   GO; GO:0004639; F:phosphoribosylaminoimidazolesuccinocarboxamide synthase activity; ISS:UniProtKB.
DR   GO; GO:0044208; P:'de novo' AMP biosynthetic process; ISO:MGI.
DR   GO; GO:0006189; P:'de novo' IMP biosynthetic process; ISO:MGI.
DR   GO; GO:0097294; P:'de novo' XMP biosynthetic process; ISO:MGI.
DR   GO; GO:0006177; P:GMP biosynthetic process; ISO:MGI.
DR   GO; GO:0009113; P:purine nucleobase biosynthetic process; ISS:UniProtKB.
DR   CDD; cd01416; SAICAR_synt_Ade5; 1.
DR   FunFam; 3.30.200.20:FF:000183; Probable multifunctional protein ADE2; 1.
DR   FunFam; 3.30.470.20:FF:000020; Probable multifunctional protein ADE2; 1.
DR   FunFam; 3.40.50.1970:FF:000006; Probable multifunctional protein ADE2; 1.
DR   Gene3D; 3.40.50.1970; -; 1.
DR   Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR   Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1.
DR   HAMAP; MF_02045; PurE_classII; 1.
DR   HAMAP; MF_00137; SAICAR_synth; 1.
DR   InterPro; IPR033626; PurE_classII.
DR   InterPro; IPR000031; PurE_dom.
DR   InterPro; IPR028923; SAICAR_synt/ADE2_N.
DR   InterPro; IPR018236; SAICAR_synthetase_CS.
DR   PANTHER; PTHR43599:SF11; BIFUNCTIONAL PHOSPHORIBOSYLAMINOIMIDAZOLE CARBOXYLASE_PHOSPHORIBOSYLAMINOIMIDAZOLE SUCCINOCARBOXAMIDE SYNTHETASE; 1.
DR   PANTHER; PTHR43599; MULTIFUNCTIONAL PROTEIN ADE2; 1.
DR   Pfam; PF00731; AIRC; 1.
DR   Pfam; PF01259; SAICAR_synt; 1.
DR   SMART; SM01001; AIRC; 1.
DR   SUPFAM; SSF52255; N5-CAIR mutase (phosphoribosylaminoimidazole carboxylase, PurE); 1.
DR   SUPFAM; SSF56104; SAICAR synthase-like; 1.
DR   PROSITE; PS01057; SAICAR_SYNTHETASE_1; 1.
DR   PROSITE; PS01058; SAICAR_SYNTHETASE_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Decarboxylase; Ligase; Lyase;
KW   Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW   Purine biosynthesis; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   CHAIN           2..425
FT                   /note="Bifunctional phosphoribosylaminoimidazole
FT                   carboxylase/phosphoribosylaminoimidazole succinocarboxamide
FT                   synthetase"
FT                   /id="PRO_0000075031"
FT   REGION          2..260
FT                   /note="SAICAR synthetase domain"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   REGION          261..266
FT                   /note="Linker"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   REGION          267..425
FT                   /note="AIR carboxylase domain"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   BINDING         332
FT                   /ligand="CO2"
FT                   /ligand_id="ChEBI:CHEBI:16526"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   MOD_RES         22
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:19131326"
FT   MOD_RES         36
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         107
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   MOD_RES         238
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   MOD_RES         247
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   MOD_RES         274
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22234"
FT   CONFLICT        5
FT                   /note="V -> Y (in Ref. 1; BAB22273)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   425 AA;  47006 MW;  CD2A4323EC02B218 CRC64;
     MATAVVVNIG KKLYEGKTKE VYELLDTPGR VLLQSKDQIT AGNAARKNHL EGKAAISNKI
     TSCIFQLLQE AGIKTAFTKK CGETAFIAPQ CEMIPIEWVC RRIATGSFLK RNPGVQEGYK
     FYPPKVEMFF KDDANNDPQW SEEQLIAAKF CFAGLVIGQT EVDIMSHATQ AIFEILEKSW
     LPQDCTLVDM KIEFGVDVTT KEIVLADVID NDSWRLWPSG DRSQQKDKQS YRDLKEVTPE
     GLQMVKKNFE WVADRVELLL KSDSQCRVVV LMGSTSDLGH CEKIKKACGN FGIPCELRVT
     SAHKGPDETL RIKAEYEGDG IPTVFVSVAG RSNGLGPVLS GNTAYPVISC PPITPDWGAQ
     DVWSSLRLPS GIGCSTILSP EGSAQFAAQI FGLNNHLVWA KLRASILNTW ISLKQADKKV
     RQCNL
//