PUR6_HUMAN
ID PUR6_HUMAN Reviewed; 425 AA.
AC P22234; E9PDH9; Q68CQ5;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase {ECO:0000305|PubMed:17224163, ECO:0000305|PubMed:31600779};
DE Short=PAICS {ECO:0000303|PubMed:17224163, ECO:0000303|PubMed:31600779};
DE Includes:
DE RecName: Full=Phosphoribosylaminoimidazole carboxylase {ECO:0000305|PubMed:31600779};
DE EC=4.1.1.21 {ECO:0000269|PubMed:17224163, ECO:0000269|PubMed:31600779};
DE AltName: Full=AIR carboxylase {ECO:0000303|PubMed:17224163, ECO:0000303|PubMed:31600779};
DE Short=AIRC {ECO:0000303|PubMed:17224163, ECO:0000303|PubMed:31600779};
DE Includes:
DE RecName: Full=Phosphoribosylaminoimidazole succinocarboxamide synthetase {ECO:0000305|PubMed:31600779};
DE EC=6.3.2.6 {ECO:0000269|PubMed:31600779};
DE AltName: Full=SAICAR synthetase {ECO:0000303|PubMed:17224163};
GN Name=PAICS {ECO:0000312|HGNC:HGNC:8587};
GN Synonyms=ADE2 {ECO:0000303|PubMed:2253271}, AIRC, PAIS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2253271; DOI=10.1007/bf00318209;
RA Minet M., Lacroute F.;
RT "Cloning and sequencing of a human cDNA coding for a multifunctional
RT polypeptide of the purine pathway by complementation of the ade2-101 mutant
RT in Saccharomyces cerevisiae.";
RL Curr. Genet. 18:287-291(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Placenta;
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 [6]
RP PROTEIN SEQUENCE OF 2-11, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V., Potts A., Brablan J., Quadroni M.;
RL Submitted (JUL-2004) to UniProtKB.
RN [7]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=2183217; DOI=10.1073/pnas.87.8.2916;
RA Schild D., Brake A.J., Kiefer M.C., Young D., Barr P.J.;
RT "Cloning of three human multifunctional de novo purine biosynthetic genes
RT by functional complementation of yeast mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2916-2920(1990).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND THR-238, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND SER-107, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-247, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27; SER-107; THR-238 AND
RP SER-274, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23] {ECO:0007744|PDB:2H31}
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH CARBON DIOXIDE,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, REGION, AND MUTAGENESIS OF HIS-303;
RP SER-332; GLY-334 AND SER-400.
RX PubMed=17224163; DOI=10.1016/j.jmb.2006.12.027;
RA Li S.-X., Tong Y.-P., Xie X.-C., Wang Q.-H., Zhou H.-N., Han Y.,
RA Zhang Z.-Y., Gao W., Li S.-G., Zhang X.C., Bi R.-C.;
RT "Octameric structure of the human bifunctional enzyme PAICS in purine
RT biosynthesis.";
RL J. Mol. Biol. 366:1603-1614(2007).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, VARIANT ARG-53, AND CHARACTERIZATION
RP OF VARIANT ARG-53.
RX PubMed=31600779; DOI=10.1093/hmg/ddz237;
RA Pelet A., Skopova V., Steuerwald U., Baresova V., Zarhrate M., Plaza J.M.,
RA Hnizda A., Krijt M., Souckova O., Wibrand F., Andorsdottir G., Joensen F.,
RA Sedlak D., Bleyer A.J., Kmoch S., Lyonnet S., Zikanova M.;
RT "PAICS deficiency, a new defect of de novo purine synthesis resulting in
RT multiple congenital anomalies and fatal outcome.";
RL Hum. Mol. Genet. 28:3805-3814(2019).
CC -!- FUNCTION: Bifunctional phosphoribosylaminoimidazole carboxylase and
CC phosphoribosylaminoimidazole succinocarboxamide synthetase catalyzing
CC two reactions of the de novo purine biosynthetic pathway.
CC {ECO:0000269|PubMed:17224163, ECO:0000269|PubMed:2183217,
CC ECO:0000269|PubMed:31600779}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + ATP +
CC L-aspartate = (2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-
CC 4-carboxamido]succinate + ADP + 2 H(+) + phosphate;
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:0000269|PubMed:17224163};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22629;
CC Evidence={ECO:0000269|PubMed:31600779};
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:0000269|PubMed:17224163, ECO:0000269|PubMed:31600779};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10794;
CC Evidence={ECO:0000269|PubMed:31600779};
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:0000305|PubMed:31600779}.
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:0000305|PubMed:31600779}.
CC -!- SUBUNIT: Homooctamer. {ECO:0000269|PubMed:17224163}.
CC -!- INTERACTION:
CC P22234; Q16543: CDC37; NbExp=3; IntAct=EBI-712261, EBI-295634;
CC P22234; P51116: FXR2; NbExp=4; IntAct=EBI-712261, EBI-740459;
CC P22234; Q969R5: L3MBTL2; NbExp=6; IntAct=EBI-712261, EBI-739909;
CC P22234; Q8TBB1: LNX1; NbExp=4; IntAct=EBI-712261, EBI-739832;
CC P22234; Q6ZVK8: NUDT18; NbExp=3; IntAct=EBI-712261, EBI-740486;
CC P22234; P22234: PAICS; NbExp=7; IntAct=EBI-712261, EBI-712261;
CC P22234; O75928-2: PIAS2; NbExp=3; IntAct=EBI-712261, EBI-348567;
CC P22234; C9JJ79: PILRA; NbExp=3; IntAct=EBI-712261, EBI-12117156;
CC P22234; Q9Y4B4: RAD54L2; NbExp=3; IntAct=EBI-712261, EBI-948156;
CC P22234; P78317: RNF4; NbExp=3; IntAct=EBI-712261, EBI-2340927;
CC P22234; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-712261, EBI-10180829;
CC P22234; Q9UBW7: ZMYM2; NbExp=3; IntAct=EBI-712261, EBI-2797576;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P22234-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P22234-2; Sequence=VSP_041265;
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; X53793; CAA37801.1; -; mRNA.
DR EMBL; BT006988; AAP35634.1; -; mRNA.
DR EMBL; CR749824; CAH18683.1; -; mRNA.
DR EMBL; AC068620; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC114766; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010273; AAH10273.1; -; mRNA.
DR EMBL; BC019255; AAH19255.1; -; mRNA.
DR CCDS; CCDS47060.1; -. [P22234-2]
DR CCDS; CCDS47061.1; -. [P22234-1]
DR PIR; S14147; S14147.
DR RefSeq; NP_001072992.1; NM_001079524.1. [P22234-1]
DR RefSeq; NP_001072993.1; NM_001079525.1. [P22234-2]
DR RefSeq; NP_006443.1; NM_006452.3. [P22234-1]
DR PDB; 2H31; X-ray; 2.80 A; A=1-425.
DR PDB; 6YB8; X-ray; 2.36 A; A/B=1-425.
DR PDB; 6YB9; X-ray; 2.41 A; A/B=1-425.
DR PDBsum; 2H31; -.
DR PDBsum; 6YB8; -.
DR PDBsum; 6YB9; -.
DR AlphaFoldDB; P22234; -.
DR SMR; P22234; -.
DR BioGRID; 115852; 177.
DR IntAct; P22234; 63.
DR MINT; P22234; -.
DR STRING; 9606.ENSP00000382595; -.
DR BindingDB; P22234; -.
DR ChEMBL; CHEMBL5922; -.
DR DrugBank; DB00128; Aspartic acid.
DR GlyGen; P22234; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P22234; -.
DR MetOSite; P22234; -.
DR PhosphoSitePlus; P22234; -.
DR SwissPalm; P22234; -.
DR BioMuta; PAICS; -.
DR DMDM; 131628; -.
DR EPD; P22234; -.
DR jPOST; P22234; -.
DR MassIVE; P22234; -.
DR MaxQB; P22234; -.
DR PaxDb; P22234; -.
DR PeptideAtlas; P22234; -.
DR PRIDE; P22234; -.
DR ProteomicsDB; 53968; -. [P22234-1]
DR ProteomicsDB; 53969; -. [P22234-2]
DR Antibodypedia; 24027; 347 antibodies from 31 providers.
DR DNASU; 10606; -.
DR Ensembl; ENST00000264221.6; ENSP00000264221.2; ENSG00000128050.9. [P22234-1]
DR Ensembl; ENST00000399688.7; ENSP00000382595.3; ENSG00000128050.9. [P22234-2]
DR Ensembl; ENST00000512576.3; ENSP00000421096.1; ENSG00000128050.9. [P22234-1]
DR GeneID; 10606; -.
DR KEGG; hsa:10606; -.
DR MANE-Select; ENST00000512576.3; ENSP00000421096.1; NM_001079524.2; NP_001072992.1.
DR UCSC; uc003hbs.1; human. [P22234-1]
DR CTD; 10606; -.
DR DisGeNET; 10606; -.
DR GeneCards; PAICS; -.
DR HGNC; HGNC:8587; PAICS.
DR HPA; ENSG00000128050; Low tissue specificity.
DR MIM; 172439; gene.
DR neXtProt; NX_P22234; -.
DR OpenTargets; ENSG00000128050; -.
DR PharmGKB; PA32914; -.
DR VEuPathDB; HostDB:ENSG00000128050; -.
DR eggNOG; KOG2835; Eukaryota.
DR GeneTree; ENSGT00390000010172; -.
DR InParanoid; P22234; -.
DR OMA; WSDEQII; -.
DR OrthoDB; 566769at2759; -.
DR PhylomeDB; P22234; -.
DR TreeFam; TF106384; -.
DR BioCyc; MetaCyc:HS05155-MON; -.
DR PathwayCommons; P22234; -.
DR Reactome; R-HSA-73817; Purine ribonucleoside monophosphate biosynthesis.
DR SignaLink; P22234; -.
DR SIGNOR; P22234; -.
DR UniPathway; UPA00074; UER00130.
DR UniPathway; UPA00074; UER00131.
DR BioGRID-ORCS; 10606; 231 hits in 1044 CRISPR screens.
DR ChiTaRS; PAICS; human.
DR EvolutionaryTrace; P22234; -.
DR GenomeRNAi; 10606; -.
DR Pharos; P22234; Tchem.
DR PRO; PR:P22234; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P22234; protein.
DR Bgee; ENSG00000128050; Expressed in ventricular zone and 205 other tissues.
DR ExpressionAtlas; P22234; baseline and differential.
DR Genevisible; P22234; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043727; F:5-amino-4-imidazole carboxylate lyase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004638; F:phosphoribosylaminoimidazole carboxylase activity; IDA:MGI.
DR GO; GO:0004639; F:phosphoribosylaminoimidazolesuccinocarboxamide synthase activity; IDA:MGI.
DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IDA:MGI.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IDA:MGI.
DR GO; GO:0097294; P:'de novo' XMP biosynthetic process; IDA:MGI.
DR GO; GO:0006177; P:GMP biosynthetic process; IDA:MGI.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IDA:UniProtKB.
DR DisProt; DP02794; -.
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 Pfam; PF00731; AIRC; 1.
DR Pfam; PF01259; SAICAR_synt; 1.
DR SMART; SM01001; AIRC; 1.
DR TIGRFAMs; TIGR01162; purE; 1.
DR PROSITE; PS01057; SAICAR_SYNTHETASE_1; 1.
DR PROSITE; PS01058; SAICAR_SYNTHETASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Decarboxylase; Direct protein sequencing; Ligase; Lyase;
KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Purine biosynthesis; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..425
FT /note="Bifunctional phosphoribosylaminoimidazole
FT carboxylase/phosphoribosylaminoimidazole succinocarboxamide
FT synthetase"
FT /id="PRO_0000075030"
FT REGION 2..260
FT /note="SAICAR synthetase domain"
FT /evidence="ECO:0000305|PubMed:17224163,
FT ECO:0007744|PDB:2H31"
FT REGION 261..266
FT /note="Linker"
FT /evidence="ECO:0000305|PubMed:17224163,
FT ECO:0007744|PDB:2H31"
FT REGION 267..425
FT /note="AIR carboxylase domain"
FT /evidence="ECO:0000269|PubMed:17224163,
FT ECO:0007744|PDB:2H31"
FT BINDING 332
FT /ligand="CO2"
FT /ligand_id="ChEBI:CHEBI:16526"
FT /evidence="ECO:0000269|PubMed:17224163,
FT ECO:0007744|PDB:2H31"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 22
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCL9"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 36
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCL9"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 238
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 247
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 72
FT /note="G -> VTSYKSNR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_041265"
FT VARIANT 53
FT /note="K -> R (found in two siblings with partial PAICS
FT deficiency and multiple malformations resulting in early
FT neonatal death; unknown pathological significance; no
FT effect on protein abundance; decreased
FT phosphoribosylaminoimidazole carboxylase activity;
FT decreased phosphoribosylaminoimidazolesuccinocarboxamide
FT synthase activity)"
FT /evidence="ECO:0000269|PubMed:31600779"
FT /id="VAR_085931"
FT VARIANT 201
FT /note="K -> N (in dbSNP:rs11549976)"
FT /id="VAR_051884"
FT MUTAGEN 303
FT /note="H->Y: Loss of phosphoribosylaminoimidazole
FT carboxylase activity."
FT /evidence="ECO:0000269|PubMed:17224163"
FT MUTAGEN 332
FT /note="S->A: Loss of phosphoribosylaminoimidazole
FT carboxylase activity."
FT /evidence="ECO:0000269|PubMed:17224163"
FT MUTAGEN 334
FT /note="G->A: Loss of phosphoribosylaminoimidazole
FT carboxylase activity."
FT /evidence="ECO:0000269|PubMed:17224163"
FT MUTAGEN 400
FT /note="S->A: No effect on phosphoribosylaminoimidazole
FT carboxylase activity."
FT /evidence="ECO:0000269|PubMed:17224163"
FT CONFLICT 217
FT /note="W -> R (in Ref. 3; CAH18683)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="S -> T (in Ref. 3; CAH18683)"
FT /evidence="ECO:0000305"
FT STRAND 9..15
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 17..27
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:6YB8"
FT TURN 42..45
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 53..71
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 107..111
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 120..130
FT /evidence="ECO:0007829|PDB:6YB8"
FT TURN 133..136
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 142..147
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 159..180
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 185..197
FT /evidence="ECO:0007829|PDB:6YB8"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 213..218
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 239..255
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 256..260
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 267..273
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 278..289
FT /evidence="ECO:0007829|PDB:6YB8"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:6YB8"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 306..317
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 323..328
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 335..342
FT /evidence="ECO:0007829|PDB:6YB8"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:6YB8"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 358..361
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 380..392
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 396..420
FT /evidence="ECO:0007829|PDB:6YB8"
FT HELIX 421..424
FT /evidence="ECO:0007829|PDB:6YB8"
SQ SEQUENCE 425 AA; 47079 MW; E08CF19BC8898F29 CRC64;
MATAEVLNIG KKLYEGKTKE VYELLDSPGK VLLQSKDQIT AGNAARKNHL EGKAAISNKI
TSCIFQLLQE AGIKTAFTRK CGETAFIAPQ CEMIPIEWVC RRIATGSFLK RNPGVKEGYK
FYPPKVELFF KDDANNDPQW SEEQLIAAKF CFAGLLIGQT EVDIMSHATQ AIFEILEKSW
LPQNCTLVDM KIEFGVDVTT KEIVLADVID NDSWRLWPSG DRSQQKDKQS YRDLKEVTPE
GLQMVKKNFE WVAERVELLL KSESQCRVVV LMGSTSDLGH CEKIKKACGN FGIPCELRVT
SAHKGPDETL RIKAEYEGDG IPTVFVAVAG RSNGLGPVMS GNTAYPVISC PPLTPDWGVQ
DVWSSLRLPS GLGCSTVLSP EGSAQFAAQI FGLSNHLVWS KLRASILNTW ISLKQADKKI
RECNL
