Full text data of PAICS
PAICS
(ADE2, AIRC, PAIS)
[Confidence: high (present in two of the MS resources)]
Multifunctional protein ADE2; Phosphoribosylaminoimidazole-succinocarboxamide synthase; 6.3.2.6 (SAICAR synthetase; Phosphoribosylaminoimidazole carboxylase; 4.1.1.21; AIR carboxylase; AIRC)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Multifunctional protein ADE2; Phosphoribosylaminoimidazole-succinocarboxamide synthase; 6.3.2.6 (SAICAR synthetase; Phosphoribosylaminoimidazole carboxylase; 4.1.1.21; AIR carboxylase; AIRC)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00217223
IPI00217223 Multifunctional protein ADE2 Phosphoribosylaminoimidazole-succinocarboxamide synthase, Phosphoribosylaminoimidazole carboxylase, de novo purine biosynthesis soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00217223 Multifunctional protein ADE2 Phosphoribosylaminoimidazole-succinocarboxamide synthase, Phosphoribosylaminoimidazole carboxylase, de novo purine biosynthesis soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P22234
ID PUR6_HUMAN Reviewed; 425 AA.
AC P22234; E9PDH9; Q68CQ5;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Multifunctional protein ADE2;
DE Includes:
DE RecName: Full=Phosphoribosylaminoimidazole-succinocarboxamide synthase;
DE EC=6.3.2.6;
DE AltName: Full=SAICAR synthetase;
DE Includes:
DE RecName: Full=Phosphoribosylaminoimidazole carboxylase;
DE EC=4.1.1.21;
DE AltName: Full=AIR carboxylase;
DE Short=AIRC;
GN Name=PAICS; Synonyms=ADE2, AIRC, PAIS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT mutant 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
RT 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA 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.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA 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.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 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
RT project: 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 MASS 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND THR-238, AND MASS
RP SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND SER-107, AND MASS
RP SPECTROMETRY.
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-247, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), SUBUNIT, ACTIVE SITE, AND
RP MUTAGENESIS OF HIS-303; SER-332 AND GLY-334.
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).
CC -!- CATALYTIC ACTIVITY: ATP + 5-amino-1-(5-phospho-D-
CC ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate +
CC (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-
CC carboxamido)succinate.
CC -!- CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-
CC carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2).
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway;
CC 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate: step 1/2.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway;
CC 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate from 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole (carboxylase route): step
CC 1/1.
CC -!- SUBUNIT: Homooctamer.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-712261, EBI-712261;
CC P51116:FXR2; NbExp=3; IntAct=EBI-712261, EBI-740459;
CC Q6ZVK8:NUDT18; NbExp=3; IntAct=EBI-712261, EBI-740486;
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
CC synthetase family.
CC -!- SIMILARITY: In the C-terminal section; belongs to the AIR
CC carboxylase family.
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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 PIR; S14147; S14147.
DR RefSeq; NP_001072992.1; NM_001079524.1.
DR RefSeq; NP_001072993.1; NM_001079525.1.
DR RefSeq; NP_006443.1; NM_006452.3.
DR UniGene; Hs.518774; -.
DR UniGene; Hs.709570; -.
DR PDB; 2H31; X-ray; 2.80 A; A=1-425.
DR PDBsum; 2H31; -.
DR ProteinModelPortal; P22234; -.
DR SMR; P22234; 7-425.
DR IntAct; P22234; 16.
DR MINT; MINT-5006326; -.
DR STRING; 9606.ENSP00000382595; -.
DR ChEMBL; CHEMBL5922; -.
DR DrugBank; DB00128; L-Aspartic Acid.
DR PhosphoSite; P22234; -.
DR DMDM; 131628; -.
DR PaxDb; P22234; -.
DR PRIDE; P22234; -.
DR DNASU; 10606; -.
DR Ensembl; ENST00000264221; ENSP00000264221; ENSG00000128050.
DR Ensembl; ENST00000399688; ENSP00000382595; ENSG00000128050.
DR Ensembl; ENST00000512576; ENSP00000421096; ENSG00000128050.
DR GeneID; 10606; -.
DR KEGG; hsa:10606; -.
DR UCSC; uc003hbs.1; human.
DR CTD; 10606; -.
DR GeneCards; GC04P057301; -.
DR HGNC; HGNC:8587; PAICS.
DR HPA; HPA035895; -.
DR MIM; 172439; gene.
DR neXtProt; NX_P22234; -.
DR PharmGKB; PA32914; -.
DR eggNOG; COG0041; -.
DR HOGENOM; HOG000082628; -.
DR HOVERGEN; HBG008335; -.
DR InParanoid; P22234; -.
DR KO; K01587; -.
DR OMA; TAFTRKC; -.
DR BioCyc; MetaCyc:HS05155-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00074; UER00130.
DR UniPathway; UPA00074; UER00131.
DR ChiTaRS; PAICS; human.
DR EvolutionaryTrace; P22234; -.
DR GenomeRNAi; 10606; -.
DR NextBio; 40280; -.
DR PRO; PR:P22234; -.
DR ArrayExpress; P22234; -.
DR Bgee; P22234; -.
DR CleanEx; HS_PAICS; -.
DR Genevestigator; P22234; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0034023; F:5-(carboxyamino)imidazole ribonucleotide mutase activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004638; F:phosphoribosylaminoimidazole carboxylase activity; TAS:Reactome.
DR GO; GO:0004639; F:phosphoribosylaminoimidazolesuccinocarboxamide synthase activity; TAS:Reactome.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; TAS:ProtInc.
DR GO; GO:0009168; P:purine ribonucleoside monophosphate biosynthetic process; TAS:Reactome.
DR Gene3D; 3.30.470.20; -; 1.
DR Gene3D; 3.40.50.7700; -; 1.
DR InterPro; IPR013816; ATP_grasp_subdomain_2.
DR InterPro; IPR000031; PurE_dom.
DR InterPro; IPR018236; SAICAR_synthetase_CS.
DR Pfam; PF00731; AIRC; 1.
DR SMART; SM01001; AIRC; 1.
DR SUPFAM; SSF52255; SSF52255; 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 Complete proteome; Decarboxylase; Direct protein sequencing; Ligase;
KW Lyase; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Purine biosynthesis; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 425 Multifunctional protein ADE2.
FT /FTId=PRO_0000075030.
FT REGION 2 260 SAICAR synthetase.
FT REGION 261 266 Linker.
FT REGION 267 425 AIR carboxylase.
FT ACT_SITE 101 101 For SAICAR synthetase activity.
FT ACT_SITE 107 107 For SAICAR synthetase activity.
FT ACT_SITE 215 215 For SAICAR synthetase activity.
FT ACT_SITE 303 303 For AIR carboxylase activity.
FT ACT_SITE 332 332 For AIR carboxylase activity.
FT SITE 334 334 Essential for AIR carboxylase activity.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 22 22 Phosphotyrosine (By similarity).
FT MOD_RES 27 27 Phosphoserine.
FT MOD_RES 107 107 Phosphoserine.
FT MOD_RES 238 238 Phosphothreonine.
FT MOD_RES 247 247 N6-acetyllysine.
FT VAR_SEQ 72 72 G -> VTSYKSNR (in isoform 2).
FT /FTId=VSP_041265.
FT VARIANT 201 201 K -> N (in dbSNP:rs11549976).
FT /FTId=VAR_051884.
FT MUTAGEN 303 303 H->Y: Loss of AIR carboxylase activity.
FT MUTAGEN 332 332 S->A: Loss of AIR carboxylase activity.
FT MUTAGEN 334 334 G->A: Loss of AIR carboxylase activity.
FT MUTAGEN 400 400 S->A: No change of AIR carboxylase
FT activity.
FT CONFLICT 217 217 W -> R (in Ref. 3; CAH18683).
FT CONFLICT 340 340 S -> T (in Ref. 3; CAH18683).
FT STRAND 20 22
FT STRAND 32 35
FT HELIX 54 71
FT STRAND 82 88
FT STRAND 91 93
FT STRAND 97 103
FT HELIX 106 111
FT STRAND 126 130
FT HELIX 142 146
FT TURN 147 149
FT HELIX 159 180
FT HELIX 181 183
FT STRAND 186 192
FT STRAND 194 197
FT TURN 198 200
FT STRAND 203 205
FT STRAND 213 217
FT STRAND 241 243
FT HELIX 249 253
FT HELIX 256 260
FT STRAND 267 273
FT HELIX 275 277
FT HELIX 278 290
FT STRAND 295 299
FT TURN 302 304
FT HELIX 306 317
FT STRAND 323 328
FT HELIX 335 342
FT STRAND 347 349
FT TURN 355 357
FT HELIX 358 361
FT HELIX 362 364
FT HELIX 380 392
FT HELIX 396 421
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
//
ID PUR6_HUMAN Reviewed; 425 AA.
AC P22234; E9PDH9; Q68CQ5;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Multifunctional protein ADE2;
DE Includes:
DE RecName: Full=Phosphoribosylaminoimidazole-succinocarboxamide synthase;
DE EC=6.3.2.6;
DE AltName: Full=SAICAR synthetase;
DE Includes:
DE RecName: Full=Phosphoribosylaminoimidazole carboxylase;
DE EC=4.1.1.21;
DE AltName: Full=AIR carboxylase;
DE Short=AIRC;
GN Name=PAICS; Synonyms=ADE2, AIRC, PAIS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT mutant 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
RT 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA 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.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA 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.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 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
RT project: 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 MASS 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND THR-238, AND MASS
RP SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND SER-107, AND MASS
RP SPECTROMETRY.
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-247, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), SUBUNIT, ACTIVE SITE, AND
RP MUTAGENESIS OF HIS-303; SER-332 AND GLY-334.
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).
CC -!- CATALYTIC ACTIVITY: ATP + 5-amino-1-(5-phospho-D-
CC ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate +
CC (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-
CC carboxamido)succinate.
CC -!- CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-
CC carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2).
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway;
CC 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate: step 1/2.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway;
CC 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate from 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole (carboxylase route): step
CC 1/1.
CC -!- SUBUNIT: Homooctamer.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-712261, EBI-712261;
CC P51116:FXR2; NbExp=3; IntAct=EBI-712261, EBI-740459;
CC Q6ZVK8:NUDT18; NbExp=3; IntAct=EBI-712261, EBI-740486;
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
CC synthetase family.
CC -!- SIMILARITY: In the C-terminal section; belongs to the AIR
CC carboxylase family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; S14147; S14147.
DR RefSeq; NP_001072992.1; NM_001079524.1.
DR RefSeq; NP_001072993.1; NM_001079525.1.
DR RefSeq; NP_006443.1; NM_006452.3.
DR UniGene; Hs.518774; -.
DR UniGene; Hs.709570; -.
DR PDB; 2H31; X-ray; 2.80 A; A=1-425.
DR PDBsum; 2H31; -.
DR ProteinModelPortal; P22234; -.
DR SMR; P22234; 7-425.
DR IntAct; P22234; 16.
DR MINT; MINT-5006326; -.
DR STRING; 9606.ENSP00000382595; -.
DR ChEMBL; CHEMBL5922; -.
DR DrugBank; DB00128; L-Aspartic Acid.
DR PhosphoSite; P22234; -.
DR DMDM; 131628; -.
DR PaxDb; P22234; -.
DR PRIDE; P22234; -.
DR DNASU; 10606; -.
DR Ensembl; ENST00000264221; ENSP00000264221; ENSG00000128050.
DR Ensembl; ENST00000399688; ENSP00000382595; ENSG00000128050.
DR Ensembl; ENST00000512576; ENSP00000421096; ENSG00000128050.
DR GeneID; 10606; -.
DR KEGG; hsa:10606; -.
DR UCSC; uc003hbs.1; human.
DR CTD; 10606; -.
DR GeneCards; GC04P057301; -.
DR HGNC; HGNC:8587; PAICS.
DR HPA; HPA035895; -.
DR MIM; 172439; gene.
DR neXtProt; NX_P22234; -.
DR PharmGKB; PA32914; -.
DR eggNOG; COG0041; -.
DR HOGENOM; HOG000082628; -.
DR HOVERGEN; HBG008335; -.
DR InParanoid; P22234; -.
DR KO; K01587; -.
DR OMA; TAFTRKC; -.
DR BioCyc; MetaCyc:HS05155-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00074; UER00130.
DR UniPathway; UPA00074; UER00131.
DR ChiTaRS; PAICS; human.
DR EvolutionaryTrace; P22234; -.
DR GenomeRNAi; 10606; -.
DR NextBio; 40280; -.
DR PRO; PR:P22234; -.
DR ArrayExpress; P22234; -.
DR Bgee; P22234; -.
DR CleanEx; HS_PAICS; -.
DR Genevestigator; P22234; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0034023; F:5-(carboxyamino)imidazole ribonucleotide mutase activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004638; F:phosphoribosylaminoimidazole carboxylase activity; TAS:Reactome.
DR GO; GO:0004639; F:phosphoribosylaminoimidazolesuccinocarboxamide synthase activity; TAS:Reactome.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; TAS:ProtInc.
DR GO; GO:0009168; P:purine ribonucleoside monophosphate biosynthetic process; TAS:Reactome.
DR Gene3D; 3.30.470.20; -; 1.
DR Gene3D; 3.40.50.7700; -; 1.
DR InterPro; IPR013816; ATP_grasp_subdomain_2.
DR InterPro; IPR000031; PurE_dom.
DR InterPro; IPR018236; SAICAR_synthetase_CS.
DR Pfam; PF00731; AIRC; 1.
DR SMART; SM01001; AIRC; 1.
DR SUPFAM; SSF52255; SSF52255; 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 Complete proteome; Decarboxylase; Direct protein sequencing; Ligase;
KW Lyase; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Purine biosynthesis; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 425 Multifunctional protein ADE2.
FT /FTId=PRO_0000075030.
FT REGION 2 260 SAICAR synthetase.
FT REGION 261 266 Linker.
FT REGION 267 425 AIR carboxylase.
FT ACT_SITE 101 101 For SAICAR synthetase activity.
FT ACT_SITE 107 107 For SAICAR synthetase activity.
FT ACT_SITE 215 215 For SAICAR synthetase activity.
FT ACT_SITE 303 303 For AIR carboxylase activity.
FT ACT_SITE 332 332 For AIR carboxylase activity.
FT SITE 334 334 Essential for AIR carboxylase activity.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 22 22 Phosphotyrosine (By similarity).
FT MOD_RES 27 27 Phosphoserine.
FT MOD_RES 107 107 Phosphoserine.
FT MOD_RES 238 238 Phosphothreonine.
FT MOD_RES 247 247 N6-acetyllysine.
FT VAR_SEQ 72 72 G -> VTSYKSNR (in isoform 2).
FT /FTId=VSP_041265.
FT VARIANT 201 201 K -> N (in dbSNP:rs11549976).
FT /FTId=VAR_051884.
FT MUTAGEN 303 303 H->Y: Loss of AIR carboxylase activity.
FT MUTAGEN 332 332 S->A: Loss of AIR carboxylase activity.
FT MUTAGEN 334 334 G->A: Loss of AIR carboxylase activity.
FT MUTAGEN 400 400 S->A: No change of AIR carboxylase
FT activity.
FT CONFLICT 217 217 W -> R (in Ref. 3; CAH18683).
FT CONFLICT 340 340 S -> T (in Ref. 3; CAH18683).
FT STRAND 20 22
FT STRAND 32 35
FT HELIX 54 71
FT STRAND 82 88
FT STRAND 91 93
FT STRAND 97 103
FT HELIX 106 111
FT STRAND 126 130
FT HELIX 142 146
FT TURN 147 149
FT HELIX 159 180
FT HELIX 181 183
FT STRAND 186 192
FT STRAND 194 197
FT TURN 198 200
FT STRAND 203 205
FT STRAND 213 217
FT STRAND 241 243
FT HELIX 249 253
FT HELIX 256 260
FT STRAND 267 273
FT HELIX 275 277
FT HELIX 278 290
FT STRAND 295 299
FT TURN 302 304
FT HELIX 306 317
FT STRAND 323 328
FT HELIX 335 342
FT STRAND 347 349
FT TURN 355 357
FT HELIX 358 361
FT HELIX 362 364
FT HELIX 380 392
FT HELIX 396 421
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
//
MIM
172439
*RECORD*
*FIELD* NO
172439
*FIELD* TI
*172439 PHOSPHORIBOSYLAMINOIMIDAZOLE CARBOXYLASE; PAICS
;;AIR CARBOXYLASE; AIRC;;
SAICAR SYNTHETASE
read more*FIELD* TX
DESCRIPTION
AIR carboxylase (EC 4.1.1.21)/SAICAR synthetase (EC 6.3.2.6) is a
bifunctional enzyme, the activities of which are required for steps 6
and 7, respectively, of purine biosynthesis (summary by Brayton et al.,
1994).
CLONING
Schild et al. (1990) used the functional complementation of mutations in
Saccharomyces cerevisiae to isolate a human cDNA clone complementing the
ade-2 (phosphoribosylaminoimidazole carboxylase; EC 4.1.1.21) yeast
mutation. The same cDNA also complemented ade-1
(phosphoribosylaminoimidazole succinocarboxamide synthetase; EC
6.3.2.6); thus, this is a bifunctional enzyme. Although these enzymes
are encoded by genes on different chromosomes in yeast, their enzymatic
activities copurify from chicken livers, and the complementation of both
activities by this single cDNA clone suggests that the enzyme is
bifunctional in humans.
MAPPING
Barton et al. (1991) mapped the PAICS gene to chromosome 4 by fusing
Chinese hamster ovary (CHO) cells carrying the Ade(-)D mutation with
human lymphocytes using inactivated Sendai virus. Two of the isolated
subclones contained only the long arm of human chromosome 4 translocated
onto a CHO chromosome, thus providing evidence that the gene in question
is on 4q. By subjecting 2 of the subclones containing chromosome 4 to
BrdU visible light segregation, Barton et al. (1991) demonstrated that
all of the isolated purine auxotrophic cell lines showed a loss of 4q.
It is noteworthy that this bifunctional enzyme maps to the same general
region as the monofunctional enzyme PPAT (172450), which catalyzes the
first step in the biosynthetic pathway for the production of AMP from
phosphoribosylpyrophosphate (PRPP) and maps to 4pter-q21.
Brayton et al. (1994) demonstrated that in the human, as in the chicken,
the GPAT gene (172450), which catalyzes the first and presumably
rate-limiting reaction in purine biosynthesis, is closely linked and
divergently transcribed. The intergenic region is approximately 625 bp
in the human and 229 bp in the chicken. Although there are several
examples for bidirectional transcription in higher eukaryotes, GPAT-AIRC
was the first example for bidirectional transcription of tightly coupled
genes that are not structurally related but are involved in the same
pathway. This may be a eukaryotic equivalent of a prokaryotic operon.
*FIELD* RF
1. Barton, J. W.; Hart, I. M.; Patterson, D.: Mapping of a locus
correcting lack of phosphoribosylaminoimidazole carboxylase activity
in Chinese hamster ovary cell Ade(-)D mutants to human chromosome
4. Genomics 9: 314-321, 1991.
2. Brayton, K. A.; Chen, Z.; Zhou, G.; Nagy, P. L.; Gavalas, A.; Trent,
J. M.; Deaven, L. L.; Dixon, J. E.; Zalkin, H.: Two genes for de
novo purine nucleotide synthesis on human chromosome 4 are closely
linked and divergently transcribed. J. Biol. Chem. 269: 5313-5321,
1994.
3. Schild, D.; Brake, A. J.; Kiefer, M. C.; Young, D.; Barr, P. J.
: Cloning of three human multifunctional de novo purine biosynthetic
genes by functional complementation of yeast mutations. Proc. Nat.
Acad. Sci. 87: 2916-2920, 1990.
*FIELD* CD
Victor A. McKusick: 6/19/1990
*FIELD* ED
alopez: 10/22/2010
alopez: 3/16/2010
joanna: 5/7/2009
carol: 4/20/1994
supermim: 3/16/1992
carol: 8/19/1991
carol: 1/18/1991
carol: 1/15/1991
carol: 6/19/1990
*RECORD*
*FIELD* NO
172439
*FIELD* TI
*172439 PHOSPHORIBOSYLAMINOIMIDAZOLE CARBOXYLASE; PAICS
;;AIR CARBOXYLASE; AIRC;;
SAICAR SYNTHETASE
read more*FIELD* TX
DESCRIPTION
AIR carboxylase (EC 4.1.1.21)/SAICAR synthetase (EC 6.3.2.6) is a
bifunctional enzyme, the activities of which are required for steps 6
and 7, respectively, of purine biosynthesis (summary by Brayton et al.,
1994).
CLONING
Schild et al. (1990) used the functional complementation of mutations in
Saccharomyces cerevisiae to isolate a human cDNA clone complementing the
ade-2 (phosphoribosylaminoimidazole carboxylase; EC 4.1.1.21) yeast
mutation. The same cDNA also complemented ade-1
(phosphoribosylaminoimidazole succinocarboxamide synthetase; EC
6.3.2.6); thus, this is a bifunctional enzyme. Although these enzymes
are encoded by genes on different chromosomes in yeast, their enzymatic
activities copurify from chicken livers, and the complementation of both
activities by this single cDNA clone suggests that the enzyme is
bifunctional in humans.
MAPPING
Barton et al. (1991) mapped the PAICS gene to chromosome 4 by fusing
Chinese hamster ovary (CHO) cells carrying the Ade(-)D mutation with
human lymphocytes using inactivated Sendai virus. Two of the isolated
subclones contained only the long arm of human chromosome 4 translocated
onto a CHO chromosome, thus providing evidence that the gene in question
is on 4q. By subjecting 2 of the subclones containing chromosome 4 to
BrdU visible light segregation, Barton et al. (1991) demonstrated that
all of the isolated purine auxotrophic cell lines showed a loss of 4q.
It is noteworthy that this bifunctional enzyme maps to the same general
region as the monofunctional enzyme PPAT (172450), which catalyzes the
first step in the biosynthetic pathway for the production of AMP from
phosphoribosylpyrophosphate (PRPP) and maps to 4pter-q21.
Brayton et al. (1994) demonstrated that in the human, as in the chicken,
the GPAT gene (172450), which catalyzes the first and presumably
rate-limiting reaction in purine biosynthesis, is closely linked and
divergently transcribed. The intergenic region is approximately 625 bp
in the human and 229 bp in the chicken. Although there are several
examples for bidirectional transcription in higher eukaryotes, GPAT-AIRC
was the first example for bidirectional transcription of tightly coupled
genes that are not structurally related but are involved in the same
pathway. This may be a eukaryotic equivalent of a prokaryotic operon.
*FIELD* RF
1. Barton, J. W.; Hart, I. M.; Patterson, D.: Mapping of a locus
correcting lack of phosphoribosylaminoimidazole carboxylase activity
in Chinese hamster ovary cell Ade(-)D mutants to human chromosome
4. Genomics 9: 314-321, 1991.
2. Brayton, K. A.; Chen, Z.; Zhou, G.; Nagy, P. L.; Gavalas, A.; Trent,
J. M.; Deaven, L. L.; Dixon, J. E.; Zalkin, H.: Two genes for de
novo purine nucleotide synthesis on human chromosome 4 are closely
linked and divergently transcribed. J. Biol. Chem. 269: 5313-5321,
1994.
3. Schild, D.; Brake, A. J.; Kiefer, M. C.; Young, D.; Barr, P. J.
: Cloning of three human multifunctional de novo purine biosynthetic
genes by functional complementation of yeast mutations. Proc. Nat.
Acad. Sci. 87: 2916-2920, 1990.
*FIELD* CD
Victor A. McKusick: 6/19/1990
*FIELD* ED
alopez: 10/22/2010
alopez: 3/16/2010
joanna: 5/7/2009
carol: 4/20/1994
supermim: 3/16/1992
carol: 8/19/1991
carol: 1/18/1991
carol: 1/15/1991
carol: 6/19/1990