ID   PUR1_HUMAN              Reviewed;         517 AA.
AC   Q06203;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   03-MAY-2023, entry version 200.
DE   RecName: Full=Amidophosphoribosyltransferase {ECO:0000303|PubMed:8380692};
DE            Short=ATase;
DE            EC=2.4.2.14;
DE   AltName: Full=Glutamine phosphoribosylpyrophosphate amidotransferase {ECO:0000303|PubMed:8106516};
DE            Short=GPAT {ECO:0000303|PubMed:8106516};
DE   Flags: Precursor;
GN   Name=PPAT; Synonyms=GPAT {ECO:0000303|PubMed:8106516};
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], AND TISSUE SPECIFICITY.
RC   TISSUE=Hepatoma;
RX   PubMed=8380692; DOI=10.1006/bbrc.1993.1030;
RA   Iwahana H., Oka J., Mizusawa N., Kudo E., Ii S., Yoshimoto K., Holmes E.W.,
RA   Itakura M.;
RT   "Molecular cloning of human amidophosphoribosyltransferase.";
RL   Biochem. Biophys. Res. Commun. 190:192-200(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=8106516; DOI=10.1016/s0021-9258(17)37689-5;
RA   Brayton K.A., Chen Z., Zhou G., Nagy P.L., Gavalas A., Trent J.M.,
RA   Deaven L.L., Dixon J.E., Zalkin H.;
RT   "Two genes for de novo purine nucleotide synthesis on human chromosome 4
RT   are closely linked and divergently transcribed.";
RL   J. Biol. Chem. 269:5313-5321(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Muscle;
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   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   [5]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC   -!- FUNCTION: Catalyzes the formation of phosphoribosylamine from
CC       phosphoribosylpyrophosphate (PRPP) and glutamine.
CC       {ECO:0000250|UniProtKB:P35433}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5-phospho-beta-D-ribosylamine + diphosphate + L-glutamate = 5-
CC         phospho-alpha-D-ribose 1-diphosphate + H2O + L-glutamine;
CC         Xref=Rhea:RHEA:14905, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58359,
CC         ChEBI:CHEBI:58681; EC=2.4.2.14;
CC         Evidence={ECO:0000250|UniProtKB:P35433};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14907;
CC         Evidence={ECO:0000250|UniProtKB:P35433};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P00497};
CC       Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:P00497};
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000250|UniProtKB:P00497};
CC       Note=Binds 1 [4Fe-4S] cluster per subunit.
CC       {ECO:0000250|UniProtKB:P00497};
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; N(1)-
CC       (5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-
CC       diphosphate: step 1/2. {ECO:0000250|UniProtKB:P35433}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P00497}.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC       {ECO:0000269|PubMed:8380692}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the purine/pyrimidine
CC       phosphoribosyltransferase family. {ECO:0000305}.
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DR   EMBL; D13757; BAA02903.1; -; mRNA.
DR   EMBL; U00238; AAC27345.1; -; mRNA.
DR   EMBL; U00239; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC004200; AAH04200.1; -; mRNA.
DR   CCDS; CCDS3505.1; -.
DR   PIR; A53342; A53342.
DR   RefSeq; NP_002694.3; NM_002703.4.
DR   AlphaFoldDB; Q06203; -.
DR   SMR; Q06203; -.
DR   BioGRID; 111467; 60.
DR   IntAct; Q06203; 10.
DR   MINT; Q06203; -.
DR   STRING; 9606.ENSP00000264220; -.
DR   ChEMBL; CHEMBL2362992; -.
DR   DrugBank; DB01254; Dasatinib.
DR   DrugBank; DB00544; Fluorouracil.
DR   DrugBank; DB00130; L-Glutamine.
DR   DrugBank; DB01033; Mercaptopurine.
DR   DrugCentral; Q06203; -.
DR   MEROPS; C44.001; -.
DR   GlyGen; Q06203; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q06203; -.
DR   MetOSite; Q06203; -.
DR   PhosphoSitePlus; Q06203; -.
DR   SwissPalm; Q06203; -.
DR   BioMuta; PPAT; -.
DR   DMDM; 548638; -.
DR   EPD; Q06203; -.
DR   jPOST; Q06203; -.
DR   MassIVE; Q06203; -.
DR   MaxQB; Q06203; -.
DR   PaxDb; Q06203; -.
DR   PeptideAtlas; Q06203; -.
DR   ProteomicsDB; 58422; -.
DR   Antibodypedia; 24019; 367 antibodies from 28 providers.
DR   DNASU; 5471; -.
DR   Ensembl; ENST00000264220.6; ENSP00000264220.2; ENSG00000128059.8.
DR   GeneID; 5471; -.
DR   KEGG; hsa:5471; -.
DR   MANE-Select; ENST00000264220.6; ENSP00000264220.2; NM_002703.5; NP_002694.3.
DR   UCSC; uc003hbr.4; human.
DR   AGR; HGNC:9238; -.
DR   CTD; 5471; -.
DR   DisGeNET; 5471; -.
DR   GeneCards; PPAT; -.
DR   HGNC; HGNC:9238; PPAT.
DR   HPA; ENSG00000128059; Low tissue specificity.
DR   MIM; 172450; gene.
DR   neXtProt; NX_Q06203; -.
DR   OpenTargets; ENSG00000128059; -.
DR   PharmGKB; PA33559; -.
DR   VEuPathDB; HostDB:ENSG00000128059; -.
DR   eggNOG; KOG0572; Eukaryota.
DR   GeneTree; ENSGT00390000003428; -.
DR   HOGENOM; CLU_022389_3_1_1; -.
DR   InParanoid; Q06203; -.
DR   OMA; ENAQPTF; -.
DR   OrthoDB; 4975at2759; -.
DR   PhylomeDB; Q06203; -.
DR   TreeFam; TF106370; -.
DR   BioCyc; MetaCyc:HS05157-MON; -.
DR   BRENDA; 2.4.2.14; 2681.
DR   BRENDA; 2.7.7.3; 2681.
DR   PathwayCommons; Q06203; -.
DR   Reactome; R-HSA-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   SignaLink; Q06203; -.
DR   SIGNOR; Q06203; -.
DR   UniPathway; UPA00074; UER00124.
DR   BioGRID-ORCS; 5471; 338 hits in 1181 CRISPR screens.
DR   ChiTaRS; PPAT; human.
DR   GeneWiki; Amidophosphoribosyltransferase; -.
DR   GenomeRNAi; 5471; -.
DR   Pharos; Q06203; Tclin.
DR   PRO; PR:Q06203; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q06203; protein.
DR   Bgee; ENSG00000128059; Expressed in ventricular zone and 148 other tissues.
DR   ExpressionAtlas; Q06203; baseline and differential.
DR   Genevisible; Q06203; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0004044; F:amidophosphoribosyltransferase activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0044208; P:'de novo' AMP biosynthetic process; IEA:Ensembl.
DR   GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0097294; P:'de novo' XMP biosynthetic process; IEA:Ensembl.
DR   GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0006177; P:GMP biosynthetic process; IEA:Ensembl.
DR   GO; GO:0009113; P:purine nucleobase biosynthetic process; IEA:InterPro.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IBA:GO_Central.
DR   CDD; cd00715; GPATase_N; 1.
DR   CDD; cd06223; PRTases_typeI; 1.
DR   Gene3D; 3.40.50.2020; -; 1.
DR   Gene3D; 3.60.20.10; Glutamine Phosphoribosylpyrophosphate, subunit 1, domain 1; 1.
DR   HAMAP; MF_01931; PurF; 1.
DR   InterPro; IPR017932; GATase_2_dom.
DR   InterPro; IPR029055; Ntn_hydrolases_N.
DR   InterPro; IPR000836; PRibTrfase_dom.
DR   InterPro; IPR029057; PRTase-like.
DR   InterPro; IPR005854; PurF.
DR   InterPro; IPR035584; PurF_N.
DR   PANTHER; PTHR11907; AMIDOPHOSPHORIBOSYLTRANSFERASE; 1.
DR   PANTHER; PTHR11907:SF20; AMIDOPHOSPHORIBOSYLTRANSFERASE; 1.
DR   Pfam; PF13522; GATase_6; 1.
DR   Pfam; PF00156; Pribosyltran; 1.
DR   PIRSF; PIRSF000485; Amd_phspho_trans; 1.
DR   SUPFAM; SSF56235; N-terminal nucleophile aminohydrolases (Ntn hydrolases); 1.
DR   SUPFAM; SSF53271; PRTase-like; 1.
DR   TIGRFAMs; TIGR01134; purF; 1.
DR   PROSITE; PS51278; GATASE_TYPE_2; 1.
DR   PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1.
PE   1: Evidence at protein level;
KW   4Fe-4S; Acetylation; Allosteric enzyme; Glutamine amidotransferase;
KW   Glycosyltransferase; Iron; Iron-sulfur; Magnesium; Metal-binding;
KW   Purine biosynthesis; Reference proteome; Transferase.
FT   PROPEP          1..11
FT                   /evidence="ECO:0000250|UniProtKB:P35433"
FT                   /id="PRO_0000029283"
FT   CHAIN           12..517
FT                   /note="Amidophosphoribosyltransferase"
FT                   /id="PRO_0000029284"
FT   DOMAIN          12..261
FT                   /note="Glutamine amidotransferase type-2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00609"
FT   ACT_SITE        12
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00609"
FT   BINDING         280
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000250|UniProtKB:P00497"
FT   BINDING         327
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P00497"
FT   BINDING         389
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P00497"
FT   BINDING         390
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P00497"
FT   BINDING         426
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000250|UniProtKB:P00497"
FT   BINDING         503
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000250|UniProtKB:P00497"
FT   BINDING         506
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000250|UniProtKB:P00497"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CONFLICT        369
FT                   /note="V -> I (in Ref. 2; AAC27345)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   517 AA;  57399 MW;  D3F2A354C36B29D9 CRC64;
     MELEELGIRE ECGVFGCIAS GEWPTQLDVP HVITLGLVGL QHRGQESAGI VTSDGSSVPT
     FKSHKGMGLV NHVFTEDNLK KLYVSNLGIG HTRYATTGKC ELENCQPFVV ETLHGKIAVA
     HNGELVNAAR LRKKLLRHGI GLSTSSDSEM ITQLLAYTPP QEQDDTPDWV ARIKNLMKEA
     PTAYSLLIMH RDVIYAVRDP YGNRPLCIGR LIPVSDINDK EKKTSETEGW VVSSESCSFL
     SIGARYYREV LPGEIVEISR HNVQTLDIIS RSEGNPVAFC IFEYVYFARP DSMFEDQMVY
     TVRYRCGQQL AIEAPVDADL VSTVPESATP AALAYAGKCG LPYVEVLCKN RYVGRTFIQP
     NMRLRQLGVA KKFGVLSDNF KGKRIVLVDD SIVRGNTISP IIKLLKESGA KEVHIRVASP
     PIKYPCFMGI NIPTKEELIA NKPEFDHLAE YLGANSVVYL SVEGLVSSVQ EGIKFKKQKE
     KKHDIMIQEN GNGLECFEKS GHCTACLTGK YPVELEW
//