PUR1_HUMAN
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-AUG-2022, entry version 196.
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; 53.
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 PRIDE; 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 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; 400911at2759; -.
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; 308 hits in 1091 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; -; 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 Pfam; PF00156; Pribosyltran; 1.
DR PIRSF; PIRSF000485; Amd_phspho_trans; 1.
DR SUPFAM; SSF53271; SSF53271; 1.
DR SUPFAM; SSF56235; SSF56235; 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
