ID   PUR2_BOVIN              Reviewed;        1010 AA.
AC   Q59A32;
DT   03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   24-JAN-2024, entry version 124.
DE   RecName: Full=Trifunctional purine biosynthetic protein adenosine-3 {ECO:0000250|UniProtKB:P22102};
DE   Includes:
DE     RecName: Full=Phosphoribosylamine--glycine ligase {ECO:0000250|UniProtKB:P22102};
DE              EC=6.3.4.13 {ECO:0000250|UniProtKB:P22102};
DE     AltName: Full=Glycinamide ribonucleotide synthetase;
DE              Short=GARS;
DE     AltName: Full=Phosphoribosylglycinamide synthetase;
DE   Includes:
DE     RecName: Full=Phosphoribosylformylglycinamidine cyclo-ligase {ECO:0000250|UniProtKB:P22102};
DE              EC=6.3.3.1 {ECO:0000250|UniProtKB:P22102};
DE     AltName: Full=AIR synthase;
DE              Short=AIRS;
DE     AltName: Full=Phosphoribosyl-aminoimidazole synthetase;
DE   Includes:
DE     RecName: Full=Phosphoribosylglycinamide formyltransferase {ECO:0000250|UniProtKB:P22102};
DE              EC=2.1.2.2 {ECO:0000250|UniProtKB:P22102};
DE     AltName: Full=5'-phosphoribosylglycinamide transformylase;
DE     AltName: Full=GAR transformylase;
DE              Short=GART;
GN   Name=GART;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-771.
RX   PubMed=15777723; DOI=10.1016/j.gene.2004.12.038;
RA   Woehlke A., Droegemueller C., Kuiper H., Leeb T., Distl O.;
RT   "Molecular characterization and chromosomal assignment of the bovine
RT   glycinamide ribonucleotide formyltransferase (GART) gene on cattle
RT   chromosome 1q12.1-q12.2.";
RL   Gene 348:73-81(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Uterus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Trifunctional enzyme that catalyzes three distinct reactions
CC       as part of the 'de novo' inosine monophosphate biosynthetic pathway.
CC       {ECO:0000250|UniProtKB:P22102}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5-phospho-beta-D-ribosylamine + ATP + glycine = ADP + H(+) +
CC         N(1)-(5-phospho-beta-D-ribosyl)glycinamide + phosphate;
CC         Xref=Rhea:RHEA:17453, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:57305, ChEBI:CHEBI:58681,
CC         ChEBI:CHEBI:143788, ChEBI:CHEBI:456216; EC=6.3.4.13;
CC         Evidence={ECO:0000250|UniProtKB:P22102};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17454;
CC         Evidence={ECO:0000250|UniProtKB:P22102};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-formamido-N(1)-(5-O-phospho-beta-D-ribosyl)acetamidine + ATP
CC         = 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + ADP + H(+) +
CC         phosphate; Xref=Rhea:RHEA:23032, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:137981,
CC         ChEBI:CHEBI:147287, ChEBI:CHEBI:456216; EC=6.3.3.1;
CC         Evidence={ECO:0000250|UniProtKB:P22102};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23033;
CC         Evidence={ECO:0000250|UniProtKB:P22102};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-10-formyltetrahydrofolate + N(1)-(5-phospho-beta-D-
CC         ribosyl)glycinamide = (6S)-5,6,7,8-tetrahydrofolate + H(+) + N(2)-
CC         formyl-N(1)-(5-phospho-beta-D-ribosyl)glycinamide;
CC         Xref=Rhea:RHEA:15053, ChEBI:CHEBI:15378, ChEBI:CHEBI:57453,
CC         ChEBI:CHEBI:143788, ChEBI:CHEBI:147286, ChEBI:CHEBI:195366;
CC         EC=2.1.2.2; Evidence={ECO:0000250|UniProtKB:P22102};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15054;
CC         Evidence={ECO:0000250|UniProtKB:P22102};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P15640, ECO:0000255|PROSITE-
CC         ProRule:PRU00409};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00409};
CC       Note=Binds 1 magnesium or manganese ion per subunit.
CC       {ECO:0000255|PROSITE-ProRule:PRU00409};
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC       amino-1-(5-phospho-D-ribosyl)imidazole from N(2)-formyl-N(1)-(5-
CC       phospho-D-ribosyl)glycinamide: step 2/2.
CC       {ECO:0000250|UniProtKB:P22102}.
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 2/2. {ECO:0000250|UniProtKB:P22102}.
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; N(2)-
CC       formyl-N(1)-(5-phospho-D-ribosyl)glycinamide from N(1)-(5-phospho-D-
CC       ribosyl)glycinamide (10-formyl THF route): step 1/1.
CC       {ECO:0000250|UniProtKB:P22102}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P22102}.
CC   -!- DOMAIN: The N-terminal ATP-grasp domain carries the
CC       phosphoribosylamine--glycine ligase activity.
CC       {ECO:0000250|UniProtKB:P22102}.
CC   -!- DOMAIN: The central AIRS domain carries the
CC       phosphoribosylformylglycinamidine cyclo-ligase activity.
CC       {ECO:0000250|UniProtKB:P22102}.
CC   -!- DOMAIN: The C-terminal GART domain carries the
CC       phosphoribosylglycinamide formyltransferase activity.
CC       {ECO:0000250|UniProtKB:P22102}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the GARS family.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: In the central section; belongs to the AIR synthase family.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the GART family.
CC       {ECO:0000305}.
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DR   EMBL; AJ780930; CAG47113.1; -; Genomic_DNA.
DR   EMBL; BC122573; AAI22574.1; -; mRNA.
DR   RefSeq; NP_001035563.1; NM_001040473.2.
DR   AlphaFoldDB; Q59A32; -.
DR   SMR; Q59A32; -.
DR   STRING; 9913.ENSBTAP00000012108; -.
DR   PaxDb; 9913-ENSBTAP00000012108; -.
DR   PeptideAtlas; Q59A32; -.
DR   Ensembl; ENSBTAT00000012108.4; ENSBTAP00000012108.3; ENSBTAG00000009188.5.
DR   GeneID; 281183; -.
DR   KEGG; bta:281183; -.
DR   CTD; 2618; -.
DR   VEuPathDB; HostDB:ENSBTAG00000009188; -.
DR   VGNC; VGNC:29255; GART.
DR   eggNOG; KOG0237; Eukaryota.
DR   eggNOG; KOG3076; Eukaryota.
DR   GeneTree; ENSGT00390000000292; -.
DR   HOGENOM; CLU_005361_0_2_1; -.
DR   InParanoid; Q59A32; -.
DR   OMA; EVMQACC; -.
DR   OrthoDB; 729at2759; -.
DR   TreeFam; TF106368; -.
DR   Reactome; R-BTA-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   UniPathway; UPA00074; UER00125.
DR   UniPathway; UPA00074; UER00126.
DR   UniPathway; UPA00074; UER00129.
DR   Proteomes; UP000009136; Chromosome 1.
DR   Bgee; ENSBTAG00000009188; Expressed in conceptus and 107 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004637; F:phosphoribosylamine-glycine ligase activity; IBA:GO_Central.
DR   GO; GO:0004641; F:phosphoribosylformylglycinamidine cyclo-ligase activity; IBA:GO_Central.
DR   GO; GO:0004644; F:phosphoribosylglycinamide formyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0046084; P:adenine biosynthetic process; IBA:GO_Central.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IBA:GO_Central.
DR   CDD; cd08645; FMT_core_GART; 1.
DR   CDD; cd02196; PurM; 1.
DR   Gene3D; 3.40.50.20; -; 1.
DR   Gene3D; 3.30.1490.20; ATP-grasp fold, A domain; 1.
DR   Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR   Gene3D; 3.40.50.170; Formyl transferase, N-terminal domain; 1.
DR   Gene3D; 3.90.600.10; Phosphoribosylglycinamide synthetase, C-terminal domain; 1.
DR   Gene3D; 3.90.650.10; PurM-like C-terminal domain; 1.
DR   Gene3D; 3.30.1330.10; PurM-like, N-terminal domain; 1.
DR   HAMAP; MF_00741; AIRS; 1.
DR   HAMAP; MF_00138; GARS; 1.
DR   HAMAP; MF_01930; PurN; 1.
DR   InterPro; IPR011761; ATP-grasp.
DR   InterPro; IPR013815; ATP_grasp_subdomain_1.
DR   InterPro; IPR002376; Formyl_transf_N.
DR   InterPro; IPR036477; Formyl_transf_N_sf.
DR   InterPro; IPR004607; GART.
DR   InterPro; IPR001555; GART_AS.
DR   InterPro; IPR016185; PreATP-grasp_dom_sf.
DR   InterPro; IPR020561; PRibGlycinamid_synth_ATP-grasp.
DR   InterPro; IPR000115; PRibGlycinamide_synth.
DR   InterPro; IPR020560; PRibGlycinamide_synth_C-dom.
DR   InterPro; IPR037123; PRibGlycinamide_synth_C_sf.
DR   InterPro; IPR020559; PRibGlycinamide_synth_CS.
DR   InterPro; IPR020562; PRibGlycinamide_synth_N.
DR   InterPro; IPR010918; PurM-like_C_dom.
DR   InterPro; IPR036676; PurM-like_C_sf.
DR   InterPro; IPR016188; PurM-like_N.
DR   InterPro; IPR036921; PurM-like_N_sf.
DR   InterPro; IPR004733; PurM_cligase.
DR   InterPro; IPR011054; Rudment_hybrid_motif.
DR   NCBIfam; TIGR00877; purD; 1.
DR   NCBIfam; TIGR00878; purM; 1.
DR   NCBIfam; TIGR00639; PurN; 1.
DR   PANTHER; PTHR10520:SF12; TRIFUNCTIONAL PURINE BIOSYNTHETIC PROTEIN ADENOSINE-3; 1.
DR   PANTHER; PTHR10520; TRIFUNCTIONAL PURINE BIOSYNTHETIC PROTEIN ADENOSINE-3-RELATED; 1.
DR   Pfam; PF00586; AIRS; 1.
DR   Pfam; PF02769; AIRS_C; 1.
DR   Pfam; PF00551; Formyl_trans_N; 1.
DR   Pfam; PF01071; GARS_A; 1.
DR   Pfam; PF02843; GARS_C; 1.
DR   Pfam; PF02844; GARS_N; 1.
DR   SMART; SM01209; GARS_A; 1.
DR   SMART; SM01210; GARS_C; 1.
DR   SUPFAM; SSF53328; Formyltransferase; 1.
DR   SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1.
DR   SUPFAM; SSF52440; PreATP-grasp domain; 1.
DR   SUPFAM; SSF56042; PurM C-terminal domain-like; 1.
DR   SUPFAM; SSF55326; PurM N-terminal domain-like; 1.
DR   SUPFAM; SSF51246; Rudiment single hybrid motif; 1.
DR   PROSITE; PS50975; ATP_GRASP; 1.
DR   PROSITE; PS00184; GARS; 1.
DR   PROSITE; PS00373; GART; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; ATP-binding; Ligase; Magnesium; Manganese; Metal-binding;
KW   Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW   Purine biosynthesis; Reference proteome; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   CHAIN           2..1010
FT                   /note="Trifunctional purine biosynthetic protein adenosine-
FT                   3"
FT                   /id="PRO_0000250715"
FT   DOMAIN          111..318
FT                   /note="ATP-grasp"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT   REGION          434..809
FT                   /note="AIRS domain"
FT                   /evidence="ECO:0000250|UniProtKB:P21872"
FT   REGION          810..1010
FT                   /note="GART domain"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   ACT_SITE        915
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P08179"
FT   BINDING         190..193
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         197
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         220
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         229
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         288
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT   BINDING         290
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT   BINDING         818..820
FT                   /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT                   /ligand_id="ChEBI:CHEBI:143788"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         871
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         896..899
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         913
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         947..951
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         977..980
FT                   /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT                   /ligand_id="ChEBI:CHEBI:143788"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   SITE            951
FT                   /note="Raises pKa of active site His"
FT                   /evidence="ECO:0000250|UniProtKB:P08179"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   MOD_RES         350
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   MOD_RES         440
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   MOD_RES         682
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   MOD_RES         802
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   VARIANT         771
FT                   /note="K -> E"
FT                   /evidence="ECO:0000269|PubMed:15777723"
SQ   SEQUENCE   1010 AA;  107907 MW;  27DFCA438661A771 CRC64;
     MAARVLVIGN GGREHTLAWK LAQSTHVKQV LVTPGNAGTA CSEKISNTDI SISDHTALAQ
     FCKDEKIEFV VVGPEAPLAA GIVGNLNSVG VRCFGPTAQA AQLESSKRFA KEFMDRHGIS
     TARWRAFTKP KEACDFIMSA DFPALVVKAS GLAAGKGVIV AKSKEEACEA VREIMQGKAF
     GEAGETVVIE ELLEGEEVSC LCFTDGRTVA PMPPAQDHKR LLEGDEGPNT GGMGAYCPAP
     QVSKDLLLKI KNNILQRTVD GMQEEGMPYT GVLYAGIMLT KNGPKVLEFN CRFGDPECQV
     ILPLLKSDLY EVIQSILDGL LCTSLPVWLD NCAAVTVVMA SKGYPGDYTK GVEITGFPEA
     QALGLEVFQA GTALKDGKVV TNGGRVLTVT AIRENLISAL EEARKGLAAI KFEGAVYRKD
     IGFRAIAFLQ QPRGLTYKES GVDIAAGNML VQKIKPLAKA TSRPGCDVDL GGFAGLFDLK
     AAGFTDPLLA CGTDGVGTKL KIAQQCSKHD TIGQDLVAMC VNDILAQGAE PLFFLDYFSC
     GKLDLRTTEA VITGIAKACK KAGCALLGGE TAEMPDMYPP GEYDLAGFAV GAMERDQKLP
     QLERITEGDA VIGIASSGLH SNGFSLVRKI VAKSSLEYSS PAPGGCGDQT LGDLLLTPTK
     IYSRSLLPVL RSGRVKAVAH ITGGGLLENI PRVLPQKLGV NLDAQTWRVP RIFSWLQQEG
     HLSEEEMART FNCGIGAALV VSEDLVKQTL QDIEQHQEEA CVIGRVVACP KGSPRVKVEH
     LIETMQINGS VLENGTLRNH FSVQPKKARV AVLISGTGSN LQALIDSTRE PSSLAHIVIV
     ISNKAAVAGL DKAEKAGIPT RVINHKLYKN RAAFDTAIDE VLEEFSTDIV CLAGFMRILS
     GPFVRKWNGK MLNIHPSLLP SFKGSNAHEQ VLDAGVTVTG CTVHFVAEDV DAGQIILQEA
     VPVKRGDTVE TLSERVKLAE HKIFPSALQL VASGAVRLGE NGRICWVTED
//