ID   PUR2_CHITE              Reviewed;        1371 AA.
AC   Q26255;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   08-NOV-2023, entry version 120.
DE   RecName: Full=Trifunctional purine biosynthetic protein adenosine-3;
DE   Includes:
DE     RecName: Full=Phosphoribosylamine--glycine ligase;
DE              EC=6.3.4.13 {ECO:0000250|UniProtKB:P00967};
DE     AltName: Full=Glycinamide ribonucleotide synthetase;
DE              Short=GARS;
DE     AltName: Full=Phosphoribosylglycinamide synthetase;
DE   Includes:
DE     RecName: Full=Phosphoribosylformylglycinamidine cyclo-ligase;
DE              EC=6.3.3.1 {ECO:0000250|UniProtKB:P00967};
DE     AltName: Full=AIR synthase;
DE              Short=AIRS;
DE     AltName: Full=Phosphoribosyl-aminoimidazole synthetase;
DE   Includes:
DE     RecName: Full=Phosphoribosylglycinamide formyltransferase;
DE              EC=2.1.2.2 {ECO:0000250|UniProtKB:P00967};
DE     AltName: Full=5'-phosphoribosylglycinamide transformylase;
DE     AltName: Full=GAR transformylase;
DE              Short=GART;
GN   Name=GART;
OS   Chironomus tentans (Midge) (Camptochironomus tentans).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Nematocera; Chironomoidea; Chironomidae;
OC   Chironominae; Chironomus.
OX   NCBI_TaxID=7153;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1518084; DOI=10.1007/bf00160260;
RA   Clark D.V., Henikoff S.;
RT   "Unusual organizational features of the Drosophila Gart locus are not
RT   conserved within Diptera.";
RL   J. Mol. Evol. 35:51-59(1992).
CC   -!- FUNCTION: Trifunctional enzyme that catalyzes three distinct reactions
CC       as part of the 'de novo' inosine monophosphate biosynthetic pathway.
CC       {ECO:0000250|UniProtKB:P00967}.
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:P00967};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17454;
CC         Evidence={ECO:0000250|UniProtKB:P00967};
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:P00967};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23033;
CC         Evidence={ECO:0000250|UniProtKB:P00967};
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:P00967};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15054;
CC         Evidence={ECO:0000250|UniProtKB:P00967};
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:P00967}.
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:P00967}.
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:P00967}.
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; S43653; AAB23115.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q26255; -.
DR   SMR; Q26255; -.
DR   UniPathway; UPA00074; UER00125.
DR   UniPathway; UPA00074; UER00126.
DR   UniPathway; UPA00074; UER00129.
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; IEA:UniProtKB-EC.
DR   GO; GO:0004641; F:phosphoribosylformylglycinamidine cyclo-ligase activity; IEA:UniProtKB-EC.
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:0009113; P:purine nucleobase biosynthetic process; IEA:InterPro.
DR   CDD; cd08645; FMT_core_GART; 1.
DR   CDD; cd02196; PurM; 2.
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; 2.
DR   Gene3D; 3.30.1330.10; PurM-like, N-terminal domain; 2.
DR   HAMAP; MF_00741; AIRS; 2.
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; 2.
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; 2.
DR   Pfam; PF02769; AIRS_C; 2.
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; 2.
DR   SUPFAM; SSF55326; PurM N-terminal domain-like; 2.
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   3: Inferred from homology;
KW   ATP-binding; Ligase; Magnesium; Manganese; Metal-binding;
KW   Multifunctional enzyme; Nucleotide-binding; Purine biosynthesis;
KW   Transferase.
FT   CHAIN           1..1371
FT                   /note="Trifunctional purine biosynthetic protein adenosine-
FT                   3"
FT                   /id="PRO_0000074933"
FT   DOMAIN          115..321
FT                   /note="ATP-grasp"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT   REGION          434..1171
FT                   /note="AIRS domain"
FT                   /evidence="ECO:0000250|UniProtKB:P21872"
FT   REGION          1169..1369
FT                   /note="GART domain"
FT                   /evidence="ECO:0000250|UniProtKB:P21872"
FT   ACT_SITE        1279
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P08179"
FT   BINDING         193..196
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         200
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         223
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         232
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         291
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT   BINDING         293
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT   BINDING         1180..1182
FT                   /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT                   /ligand_id="ChEBI:CHEBI:143788"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         1235
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         1260..1263
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         1277
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         1311..1315
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   BINDING         1341..1344
FT                   /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT                   /ligand_id="ChEBI:CHEBI:143788"
FT                   /evidence="ECO:0000250|UniProtKB:P22102"
FT   SITE            1315
FT                   /note="Raises pKa of active site His"
FT                   /evidence="ECO:0000250|UniProtKB:P08179"
SQ   SEQUENCE   1371 AA;  149103 MW;  7BF4664DB1538946 CRC64;
     MTGKKLLLIG SGGREHALAW KLQQSKNVTE IFAFPGSIGI SQLEKVQLVN NNEMNLKDFK
     GIASWCKINH IDLVIVGPED PLAEGIADQL KAANIHCFGP SKAGARIESD KSWSKDFMIR
     HHIPTAQYGS FIDALKAKDF IRNTPNALVV KASGLAAGKG VIVAENIEEA CAAVDEILGD
     HKFGTAGDVV VVEEKLSGQE VSVLGFVDSN SVRILPPAQD HKRLKDNDEG LNTGGMGAYC
     PCPLISQQEL DIVKSQVLQR AVDGLRKENI LYNGILYAGI MLTHDGPKTL EFNCRFGDPE
     TQIILPLLDE DLYDLMMASC TNHLCNVPEL KFKSNINAVG VVMASKGYPE TSTKGCVISG
     IESVETMDNH IVFHSGTSKN NKDEWITNGG RVLINIALAD NLKKAADLAT KACDVVKFDG
     SQYRRDIGKK AFQIHSLTYK ESGVNIEAGN SLVGRIKSLS YGTHRSGVVG QIGSFGGLMR
     LNDIKYINSN GEESNYKDIV LVQGTDGVGT KLKIAESMNV WDTIGIDLVA MCVNDVLCNG
     AEPIGFLDYI ACGHLEVPTV ATIVKGIADG CRKANCALIG GETAEMPSMY GKGKYDLAGY
     CVGITEYDEI LPKINDVHVG DVVIGLPSSG IHSNGFSLVN KIFQQTGFKL TDIAEFSDSH
     KSYGMEFLTP TRLYVSETLP FLRNGYVKAL AHITGGGLLE NIPRILPNHL SVQIDALTWK
     LPKVFSWLAA HGNVNANEML RTFNCGIGMI IIMPRNDIEW ETIPEARMIG SITQRDHNGP
     QVIVKNFKEV LHKEVTHWKK GDAETTSISY KDSGVDITAG NELVDNIKPH AKSTNRKGVI
     GGLGSFGGLF RINECGTKFE DPMLVLATDG VGTKLKIAQQ LGKHDTVGID LVAMCNNDIL
     CNGAEPLTFL DYFACGKLDV NVATNVVSGI AEGCRQSDST LLGGETAEMP GMYNPNVYDL
     AGFSLGVAEH EDILPKKNCL EVGDIIIGFP SNGVHSNGFS LIHKLFELTG YKWTDIAPFS
     AYGKTFGEEF LEPTKVYVKE ISPALKTGYV KALAHITGGG LWDNIPRVLP YNLTAELDAK
     KINISPVFAW LSLNGNIDKL ELLKTFNCGI GMIMIASKEH ELEILKSLYG SRASVIGKII
     PTKPHGHQVI VRHFATCFER VERLLSIPKK RVGVLISGSG SNLQALIDAT KSTNMGMCSE
     IVFVLSNKAG IFGLERAAKA NIPSTVISNK DYATREAFDV ALHNELIKHN VEIICLAGFM
     RILTPCFVNK WKGKLLNIHP SLLPKYKGIT AQKDALESGD NESGCTVHFV DENVDTGAII
     VQEIVPIFEN DTVESLTERI HVAEHIAFPK ALRLVASGYV RLNDKCETEW A
//