PUR2_CHITE
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 03-AUG-2022, entry version 116.
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=(6S)-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:57454, ChEBI:CHEBI:143788, ChEBI:CHEBI:147286;
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,
CC ECO:0000255|PROSITE-ProRule:PRU00409};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-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; 3.30.1330.10; -; 2.
DR Gene3D; 3.30.1490.20; -; 1.
DR Gene3D; 3.90.600.10; -; 1.
DR Gene3D; 3.90.650.10; -; 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 PANTHER; PTHR10520; PTHR10520; 2.
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; SM01210; GARS_C; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR SUPFAM; SSF53328; SSF53328; 1.
DR SUPFAM; SSF55326; SSF55326; 2.
DR SUPFAM; SSF56042; SSF56042; 2.
DR TIGRFAMs; TIGR00877; purD; 1.
DR TIGRFAMs; TIGR00878; purM; 2.
DR TIGRFAMs; TIGR00639; PurN; 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="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 1260..1263
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 1277
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 1311..1315
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
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
