PUR2_CHICK
ID PUR2_CHICK Reviewed; 1003 AA.
AC P21872;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Trifunctional purine biosynthetic protein adenosine-3 {ECO:0000305|PubMed:2147474};
DE Includes:
DE RecName: Full=Phosphoribosylamine--glycine ligase {ECO:0000305|PubMed:2147474};
DE EC=6.3.4.13 {ECO:0000305|PubMed:2147474};
DE AltName: Full=Glycinamide ribonucleotide synthetase;
DE Short=GARS;
DE AltName: Full=Phosphoribosylglycinamide synthetase;
DE Includes:
DE RecName: Full=Phosphoribosylformylglycinamidine cyclo-ligase {ECO:0000305|PubMed:2147474};
DE EC=6.3.3.1 {ECO:0000305|PubMed:2147474};
DE AltName: Full=AIR synthase;
DE Short=AIRS;
DE AltName: Full=Phosphoribosyl-aminoimidazole synthetase;
DE Includes:
DE RecName: Full=Phosphoribosylglycinamide formyltransferase {ECO:0000305|PubMed:2147474};
DE EC=2.1.2.2 {ECO:0000305|PubMed:2147474};
DE AltName: Full=5'-phosphoribosylglycinamide transformylase;
DE AltName: Full=GAR transformylase;
DE Short=GART;
GN Name=GART;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2111814; DOI=10.1016/s0021-9258(19)38804-0;
RA Aimi J., Badylak J., Williams J., Chen Z., Zalkin H., Dixon J.E.;
RT "Cloning of a cDNA encoding adenylosuccinate lyase by functional
RT complementation in Escherichia coli.";
RL J. Biol. Chem. 265:9011-9014(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, DOMAIN, AND REGION.
RC TISSUE=Liver;
RX PubMed=2147474; DOI=10.1093/nar/18.22.6665;
RA Aimi J., Qiu H., Williams J., Zalkin H., Dixon J.E.;
RT "De novo purine nucleotide biosynthesis: cloning of human and avian cDNAs
RT encoding the trifunctional glycinamide ribonucleotide synthetase-
RT aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide
RT transformylase by functional complementation in E. coli.";
RL Nucleic Acids Res. 18:6665-6672(1990).
CC -!- FUNCTION: Trifunctional enzyme that catalyzes three distinct reactions
CC as part of the 'de novo' inosine monophosphate biosynthetic pathway.
CC {ECO:0000305|PubMed:2147474}.
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:0000305|PubMed:2147474};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17454;
CC Evidence={ECO:0000305|PubMed:2147474};
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:0000305|PubMed:2147474};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23033;
CC Evidence={ECO:0000305|PubMed:2147474};
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:0000305|PubMed:2147474};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15054;
CC Evidence={ECO:0000305|PubMed:2147474};
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. {ECO:0000305|PubMed:2147474}.
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:0000305|PubMed:2147474}.
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:0000305|PubMed:2147474}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P22102}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P21872-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P21872-2; Sequence=VSP_005516;
CC -!- DOMAIN: The N-terminal ATP-grasp domain carries the
CC phosphoribosylamine--glycine ligase activity.
CC {ECO:0000305|PubMed:2147474}.
CC -!- DOMAIN: The central AIRS domain carries the
CC phosphoribosylformylglycinamidine cyclo-ligase activity.
CC {ECO:0000305|PubMed:2147474}.
CC -!- DOMAIN: The C-terminal GART domain carries the
CC phosphoribosylglycinamide formyltransferase activity.
CC {ECO:0000305|PubMed:2147474}.
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; X56339; CAA39779.1; -; mRNA.
DR EMBL; X54200; CAA38120.1; -; mRNA.
DR PIR; S12617; AJCHPR.
DR RefSeq; NP_001001469.1; NM_001001469.1. [P21872-1]
DR AlphaFoldDB; P21872; -.
DR SMR; P21872; -.
DR STRING; 9031.ENSGALP00000035973; -.
DR PaxDb; P21872; -.
DR GeneID; 395315; -.
DR KEGG; gga:395315; -.
DR CTD; 2618; -.
DR VEuPathDB; HostDB:geneid_395315; -.
DR eggNOG; KOG0237; Eukaryota.
DR eggNOG; KOG3076; Eukaryota.
DR InParanoid; P21872; -.
DR OrthoDB; 105366at2759; -.
DR PhylomeDB; P21872; -.
DR Reactome; R-GGA-419140; De novo synthesis of IMP.
DR UniPathway; UPA00074; UER00125.
DR UniPathway; UPA00074; UER00126.
DR UniPathway; UPA00074; UER00129.
DR PRO; PR:P21872; -.
DR Proteomes; UP000000539; Unplaced.
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; TAS:Reactome.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; TAS:Reactome.
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; 3.30.1330.10; -; 1.
DR Gene3D; 3.30.1490.20; -; 1.
DR Gene3D; 3.90.600.10; -; 1.
DR Gene3D; 3.90.650.10; -; 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 PANTHER; PTHR10520; PTHR10520; 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; SM01210; GARS_C; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR SUPFAM; SSF53328; SSF53328; 1.
DR SUPFAM; SSF55326; SSF55326; 1.
DR SUPFAM; SSF56042; SSF56042; 1.
DR TIGRFAMs; TIGR00877; purD; 1.
DR TIGRFAMs; TIGR00878; purM; 1.
DR TIGRFAMs; TIGR00639; PurN; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS00184; GARS; 1.
DR PROSITE; PS00373; GART; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Ligase; Magnesium; Manganese;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW Purine biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..1003
FT /note="Trifunctional purine biosynthetic protein adenosine-
FT 3"
FT /id="PRO_0000074936"
FT DOMAIN 111..318
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT REGION 214..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 434..805
FT /note="AIRS domain"
FT /evidence="ECO:0000305|PubMed:2147474"
FT REGION 806..1003
FT /note="GART domain"
FT /evidence="ECO:0000305|PubMed:2147474"
FT ACT_SITE 911
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 814..816
FT /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT /ligand_id="ChEBI:CHEBI:143788"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 867
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 892..895
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 909
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 943..947
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT BINDING 973..976
FT /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT /ligand_id="ChEBI:CHEBI:143788"
FT /evidence="ECO:0000250|UniProtKB:P22102"
FT SITE 947
FT /note="Raises pKa of active site His"
FT /evidence="ECO:0000250|UniProtKB:P08179"
FT VAR_SEQ 434..1003
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_005516"
SQ SEQUENCE 1003 AA; 106544 MW; A0C66BA0EBF791DE CRC64;
MADRVLVIGS GGREHALAWK LAQSPHVKQV FVAPGNAGTA NSGKISNSAV SVSNHAALAQ
FCRDQEIRLV VVGPEVPLAA GIVDDLTAAG VRCFGPTARA AQLESSKSFT KSFLDRHGIP
TARWKSFTDP KAACSFINSA NFPALVVKAS GLAAGKGVIV ASNKEEACKA VNDIMQDKTF
GTAGETVVVE ELLEGEEVSC LCFTDGVTIA PMPPAQDHKR LKDGDEGPNT GGMGAYSPAP
QISKDLLLKI RETVLQKTLD GMRKEGIPYL GVLYAGLMLT KDGPKVLEFN CRFGDPECQV
ILPLLKSDLY EVMQAVINKK LSSSMPIWYE DSAAVTVVMA SEGYPGTYPK GLEITGLSKA
KELGLEVFHA GTALKDGKVV TNGGRVLTVT AIKEDLMTAL QEANKGVAAI NFKGSIYRKD
IGYRAIAFLS QSRGLTYKNS GVDIAAGNIL VQKIKPLAAA TSRSGCNAEL GGFAGLFDLK
AAGYKDPILV SGTDGVGTKL KIAQVCKKHD TIGQDLVAMC VNDILAQGAE PLFFLDYFAC
GKLDVEVAQG VIAGIAEACQ KAGCALLGGE TAEMPGMYPP GEYDLAGFAV GAVERGQMLP
QLERIADGDV VIGVASSGVH SNGYSLVRRI VEKSSLDFSS QVGVSGDQTL GDLLLTPTKI
YSKTLLPVLR SGHVKAYAHI TGGGLLENIP RVLPDSFGVV LDALSWKIPE IFCWLHKEGN
LSEEEMARTF NCGIGAVLVV QKELAQQVLK DVQKHEAAWL IGKVVPLQKG SAHVKVHNLL
QALQANRSLS VHSHIQGKIQ TNKVKVAVLI SGTGTNLEAL INSTKKPTSF AEIVLVVSNK
AGVEGLRKAE RAGIPTRVID HKQYGSRTEF DSAVDRVLEE FSVELICLAG FMRILSGPFV
KKWEGKILNI HPSLLPSFKG ANAHKLVLEA GVRVTGCTVH FVAEEVDAGA IIFQEAVPVK
IGDTVETLSE RVKEAEHRAF PAALQLVASG AVQVGEAGKI CWK
