PUR4_DROME
ID PUR4_DROME Reviewed; 1354 AA.
AC P35421; A4V099; Q6NNY9; Q9VMI7;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Phosphoribosylformylglycinamidine synthase {ECO:0000312|FlyBase:FBgn0000052};
DE Short=FGAM synthase;
DE Short=FGAMS;
DE EC=6.3.5.3 {ECO:0000269|PubMed:3086869};
DE AltName: Full=Formylglycinamide ribonucleotide amidotransferase;
DE Short=FGAR amidotransferase;
DE Short=FGAR-AT;
DE AltName: Full=Formylglycinamide ribotide amidotransferase;
DE AltName: Full=Protein adenosine-2;
GN Name=Pfas {ECO:0000312|FlyBase:FBgn0000052};
GN Synonyms=ade2 {ECO:0000312|FlyBase:FBgn0000052};
GN ORFNames=CG9127 {ECO:0000312|FlyBase:FBgn0000052};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Oregon-R;
RX PubMed=8270203; DOI=10.1139/g93-122;
RA Tiong S.Y.K., Nash D.;
RT "The adenosine2 gene of Drosophila melanogaster encodes a
RT formylglycineamide ribotide amidotransferase.";
RL Genome 36:924-934(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=3086869; DOI=10.1073/pnas.83.11.3919;
RA Henikoff S., Nash D., Hards R., Bleskan J., Woolford J.F., Naguib F.,
RA Patterson D.;
RT "Two Drosophila melanogaster mutations block successive steps of de novo
RT purine synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3919-3923(1986).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=21441212; DOI=10.1534/genetics.110.124222;
RA Holland C., Lipsett D.B., Clark D.V.;
RT "A link between impaired purine nucleotide synthesis and apoptosis in
RT Drosophila melanogaster.";
RL Genetics 188:359-367(2011).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=30249751; DOI=10.1534/g3.118.200554;
RA Yurgel M.E., Shah K.D., Brown E.B., Burns C., Bennick R.A., DiAngelo J.R.,
RA Keene A.C.;
RT "Ade2 Functions in the Drosophila Fat Body To Promote Sleep.";
RL G3 (Bethesda) 8:3385-3395(2018).
CC -!- FUNCTION: Phosphoribosylformylglycinamidine synthase involved in the
CC purines biosynthetic pathway (PubMed:3086869). Catalyzes the ATP-
CC dependent conversion of formylglycinamide ribonucleotide (FGAR) and
CC glutamine to yield formylglycinamidine ribonucleotide (FGAM) and
CC glutamate (PubMed:3086869). Because of its role in metabolisms, is
CC involved in sleep regulation (PubMed:3086869).
CC {ECO:0000269|PubMed:3086869}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-glutamine + N(2)-formyl-N(1)-(5-phospho-beta-D-
CC ribosyl)glycinamide = 2-formamido-N(1)-(5-O-phospho-beta-D-
CC ribosyl)acetamidine + ADP + H(+) + L-glutamate + phosphate;
CC Xref=Rhea:RHEA:17129, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58359, ChEBI:CHEBI:147286, ChEBI:CHEBI:147287,
CC ChEBI:CHEBI:456216; EC=6.3.5.3;
CC Evidence={ECO:0000269|PubMed:3086869};
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 1/2. {ECO:0000269|PubMed:3086869}.
CC -!- DISRUPTION PHENOTYPE: Pupal lethal (PubMed:21441212). RNAi-mediated
CC knockdown in the fat body reduces energy storage of both triglyceride
CC and free glucose, increases waking activity during the day and the
CC night, reduces sleep bout length, with total sleep bout number reduced
CC during the day and increased during the night (PubMed:30249751).
CC {ECO:0000269|PubMed:21441212, ECO:0000269|PubMed:30249751}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the FGAMS family.
CC {ECO:0000305}.
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DR EMBL; U00683; AAC46468.1; -; Unassigned_DNA.
DR EMBL; AE014134; AAF52329.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10573.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10574.1; -; Genomic_DNA.
DR EMBL; BT011143; AAR82811.1; -; mRNA.
DR PIR; T13363; T13363.
DR RefSeq; NP_477212.1; NM_057864.4.
DR RefSeq; NP_723146.1; NM_164675.2.
DR RefSeq; NP_723147.1; NM_164676.2.
DR AlphaFoldDB; P35421; -.
DR SMR; P35421; -.
DR BioGRID; 60012; 4.
DR DIP; DIP-22769N; -.
DR IntAct; P35421; 2.
DR STRING; 7227.FBpp0078850; -.
DR PaxDb; P35421; -.
DR PRIDE; P35421; -.
DR EnsemblMetazoa; FBtr0079219; FBpp0078850; FBgn0000052.
DR EnsemblMetazoa; FBtr0079220; FBpp0078851; FBgn0000052.
DR EnsemblMetazoa; FBtr0079221; FBpp0078852; FBgn0000052.
DR GeneID; 33847; -.
DR KEGG; dme:Dmel_CG9127; -.
DR CTD; 5198; -.
DR FlyBase; FBgn0000052; Pfas.
DR VEuPathDB; VectorBase:FBgn0000052; -.
DR eggNOG; KOG1907; Eukaryota.
DR GeneTree; ENSGT00390000007600; -.
DR HOGENOM; CLU_001031_0_0_1; -.
DR InParanoid; P35421; -.
DR OMA; LSANWMW; -.
DR OrthoDB; 38224at2759; -.
DR PhylomeDB; P35421; -.
DR Reactome; R-DME-73817; Purine ribonucleoside monophosphate biosynthesis.
DR SignaLink; P35421; -.
DR UniPathway; UPA00074; UER00128.
DR BioGRID-ORCS; 33847; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33847; -.
DR PRO; PR:P35421; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0000052; Expressed in capitellum (Drosophila) and 37 other tissues.
DR Genevisible; P35421; DM.
DR GO; GO:0005737; C:cytoplasm; ISS:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004642; F:phosphoribosylformylglycinamidine synthase activity; IMP:UniProtKB.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; ISS:FlyBase.
DR Gene3D; 3.30.1330.10; -; 2.
DR Gene3D; 3.40.50.880; -; 1.
DR Gene3D; 3.90.650.10; -; 2.
DR HAMAP; MF_00419; PurL_1; 1.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR040707; FGAR-AT_N.
DR InterPro; IPR010073; PurL_large.
DR InterPro; IPR041609; PurL_linker.
DR InterPro; IPR010918; PurM-like_C_dom.
DR InterPro; IPR036676; PurM-like_C_sf.
DR InterPro; IPR036921; PurM-like_N_sf.
DR InterPro; IPR036604; PurS-like_sf.
DR Pfam; PF02769; AIRS_C; 2.
DR Pfam; PF18072; FGAR-AT_linker; 1.
DR Pfam; PF18076; FGAR-AT_N; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR SUPFAM; SSF55326; SSF55326; 2.
DR SUPFAM; SSF56042; SSF56042; 2.
DR SUPFAM; SSF82697; SSF82697; 1.
DR TIGRFAMs; TIGR01735; FGAM_synt; 1.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Glutamine amidotransferase; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Purine biosynthesis; Reference proteome.
FT CHAIN 1..1354
FT /note="Phosphoribosylformylglycinamidine synthase"
FT /id="PRO_0000100403"
FT DOMAIN 1087..1337
FT /note="Glutamine amidotransferase type-1"
FT ACT_SITE 1180
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 1310
FT /evidence="ECO:0000250"
FT ACT_SITE 1312
FT /evidence="ECO:0000250"
FT BINDING 327..338
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 407..409
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 714
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 715
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 754
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 758
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 918
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 920
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT CONFLICT 558
FT /note="I -> Y (in Ref. 1; AAC46468)"
FT /evidence="ECO:0000305"
FT CONFLICT 625
FT /note="S -> F (in Ref. 1; AAC46468)"
FT /evidence="ECO:0000305"
FT CONFLICT 766
FT /note="E -> V (in Ref. 4; AAR82811)"
FT /evidence="ECO:0000305"
FT CONFLICT 910
FT /note="D -> E (in Ref. 4; AAR82811)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1354 AA; 148085 MW; 8AA167C2D2920B2C CRC64;
MVILRYYDVQ AHSAAEEESV LRRLREEDGA VVSVRMERCY HLEYSAQAEH SLALDELLVW
LVKQPLSKGQ SLSRQPALQS TGSSQLLLEI GPRFNFSTPY STNCVNIFQN LGYSEVRRME
TSTRYLVTFG EGSKAPEAAR FVPLLGDRMT QCLYTEENTP KASFDEQLPE RQANWHFVPV
LEEGRAALER INQELGLAFN DYDLDYYHDL FAKELGRNPT TVELFDCAQS NSEHSRHWFF
RGRMVIDGVE QPKSLIRMIM DTQAHTNPNN TIKFSDNSSA MVGFDHQTIV PSSVVAPGAV
RLQSVQSDLI FTAETHNMPT AVAPFSGATT GTGGRLRDVQ GVGRGGVPIA GTAGYCVGAL
HIPGYKQPYE PLDFKYPATF APPLQVLIEA SNGASDYGNK FGEPVISGFA LSYGLNSAAD
ASQRDEYVKP IMFSGGLGTM PATMREKLPP ARGQLLAKIG GPVYRIGVGG GAASSVEIQG
SGDAELDFNA VQRGDAEMEN KLNRVVRACL DLGEQNPILA IHDQGAGGNG NVLKELVEPG
FAGAVIFSKE FQLGDPTITA LELWGAEYQE NNAILCNADQ RELLEKICRR ERCPISFVGV
VTGDGRVTLL EKPAPKDLEQ ALNASNRSEV SPFDLELKYV LGDMPKRTYD LKREQTPLKE
LSLPKGLLLD EALERVLSLV AVGSKRFLTN KVDRCVGGLI AQQQCVGPLQ APLADYALTT
VSHFSHSGIA TSIGTQPLKG LLDPAAMARM CVAEALSNLV FVKISELADV KCSGNWMWAA
KLPGEGARMF DACKELCQIL EELHIAIDGG KDSLSMAAKV GGETIKSPGT LVISTYAPCP
DVRLKVTPDL KGPGAGSKTS LLWINLENSA RLGGSALAQA YAQQGKDTPN LTRSDVLGKA
FAVTQSLLGD GLIQAGHDVS DGGLLVCVLE MAIGGLSGLR VDLSEPLAKL KNFDKSVEKL
NRPELAVLFA EECGWVVEVL DTDLERVRST YEKAGVPNYY LGVTEGFGLD SRVVLKNGKS
ELLDQPLRVL YKKWERTSYE LEKLQANPEC AEAEYNSLEY RQAPQYRGPQ NVQAELTLKR
SSAPVRVAVL REEGVNSERE MMACLLRANF EVHDVTMSDL LQGTASVSQY RGLIFPGGFS
YADTLGSAKG WAANILHNPR LLPQFEAFKR RQDVFSLGIC NGCQLMTLIG FVGSAKSEVG
ADPDVALLHN KSQRFECRWA TVKIPSNRSI MLGSMKDLVL GCWVAHGEGR FAFRDEKLIS
HLQSEQLVTL QYVDDVGKPT ELYPLNPNGS PQGIAGLCSS DGRHLALMPH PERCSSMYQW
PYVPSSFEVS PTQSESPWQI MFNNAYNWCV KSNQ
