BGM_DROME
ID BGM_DROME Reviewed; 666 AA.
AC Q9V3S9; Q8MT84;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Very long-chain-fatty-acid--CoA ligase bubblegum {ECO:0000303|PubMed:10373116, ECO:0000312|FlyBase:FBgn0027348};
DE EC=6.2.1.3 {ECO:0000305|PubMed:10373116, ECO:0000305|PubMed:26893370};
GN Name=bgm {ECO:0000303|PubMed:10373116, ECO:0000312|FlyBase:FBgn0027348};
GN ORFNames=CG4501 {ECO:0000312|FlyBase:FBgn0027348};
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10373116; DOI=10.1126/science.284.5422.1985;
RA Min K.-T., Benzer S.;
RT "Preventing neurodegeneration in the Drosophila mutant bubblegum.";
RL Science 284:1985-1988(1999).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25409104; DOI=10.5665/sleep.4680;
RA Thimgan M.S., Seugnet L., Turk J., Shaw P.J.;
RT "Identification of genes associated with resilience/vulnerability to sleep
RT deprivation and starvation in Drosophila.";
RL Sleep 38:801-814(2015).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26893370; DOI=10.1242/dmm.022244;
RA Sivachenko A., Gordon H.B., Kimball S.S., Gavin E.J., Bonkowsky J.L.,
RA Letsou A.;
RT "Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles
RT of the Bubblegum and Double bubble acyl-CoA synthetases.";
RL Dis. Model. Mech. 9:377-387(2016).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29739804; DOI=10.1242/dmm.031286;
RA Gordon H.B., Valdez L., Letsou A.;
RT "Etiology and treatment of adrenoleukodystrophy: new insights from
RT Drosophila.";
RL Dis. Model. Mech. 11:0-0(2018).
CC -!- FUNCTION: Mediates activation of long-chain fatty acids for both
CC synthesis of cellular lipids, and degradation via beta-oxidation
CC (PubMed:10373116, PubMed:26893370, PubMed:29739804). Probably by
CC regulating lipid storage and catabolism, plays a role in neuronal
CC function (PubMed:25409104). {ECO:0000269|PubMed:10373116,
CC ECO:0000269|PubMed:25409104, ECO:0000269|PubMed:26893370,
CC ECO:0000269|PubMed:29739804}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-
CC CoA + AMP + diphosphate; Xref=Rhea:RHEA:15421, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57560,
CC ChEBI:CHEBI:83139, ChEBI:CHEBI:456215; EC=6.2.1.3;
CC Evidence={ECO:0000305|PubMed:10373116, ECO:0000305|PubMed:26893370};
CC -!- DISRUPTION PHENOTYPE: Adult neurodegeneration, with marked dilation of
CC photoreceptor axons (PubMed:10373116, PubMed:26893370,
CC PubMed:29739804). Results in degeneration of lamina and retina, defects
CC in the fenestrated basement membrane and ommatidial disarray
CC (PubMed:26893370, PubMed:29739804). The phenotype is exacerbated in
CC constant light conditions and improves in total darkness
CC (PubMed:29739804). Effects are probably due to elevated levels of very
CC long chain fatty acids (VLCFAs) (PubMed:10373116, PubMed:29739804).
CC Feeding the fly mutant with glyceryl trioleate oil or medium-chain
CC fatty acids, blocks the accumulation of excess VLCFAs as well as
CC development of the pathology (PubMed:10373116, PubMed:29739804).
CC Results in altered neuronal function, including altered sleep rebound
CC following sleep deprivation (PubMed:25409104). Simultaneous knockout of
CC hll results in enhanced retinal degeneration and altered fatty acids
CC metabolism (PubMed:26893370). {ECO:0000269|PubMed:10373116,
CC ECO:0000269|PubMed:25409104, ECO:0000269|PubMed:26893370,
CC ECO:0000269|PubMed:29739804}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC Bubblegum subfamily. {ECO:0000305}.
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DR EMBL; AE014134; AAF53368.1; -; Genomic_DNA.
DR EMBL; AY118315; AAM48344.1; -; mRNA.
DR RefSeq; NP_001285923.1; NM_001298994.1.
DR RefSeq; NP_524698.1; NM_079959.4.
DR AlphaFoldDB; Q9V3S9; -.
DR SMR; Q9V3S9; -.
DR BioGRID; 68840; 2.
DR STRING; 7227.FBpp0080167; -.
DR PaxDb; Q9V3S9; -.
DR PRIDE; Q9V3S9; -.
DR EnsemblMetazoa; FBtr0080590; FBpp0080167; FBgn0027348.
DR EnsemblMetazoa; FBtr0346624; FBpp0312204; FBgn0027348.
DR GeneID; 44117; -.
DR KEGG; dme:Dmel_CG4501; -.
DR UCSC; CG4501-RA; d. melanogaster.
DR CTD; 44117; -.
DR FlyBase; FBgn0027348; bgm.
DR VEuPathDB; VectorBase:FBgn0027348; -.
DR eggNOG; KOG1256; Eukaryota.
DR GeneTree; ENSGT00940000172512; -.
DR HOGENOM; CLU_000022_45_5_1; -.
DR InParanoid; Q9V3S9; -.
DR OMA; AINECCC; -.
DR OrthoDB; 806831at2759; -.
DR PhylomeDB; Q9V3S9; -.
DR Reactome; R-DME-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR BioGRID-ORCS; 44117; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 44117; -.
DR PRO; PR:Q9V3S9; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0027348; Expressed in insect adult head and 18 other tissues.
DR ExpressionAtlas; Q9V3S9; baseline and differential.
DR Genevisible; Q9V3S9; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016405; F:CoA-ligase activity; IBA:GO_Central.
DR GO; GO:0015645; F:fatty acid ligase activity; TAS:FlyBase.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:FlyBase.
DR GO; GO:0006633; P:fatty acid biosynthetic process; TAS:FlyBase.
DR GO; GO:0006631; P:fatty acid metabolic process; IMP:FlyBase.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IMP:UniProtKB.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:FlyBase.
DR GO; GO:0045938; P:positive regulation of circadian sleep/wake cycle, sleep; IMP:FlyBase.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:FlyBase.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Fatty acid metabolism; Ligase; Lipid metabolism;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..666
FT /note="Very long-chain-fatty-acid--CoA ligase bubblegum"
FT /id="PRO_0000315817"
FT BINDING 229..237
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 417..422
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 495
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 510
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 624
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT CONFLICT 212
FT /note="M -> K (in Ref. 3; AAM48344)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 666 AA; 73611 MW; 6F437947FE6B922C CRC64;
MSTIDALYNR PGPNRLRQAD AYRTTNRQDA VKIRMAKDGI GAEEPISVPG LLKRTVNNYG
DYPALRTKNG KNGYHTVTYK QYEQKVHQVA KAFIKLGLEE HHSVGVLAFN CAEWFYSAMG
AIHARGIIAG IYTTNSADAV QHVLESSHAQ IVVVDDAKQM DKIHAIRDKL PKLKAAIQIQ
EPYSPYLKKE DGYYRWSEIE SMNVSDVEDQ YMTRLENVAI NECCCLVYTS GTVGMPKGVM
LSHDNITFDV RGIVKAMDRV VVGAESIVSY LPLSHVAAQT VDIYTCAFVA GCIWFADKDA
LKGTLVKSLQ DARPTRFMGV PRVYEKFQER MVAVASSSGS LKKMLASWAK GITLKHYMVS
QGKSSGGFRY KIAKSLIMSK VKQALGFDRV LTLASAAAPM SPETKKYFLS LDLKIVDAFG
MSETAGCHTI CLPDSVGLNT IGKTLPGCES KFINKDANGH GELCIRGRHV FMGYIDNKEK
TEESLDDDCW LHSGDLGFVD DKGYVSLTGR SKEIIITAGG ENIPPVHIEN TIKKELDAIS
NAFLVGEQRK YLTVLITLKT EVDKDSGEPL DELSHESSVW VKSLGVEHKT VSDILAAGPC
PKVWKSIEDA IKRANKQSIS NAQKVQKFTI LPHDFSIPTG ELGPTLKVKR NVVSKMYADE
IEKLYA
