ID   HMLL_DROME              Reviewed;         681 AA.
AC   Q9V3U0; Q8SWR5;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 145.
DE   RecName: Full=Long-chain-fatty-acid--CoA ligase heimdall {ECO:0000303|PubMed:25409104, ECO:0000312|FlyBase:FBgn0286723};
DE            EC=6.2.1.3 {ECO:0000305|PubMed:26893370};
DE   AltName: Full=Very long-chain-fatty-acid--CoA ligase double bubble {ECO:0000303|PubMed:26893370};
GN   Name=hll {ECO:0000303|PubMed:25409104,
GN   ECO:0000312|FlyBase:FBgn0286723};
GN   Synonyms=BG:DS05899.1 {ECO:0000312|FlyBase:FBgn0286723}, dbb
GN   {ECO:0000312|FlyBase:FBgn0286723};
GN   ORFNames=CG4500 {ECO:0000312|FlyBase:FBgn0286723};
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] OF 2-681.
RC   STRAIN=Berkeley; TISSUE=Embryo;
RA   Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA   Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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   [5]
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   [6]
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:26893370, PubMed:29739804). Probably by regulating lipid
CC       storage and catabolism, plays a role in neuronal function
CC       (PubMed:25409104). {ECO:0000269|PubMed:25409104,
CC       ECO:0000269|PubMed:26893370, 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:26893370};
CC   -!- DISRUPTION PHENOTYPE: Results in neurodegeneration in the central
CC       nervous system including degeneration of lamina and retina, defects in
CC       the fenestrated basement membrane, ommatidial disarray, locomotor
CC       defects and shortened lifespan (PubMed:26893370, PubMed:29739804). The
CC       phenotype is exacerbated in constant light conditions and improves in
CC       total darkness (PubMed:29739804). Effects are probably due to elevated
CC       levels of very long chain fatty acids (VLCFAs) (PubMed:29739804).
CC       Feeding the fly mutant with medium-chain fatty acids, blocks the
CC       accumulation of excess VLCFAs as well as development of the pathology
CC       (PubMed:29739804). Simultaneous knockout of bgm results in enhanced
CC       retinal degeneration and altered fatty acids metabolism
CC       (PubMed:26893370). RNAi-mediated knockdown in the adult results in
CC       reduction of triglycerides and altered neuronal function, including
CC       altered sleep rebound following sleep deprivation (PubMed:25409104).
CC       {ECO:0000269|PubMed:25409104, ECO:0000269|PubMed:26893370,
CC       ECO:0000269|PubMed:29739804}.
CC   -!- MISCELLANEOUS: In Norse mythology, Heimdall is the fictional character
CC       that for ages guarded the bridge to Asgard without sleeping and without
CC       the consequences of sleep deprivation. {ECO:0000305|PubMed:25409104}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       Bubblegum subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAM12254.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AE014134; AAF53370.1; -; Genomic_DNA.
DR   EMBL; BT021247; AAX33395.1; -; mRNA.
DR   EMBL; AY095523; AAM12254.1; ALT_SEQ; mRNA.
DR   RefSeq; NP_609696.1; NM_135852.4.
DR   AlphaFoldDB; Q9V3U0; -.
DR   SMR; Q9V3U0; -.
DR   BioGRID; 60849; 1.
DR   STRING; 7227.FBpp0080168; -.
DR   PaxDb; 7227-FBpp0080168; -.
DR   DNASU; 34822; -.
DR   EnsemblMetazoa; FBtr0080591; FBpp0080168; FBgn0286723.
DR   GeneID; 34822; -.
DR   KEGG; dme:Dmel_CG4500; -.
DR   UCSC; CG4500-RA; d. melanogaster.
DR   AGR; FB:FBgn0286723; -.
DR   CTD; 34822; -.
DR   FlyBase; FBgn0286723; hll.
DR   VEuPathDB; VectorBase:FBgn0286723; -.
DR   eggNOG; KOG1256; Eukaryota.
DR   GeneTree; ENSGT00940000172512; -.
DR   HOGENOM; CLU_000022_45_5_1; -.
DR   InParanoid; Q9V3U0; -.
DR   OMA; IGDHRKY; -.
DR   OrthoDB; 443463at2759; -.
DR   PhylomeDB; Q9V3U0; -.
DR   Reactome; R-DME-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR   BioGRID-ORCS; 34822; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 34822; -.
DR   PRO; PR:Q9V3U0; -.
DR   Proteomes; UP000000803; Chromosome 2L.
DR   Bgee; FBgn0286723; Expressed in arthropod fat body and 20 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0007498; P:mesoderm development; IEP:FlyBase.
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:0070328; P:triglyceride homeostasis; IMP:FlyBase.
DR   Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig_com.
DR   InterPro; IPR042099; ANL_N_sf.
DR   PANTHER; PTHR43272:SF32; AMP-BINDING DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR43272; LONG-CHAIN-FATTY-ACID--COA LIGASE; 1.
DR   Pfam; PF00501; AMP-binding; 1.
DR   SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR   Genevisible; Q9V3U0; DM.
PE   1: Evidence at protein level;
KW   ATP-binding; Fatty acid metabolism; Ligase; Lipid metabolism;
KW   Nucleotide-binding; Reference proteome.
FT   CHAIN           1..681
FT                   /note="Long-chain-fatty-acid--CoA ligase heimdall"
FT                   /id="PRO_0000315818"
FT   BINDING         223..231
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         414..419
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         491
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         506
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         639
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   681 AA;  75152 MW;  6310902CC494712E CRC64;
     MNDLKPATSY RSTSLHDAVK LRLDEPSSFS QTVPPQTIPE FFKESCEKYS DLPALVWETP
     GSGNDGWTTL TFGEYQERVE QAALMLLSVG VEERSSVGIL AFNCPEWFFA EFGALRAGAV
     VAGVYPSNSA EAVHHVLATG ESSVCVVDDA QQMAKLRAIK ERLPRLKAVI QLHGPFEAFV
     DHEPGYFSWQ KLQEQTFSSE LKEELLARES RIRANECAML IFTSGTVGMP KAVMLSHDNL
     VFDTKSAAAH MQDIQVGKES FVSYLPLSHV AAQIFDVFLG LSHAGCVTFA DKDALKGTLI
     KTFRKARPTK MFGVPRVFEK LQERLVAAEA KARPYSRLLL ARARAAVAEH QTTLMAGKSP
     SIYGNAKYWL ACRVVKPIRE MIGVDNCRVF FTGGAPTSEE LKQFFLGLDI ALGECYGMSE
     TSGAITLNVD ISNLYSAGQA CEGVTLKIHE PDCNGQGEIL MRGRLVFMGY LGLPDKTEET
     VKEDGWLHSG DLGYIDPKGN LIISGRLKEL IITAGGENIP PVHIEELIKK ELPCVSNVLL
     IGDHRKYLTV LLSLKTKCDA KTGIPLDALR EETIEWLRDL DIHETRLSEL LNIPADLQLP
     NDTAALAATL EITAKPKLLE AIEEGIKRAN KYAISNAQKV QKFALIAHEF SVATGELGPT
     LKIRRNIVHA KYAKVIERLY K
//