ELOV6_DROME
ID ELOV6_DROME Reviewed; 316 AA.
AC Q9VV87; Q95T92; Q9NB55;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Elongation of very long chain fatty acids protein 6 {ECO:0000303|PubMed:26214738};
DE Short=ELOVL6 {ECO:0000303|PubMed:26214738};
DE EC=2.3.1.199 {ECO:0000255|RuleBase:RU361115, ECO:0000269|PubMed:26214738};
DE AltName: Full=Neighbor of abl {ECO:0000303|PubMed:17666430, ECO:0000312|FlyBase:FBgn0260960};
DE AltName: Full=Very-long-chain 3-oxoacyl-CoA synthase {ECO:0000255|RuleBase:RU361115};
GN Name=Baldspot {ECO:0000312|FlyBase:FBgn0260960};
GN Synonyms=l(3)01895 {ECO:0000303|PubMed:17666430,
GN ECO:0000312|FlyBase:FBgn0260960}, l(3)02281 {ECO:0000303|PubMed:17666430,
GN ECO:0000312|FlyBase:FBgn0260960}, l(3)04106 {ECO:0000303|PubMed:17666430,
GN ECO:0000312|FlyBase:FBgn0260960},
GN l(3)neo21 {ECO:0000312|FlyBase:FBgn0260960},
GN l(3)neo22 {ECO:0000312|FlyBase:FBgn0260960},
GN noa {ECO:0000303|PubMed:17666430, ECO:0000312|FlyBase:FBgn0260960};
GN ORFNames=CG3971 {ECO:0000312|FlyBase:FBgn0260960};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|EMBL:AAG02080.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=17666430; DOI=10.1242/jcs.006551;
RA Jung A., Hollmann M., Schaefer M.A.;
RT "The fatty acid elongase NOA is necessary for viability and has a somatic
RT role in Drosophila sperm development.";
RL J. Cell Sci. 120:2924-2934(2007).
RN [2] {ECO:0000312|EMBL:AAF75771.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Rice A.H., Page C., Duffy J.B.;
RT "Sequence analysis and characterization of baldspot.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [4] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [5] {ECO:0000312|EMBL:AAL25316.1, ECO:0000312|EMBL:AAL28669.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL28669.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL28669.1}, and
RC Head {ECO:0000312|EMBL:AAL25316.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Farfan D., Frise E., George R., Gonzalez M.,
RA Guarin H., Li P., Liao G., Miranda A., Mungall C.J., Nunoo J., Pacleb J.,
RA Paragas V., Park S., Phouanenavong S., Wan K., Yu C., Lewis S.E.,
RA Rubin G.M., Celniker S.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26214738; DOI=10.1038/nature14601;
RA Senyilmaz D., Virtue S., Xu X., Tan C.Y., Griffin J.L., Miller A.K.,
RA Vidal-Puig A., Teleman A.A.;
RT "Regulation of mitochondrial morphology and function by stearoylation of
RT TFR1.";
RL Nature 525:124-128(2015).
RN [7] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=30081392; DOI=10.1371/journal.pgen.1007557;
RA Palu R.A.S., Chow C.Y.;
RT "Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress
RT response.";
RL PLoS Genet. 14:e1007557-e1007557(2018).
CC -!- FUNCTION: Catalyzes the first and rate-limiting reaction of the four
CC reactions that constitute the long-chain fatty acids elongation cycle
CC (PubMed:26214738). This process allows the addition of 2 carbons to the
CC chain of long- and very long-chain fatty acids (VLCFAs) per cycle
CC (PubMed:26214738). Condensing enzyme that elongates fatty acids with
CC 12, 14 and 16 carbons with higher activity toward C16:0 acyl-CoAs (By
CC similarity). Catalyzes the synthesis of unsaturated C16 long chain
CC fatty acids and, to a lesser extent, C18:0 and those with low
CC desaturation degree (By similarity). May participate in the production
CC of saturated and monounsaturated VLCFAs of different chain lengths that
CC are involved in multiple biological processes as precursors of membrane
CC lipids and lipid mediators (By similarity).
CC {ECO:0000250|UniProtKB:Q9H5J4, ECO:0000269|PubMed:26214738}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-
CC chain 3-oxoacyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:32727,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:90725, ChEBI:CHEBI:90736;
CC EC=2.3.1.199; Evidence={ECO:0000255|RuleBase:RU361115,
CC ECO:0000269|PubMed:26214738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32728;
CC Evidence={ECO:0000269|PubMed:26214738};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + malonyl-CoA = 3-oxooctadecanoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:35315, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:71407;
CC Evidence={ECO:0000269|PubMed:26214738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35316;
CC Evidence={ECO:0000269|PubMed:26214738};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:26214738}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:26214738}; Multi-pass membrane protein
CC {ECO:0000305}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q920L5}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in the CNS (central nervous system) of
CC third larval instar (at protein level) (PubMed:17666430). Expressed in
CC cyst progenitor cells (at protein level) (PubMed:17666430). In the
CC adult fly, expressed in several tissues including, sperm, follicular
CC epithelium, nurse cells and cyst cells (PubMed:17666430).
CC {ECO:0000269|PubMed:17666430}.
CC -!- DEVELOPMENTAL STAGE: During embryogenesis, expressed in early cellular
CC blastoderm, involuting mesoderm, invaginating foregut, hindgut, in the
CC CNS (central nervous system) and PNS (peripheral nervous system) during
CC organogenesis, and imaginal disks (PubMed:17666430). In cyst cells,
CC expression is restricted to post-meiotic stages during spermatid
CC differentiation (PubMed:17666430). {ECO:0000269|PubMed:17666430}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in larvae confers
CC resistance to tunicamycin (PubMed:30081392). RNAi-mediated knockdown
CC reduces ER stress response caused by the accumulation of unfolded
CC protein in the ER by reducing Ire1 and PEK/PERK signaling
CC (PubMed:30081392). RNAi-mediated knockdown in imaginal disks results in
CC lethality (PubMed:17666430). RNAi-mediated knockdown in cyst cells
CC results in abnormal sperm cell development with abnormal organization
CC of individualization cones (PubMed:17666430).
CC {ECO:0000269|PubMed:17666430, ECO:0000269|PubMed:30081392}.
CC -!- SIMILARITY: Belongs to the ELO family. ELOVL6 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL25316.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AH009765; AAG02080.1; -; Genomic_DNA.
DR EMBL; AF279257; AAG02080.1; JOINED; Genomic_DNA.
DR EMBL; AF265296; AAF75771.1; -; mRNA.
DR EMBL; AE014296; AAF49430.2; -; Genomic_DNA.
DR EMBL; AE014296; AAN11736.2; -; Genomic_DNA.
DR EMBL; AY060277; AAL25316.1; ALT_SEQ; mRNA.
DR EMBL; AY061121; AAL28669.1; -; mRNA.
DR RefSeq; NP_648909.1; NM_140652.4.
DR RefSeq; NP_730187.2; NM_168678.3.
DR AlphaFoldDB; Q9VV87; -.
DR SMR; Q9VV87; -.
DR IntAct; Q9VV87; 34.
DR STRING; 7227.FBpp0075114; -.
DR GlyGen; Q9VV87; 2 sites.
DR PaxDb; Q9VV87; -.
DR PRIDE; Q9VV87; -.
DR DNASU; 39860; -.
DR EnsemblMetazoa; FBtr0075355; FBpp0075114; FBgn0260960.
DR EnsemblMetazoa; FBtr0075356; FBpp0075115; FBgn0260960.
DR GeneID; 39860; -.
DR KEGG; dme:Dmel_CG3971; -.
DR UCSC; CG3971-RA; d. melanogaster.
DR CTD; 39860; -.
DR FlyBase; FBgn0260960; Baldspot.
DR VEuPathDB; VectorBase:FBgn0260960; -.
DR eggNOG; KOG3072; Eukaryota.
DR GeneTree; ENSGT01050000244965; -.
DR HOGENOM; CLU_048483_1_1_1; -.
DR InParanoid; Q9VV87; -.
DR OMA; PISWVPI; -.
DR OrthoDB; 1094172at2759; -.
DR PhylomeDB; Q9VV87; -.
DR Reactome; R-DME-2046105; Linoleic acid (LA) metabolism.
DR Reactome; R-DME-2046106; alpha-linolenic acid (ALA) metabolism.
DR Reactome; R-DME-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR SignaLink; Q9VV87; -.
DR UniPathway; UPA00094; -.
DR BioGRID-ORCS; 39860; 1 hit in 3 CRISPR screens.
DR ChiTaRS; Baldspot; fly.
DR GenomeRNAi; 39860; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0260960; Expressed in crop (Drosophila) and 41 other tissues.
DR ExpressionAtlas; Q9VV87; baseline and differential.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISM:FlyBase.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:FlyBase.
DR GO; GO:0009922; F:fatty acid elongase activity; IMP:UniProtKB.
DR GO; GO:0102756; F:very-long-chain 3-ketoacyl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0030497; P:fatty acid elongation; ISS:FlyBase.
DR GO; GO:0034625; P:fatty acid elongation, monounsaturated fatty acid; IBA:GO_Central.
DR GO; GO:0034626; P:fatty acid elongation, polyunsaturated fatty acid; IBA:GO_Central.
DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; IMP:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; ISS:FlyBase.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0042761; P:very long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR InterPro; IPR030457; ELO_CS.
DR InterPro; IPR002076; ELO_fam.
DR PANTHER; PTHR11157; PTHR11157; 1.
DR Pfam; PF01151; ELO; 1.
DR PROSITE; PS01188; ELO; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..316
FT /note="Elongation of very long chain fatty acids protein 6"
FT /id="PRO_0000451162"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 64..84
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 316 AA; 36829 MW; E741960F28D2A3AD CRC64;
MINMDISVTP NYSYIFDFEN DFIHQRTRKW MLENWTWVFY YCGIYMLVIF GGQHFMQNRP
RFQLRGPLII WNTLLAMFSI MGAARTAPEL IHVLRHYGLF HSVCVPSYIE QDRVCGFWTW
LFVLSKLPEL GDTIFIVLRK QPLIFLHWYH HITVLIYSWF SYTEYTSSAR WFIVMNYCVH
SVMYSYYALK AARFNPPRFI SMIITSLQLA QMIIGCAINV WANGFLKTHG TSSCHISQRN
INLSIAMYSS YFVLFARFFY KAYLAPGGHK SRRMAASLAA QNVVKQSSSP QQASESSKFI
GAGEDQAAYL RKAKAQ
