ID   ACSL6_MOUSE             Reviewed;         697 AA.
AC   Q91WC3; Q80ZF1;
DT   15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 162.
DE   RecName: Full=Long-chain-fatty-acid--CoA ligase 6 {ECO:0000305};
DE            EC=6.2.1.3 {ECO:0000250|UniProtKB:P33124};
DE   AltName: Full=Arachidonate--CoA ligase {ECO:0000305};
DE            EC=6.2.1.15 {ECO:0000250|UniProtKB:P33124};
DE   AltName: Full=Long-chain acyl-CoA synthetase 6;
DE            Short=LACS 6;
GN   Name=Acsl6; Synonyms=Facl6;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   STRAIN=ICR; TISSUE=Brain;
RX   PubMed=12767919; DOI=10.1016/s0006-291x(03)00859-3;
RA   Kee H.J., Koh J.T., Yang S.Y., Lee Z.H., Baik Y.H., Kim K.K.;
RT   "A novel murine long-chain acyl-CoA synthetase expressed in brain
RT   participates in neuronal cell proliferation.";
RL   Biochem. Biophys. Res. Commun. 305:925-933(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Retina;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Catalyzes the conversion of long-chain fatty acids to their
CC       active form acyl-CoA for both synthesis of cellular lipids, and
CC       degradation via beta-oxidation (By similarity). Plays an important role
CC       in fatty acid metabolism in brain and the acyl-CoAs produced may be
CC       utilized exclusively for the synthesis of the brain lipid (By
CC       similarity). {ECO:0000250, ECO:0000250|UniProtKB:P33124}.
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:0000250|UniProtKB:P33124};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422;
CC         Evidence={ECO:0000250|UniProtKB:P33124};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA =
CC         (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate;
CC         Xref=Rhea:RHEA:19713, ChEBI:CHEBI:30616, ChEBI:CHEBI:32395,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57368,
CC         ChEBI:CHEBI:456215; EC=6.2.1.15;
CC         Evidence={ECO:0000250|UniProtKB:P33124};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714;
CC         Evidence={ECO:0000250|UniProtKB:P33124};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-
CC         hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate;
CC         Xref=Rhea:RHEA:52116, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:78832, ChEBI:CHEBI:136409,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P33124};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52117;
CC         Evidence={ECO:0000250|UniProtKB:P33124};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-
CC         hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate;
CC         Xref=Rhea:RHEA:52112, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:90718, ChEBI:CHEBI:136408,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P33124};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52113;
CC         Evidence={ECO:0000250|UniProtKB:P33124};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-
CC         hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate;
CC         Xref=Rhea:RHEA:52108, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:65341, ChEBI:CHEBI:136407,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P33124};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52109;
CC         Evidence={ECO:0000250|UniProtKB:P33124};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + CoA + hexadecanoate = AMP + diphosphate + hexadecanoyl-
CC         CoA; Xref=Rhea:RHEA:30751, ChEBI:CHEBI:7896, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:Q9UKU0};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752;
CC         Evidence={ECO:0000250|UniProtKB:Q9UKU0};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP
CC         + diphosphate; Xref=Rhea:RHEA:36139, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:61526,
CC         ChEBI:CHEBI:72745, ChEBI:CHEBI:456215;
CC         Evidence={ECO:0000250|UniProtKB:Q9UKU0};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36140;
CC         Evidence={ECO:0000250|UniProtKB:Q9UKU0};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250};
CC       Single-pass type III membrane protein {ECO:0000250}. Peroxisome
CC       membrane {ECO:0000250}; Single-pass type III membrane protein
CC       {ECO:0000250}. Microsome membrane {ECO:0000250}; Single-pass type III
CC       membrane protein {ECO:0000250}. Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q9UKU0}; Single-pass type III membrane protein
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q91WC3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q91WC3-2; Sequence=VSP_037824;
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
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DR   EMBL; AY167035; AAO38689.1; -; mRNA.
DR   EMBL; BC016114; AAH16114.1; -; mRNA.
DR   CCDS; CCDS24695.1; -. [Q91WC3-2]
DR   CCDS; CCDS24696.1; -. [Q91WC3-1]
DR   RefSeq; NP_001028770.1; NM_001033598.1. [Q91WC3-1]
DR   RefSeq; XP_006532906.1; XM_006532843.1. [Q91WC3-1]
DR   RefSeq; XP_006532907.1; XM_006532844.1. [Q91WC3-1]
DR   AlphaFoldDB; Q91WC3; -.
DR   SMR; Q91WC3; -.
DR   BioGRID; 229776; 10.
DR   IntAct; Q91WC3; 2.
DR   MINT; Q91WC3; -.
DR   STRING; 10090.ENSMUSP00000104533; -.
DR   GlyGen; Q91WC3; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q91WC3; -.
DR   MetOSite; Q91WC3; -.
DR   PhosphoSitePlus; Q91WC3; -.
DR   SwissPalm; Q91WC3; -.
DR   jPOST; Q91WC3; -.
DR   MaxQB; Q91WC3; -.
DR   PaxDb; 10090-ENSMUSP00000104533; -.
DR   ProteomicsDB; 285708; -. [Q91WC3-1]
DR   ProteomicsDB; 285709; -. [Q91WC3-2]
DR   DNASU; 216739; -.
DR   Ensembl; ENSMUST00000072178.11; ENSMUSP00000072040.5; ENSMUSG00000020333.18. [Q91WC3-1]
DR   Ensembl; ENSMUST00000093106.12; ENSMUSP00000090795.6; ENSMUSG00000020333.18. [Q91WC3-1]
DR   Ensembl; ENSMUST00000094194.10; ENSMUSP00000091746.4; ENSMUSG00000020333.18. [Q91WC3-1]
DR   Ensembl; ENSMUST00000108905.10; ENSMUSP00000104533.4; ENSMUSG00000020333.18. [Q91WC3-2]
DR   GeneID; 216739; -.
DR   KEGG; mmu:216739; -.
DR   UCSC; uc007ixo.1; mouse. [Q91WC3-1]
DR   AGR; MGI:894291; -.
DR   CTD; 23305; -.
DR   MGI; MGI:894291; Acsl6.
DR   VEuPathDB; HostDB:ENSMUSG00000020333; -.
DR   eggNOG; KOG1256; Eukaryota.
DR   GeneTree; ENSGT00940000162308; -.
DR   InParanoid; Q91WC3; -.
DR   OMA; PRIWTKF; -.
DR   OrthoDB; 443463at2759; -.
DR   PhylomeDB; Q91WC3; -.
DR   BRENDA; 6.2.1.3; 3474.
DR   Reactome; R-MMU-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR   BioGRID-ORCS; 216739; 4 hits in 81 CRISPR screens.
DR   ChiTaRS; Acsl6; mouse.
DR   PRO; PR:Q91WC3; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q91WC3; Protein.
DR   Bgee; ENSMUSG00000020333; Expressed in olfactory epithelium and 157 other cell types or tissues.
DR   ExpressionAtlas; Q91WC3; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; ISO:MGI.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0047676; F:arachidonate-CoA ligase activity; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR   GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0015908; P:fatty acid transport; ISO:MGI.
DR   GO; GO:0001676; P:long-chain fatty acid metabolic process; ISO:MGI.
DR   GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; ISO:MGI.
DR   GO; GO:0007405; P:neuroblast proliferation; IDA:MGI.
DR   GO; GO:0008654; P:phospholipid biosynthetic process; ISO:MGI.
DR   GO; GO:0010747; P:positive regulation of long-chain fatty acid import across plasma membrane; ISO:MGI.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR   GO; GO:0019432; P:triglyceride biosynthetic process; ISO:MGI.
DR   GO; GO:0000038; P:very long-chain fatty acid metabolic process; IBA:GO_Central.
DR   CDD; cd05927; LC-FACS_euk; 1.
DR   Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig_com.
DR   InterPro; IPR042099; ANL_N_sf.
DR   InterPro; IPR045311; LC-FACS_euk.
DR   PANTHER; PTHR43272; LONG-CHAIN-FATTY-ACID--COA LIGASE; 1.
DR   PANTHER; PTHR43272:SF54; LONG-CHAIN-FATTY-ACID--COA LIGASE 6; 1.
DR   Pfam; PF00501; AMP-binding; 1.
DR   SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   Genevisible; Q91WC3; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Endoplasmic reticulum;
KW   Fatty acid metabolism; Ligase; Lipid metabolism; Magnesium; Membrane;
KW   Microsome; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW   Peroxisome; Reference proteome; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..697
FT                   /note="Long-chain-fatty-acid--CoA ligase 6"
FT                   /id="PRO_0000193116"
FT   TRANSMEM        25..45
FT                   /note="Helical; Signal-anchor for type III membrane
FT                   protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        46..697
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1
FT                   /note="M -> MLTFFLVSGGSLWLFAEIALSLLEKM (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12767919"
FT                   /id="VSP_037824"
FT   CONFLICT        364
FT                   /note="P -> S (in Ref. 1; AAO38689)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        680
FT                   /note="E -> G (in Ref. 1; AAO38689)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   697 AA;  78017 MW;  ADAFC99E5D97DC22 CRC64;
     MQTQEILRIL RLPELSDLGQ FFRSLSATTL VSVGALAAVL AYWLTHRPKA LQPPCNLLKQ
     SEEVEDGGGA RRSVIGGCTQ LLTHYYDDAR TMYQVFRRGL SISGNGPCLG FRKPEQPYQW
     LSYQEVAKRA EFLGSGLLQH DCKVGTEQFV GVFAQNRPEW IIAELACYTY SMVVVPLYDT
     LGPGSISYII NTADICTVIV DKPHKATLLL EHVERKETPG LKLVILMEPF EDALRERGKK
     CGVDIKSMQA IEDCGRENHH APVPPRPDDL SIVCFTSGTT GNPKGAMLTH GNVVADFSGF
     LKVTEKVIFP RQDDVLISFL PLAHMFERVI QSVVYCHGGR VGFFQGDIRL LSDDMKALRP
     TIFPVVPRLL NRMYDKIFHQ ADTSLKRWLL EFAAKRKQAE VRSGIIRNNS IWDELFFNKI
     QASLGGHVRM IVTGAAPASP TVLGFLRAAL GCQVYEGYGQ TECTAGCTFT TPGDWTSGHV
     GAPLPCNHIK LVDAEELNYW TCKGEGEICV KGPNVFKGYL KDEDRTKEAL DSDGWLHTGD
     IGKWLPEGTL KIIDRKKHIF KLAQGEYVAP EKIENIYIRS EPVAQIYVHG DSLKAFLVGI
     VVPDPEVMPS WAQKKGIEGT YQELCMKKEL KKAILDDMVM LGKESGLHSF EQVKAIYIHC
     DMFSVQNGLL TPTLKAKRPE LREYFKKQIE ELYLVSV
//