ACSL6_RAT
ID ACSL6_RAT Reviewed; 697 AA.
AC P33124; Q63835; Q6IU14;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Long-chain-fatty-acid--CoA ligase 6 {ECO:0000305};
DE EC=6.2.1.3 {ECO:0000269|PubMed:28209804};
DE AltName: Full=Arachidonate--CoA ligase {ECO:0000305};
DE EC=6.2.1.15 {ECO:0000269|PubMed:28209804};
DE AltName: Full=Long-chain acyl-CoA synthetase 6;
DE Short=LACS 6;
DE AltName: Full=Long-chain-fatty-acid--CoA ligase, brain isozyme;
GN Name=Acsl6 {ECO:0000312|RGD:69403}; Synonyms=Acs2, Facl6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=1569043; DOI=10.1093/oxfordjournals.jbchem.a123737;
RA Fujino T., Yamamoto T.;
RT "Cloning and functional expression of a novel long-chain acyl-CoA
RT synthetase expressed in brain.";
RL J. Biochem. 111:197-203(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Brain;
RX PubMed=15683247; DOI=10.1021/bi047721l;
RA Van Horn C.G., Caviglia J.M., Li L.O., Wang S., Granger D.A., Coleman R.A.;
RT "Characterization of recombinant long-chain rat acyl-CoA synthetase
RT isoforms 3 and 6: identification of a novel variant of isoform 6.";
RL Biochemistry 44:1635-1642(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-160 (ISOFORM 1).
RC TISSUE=Spinal ganglion;
RG Amgen EST program;
RT "Amgen rat EST program.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP RETRACTED PAPER.
RC TISSUE=Brain;
RX PubMed=1654331; DOI=10.1016/s0021-9258(19)47411-5;
RA Yamakawa A., Nishizawa M., Fujiwara K.T., Kawai S., Kawasaki H., Suzuki K.,
RA Takenawa T.;
RT "Molecular cloning and sequencing of cDNA encoding the phosphatidylinositol
RT kinase from rat brain.";
RL J. Biol. Chem. 266:17580-17583(1991).
RN [5]
RP RETRACTION NOTICE OF PUBMED:1654331.
RX PubMed=1460058; DOI=10.1016/s0021-9258(19)74086-1;
RA Yamakawa A., Nishizawa M., Fujiwara K.T., Kawai S., Kawasaki H., Suzuki K.,
RA Takenawa T.;
RL J. Biol. Chem. 267:25620-25620(1992).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=8973631; DOI=10.1111/j.1432-1033.1996.0186r.x;
RA Iijima H., Fujino T., Minekura H., Suzuki H., Kang M.-J., Yamamoto T.T.;
RT "Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2.";
RL Eur. J. Biochem. 242:186-190(1996).
RN [7]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=28209804; DOI=10.1194/jlr.m072512;
RA Klett E.L., Chen S., Yechoor A., Lih F.B., Coleman R.A.;
RT "Long-chain acyl-CoA synthetase isoforms differ in preferences for
RT eicosanoid species and long-chain fatty acids.";
RL J. Lipid Res. 58:884-894(2017).
RN [8]
RP ERRATUM OF PUBMED:28209804.
RX PubMed=29196521; DOI=10.1194/jlr.m072512err;
RA Klett E.L., Chen S., Yechoor A., Lih F.B., Coleman R.A.;
RL J. Lipid Res. 58:2365-2365(2017).
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 (PubMed:28209804). Plays an important
CC role in fatty acid metabolism in brain and the acyl-CoAs produced may
CC be utilized exclusively for the synthesis of the brain lipid.
CC {ECO:0000269|PubMed:28209804}.
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:0000269|PubMed:28209804};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422;
CC Evidence={ECO:0000305|PubMed:28209804};
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:0000269|PubMed:28209804};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714;
CC Evidence={ECO:0000305|PubMed:28209804};
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:0000269|PubMed:28209804};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52117;
CC Evidence={ECO:0000305|PubMed:28209804};
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:0000269|PubMed:28209804};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52113;
CC Evidence={ECO:0000305|PubMed:28209804};
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:0000269|PubMed:28209804};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52109;
CC Evidence={ECO:0000305|PubMed:28209804};
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;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12210 uM for ATP (Isoform 1) {ECO:0000269|PubMed:15683247};
CC KM=4.7 uM for CoA (Isoform 1) {ECO:0000269|PubMed:15683247};
CC KM=6.0 uM for palmitate (Isoform 1) {ECO:0000269|PubMed:15683247};
CC KM=3.0 uM for oleate (Isoform 1) {ECO:0000269|PubMed:15683247};
CC KM=9.7 uM for arachidonate (Isoform 1) {ECO:0000269|PubMed:15683247};
CC KM=1480 uM for ATP (Isoform 2) {ECO:0000269|PubMed:15683247};
CC KM=2.4 uM for CoA (Isoform 2) {ECO:0000269|PubMed:15683247};
CC KM=3.6 uM for palmitate (Isoform 2) {ECO:0000269|PubMed:15683247};
CC KM=5.3 uM for oleate (Isoform 2) {ECO:0000269|PubMed:15683247};
CC KM=6.5 uM for arachidonate (Isoform 2) {ECO:0000269|PubMed:15683247};
CC KM=3 uM for palmitate (when expreesed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=4.4 uM for stearate (when expreesed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=4.4 uM for oleate (when expreesed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=6 uM for linoleate (when expreesed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=2.9 uM for arachidonate (when expreesed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC Vmax=208 nmol/min/mg enzyme with palmitate as substrate (Isoform 1)
CC {ECO:0000269|PubMed:15683247};
CC Vmax=153 nmol/min/mg enzyme with oleate as substrate (Isoform 1)
CC {ECO:0000269|PubMed:15683247};
CC Vmax=139 nmol/min/mg enzyme with arachidonate as substrate (Isoform
CC 1) {ECO:0000269|PubMed:15683247};
CC Vmax=739 nmol/min/mg enzyme with palmitate as substrate (Isoform 2)
CC {ECO:0000269|PubMed:15683247};
CC Vmax=1088 nmol/min/mg enzyme with oleate as substrate (Isoform 2)
CC {ECO:0000269|PubMed:15683247};
CC Vmax=1212 nmol/min/mg enzyme with arachidonate as substrate (Isoform
CC 2) {ECO:0000269|PubMed:15683247};
CC Vmax=3993 nmol/min/mg enzyme with palmitate as substrate (when
CC expreesed in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=1727 nmol/min/mg enzyme with stearate as substrate (when
CC expreesed in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=2238 nmol/min/mg enzyme with oleate as substrate (when expreesed
CC in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=1763 nmol/min/mg enzyme with linoleate as substrate (when
CC expreesed in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=1682 nmol/min/mg enzyme with arachidonate as substrate (when
CC expreesed in bacteria) {ECO:0000269|PubMed:28209804};
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; Synonyms=ACSL6_vs1;
CC IsoId=P33124-1; Sequence=Displayed;
CC Name=2; Synonyms=ACSL6_vs2;
CC IsoId=P33124-2; Sequence=VSP_057107, VSP_057108;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in brain and, to a much
CC lesser extent, in heart and adrenal.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 is detected 10 days after birth, and
CC increased in a coordinate fashion during the development of brain, and
CC the amount did not decrease when myelination was completed.
CC {ECO:0000269|PubMed:8973631}.
CC -!- MISCELLANEOUS: 5 rat isozymes encoded by different genes have been
CC described. ACSL6 corresponds to isozyme 2 (ACS2).
CC {ECO:0000303|PubMed:15683247}.
CC -!- MISCELLANEOUS: [Isoform 1]: Contains exon 14.
CC -!- MISCELLANEOUS: [Isoform 2]: Contains exon 13. No differences in the
CC affinity for fatty acids and CoA. Decreased affinity for ATP. Could
CC play an important role at lower ATP levels. Expressed at lower level in
CC the brain compared to isoform 1. {ECO:0000269|PubMed:15683247}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; S56508; AAB19809.2; -; mRNA.
DR EMBL; D10041; BAA00932.1; -; mRNA.
DR EMBL; CB582512; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY625254; AAT41589.1; -; mRNA.
DR PIR; JX0205; JX0205.
DR RefSeq; NP_570095.1; NM_130739.1. [P33124-1]
DR RefSeq; XP_006246285.1; XM_006246223.3. [P33124-2]
DR RefSeq; XP_006246286.1; XM_006246224.3. [P33124-2]
DR AlphaFoldDB; P33124; -.
DR SMR; P33124; -.
DR STRING; 10116.ENSRNOP00000055608; -.
DR SwissLipids; SLP:000001686; -.
DR iPTMnet; P33124; -.
DR PhosphoSitePlus; P33124; -.
DR jPOST; P33124; -.
DR PaxDb; P33124; -.
DR PRIDE; P33124; -.
DR Ensembl; ENSRNOT00000030760; ENSRNOP00000033248; ENSRNOG00000026745. [P33124-2]
DR GeneID; 117243; -.
DR KEGG; rno:117243; -.
DR UCSC; RGD:69403; rat. [P33124-1]
DR CTD; 23305; -.
DR RGD; 69403; Acsl6.
DR VEuPathDB; HostDB:ENSRNOG00000026745; -.
DR eggNOG; KOG1256; Eukaryota.
DR GeneTree; ENSGT00940000162308; -.
DR InParanoid; P33124; -.
DR OrthoDB; 630541at2759; -.
DR PhylomeDB; P33124; -.
DR BRENDA; 6.2.1.3; 5301.
DR Reactome; R-RNO-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR PRO; PR:P33124; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000026745; Expressed in frontal cortex and 12 other tissues.
DR ExpressionAtlas; P33124; baseline and differential.
DR Genevisible; P33124; RN.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0047676; F:arachidonate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0015908; P:fatty acid transport; IGI:RGD.
DR GO; GO:0008610; P:lipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; IGI:RGD.
DR GO; GO:0007405; P:neuroblast proliferation; ISO:RGD.
DR GO; GO:0048666; P:neuron development; IEP:RGD.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IMP:RGD.
DR GO; GO:0010747; P:positive regulation of long-chain fatty acid import across plasma membrane; IMP:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
DR GO; GO:0009629; P:response to gravity; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0019432; P:triglyceride biosynthetic process; IGI:RGD.
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; -; 1.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR045311; LC-FACS_euk.
DR Pfam; PF00501; AMP-binding; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
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_0000193117"
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 306..319
FT /note="SQWAPTCADVHFSY -> KVIFPRQDDVLISF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15683247"
FT /id="VSP_057107"
FT VAR_SEQ 329..330
FT /note="MV -> VI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15683247"
FT /id="VSP_057108"
SQ SEQUENCE 697 AA; 78180 MW; 0B0CA7EFD653E2BE CRC64;
MQTQEILRIL RLPELSDLGQ FFRSLSATTL VSMGALAAIL AYWLTHRPKA LQPPCNLLMQ
SEEVEDSGGA RRSVIGDCTQ LLTHYYDDAR TMYQVFRRGL SISGNGPCLG FRKPEQPYQW
LSYQEVAKRA EFLGSGLLQH DCKVGTEQFI GVFAQNRPEW IIAELACYTY SMVVVPLYDT
LGPGSIRYII NTADICTVIV DKPHKAILLL EHVERKETPG LKLVILMEPF DDALRERGKK
CGVDIKSMQA IEDSGQENHR VPVPPRPDDL SIVCFTSGTT GNPKGAMLTH GNVVADFSGF
LKVTESQWAP TCADVHFSYL PLAHMFERMV QSVVYCHGGR VGFFQGDIRL LSDDMKALRP
TIFPVVPRLL NRMYDKIFHQ ADTSLKRWLL EFAAKRKQAE VRSGIIRNNS IWDELFFNKI
QASLGGHVRM IVTGAAPASP TVLGFLRAAL GCQVYEGYGQ TECTAGCTFT TPGDWTSGHV
GAPLPCNHIK LVDAEELNYW TSKGEGEICV KGPNVFKGYL KDEDRTKEAL DSDGWLHTGD
IGKWLPEGTL KIIDRKKHIF KLAQGEYVAP EKIENIYIRS EPVAQIYVHG DSLKAFLVGI
VVPDPEVMPC WAQKKGIEGN YQELCKSKEL KKAILDDMVM LGKESGLHSF EQVKAIYIHC
DMFSVQNGLL TPTLKAKRPE LREYFKKQIE ELYSISM
