ACSL5_RAT
ID ACSL5_RAT Reviewed; 683 AA.
AC O88813;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Long-chain-fatty-acid--CoA ligase 5 {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 5;
DE Short=LACS 5;
GN Name=Acsl5 {ECO:0000312|RGD:69402}; Synonyms=Acs5, Facl5;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=9722683; DOI=10.1093/oxfordjournals.jbchem.a022165;
RA Oikawa E., Iijima H., Suzuki T., Sasano H., Sato H., Kamataki A.,
RA Nagura H., Kang M.-J., Fujino T., Suzuki H., Yamamoto T.T.;
RT "A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial
RT cells and proliferating preadipocytes.";
RL J. Biochem. 124:679-685(1998).
RN [2]
RP 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 FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=16263710; DOI=10.1074/jbc.m507646200;
RA Mashek D.G., McKenzie M.A., Van Horn C.G., Coleman R.A.;
RT "Rat long chain acyl-CoA synthetase 5 increases fatty acid uptake and
RT partitioning to cellular triacylglycerol in McArdle-RH7777 cells.";
RL J. Biol. Chem. 281:945-950(2006).
RN [4]
RP FUNCTION.
RX PubMed=17761945; DOI=10.1161/atvbaha.107.148429;
RA Zhou Y., Abidi P., Kim A., Chen W., Huang T.-T., Kraemer F.B., Liu J.;
RT "Transcriptional activation of hepatic ACSL3 and ACSL5 by oncostatin m
RT reduces hypertriglyceridemia through enhanced beta-oxidation.";
RL Arterioscler. Thromb. Vasc. Biol. 27:2198-2205(2007).
RN [5]
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 [6]
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-CoAs for both synthesis of cellular lipids, and
CC degradation via beta-oxidation (PubMed:28209804). ACSL5 may sensitize
CC epithelial cells to apoptosis specifically triggered by the death
CC ligand TRAIL at the villus tip of the crypt-villus axis of the small
CC intestine (By similarity). May have a role in the survival of glioma
CC cells (By similarity). May activate fatty acids from exogenous sources
CC for the synthesis of triacylglycerol destined for intracellular
CC storage. It was suggested that it may also stimulate fatty acid
CC oxidation. Utilizes a wide range of saturated fatty acids with a
CC preference for C16-C18 unsaturated fatty acids. {ECO:0000250,
CC ECO:0000269|PubMed:16263710, ECO:0000269|PubMed:17761945,
CC ECO:0000269|PubMed:28209804, ECO:0000269|PubMed:9722683}.
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=14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-
CC epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate;
CC Xref=Rhea:RHEA:52016, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:84024, ChEBI:CHEBI:136117,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:28209804};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52017;
CC Evidence={ECO:0000305|PubMed:28209804};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-
CC epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate;
CC Xref=Rhea:RHEA:52012, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:76625, ChEBI:CHEBI:136115,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:28209804};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52013;
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:Q9ULC5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752;
CC Evidence={ECO:0000250|UniProtKB:Q9ULC5};
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:Q9ULC5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36140;
CC Evidence={ECO:0000250|UniProtKB:Q9ULC5};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=666 uM for ATP {ECO:0000269|PubMed:15683247};
CC KM=2.4 uM for CoA {ECO:0000269|PubMed:15683247};
CC KM=8.6 uM for palmitate {ECO:0000269|PubMed:15683247};
CC KM=6.5 uM for palmitate (when expressed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=4.4 uM for stearate (when expressed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=6.3 uM for oleate (when expressed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=5.8 uM for linoleate (when expressed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC KM=1.8 uM for arachidonate (when expressed in bacteria)
CC {ECO:0000269|PubMed:28209804};
CC Vmax=5053 nmol/min/mg enzyme with palmitate as substrate (when
CC expressed in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=2164 nmol/min/mg enzyme with stearate as substrate (when
CC expressed in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=3726 nmol/min/mg enzyme with oleate as substrate (when expressed
CC in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=1351 nmol/min/mg enzyme with linoleate as substrate (when
CC expressed in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=1880 nmol/min/mg enzyme with arachidonate as substrate (when
CC expressed in bacteria) {ECO:0000269|PubMed:28209804};
CC Vmax=130 nmol/min/mg enzyme with palmitate as substrate
CC {ECO:0000269|PubMed:15683247};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16263710}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:16263710}. Mitochondrion
CC outer membrane {ECO:0000250}; Single-pass type III membrane protein
CC {ECO:0000250}. Endoplasmic reticulum membrane {ECO:0000250}; Single-
CC pass type III membrane protein {ECO:0000250}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9ULC5}.
CC -!- TISSUE SPECIFICITY: Expressed most abundantly in the small intestine,
CC and to a much lesser extent in the lung, liver, adrenal gland, adipose
CC tissue and kidney. {ECO:0000269|PubMed:9722683}.
CC -!- INDUCTION: Expression decreases in response to fast and increases after
CC high sucrose diet. {ECO:0000269|PubMed:16263710}.
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 -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AB012933; BAA33581.1; -; mRNA.
DR PIR; JE0262; JE0262.
DR RefSeq; NP_446059.1; NM_053607.1.
DR AlphaFoldDB; O88813; -.
DR SMR; O88813; -.
DR IntAct; O88813; 1.
DR STRING; 10116.ENSRNOP00000022126; -.
DR SwissLipids; SLP:000001685; -.
DR iPTMnet; O88813; -.
DR PhosphoSitePlus; O88813; -.
DR PaxDb; O88813; -.
DR PRIDE; O88813; -.
DR GeneID; 94340; -.
DR KEGG; rno:94340; -.
DR UCSC; RGD:69402; rat.
DR CTD; 51703; -.
DR RGD; 69402; Acsl5.
DR eggNOG; KOG1256; Eukaryota.
DR InParanoid; O88813; -.
DR OrthoDB; 630541at2759; -.
DR PhylomeDB; O88813; -.
DR BRENDA; 6.2.1.3; 5301.
DR Reactome; R-RNO-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR SABIO-RK; O88813; -.
DR PRO; PR:O88813; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
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; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0047676; F:arachidonate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; TAS: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:0010747; P:positive regulation of long-chain fatty acid import across plasma membrane; IDA:RGD.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IDA:RGD.
DR GO; GO:0070723; P:response to cholesterol; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0009744; P:response to sucrose; IEP:RGD.
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 Acetylation; ATP-binding; Cell membrane; Endoplasmic reticulum;
KW Fatty acid metabolism; Ligase; Lipid metabolism; Magnesium; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..683
FT /note="Long-chain-fatty-acid--CoA ligase 5"
FT /id="PRO_0000193114"
FT TRANSMEM 12..32
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..683
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 361
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8JZR0"
SQ SEQUENCE 683 AA; 76405 MW; D4EC2A58FD29040C CRC64;
MLFIFNFLFS PLPTPALICL LTFGTAIFLW LINRPQPVLP LIDLDNQSVG IEGGARRGAF
QKNNDLILYY FSDAKTLYEV FQRGLAVSDN GPCLGYRKPN QPYKWISYKQ VSDRAEYLGS
CLLHKGYKPS QDQFIGIFAQ NRPEWVISEL ACYTYSMVAV PLYDTLGAEA IIYVINRADI
SVVICDTPQK ATMLIENVEK DLTPGLKTVI LMDPFDDDLM KRGEKCGIEM LSLHDAENLG
KENFKKPMPP NPEDLSVICF TSGTTGDPKG AMLTHQNIVS NMAAFLKFLE PIFQPTPEDV
TISYLPLAHM FERLVQGVIF SCGGKIGFFQ GDIRLLPDDM KALKPTVFPT VPRLLNRVYD
KVQNEAKTPL KKFLLNLAII SKFNEVRNGI IRRNSLWDKL VFSKIQSSLG GKVRLMITGA
APISTPVLTF FRAAMGCWVF EAYGQTECTA GCSITSPGDW TAGHVGTPVS CNFVKLEDVA
DMNYFSVNNE GEICIKGNNV FKGYLKDPEK TQEVLDKDGW LHTGDIGRWL PNGTLKIIDR
KKNIFKLAQG EYIAPEKIEN VYSRSRPILQ VFVHGESLRS FLIGVVVPDP ESLPSFAAKI
GVKGSFEELC QNQCVKKAIL EDLQKVGKEG GLKSFEQVKS IFVHPEPFSI ENGLLTPTLK
AKRVELAKFF QTQIKSLYES IEE
