ID ACSL5_MOUSE Reviewed; 683 AA. AC Q8JZR0; DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 164. DE RecName: Full=Long-chain-fatty-acid--CoA ligase 5 {ECO:0000305}; DE EC=6.2.1.3 {ECO:0000250|UniProtKB:O88813}; DE AltName: Full=Arachidonate--CoA ligase {ECO:0000305}; DE EC=6.2.1.15 {ECO:0000250|UniProtKB:O88813}; DE AltName: Full=Long-chain acyl-CoA synthetase 5; DE Short=LACS 5; GN Name=Acsl5 {ECO:0000312|MGI:MGI:1919129}; Synonyms=Facl5; 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 [LARGE SCALE MRNA]. RC TISSUE=Mammary tumor; 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 [2] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, Pancreas, and RC Spleen; 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). RN [3] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-361, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=23576753; DOI=10.1073/pnas.1302961110; RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.; RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria RT identifies substrates of SIRT3 in metabolic pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013). 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 (By similarity). ACSL5 may activate CC fatty acids from exogenous sources for the synthesis of triacylglycerol CC destined for intracellular storage (By similarity). It was suggested CC that it may also stimulate fatty acid oxidation (By similarity). At the CC villus tip of the crypt-villus axis of the small intestine may CC sensitize epithelial cells to apoptosis specifically triggered by the CC death ligand TRAIL (By similarity). May have a role in the survival of CC glioma cells (By similarity). Utilizes a wide range of saturated fatty CC acids with a preference for C16-C18 unsaturated fatty acids (By CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:O88813}. 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:Q9ULC5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422; CC Evidence={ECO:0000250|UniProtKB:Q9ULC5}; 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:O88813}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714; CC Evidence={ECO:0000250|UniProtKB:O88813}; 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 -!- 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:O88813}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52117; CC Evidence={ECO:0000250|UniProtKB:O88813}; 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:O88813}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52113; CC Evidence={ECO:0000250|UniProtKB:O88813}; 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:O88813}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52109; CC Evidence={ECO:0000250|UniProtKB:O88813}; 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:0000250|UniProtKB:O88813}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52017; CC Evidence={ECO:0000250|UniProtKB:O88813}; 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:0000250|UniProtKB:O88813}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52013; CC Evidence={ECO:0000250|UniProtKB:O88813}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + CC diphosphate; Xref=Rhea:RHEA:33607, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57387, ChEBI:CHEBI:456215; CC Evidence={ECO:0000250|UniProtKB:Q9ULC5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608; CC Evidence={ECO:0000250|UniProtKB:Q9ULC5}; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9ULC5}. CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9ULC5}. 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 -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC031544; AAH31544.1; -; mRNA. DR CCDS; CCDS29908.1; -. DR PIR; S49487; S49487. DR RefSeq; NP_082252.1; NM_027976.2. DR RefSeq; XP_006527241.1; XM_006527178.2. DR AlphaFoldDB; Q8JZR0; -. DR SMR; Q8JZR0; -. DR BioGRID; 241124; 8. DR STRING; 10090.ENSMUSP00000046585; -. DR iPTMnet; Q8JZR0; -. DR PhosphoSitePlus; Q8JZR0; -. DR SwissPalm; Q8JZR0; -. DR EPD; Q8JZR0; -. DR jPOST; Q8JZR0; -. DR MaxQB; Q8JZR0; -. DR PaxDb; 10090-ENSMUSP00000046585; -. DR ProteomicsDB; 285660; -. DR Pumba; Q8JZR0; -. DR Antibodypedia; 31809; 310 antibodies from 34 providers. DR DNASU; 433256; -. DR Ensembl; ENSMUST00000043150.6; ENSMUSP00000046585.5; ENSMUSG00000024981.7. DR GeneID; 433256; -. DR KEGG; mmu:433256; -. DR UCSC; uc008hxp.1; mouse. DR AGR; MGI:1919129; -. DR CTD; 51703; -. DR MGI; MGI:1919129; Acsl5. DR VEuPathDB; HostDB:ENSMUSG00000024981; -. DR eggNOG; KOG1256; Eukaryota. DR GeneTree; ENSGT00940000156651; -. DR HOGENOM; CLU_000022_45_4_1; -. DR InParanoid; Q8JZR0; -. DR OMA; ARATMAH; -. DR OrthoDB; 443463at2759; -. DR PhylomeDB; Q8JZR0; -. DR TreeFam; TF313877; -. DR BRENDA; 6.2.1.3; 3474. DR Reactome; R-MMU-75876; Synthesis of very long-chain fatty acyl-CoAs. DR BioGRID-ORCS; 433256; 4 hits in 80 CRISPR screens. DR ChiTaRS; Acsl5; mouse. DR PRO; PR:Q8JZR0; -. DR Proteomes; UP000000589; Chromosome 19. DR RNAct; Q8JZR0; Protein. DR Bgee; ENSMUSG00000024981; Expressed in small intestine Peyer's patch and 296 other cell types or tissues. DR ExpressionAtlas; Q8JZR0; 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; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; HDA:MGI. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0047676; F:arachidonate-CoA ligase activity; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IMP:UniProtKB. DR GO; GO:0090434; F:oleoyl-CoA ligase activity; ISS:UniProtKB. DR GO; GO:0015908; P:fatty acid transport; ISO:MGI. DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IMP:UniProtKB. DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; ISO:MGI. DR GO; GO:0008654; P:phospholipid biosynthetic process; ISO:MGI. DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; ISO:MGI. DR GO; GO:0010747; P:positive regulation of long-chain fatty acid import across plasma membrane; ISO:MGI. DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISO:MGI. DR GO; GO:2001236; P:regulation of extrinsic apoptotic signaling pathway; ISO:MGI. 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:SF3; LONG-CHAIN-FATTY-ACID--COA LIGASE 5; 1. DR Pfam; PF00501; AMP-binding; 1. DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1. DR PROSITE; PS00455; AMP_BINDING; 1. DR Genevisible; Q8JZR0; MM. 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_0000193113" 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:0007744|PubMed:23576753" SQ SEQUENCE 683 AA; 76206 MW; 734A1A5878741D70 CRC64; MLFIFNFLFS PLPTPALICL LTFGTAIFLW LINRPQPVLP LIDLDNQSVG IEGGARRGAF QKNNDLILYY FSDAKTLYEN FQRGLAVSDN GPCLGYRKPN QPYKWISYKQ VSDRAEYLGS CLLHKGYKSS QDQFVGIFAQ NRPEWVISEL ACYTYSMVAV PLYDTLGTEA IIFVINRADI PVVICDTPQK ATMLVENVEK GLTPGLKTII LMDPFDDDLM KRGEKCGVEM LSLHDAENIG KENFKKPVPP KPEDLSVICF TSGTTGDPKG AMLTHENVVS NMAAFLKFLE PIFQPTSDDV TISYLPLAHM FERLVQGILF SCGGKIGFFQ GDIRLLPDDM KALKPTVFPT VPRLLNRVYD KVQNEAKTPL KKFLLNLAII SKFNEVKNGI IRRDSLWDKL VFSKIQGSLG GKVRLMITGA APISTPVLTF FRAAMGCWVF EAYGQTECTG GCSITSPGDW TAGHVGTPVA CNFVKLEDVA DMNYFSVNNE GEICIKGNNV FKGYLKDPEK TQEVLDKDGW LHTGDIGRWL PNGTLKIVDR KKNIFKLAQG EYIAPEKIEN VYSRSRPVLQ VFVHGESLRS FLIGVVVPDP DSLPSFAAKI GVKGSFEELC KNQCVKEAIL EDLQKIGKEG GLKSFEQVKS IFVHPEPFTI ENGLLTPTLK AKRVELAKFF QTQIKSLYES IEE //