ID ACSL5_HUMAN Reviewed; 683 AA. AC Q9ULC5; A6GV77; D3DRB3; Q6UX44; Q9UIU4; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 200. DE RecName: Full=Long-chain-fatty-acid--CoA ligase 5 {ECO:0000305}; DE EC=6.2.1.3 {ECO:0000269|PubMed:17681178, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}; 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|HGNC:HGNC:16526}; GN Synonyms=ACS5 {ECO:0000303|Ref.8}, FACL5 {ECO:0000303|Ref.8}; GN ORFNames=UNQ633/PRO1250; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, RP ALTERNATIVE SPLICING, BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC RP ACTIVITY. RC TISSUE=Small intestine mucosa; RX PubMed=17681178; DOI=10.1053/j.gastro.2007.06.005; RA Gassler N., Roth W., Funke B., Schneider A., Herzog F., Ehemann V., RA Sykora J., Haas T.L., Walczak H., Ganten T., Zentgraf H., Erb P., RA Alonso A., Autschbach F., Schirmacher P., Knuechel R., Kopitz J.; RT "Regulation of enterocyte apoptosis by acyl-CoA synthetase 5 splicing."; RL Gastroenterology 133:587-598(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Hepatoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Colon; 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 [8] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2). RA Yamashita Y.; RT "Human FACL5 (or ACS5)."; RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases. RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32 (ISOFORM 2), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [10] RP FUNCTION. RX PubMed=19459852; DOI=10.1111/j.1349-7006.2009.01203.x; RA Mashima T., Sato S., Okabe S., Miyata S., Matsuura M., Sugimoto Y., RA Tsuruo T., Seimiya H.; RT "Acyl-CoA synthetase as a cancer survival factor: its inhibition enhances RT the efficacy of etoposide."; RL Cancer Sci. 100:1556-1562(2009). RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18806831; DOI=10.1038/onc.2008.355; RA Mashima T., Sato S., Sugimoto Y., Tsuruo T., Seimiya H.; RT "Promotion of glioma cell survival by acyl-CoA synthetase 5 under RT extracellular acidosis conditions."; RL Oncogene 28:9-19(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=22633490; DOI=10.1016/j.molcel.2012.04.033; RA Nakahara K., Ohkuni A., Kitamura T., Abe K., Naganuma T., Ohno Y., RA Zoeller R.A., Kihara A.; RT "The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of RT the sphingosine 1-phosphate degradation pathway."; RL Mol. Cell 46:461-471(2012). RN [14] RP CATALYTIC ACTIVITY, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=24269233; DOI=10.1016/j.bbrc.2013.11.036; RA Ohkuni A., Ohno Y., Kihara A.; RT "Identification of acyl-CoA synthetases involved in the mammalian RT sphingosine 1-phosphate metabolic pathway."; RL Biochem. Biophys. Res. Commun. 442:195-201(2013). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP VARIANTS [LARGE SCALE ANALYSIS] ARG-388 AND ASP-466. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [17] RP VARIANT DIAR13 LYS-453, CHARACTERIZATION OF VARIANT DIAR13 LYS-453, RP INVOLVEMENT IN DIAR13, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR RP LOCATION. RX PubMed=33191500; DOI=10.1111/cge.13883; RA Al-Thihli K., Afting C., Al-Hashmi N., Mohammed M., Sliwinski S., RA Al Shibli N., Al-Said K., Al-Kasbi G., Al-Kharusi K., Merle U., RA Fuellekrug J., Al-Maawali A.; RT "Deficiency of acyl-CoA synthetase 5 is associated with a severe and RT treatable failure to thrive of neonatal onset."; RL Clin. Genet. 99:376-383(2021). 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:17681178, PubMed:24269233, CC PubMed:22633490, PubMed:33191500). ACSL5 may activate fatty acids from CC exogenous sources for the synthesis of triacylglycerol destined for CC intracellular storage (By similarity). Utilizes a wide range of CC saturated fatty acids with a preference for C16-C18 unsaturated fatty CC acids (By similarity). It was suggested that it may also stimulate CC fatty acid oxidation (By similarity). At the villus tip of the crypt- CC villus axis of the small intestine may sensitize epithelial cells to CC apoptosis specifically triggered by the death ligand TRAIL. May have a CC role in the survival of glioma cells. {ECO:0000250, CC ECO:0000269|PubMed:17681178, ECO:0000269|PubMed:18806831, CC ECO:0000269|PubMed:19459852, ECO:0000269|PubMed:22633490, CC ECO:0000269|PubMed:24269233, ECO:0000269|PubMed:33191500}. 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:17681178, ECO:0000269|PubMed:22633490, CC ECO:0000269|PubMed:24269233}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422; CC Evidence={ECO:0000305|PubMed:22633490, ECO:0000305|PubMed:24269233}; 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:0000269|PubMed:24269233}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752; CC Evidence={ECO:0000305|PubMed:24269233}; 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:0000269|PubMed:22633490, ECO:0000305|PubMed:24269233}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36140; CC Evidence={ECO:0000305|PubMed:22633490, ECO:0000305|PubMed:24269233}; 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:0000269|PubMed:33191500}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608; CC Evidence={ECO:0000305|PubMed:33191500}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]: CC Kinetic parameters: CC KM=0.11 uM for palmitic acid (at pH 7.5) CC {ECO:0000269|PubMed:17681178}; CC KM=0.38 uM for palmitic acid (at pH 9.5) CC {ECO:0000269|PubMed:17681178}; CC pH dependence: CC Optimum pH is 9.5. {ECO:0000269|PubMed:17681178}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 3]: CC Kinetic parameters: CC KM=0.04 uM for palmitic acid (at pH 7.5) CC {ECO:0000269|PubMed:17681178}; CC KM=0.15 uM for palmitic acid (at pH 8.5) CC {ECO:0000269|PubMed:17681178}; CC pH dependence: CC Optimum pH is 7.5-8.5. {ECO:0000269|PubMed:17681178}; CC -!- INTERACTION: CC Q9ULC5; Q13520: AQP6; NbExp=3; IntAct=EBI-2876927, EBI-13059134; CC Q9ULC5; O00559: EBAG9; NbExp=3; IntAct=EBI-2876927, EBI-8787095; CC Q9ULC5; O00623: PEX12; NbExp=3; IntAct=EBI-2876927, EBI-594836; CC Q9ULC5; Q86VR2: RETREG3; NbExp=5; IntAct=EBI-2876927, EBI-10192441; CC Q9ULC5; Q8WU57: SELI; NbExp=3; IntAct=EBI-2876927, EBI-751012; CC Q9ULC5; Q14973: SLC10A1; NbExp=3; IntAct=EBI-2876927, EBI-3923031; CC Q9ULC5; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-2876927, EBI-18159983; CC Q9ULC5; O60669: SLC16A7; NbExp=3; IntAct=EBI-2876927, EBI-3921243; CC Q9ULC5; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-2876927, EBI-17295964; CC Q9ULC5; Q8TBB6: SLC7A14; NbExp=3; IntAct=EBI-2876927, EBI-5235586; CC Q9ULC5; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-2876927, EBI-8638294; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:17681178, CC ECO:0000269|PubMed:33191500}. Endoplasmic reticulum CC {ECO:0000269|PubMed:17681178, ECO:0000269|PubMed:24269233, CC ECO:0000269|PubMed:33191500}. Mitochondrion outer membrane CC {ECO:0000250}; Single-pass type III membrane protein {ECO:0000250}. CC Endoplasmic reticulum membrane {ECO:0000250}; Single-pass type III CC membrane protein {ECO:0000250}. Cell membrane CC {ECO:0000269|PubMed:24269233}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=ACSL5b, ACSL5-fl; CC IsoId=Q9ULC5-1; Sequence=Displayed; CC Name=2; Synonyms=ACSL5a; CC IsoId=Q9ULC5-3; Sequence=VSP_037947; CC Name=3; Synonyms=ACSL5delta20; CC IsoId=Q9ULC5-4; Sequence=VSP_038233; CC -!- DISEASE: Diarrhea 13 (DIAR13) [MIM:620357]: An autosomal recessive CC disorder characterized by neonatal onset of recurrent vomiting and CC diarrhea, leading to severe failure to thrive. CC {ECO:0000269|PubMed:33191500}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 1]: Localize in mitochondrion and endoplasmic CC reticulum. CC -!- MISCELLANEOUS: [Isoform 3]: Localize in mitochondrion and endoplasmic CC reticulum. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA85979.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA86054.1; Type=Erroneous gene model prediction; Evidence={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; AM262166; CAK18174.1; -; mRNA. DR EMBL; AY358520; AAQ88884.1; -; mRNA. DR EMBL; AK000339; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK222782; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AL157786; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49532.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49535.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49536.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49539.1; -; Genomic_DNA. DR EMBL; BC007985; AAH07985.2; -; mRNA. DR EMBL; AB033899; BAA85979.1; ALT_INIT; mRNA. DR EMBL; AB033920; BAA86054.1; ALT_SEQ; Genomic_DNA. DR CCDS; CCDS7572.1; -. [Q9ULC5-3] DR CCDS; CCDS7573.1; -. [Q9ULC5-1] DR RefSeq; NP_057318.2; NM_016234.3. [Q9ULC5-3] DR RefSeq; NP_976313.1; NM_203379.1. [Q9ULC5-1] DR RefSeq; NP_976314.1; NM_203380.1. [Q9ULC5-1] DR AlphaFoldDB; Q9ULC5; -. DR SMR; Q9ULC5; -. DR BioGRID; 119687; 31. DR IntAct; Q9ULC5; 28. DR MINT; Q9ULC5; -. DR STRING; 9606.ENSP00000348429; -. DR BindingDB; Q9ULC5; -. DR ChEMBL; CHEMBL4105818; -. DR SwissLipids; SLP:000000202; -. DR SwissLipids; SLP:000000517; -. [Q9ULC5-3] DR SwissLipids; SLP:000000518; -. [Q9ULC5-1] DR GlyCosmos; Q9ULC5; 1 site, 1 glycan. DR GlyGen; Q9ULC5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9ULC5; -. DR PhosphoSitePlus; Q9ULC5; -. DR SwissPalm; Q9ULC5; -. DR BioMuta; ACSL5; -. DR DMDM; 13431659; -. DR EPD; Q9ULC5; -. DR jPOST; Q9ULC5; -. DR MassIVE; Q9ULC5; -. DR MaxQB; Q9ULC5; -. DR PaxDb; 9606-ENSP00000348429; -. DR PeptideAtlas; Q9ULC5; -. DR ProteomicsDB; 84979; -. [Q9ULC5-1] DR ProteomicsDB; 84980; -. [Q9ULC5-3] DR ProteomicsDB; 84981; -. [Q9ULC5-4] DR Pumba; Q9ULC5; -. DR Antibodypedia; 31809; 310 antibodies from 34 providers. DR DNASU; 51703; -. DR Ensembl; ENST00000354655.9; ENSP00000346680.4; ENSG00000197142.11. [Q9ULC5-1] DR Ensembl; ENST00000356116.6; ENSP00000348429.1; ENSG00000197142.11. [Q9ULC5-3] DR Ensembl; ENST00000393081.6; ENSP00000376796.1; ENSG00000197142.11. [Q9ULC5-1] DR GeneID; 51703; -. DR KEGG; hsa:51703; -. DR MANE-Select; ENST00000354655.9; ENSP00000346680.4; NM_203379.2; NP_976313.1. DR UCSC; uc001kzs.4; human. [Q9ULC5-1] DR AGR; HGNC:16526; -. DR CTD; 51703; -. DR DisGeNET; 51703; -. DR GeneCards; ACSL5; -. DR HGNC; HGNC:16526; ACSL5. DR HPA; ENSG00000197142; Tissue enhanced (epididymis, intestine, liver). DR MalaCards; ACSL5; -. DR MIM; 605677; gene. DR MIM; 620357; phenotype. DR neXtProt; NX_Q9ULC5; -. DR OpenTargets; ENSG00000197142; -. DR PharmGKB; PA27969; -. DR VEuPathDB; HostDB:ENSG00000197142; -. DR eggNOG; KOG1256; Eukaryota. DR GeneTree; ENSGT00940000156651; -. DR HOGENOM; CLU_000022_45_4_1; -. DR InParanoid; Q9ULC5; -. DR OMA; ARATMAH; -. DR OrthoDB; 443463at2759; -. DR PhylomeDB; Q9ULC5; -. DR TreeFam; TF313877; -. DR BioCyc; MetaCyc:HS01349-MONOMER; -. DR PathwayCommons; Q9ULC5; -. DR Reactome; R-HSA-75876; Synthesis of very long-chain fatty acyl-CoAs. DR SABIO-RK; Q9ULC5; -. DR SignaLink; Q9ULC5; -. DR SIGNOR; Q9ULC5; -. DR BioGRID-ORCS; 51703; 23 hits in 1151 CRISPR screens. DR ChiTaRS; ACSL5; human. DR GeneWiki; ACSL5; -. DR GenomeRNAi; 51703; -. DR Pharos; Q9ULC5; Tchem. DR PRO; PR:Q9ULC5; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9ULC5; Protein. DR Bgee; ENSG00000197142; Expressed in jejunal mucosa and 181 other cell types or tissues. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA: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; IDA:UniProtKB. DR GO; GO:0090434; F:oleoyl-CoA ligase activity; IDA:UniProtKB. 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; IBA:GO_Central. DR GO; GO:0010747; P:positive regulation of long-chain fatty acid import across plasma membrane; IBA:GO_Central. DR GO; GO:2001236; P:regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB. 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; Q9ULC5; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Cell membrane; KW Disease variant; Endoplasmic reticulum; Fatty acid metabolism; Ligase; KW Lipid metabolism; Magnesium; Membrane; Mitochondrion; KW Mitochondrion outer membrane; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1..683 FT /note="Long-chain-fatty-acid--CoA ligase 5" FT /id="PRO_0000193112" 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" FT VAR_SEQ 1 FT /note="M -> MDALKPPCLWRNHERGKKDRDSCGRKNSEPGSPHSLEALRDAAPSQG FT LNFLLLFTKM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4" FT /id="VSP_037947" FT VAR_SEQ 614..637 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17681178" FT /id="VSP_038233" FT VARIANT 182 FT /note="M -> V (in dbSNP:rs3736946)" FT /id="VAR_022117" FT VARIANT 388 FT /note="K -> R (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036377" FT VARIANT 453 FT /note="T -> K (in DIAR13; loss of oleoyl-CoA ligase FT activity; does not affect localization to mitochondrion; FT does not affect localization to endoplasmic reticulum)" FT /evidence="ECO:0000269|PubMed:33191500" FT /id="VAR_088452" FT VARIANT 466 FT /note="G -> D (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036378" FT VARIANT 486 FT /note="T -> A (in dbSNP:rs12254915)" FT /id="VAR_048240" FT MOD_RES Q9ULC5-3:32 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" SQ SEQUENCE 683 AA; 75991 MW; 781AFE1A7A78C286 CRC64; MLFIFNFLFS PLPTPALICI LTFGAAIFLW LITRPQPVLP LLDLNNQSVG IEGGARKGVS QKNNDLTSCC FSDAKTMYEV FQRGLAVSDN GPCLGYRKPN QPYRWLSYKQ VSDRAEYLGS CLLHKGYKSS PDQFVGIFAQ NRPEWIISEL ACYTYSMVAV PLYDTLGPEA IVHIVNKADI AMVICDTPQK ALVLIGNVEK GFTPSLKVII LMDPFDDDLK QRGEKSGIEI LSLYDAENLG KEHFRKPVPP SPEDLSVICF TSGTTGDPKG AMITHQNIVS NAAAFLKCVE HAYEPTPDDV AISYLPLAHM FERIVQAVVY SCGARVGFFQ GDIRLLADDM KTLKPTLFPA VPRLLNRIYD KVQNEAKTPL KKFLLKLAVS SKFKELQKGI IRHDSFWDKL IFAKIQDSLG GRVRVIVTGA APMSTSVMTF FRAAMGCQVY EAYGQTECTG GCTFTLPGDW TSGHVGVPLA CNYVKLEDVA DMNYFTVNNE GEVCIKGTNV FKGYLKDPEK TQEALDSDGW LHTGDIGRWL PNGTLKIIDR KKNIFKLAQG EYIAPEKIEN IYNRSQPVLQ IFVHGESLRS SLVGVVVPDT DVLPSFAAKL GVKGSFEELC QNQVVREAIL EDLQKIGKES GLKTFEQVKA IFLHPEPFSI ENGLLTPTLK AKRGELSKYF RTQIDSLYEH IQD //