ACSL5_HUMAN
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 03-AUG-2022, entry version 191.
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).
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). ACSL5 may activate fatty acids from exogenous sources
CC for the synthesis of triacylglycerol destined for intracellular storage
CC (By similarity). Utilizes a wide range of saturated fatty acids with a
CC preference for C16-C18 unsaturated fatty acids (By similarity). It was
CC suggested that it may also stimulate fatty acid oxidation (By
CC similarity). At the villus tip of the crypt-villus axis of the small
CC intestine may sensitize epithelial cells to apoptosis specifically
CC triggered by the death ligand TRAIL. May have a role in the survival of
CC glioma cells. {ECO:0000250, ECO:0000269|PubMed:17681178,
CC ECO:0000269|PubMed:18806831, ECO:0000269|PubMed:19459852,
CC ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}.
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 -!- 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 Endoplasmic reticulum {ECO:0000269|PubMed:17681178,
CC ECO:0000269|PubMed:24269233}. 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 -!- 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};
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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; 29.
DR IntAct; Q9ULC5; 27.
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 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; Q9ULC5; -.
DR PeptideAtlas; Q9ULC5; -.
DR PRIDE; Q9ULC5; -.
DR ProteomicsDB; 84979; -. [Q9ULC5-1]
DR ProteomicsDB; 84980; -. [Q9ULC5-3]
DR ProteomicsDB; 84981; -. [Q9ULC5-4]
DR Antibodypedia; 31809; 280 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 CTD; 51703; -.
DR DisGeNET; 51703; -.
DR GeneCards; ACSL5; -.
DR HGNC; HGNC:16526; ACSL5.
DR HPA; ENSG00000197142; Tissue enhanced (epididymis, intestine, liver).
DR MIM; 605677; gene.
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; PRIWTKF; -.
DR OrthoDB; 630541at2759; -.
DR PhylomeDB; Q9ULC5; -.
DR TreeFam; TF313877; -.
DR BioCyc; MetaCyc:HS01349-MON; -.
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; 22 hits in 1070 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 179 other tissues.
DR Genevisible; Q9ULC5; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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; 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; -; 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; Alternative splicing; ATP-binding; Cell membrane;
KW Endoplasmic reticulum; Fatty acid metabolism; Ligase; Lipid metabolism;
KW Magnesium; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Signal-anchor;
KW 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 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
