ID ACSL4_HUMAN Reviewed; 711 AA. AC O60488; D3DUY2; O60848; O60849; Q5JWV8; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 27-MAR-2024, entry version 221. DE RecName: Full=Long-chain-fatty-acid--CoA ligase 4 {ECO:0000305}; DE EC=6.2.1.3 {ECO:0000269|PubMed:21242590, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}; DE AltName: Full=Arachidonate--CoA ligase {ECO:0000305}; DE EC=6.2.1.15 {ECO:0000269|PubMed:21242590}; DE AltName: Full=Long-chain acyl-CoA synthetase 4; DE Short=LACS 4; GN Name=ACSL4; Synonyms=ACS4, FACL4, LACS4; 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 SHORT). RX PubMed=9598324; DOI=10.1006/geno.1998.5268; RA Cao Y., Traer E., Zimmerman G.A., McIntyre T.M., Prescott S.M.; RT "Cloning, expression, and chromosomal localization of human long-chain RT fatty acid-CoA ligase 4 (FACL4)."; RL Genomics 49:327-330(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), AND INVOLVEMENT IN RP ATS-MR. RC TISSUE=Placenta, and Retina; RX PubMed=9480748; DOI=10.1006/geno.1997.5104; RA Piccini M., Vitelli F., Bruttini M., Pober B.R., Jonsson J.J., RA Villanova M., Zollo M., Borsani G., Ballabio A., Renieri A.; RT "FACL4, a new gene encoding long-chain acyl-CoA synthetase 4, is deleted in RT a family with Alport syndrome, elliptocytosis, and mental retardation."; RL Genomics 47:350-358(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). RC TISSUE=Stomach; 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 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). RC TISSUE=Testis; 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] 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 [8] RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=21242590; DOI=10.1194/jlr.m013292; RA Golej D.L., Askari B., Kramer F., Barnhart S., Vivekanandan-Giri A., RA Pennathur S., Bornfeldt K.E.; RT "Long-chain acyl-CoA synthetase 4 modulates prostaglandin E(2) release from RT human arterial smooth muscle cells."; RL J. Lipid Res. 52:782-793(2011). RN [9] RP FUNCTION, AND CATALYTIC ACTIVITY. 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 [10] 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP VARIANT XLID63 SER-570. RX PubMed=11889465; DOI=10.1038/ng857; RA Meloni I., Muscettola M., Raynaud M., Longo I., Bruttini M., Moizard M.-P., RA Gomot M., Chelly J., des Portes V., Fryns J.-P., Ropers H.-H., Magi B., RA Bellan C., Volpi N., Yntema H.G., Lewis S.E., Schaffer J.E., Renieri A.; RT "FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X- RT linked mental retardation."; RL Nat. Genet. 30:436-440(2002). RN [14] RP VARIANT [LARGE SCALE ANALYSIS] CYS-133. 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 [15] RP VARIANT ASN-379. RX PubMed=29961568; DOI=10.1016/j.ajhg.2018.06.001; RG NIHR BioResource; RG Care4Rare Canada Consortium; RA Ito Y., Carss K.J., Duarte S.T., Hartley T., Keren B., Kurian M.A., RA Marey I., Charles P., Mendonca C., Nava C., Pfundt R., Sanchis-Juan A., RA van Bokhoven H., van Essen A., van Ravenswaaij-Arts C., Boycott K.M., RA Kernohan K.D., Dyack S., Raymond F.L.; RT "De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with RT Seizures."; RL Am. J. Hum. Genet. 103:144-153(2018). 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:24269233, PubMed:22633490, CC PubMed:21242590). Preferentially activates arachidonate and CC eicosapentaenoate as substrates (PubMed:21242590). Preferentially CC activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose- CC stimulated insulin secretion by regulating the levels of unesterified CC EETs (By similarity). Modulates prostaglandin E2 secretion CC (PubMed:21242590). {ECO:0000250|UniProtKB:O35547, CC ECO:0000269|PubMed:21242590, ECO:0000269|PubMed:22633490, CC 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:21242590, ECO:0000269|PubMed:22633490, CC ECO:0000269|PubMed:24269233}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422; CC Evidence={ECO:0000269|PubMed:21242590, ECO:0000269|PubMed:22633490, CC ECO:0000269|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:0000269|PubMed:21242590}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714; CC Evidence={ECO:0000269|PubMed:21242590}; 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:21242590, CC ECO:0000269|PubMed:24269233}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752; CC Evidence={ECO:0000269|PubMed:21242590}; 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:0000269|PubMed:24269233}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36140; CC Evidence={ECO:0000269|PubMed:22633490}; 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:O35547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52117; CC Evidence={ECO:0000250|UniProtKB:O35547}; 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:O35547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52113; CC Evidence={ECO:0000250|UniProtKB:O35547}; 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:O35547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52109; CC Evidence={ECO:0000250|UniProtKB:O35547}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 5,6- CC epoxy-(8Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate; CC Xref=Rhea:RHEA:52088, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:57287, ChEBI:CHEBI:131992, ChEBI:CHEBI:136351, CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:O35547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52089; CC Evidence={ECO:0000250|UniProtKB:O35547}; 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:O35547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52017; CC Evidence={ECO:0000250|UniProtKB:O35547}; 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:O35547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52013; CC Evidence={ECO:0000250|UniProtKB:O35547}; CC -!- CATALYTIC ACTIVITY: CC Reaction=8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 8,9- CC epoxy-(5Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate; CC Xref=Rhea:RHEA:52008, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:57287, ChEBI:CHEBI:84025, ChEBI:CHEBI:136107, CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:O35547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52009; CC Evidence={ECO:0000250|UniProtKB:O35547}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Both triacsin C and rosiglitazone inhibit CC arachidonoyl-CoA ligase activity. {ECO:0000269|PubMed:21242590}. 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:0000269|PubMed:24269233}; Single-pass type III membrane protein CC {ECO:0000250}. Cell membrane {ECO:0000269|PubMed:24269233}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=O60488-1; Sequence=Displayed; CC Name=Short; CC IsoId=O60488-2; Sequence=VSP_000238; CC -!- DISEASE: Intellectual developmental disorder, X-linked 63 (XLID63) CC [MIM:300387]: A disorder characterized by significantly below average CC general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. CC Intellectual deficiency is the only primary symptom of non-syndromic X- CC linked intellectual disability, while syndromic forms presents with CC associated physical, neurological and/or psychiatric manifestations. CC {ECO:0000269|PubMed:11889465}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: AMME complex (ATS-MR) [MIM:300194]: An X-linked contiguous CC gene deletion syndrome characterized by glomerulonephritis, CC sensorineural hearing loss, intellectual disability, midface hypoplasia CC and elliptocytosis. {ECO:0000269|PubMed:9480748}. Note=The gene CC represented in this entry may be involved in disease pathogenesis. 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; AF030555; AAC17493.1; -; mRNA. DR EMBL; Y12777; CAA73314.1; -; mRNA. DR EMBL; Y13058; CAA73501.1; -; mRNA. DR EMBL; AK292070; BAF84759.1; -; mRNA. DR EMBL; CH471120; EAX02671.1; -; Genomic_DNA. DR EMBL; CH471120; EAX02672.1; -; Genomic_DNA. DR EMBL; CH471120; EAX02673.1; -; Genomic_DNA. DR EMBL; CH471120; EAX02674.1; -; Genomic_DNA. DR EMBL; BC034959; AAH34959.1; -; mRNA. DR CCDS; CCDS14548.1; -. [O60488-1] DR CCDS; CCDS14549.1; -. [O60488-2] DR RefSeq; NP_001305438.1; NM_001318509.1. [O60488-1] DR RefSeq; NP_001305439.1; NM_001318510.1. [O60488-2] DR RefSeq; NP_004449.1; NM_004458.2. [O60488-2] DR RefSeq; NP_075266.1; NM_022977.2. [O60488-1] DR RefSeq; XP_005262166.1; XM_005262109.2. [O60488-1] DR RefSeq; XP_006724698.1; XM_006724635.2. [O60488-2] DR RefSeq; XP_011529190.1; XM_011530888.2. [O60488-1] DR RefSeq; XP_011529191.1; XM_011530889.2. [O60488-1] DR AlphaFoldDB; O60488; -. DR SMR; O60488; -. DR BioGRID; 108478; 160. DR IntAct; O60488; 58. DR MINT; O60488; -. DR STRING; 9606.ENSP00000339787; -. DR BindingDB; O60488; -. DR ChEMBL; CHEMBL4680022; -. DR DrugBank; DB00159; Icosapent. DR DrugBank; DB00412; Rosiglitazone. DR DrugBank; DB00197; Troglitazone. DR SwissLipids; SLP:000000201; -. DR SwissLipids; SLP:000000515; -. [O60488-1] DR SwissLipids; SLP:000000516; -. [O60488-2] DR GlyGen; O60488; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; O60488; -. DR MetOSite; O60488; -. DR PhosphoSitePlus; O60488; -. DR SwissPalm; O60488; -. DR BioMuta; ACSL4; -. DR EPD; O60488; -. DR jPOST; O60488; -. DR MassIVE; O60488; -. DR MaxQB; O60488; -. DR PaxDb; 9606-ENSP00000339787; -. DR PeptideAtlas; O60488; -. DR ProteomicsDB; 49426; -. [O60488-1] DR ProteomicsDB; 49427; -. [O60488-2] DR Pumba; O60488; -. DR Antibodypedia; 444; 409 antibodies from 37 providers. DR DNASU; 2182; -. DR Ensembl; ENST00000340800.7; ENSP00000339787.2; ENSG00000068366.21. [O60488-1] DR Ensembl; ENST00000348502.10; ENSP00000262835.7; ENSG00000068366.21. [O60488-2] DR Ensembl; ENST00000469796.7; ENSP00000419171.2; ENSG00000068366.21. [O60488-1] DR Ensembl; ENST00000502391.6; ENSP00000425408.2; ENSG00000068366.21. [O60488-1] DR Ensembl; ENST00000671846.1; ENSP00000500897.1; ENSG00000068366.21. [O60488-1] DR Ensembl; ENST00000672282.1; ENSP00000500678.1; ENSG00000068366.21. [O60488-2] DR Ensembl; ENST00000672401.1; ENSP00000500273.1; ENSG00000068366.21. [O60488-2] DR Ensembl; ENST00000673016.1; ENSP00000499969.1; ENSG00000068366.21. [O60488-2] DR GeneID; 2182; -. DR KEGG; hsa:2182; -. DR MANE-Select; ENST00000672401.1; ENSP00000500273.1; NM_001318510.2; NP_001305439.1. [O60488-2] DR UCSC; uc004eoi.3; human. [O60488-1] DR AGR; HGNC:3571; -. DR CTD; 2182; -. DR DisGeNET; 2182; -. DR GeneCards; ACSL4; -. DR HGNC; HGNC:3571; ACSL4. DR HPA; ENSG00000068366; Low tissue specificity. DR MalaCards; ACSL4; -. DR MIM; 300157; gene. DR MIM; 300194; phenotype. DR MIM; 300387; phenotype. DR neXtProt; NX_O60488; -. DR OpenTargets; ENSG00000068366; -. DR Orphanet; 86818; Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome. DR Orphanet; 777; X-linked non-syndromic intellectual disability. DR PharmGKB; PA27968; -. DR VEuPathDB; HostDB:ENSG00000068366; -. DR eggNOG; KOG1180; Eukaryota. DR GeneTree; ENSGT00940000157427; -. DR HOGENOM; CLU_000022_45_2_1; -. DR InParanoid; O60488; -. DR OrthoDB; 443463at2759; -. DR PhylomeDB; O60488; -. DR TreeFam; TF314012; -. DR BioCyc; MetaCyc:HS00935-MONOMER; -. DR BRENDA; 6.2.1.15; 2681. DR BRENDA; 6.2.1.3; 2681. DR PathwayCommons; O60488; -. DR Reactome; R-HSA-434313; Intracellular metabolism of fatty acids regulates insulin secretion. DR Reactome; R-HSA-75876; Synthesis of very long-chain fatty acyl-CoAs. DR SignaLink; O60488; -. DR BioGRID-ORCS; 2182; 88 hits in 803 CRISPR screens. DR ChiTaRS; ACSL4; human. DR GeneWiki; ACSL4; -. DR GenomeRNAi; 2182; -. DR Pharos; O60488; Tbio. DR PRO; PR:O60488; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; O60488; Protein. DR Bgee; ENSG00000068366; Expressed in adrenal tissue and 194 other cell types or tissues. DR ExpressionAtlas; O60488; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; IDA:MGI. DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome. DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA: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:0090433; F:palmitoyl-CoA ligase activity; TAS:Reactome. DR GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IMP:UniProtKB. DR GO; GO:0060136; P:embryonic process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0006631; P:fatty acid metabolic process; TAS:Reactome. DR GO; GO:0008610; P:lipid biosynthetic process; IDA:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; 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; TAS:Reactome. DR GO; GO:0035336; P:long-chain fatty-acyl-CoA metabolic process; IBA:GO_Central. DR GO; GO:0032307; P:negative regulation of prostaglandin secretion; IDA:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB. DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB. DR CDD; cd17639; LC_FACS_euk1; 1. DR Gene3D; 3.30.300.30; -; 1. DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1. DR InterPro; IPR045851; AMP-bd_C_sf. DR InterPro; IPR020845; AMP-binding_CS. DR InterPro; IPR000873; AMP-dep_Synth/Lig_com. DR InterPro; IPR042099; ANL_N_sf. DR PANTHER; PTHR43272; LONG-CHAIN-FATTY-ACID--COA LIGASE; 1. DR PANTHER; PTHR43272:SF22; LONG-CHAIN-FATTY-ACID--COA LIGASE 4; 1. DR Pfam; PF00501; AMP-binding; 1. DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1. DR PROSITE; PS00455; AMP_BINDING; 1. DR Genevisible; O60488; HS. PE 1: Evidence at protein level; KW Alport syndrome; Alternative splicing; ATP-binding; Cell membrane; KW Deafness; Disease variant; Elliptocytosis; Endoplasmic reticulum; KW Fatty acid metabolism; Hereditary hemolytic anemia; KW Intellectual disability; Ligase; Lipid metabolism; Magnesium; Membrane; KW Microsome; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; KW Peroxisome; Phosphoprotein; Reference proteome; Signal-anchor; KW Transmembrane; Transmembrane helix. FT CHAIN 1..711 FT /note="Long-chain-fatty-acid--CoA ligase 4" FT /id="PRO_0000193109" FT TRANSMEM 8..28 FT /note="Helical; Signal-anchor for type III membrane FT protein" FT /evidence="ECO:0000255" FT TOPO_DOM 29..711 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 447 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..41 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9480748, FT ECO:0000303|PubMed:9598324" FT /id="VSP_000238" FT VARIANT 133 FT /note="R -> C (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs753267653)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036376" FT VARIANT 379 FT /note="D -> N" FT /evidence="ECO:0000269|PubMed:29961568" FT /id="VAR_083476" FT VARIANT 570 FT /note="R -> S (in XLID63; dbSNP:rs122458138)" FT /evidence="ECO:0000269|PubMed:11889465" FT /id="VAR_013180" FT CONFLICT 181 FT /note="Y -> C (in Ref. 2; CAA73314)" FT /evidence="ECO:0000305" SQ SEQUENCE 711 AA; 79188 MW; 6483CD17FE78FE73 CRC64; MKLKLNVLTI ILLPVHLLIT IYSALIFIPW YFLTNAKKKN AMAKRIKAKP TSDKPGSPYR SVTHFDSLAV IDIPGADTLD KLFDHAVSKF GKKDSLGTRE ILSEENEMQP NGKVFKKLIL GNYKWMNYLE VNRRVNNFGS GLTALGLKPK NTIAIFCETR AEWMIAAQTC FKYNFPLVTL YATLGKEAVV HGLNESEASY LITSVELLES KLKTALLDIS CVKHIIYVDN KAINKAEYPE GFEIHSMQSV EELGSNPENL GIPPSRPTPS DMAIVMYTSG STGRPKGVMM HHSNLIAGMT GQCERIPGLG PKDTYIGYLP LAHVLELTAE ISCFTYGCRI GYSSPLTLSD QSSKIKKGSK GDCTVLKPTL MAAVPEIMDR IYKNVMSKVQ EMNYIQKTLF KIGYDYKLEQ IKKGYDAPLC NLLLFKKVKA LLGGNVRMML SGGAPLSPQT HRFMNVCFCC PIGQGYGLTE SCGAGTVTEV TDYTTGRVGA PLICCEIKLK DWQEGGYTIN DKPNPRGEIV IGGQNISMGY FKNEEKTAED YSVDENGQRW FCTGDIGEFH PDGCLQIIDR KKDLVKLQAG EYVSLGKVEA ALKNCPLIDN ICAFAKSDQS YVISFVVPNQ KRLTLLAQQK GVEGTWVDIC NNPAMEAEIL KEIREAANAM KLERFEIPIK VRLSPEPWTP ETGLVTDAFK LKRKELRNHY LKDIERMYGG K //