ACSL4_HUMAN
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 03-AUG-2022, entry version 212.
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}.
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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; 142.
DR IntAct; O60488; 55.
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; 1 site, 1 O-linked glycan (1 site).
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; O60488; -.
DR PeptideAtlas; O60488; -.
DR PRIDE; O60488; -.
DR ProteomicsDB; 49426; -. [O60488-1]
DR ProteomicsDB; 49427; -. [O60488-2]
DR Antibodypedia; 444; 358 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 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; 172471at2759; -.
DR PhylomeDB; O60488; -.
DR TreeFam; TF314012; -.
DR BioCyc; MetaCyc:HS00935-MON; -.
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; 85 hits in 725 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 192 other tissues.
DR ExpressionAtlas; O60488; baseline and differential.
DR Genevisible; O60488; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
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
