ID   ACSL1_HUMAN             Reviewed;         698 AA.
AC   P33121; B7Z452; D3DP57; P41215; Q8N8V7; Q8TA99;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   27-MAR-2024, entry version 210.
DE   RecName: Full=Long-chain-fatty-acid--CoA ligase 1 {ECO:0000305};
DE            EC=6.2.1.3 {ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233};
DE   AltName: Full=Acyl-CoA synthetase 1;
DE            Short=ACS1;
DE   AltName: Full=Arachidonate--CoA ligase;
DE            EC=6.2.1.15 {ECO:0000250|UniProtKB:P18163};
DE   AltName: Full=Long-chain acyl-CoA synthetase 1;
DE            Short=LACS 1;
DE   AltName: Full=Long-chain acyl-CoA synthetase 2;
DE            Short=LACS 2;
DE   AltName: Full=Long-chain fatty acid-CoA ligase 2;
DE   AltName: Full=Palmitoyl-CoA ligase 1;
DE   AltName: Full=Palmitoyl-CoA ligase 2;
DE   AltName: Full=Phytanate--CoA ligase;
DE            EC=6.2.1.24 {ECO:0000250|UniProtKB:P18163};
GN   Name=ACSL1 {ECO:0000312|HGNC:HGNC:3569};
GN   Synonyms=FACL1, FACL2, LACS, LACS1, LACS2;
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 1).
RC   TISSUE=Liver;
RX   PubMed=1607358; DOI=10.1093/oxfordjournals.jbchem.a123707;
RA   Abe T., Fujino T., Fukuyama R., Minoshima S., Shimizu N., Toh H.,
RA   Suzuki H., Yamamoto T.;
RT   "Human long-chain acyl-CoA synthetase: structure and chromosomal
RT   location.";
RL   J. Biochem. 111:123-128(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=8584017; DOI=10.1007/bf01076899;
RA   Ghosh B., Barbosa E., Singh I.;
RT   "Molecular cloning and sequencing of human palmitoyl-CoA ligase and its
RT   tissue specific expression.";
RL   Mol. Cell. Biochem. 151:77-81(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 395-698 (ISOFORM 2).
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].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [7]
RP   PROTEIN SEQUENCE OF 1-8; 12-19; 341-349; 377-386; 562-572; 633-640 AND
RP   655-675, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=B-cell lymphoma;
RA   Bienvenut W.V.;
RL   Submitted (JUN-2005) to UniProtKB.
RN   [8]
RP   TISSUE SPECIFICITY.
RX   PubMed=10548543; DOI=10.1042/bj3440135;
RA   Malhotra K.T., Malhotra K., Lubin B.H., Kuypers F.A.;
RT   "Identification and molecular characterization of acyl-CoA synthetase in
RT   human red cells and erythroid precursor.";
RL   Biochem. J. 344:135-143(1999).
RN   [9]
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   [10]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
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   [11]
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   [12]
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   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-620, AND IDENTIFICATION BY
RP   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   [14]
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).
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:24269233, PubMed:22633490,
CC       PubMed:21242590). Preferentially uses palmitoleate, oleate and
CC       linoleate (PubMed:24269233). Preferentially activates arachidonate than
CC       epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs)
CC       (By similarity). {ECO:0000250|UniProtKB:P18163,
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:22633490, 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:P18163};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3,7,11,15-tetramethylhexadecanoate + ATP + CoA = AMP +
CC         diphosphate + phytanoyl-CoA; Xref=Rhea:RHEA:21380, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37257, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:57391, ChEBI:CHEBI:456215; EC=6.2.1.24;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21381;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
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:0000305|PubMed:21242590, 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:0000269|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=2,6,10,14-tetramethylpentadecanoate + ATP + CoA = AMP +
CC         diphosphate + pristanoyl-CoA; Xref=Rhea:RHEA:47264,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:77250, ChEBI:CHEBI:77268, ChEBI:CHEBI:456215;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47265;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
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:P18163};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52017;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
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:P18163};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52109;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
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:P18163};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52113;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
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:P18163};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52117;
CC         Evidence={ECO:0000250|UniProtKB:P18163};
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:21242590};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608;
CC         Evidence={ECO:0000305|PubMed:21242590};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- ACTIVITY REGULATION: Inhibited at high temperature and by arachidonate.
CC       {ECO:0000250|UniProtKB:P18163}.
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}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P33121-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P33121-2; Sequence=VSP_009604;
CC       Name=3;
CC         IsoId=P33121-3; Sequence=VSP_054391;
CC   -!- TISSUE SPECIFICITY: Highly expressed in liver, heart, skeletal muscle,
CC       kidney and erythroid cells, and to a lesser extent in brain, lung,
CC       placenta and pancreas. {ECO:0000269|PubMed:10548543}.
CC   -!- DEVELOPMENTAL STAGE: Expressed during the early stages of erythroid
CC       development while expression is very low in reticulocytes and young
CC       erythrocytes.
CC   -!- MISCELLANEOUS: [Isoform 2]: May be due to a competing acceptor splice
CC       site. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAC04704.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; D10040; BAA00931.1; -; mRNA.
DR   EMBL; L09229; AAB00959.1; -; mRNA.
DR   EMBL; AK096117; BAC04704.1; ALT_INIT; mRNA.
DR   EMBL; AK296826; BAH12438.1; -; mRNA.
DR   EMBL; AC079257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC084871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471056; EAX04662.1; -; Genomic_DNA.
DR   EMBL; CH471056; EAX04663.1; -; Genomic_DNA.
DR   EMBL; CH471056; EAX04665.1; -; Genomic_DNA.
DR   EMBL; BC026290; AAH26290.1; -; mRNA.
DR   EMBL; BC050073; AAH50073.1; -; mRNA.
DR   CCDS; CCDS3839.1; -. [P33121-1]
DR   CCDS; CCDS68826.1; -. [P33121-3]
DR   PIR; JX0202; JX0202.
DR   RefSeq; NP_001273637.1; NM_001286708.1. [P33121-1]
DR   RefSeq; NP_001273639.1; NM_001286710.1. [P33121-3]
DR   RefSeq; NP_001273640.1; NM_001286711.1.
DR   RefSeq; NP_001273641.1; NM_001286712.1.
DR   RefSeq; NP_001986.2; NM_001995.3. [P33121-1]
DR   RefSeq; XP_005262885.1; XM_005262828.1.
DR   RefSeq; XP_005262886.1; XM_005262829.1.
DR   RefSeq; XP_005262888.1; XM_005262831.1.
DR   RefSeq; XP_011530044.1; XM_011531742.1.
DR   RefSeq; XP_016863376.1; XM_017007887.1. [P33121-1]
DR   RefSeq; XP_016863377.1; XM_017007888.1.
DR   RefSeq; XP_016863378.1; XM_017007889.1.
DR   AlphaFoldDB; P33121; -.
DR   SMR; P33121; -.
DR   BioGRID; 108476; 125.
DR   IntAct; P33121; 11.
DR   MINT; P33121; -.
DR   STRING; 9606.ENSP00000422607; -.
DR   BindingDB; P33121; -.
DR   ChEMBL; CHEMBL4295746; -.
DR   DrugBank; DB00131; Adenosine phosphate.
DR   DrugBank; DB00171; ATP.
DR   SwissLipids; SLP:000000199; -.
DR   SwissLipids; SLP:000001468; -. [P33121-1]
DR   GlyCosmos; P33121; 1 site, No reported glycans.
DR   GlyGen; P33121; 2 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P33121; -.
DR   PhosphoSitePlus; P33121; -.
DR   SwissPalm; P33121; -.
DR   BioMuta; ACSL1; -.
DR   DMDM; 417241; -.
DR   CPTAC; CPTAC-305; -.
DR   CPTAC; CPTAC-306; -.
DR   EPD; P33121; -.
DR   jPOST; P33121; -.
DR   MassIVE; P33121; -.
DR   MaxQB; P33121; -.
DR   PaxDb; 9606-ENSP00000422607; -.
DR   PeptideAtlas; P33121; -.
DR   ProteomicsDB; 54898; -. [P33121-1]
DR   ProteomicsDB; 54899; -. [P33121-2]
DR   ProteomicsDB; 6570; -.
DR   Pumba; P33121; -.
DR   Antibodypedia; 1946; 333 antibodies from 35 providers.
DR   DNASU; 2180; -.
DR   Ensembl; ENST00000281455.7; ENSP00000281455.2; ENSG00000151726.16. [P33121-1]
DR   Ensembl; ENST00000503407.6; ENSP00000425098.2; ENSG00000151726.16. [P33121-2]
DR   Ensembl; ENST00000504342.5; ENSP00000425006.1; ENSG00000151726.16. [P33121-1]
DR   Ensembl; ENST00000513317.5; ENSP00000426150.1; ENSG00000151726.16. [P33121-3]
DR   Ensembl; ENST00000515030.5; ENSP00000422607.1; ENSG00000151726.16. [P33121-1]
DR   Ensembl; ENST00000706366.1; ENSP00000516351.1; ENSG00000151726.16. [P33121-3]
DR   Ensembl; ENST00000706367.1; ENSP00000516352.1; ENSG00000151726.16. [P33121-1]
DR   Ensembl; ENST00000706368.1; ENSP00000516353.1; ENSG00000151726.16. [P33121-3]
DR   Ensembl; ENST00000706369.1; ENSP00000516354.1; ENSG00000151726.16. [P33121-1]
DR   GeneID; 2180; -.
DR   KEGG; hsa:2180; -.
DR   MANE-Select; ENST00000281455.7; ENSP00000281455.2; NM_001995.5; NP_001986.2.
DR   UCSC; uc003iwt.2; human. [P33121-1]
DR   AGR; HGNC:3569; -.
DR   CTD; 2180; -.
DR   DisGeNET; 2180; -.
DR   GeneCards; ACSL1; -.
DR   HGNC; HGNC:3569; ACSL1.
DR   HPA; ENSG00000151726; Tissue enhanced (adipose tissue, liver, skeletal muscle).
DR   MIM; 152425; gene.
DR   neXtProt; NX_P33121; -.
DR   OpenTargets; ENSG00000151726; -.
DR   PharmGKB; PA27966; -.
DR   VEuPathDB; HostDB:ENSG00000151726; -.
DR   eggNOG; KOG1256; Eukaryota.
DR   GeneTree; ENSGT00940000154508; -.
DR   InParanoid; P33121; -.
DR   OMA; IMARTTY; -.
DR   OrthoDB; 443463at2759; -.
DR   PhylomeDB; P33121; -.
DR   TreeFam; TF313877; -.
DR   BioCyc; MetaCyc:HS07766-MONOMER; -.
DR   BRENDA; 6.2.1.3; 2681.
DR   PathwayCommons; P33121; -.
DR   Reactome; R-HSA-1989781; PPARA activates gene expression.
DR   Reactome; R-HSA-2046105; Linoleic acid (LA) metabolism.
DR   Reactome; R-HSA-2046106; alpha-linolenic acid (ALA) metabolism.
DR   Reactome; R-HSA-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR   SignaLink; P33121; -.
DR   SIGNOR; P33121; -.
DR   BioGRID-ORCS; 2180; 17 hits in 1165 CRISPR screens.
DR   ChiTaRS; ACSL1; human.
DR   GeneWiki; ACSL1; -.
DR   GenomeRNAi; 2180; -.
DR   Pharos; P33121; Tchem.
DR   PRO; PR:P33121; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P33121; Protein.
DR   Bgee; ENSG00000151726; Expressed in right lobe of liver and 203 other cell types or tissues.
DR   ExpressionAtlas; P33121; baseline and differential.
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; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
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; ISS:ARUK-UCL.
DR   GO; GO:0050197; F:phytanate-CoA ligase activity; ISS:UniProtKB.
DR   GO; GO:0070251; F:pristanate-CoA ligase activity; IEA:RHEA.
DR   GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl.
DR   GO; GO:0033211; P:adiponectin-activated signaling pathway; IEA:Ensembl.
DR   GO; GO:0015908; P:fatty acid transport; IMP:ARUK-UCL.
DR   GO; GO:0008610; P:lipid biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0044539; P:long-chain fatty acid import into cell; 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:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:0010747; P:positive regulation of long-chain fatty acid import across plasma membrane; ISS:ARUK-UCL.
DR   GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR   GO; GO:0034201; P:response to oleic acid; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   GO; GO:0019432; P:triglyceride biosynthetic process; IEA:Ensembl.
DR   GO; GO:0000038; P:very long-chain fatty acid metabolic process; IBA:GO_Central.
DR   GO; GO:0042178; P:xenobiotic catabolic process; IEA:Ensembl.
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:SF28; LONG-CHAIN-FATTY-ACID--COA LIGASE 1; 1.
DR   Pfam; PF00501; AMP-binding; 1.
DR   SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   Genevisible; P33121; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; ATP-binding; Direct protein sequencing;
KW   Endoplasmic reticulum; Fatty acid metabolism; Glycoprotein; Ligase;
KW   Lipid metabolism; Magnesium; Membrane; Microsome; Mitochondrion;
KW   Mitochondrion outer membrane; Nitration; Nucleotide-binding; Peroxisome;
KW   Phosphoprotein; Reference proteome; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..698
FT                   /note="Long-chain-fatty-acid--CoA ligase 1"
FT                   /id="PRO_0000193104"
FT   TRANSMEM        25..45
FT                   /note="Helical; Signal-anchor for type III membrane
FT                   protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        46..698
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000269|Ref.7"
FT   MOD_RES         9
FT                   /note="3'-nitrotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P18163"
FT   MOD_RES         84
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P18163"
FT   MOD_RES         207
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P41216"
FT   MOD_RES         356
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P41216"
FT   MOD_RES         386
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P41216"
FT   MOD_RES         620
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         632
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P18163"
FT   CARBOHYD        135
FT                   /note="O-linked (GlcNAc) serine"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         306..331
FT                   /note="NTVNPCPDDTLISFLPLAHMFERVVE -> KALPLSASDTHISYLPLAHIYE
FT                   QLLK (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_054391"
FT   VAR_SEQ         508..517
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_009604"
FT   CONFLICT        21..23
FT                   /note="YVR -> CV (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        37..38
FT                   /note="AA -> SRR (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        44..47
FT                   /note="YATR -> RPRH (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        55..56
FT                   /note="CD -> WH (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        229
FT                   /note="A -> S (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        385
FT                   /note="L -> V (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        400..401
FT                   /note="EL -> DV (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        477
FT                   /note="A -> T (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        492..494
FT                   /note="VDV -> GWQL (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        502
FT                   /note="A -> S (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        695
FT                   /note="T -> I (in Ref. 2; AAB00959)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   698 AA;  77943 MW;  FD6669453589D362 CRC64;
     MQAHELFRYF RMPELVDFRQ YVRTLPTNTL MGFGAFAALT TFWYATRPKP LKPPCDLSMQ
     SVEVAGSGGA RRSALLDSDE PLVYFYDDVT TLYEGFQRGI QVSNNGPCLG SRKPDQPYEW
     LSYKQVAELS ECIGSALIQK GFKTAPDQFI GIFAQNRPEW VIIEQGCFAY SMVIVPLYDT
     LGNEAITYIV NKAELSLVFV DKPEKAKLLL EGVENKLIPG LKIIVVMDAY GSELVERGQR
     CGVEVTSMKA MEDLGRANRR KPKPPAPEDL AVICFTSGTT GNPKGAMVTH RNIVSDCSAF
     VKATENTVNP CPDDTLISFL PLAHMFERVV ECVMLCHGAK IGFFQGDIRL LMDDLKVLQP
     TVFPVVPRLL NRMFDRIFGQ ANTTLKRWLL DFASKRKEAE LRSGIIRNNS LWDRLIFHKV
     QSSLGGRVRL MVTGAAPVSA TVLTFLRAAL GCQFYEGYGQ TECTAGCCLT MPGDWTAGHV
     GAPMPCNLIK LVDVEEMNYM AAEGEGEVCV KGPNVFQGYL KDPAKTAEAL DKDGWLHTGD
     IGKWLPNGTL KIIDRKKHIF KLAQGEYIAP EKIENIYMRS EPVAQVFVHG ESLQAFLIAI
     VVPDVETLCS WAQKRGFEGS FEELCRNKDV KKAILEDMVR LGKDSGLKPF EQVKGITLHP
     ELFSIDNGLL TPTMKAKRPE LRNYFRSQID DLYSTIKV
//