ID   ACSL3_HUMAN             Reviewed;         720 AA.
AC   O95573; Q60I92; Q8IUM9;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 3.
DT   25-JAN-2012, entry version 105.
DE   RecName: Full=Long-chain-fatty-acid--CoA ligase 3;
DE            EC=6.2.1.3;
DE   AltName: Full=Long-chain acyl-CoA synthetase 3;
DE            Short=LACS 3;
GN   Name=ACSL3; Synonyms=ACS3, FACL3, LACS3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-551.
RC   TISSUE=Placenta;
RX   MEDLINE=97321062; PubMed=9177793; DOI=10.1006/geno.1997.4710;
RA   Minekura H., Fujino T., Kang M.-J., Fujita T., Endo Y., Yamamoto T.T.;
RT   "Human acyl-coenzyme A synthetase 3 cDNA and localization of its gene
RT   (ACS3) to chromosome band 2q34-q35.";
RL   Genomics 42:180-181(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT SER-551.
RX   MEDLINE=21564184; PubMed=11707336; DOI=10.1016/S0378-1119(01)00714-4;
RA   Minekura H., Kang M.-J., Inagaki Y., Suzuki H., Sato H., Fujino T.,
RA   Yamamoto T.T.;
RT   "Genomic organization and transcription units of the human acyl-CoA
RT   synthetase 3 gene.";
RL   Gene 278:185-192(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-593, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=15302935; DOI=10.1073/pnas.0404720101;
RA   Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,
RA   Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
RT   "Large-scale characterization of HeLa cell nuclear phosphoproteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
RN   [5]
RP   FUNCTION.
RX   PubMed=18003621; DOI=10.1074/jbc.M706160200;
RA   Yao H., Ye J.;
RT   "Long chain acyl-CoA synthetase 3-mediated phosphatidylcholine
RT   synthesis is required for assembly of very low density lipoproteins in
RT   human hepatoma Huh7 cells.";
RL   J. Biol. Chem. 283:849-854(2008).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-683 AND THR-688, AND
RP   MASS SPECTROMETRY.
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
RT   the kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(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.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
CC   -!- FUNCTION: Acyl-CoA synthetases (ACSL) activates long-chain fatty
CC       acids for both synthesis of cellular lipids, and degradation via
CC       beta-oxidation. ACSL3 mediates hepatic lipogenesis (By
CC       similarity). Preferentially uses myristate, laurate, arachidonate
CC       and eicosapentaenoate as substrates (By similarity). Has mainly an
CC       anabolic role in energy metabolism. Required for the incorporation
CC       of fatty acids into phosphatidylcholine, the major phospholipid
CC       located on the surface of VLDL (very low density lipoproteins).
CC   -!- CATALYTIC ACTIVITY: ATP + a long-chain carboxylic acid + CoA = AMP
CC       + diphosphate + an acyl-CoA.
CC   -!- COFACTOR: Magnesium (By similarity).
CC   -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass
CC       type III membrane protein (By similarity). Peroxisome membrane;
CC       Single-pass type III membrane protein (By similarity). Microsome
CC       membrane; Single-pass type III membrane protein (By similarity).
CC       Endoplasmic reticulum membrane; Single-pass type III membrane
CC       protein (By similarity).
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme
CC       family.
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DR   EMBL; D89053; BAA37142.1; -; mRNA.
DR   EMBL; AB061712; BAB72074.1; -; mRNA.
DR   EMBL; AB061436; BAB72139.1; -; Genomic_DNA.
DR   EMBL; BC041692; AAH41692.1; -; mRNA.
DR   IPI; IPI00031397; -.
DR   RefSeq; NP_004448.2; NM_004457.3.
DR   RefSeq; NP_976251.1; NM_203372.1.
DR   UniGene; Hs.655772; -.
DR   ProteinModelPortal; O95573; -.
DR   IntAct; O95573; 3.
DR   STRING; O95573; -.
DR   PhosphoSite; O95573; -.
DR   PeptideAtlas; O95573; -.
DR   PRIDE; O95573; -.
DR   Ensembl; ENST00000357430; ENSP00000350012; ENSG00000123983.
DR   Ensembl; ENST00000392066; ENSP00000375918; ENSG00000123983.
DR   GeneID; 2181; -.
DR   KEGG; hsa:2181; -.
DR   UCSC; uc002vni.1; human.
DR   CTD; 2181; -.
DR   GeneCards; GC02P223725; -.
DR   H-InvDB; HIX0002880; -.
DR   HGNC; HGNC:3570; ACSL3.
DR   HPA; HPA011315; -.
DR   MIM; 602371; gene.
DR   neXtProt; NX_O95573; -.
DR   eggNOG; prNOG10875; -.
DR   HOGENOM; HBG721674; -.
DR   HOVERGEN; HBG106947; -.
DR   InParanoid; O95573; -.
DR   OMA; NQIKAKP; -.
DR   OrthoDB; EOG4Z8XVW; -.
DR   PhylomeDB; O95573; -.
DR   BRENDA; 6.2.1.3; 2681.
DR   Reactome; REACT_22258; Metabolism of lipids and lipoproteins.
DR   DrugBank; DB00159; Icosapent.
DR   NextBio; 8805; -.
DR   ArrayExpress; O95573; -.
DR   Bgee; O95573; -.
DR   CleanEx; HS_ACSL3; -.
DR   Genevestigator; O95573; -.
DR   GermOnline; ENSG00000123983; Homo sapiens.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005792; C:microsome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004321; F:fatty-acyl-CoA synthase activity; TAS:ProtInc.
DR   GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IEA:EC.
DR   GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR   GO; GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   KO; K01897; -.
DR   Pfam; PF00501; AMP-binding; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Complete proteome; Endoplasmic reticulum;
KW   Fatty acid metabolism; Ligase; Lipid metabolism; Magnesium; Membrane;
KW   Microsome; Mitochondrion; Mitochondrion outer membrane;
KW   Nucleotide-binding; Peroxisome; Phosphoprotein; Polymorphism;
KW   Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN         1    720       Long-chain-fatty-acid--CoA ligase 3.
FT                                /FTId=PRO_0000193107.
FT   TRANSMEM     21     41       Helical; Signal-anchor for type III
FT                                membrane protein; (Potential).
FT   TOPO_DOM     42    720       Cytoplasmic (Potential).
FT   MOD_RES     593    593       Phosphoserine.
FT   MOD_RES     683    683       Phosphoserine.
FT   MOD_RES     688    688       Phosphothreonine.
FT   VARIANT     551    551       F -> S (in dbSNP:rs1046032).
FT                                /FTId=VAR_026716.
FT   CONFLICT    246    246       E -> D (in Ref. 1; BAA37142 and 2;
FT                                BAB72074/BAB72139).
SQ   SEQUENCE   720 AA;  80420 MW;  AAC4B0B4543EC8DD CRC64;
     MNNHVSSKPS TMKLKHTINP ILLYFIHFLI SLYTILTYIP FYFFSESRQE KSNRIKAKPV
     NSKPDSAYRS VNSLDGLASV LYPGCDTLDK VFTYAKNKFK NKRLLGTREV LNEEDEVQPN
     GKIFKKVILG QYNWLSYEDV FVRAFNFGNG LQMLGQKPKT NIAIFCETRA EWMIAAQACF
     MYNFQLVTLY ATLGGPAIVH ALNETEVTNI ITSKELLQTK LKDIVSLVPR LRHIITVDGK
     PPTWSEFPKG IIVHTMAAVE ALGAKASMEN QPHSKPLPSD IAVIMYTSGS TGLPKGVMIS
     HSNIIAGITG MAERIPELGE EDVYIGYLPL AHVLELSAEL VCLSHGCRIG YSSPQTLADQ
     SSKIKKGSKG DTSMLKPTLM AAVPEIMDRI YKNVMNKVSE MSSFQRNLFI LAYNYKMEQI
     SKGRNTPLCD SFVFRKVRSL LGGNIRLLLC GGAPLSATTQ RFMNICFCCP VGQGYGLTES
     AGAGTISEVW DYNTGRVGAP LVCCEIKLKN WEEGGYFNTD KPHPRGEILI GGQSVTMGYY
     KNEAKTKADF FEDENGQRWL CTGDIGEFEP DGCLKIIDRK KDLVKLQAGE YVSLGKVEAA
     LKNLPLVDNI CAYANSYHSY VIGFVVPNQK ELTELARKKG LKGTWEELCN SCEMENEVLK
     VLSEAAISAS LEKFEIPVKI RLSPEPWTPE TGLVTDAFKL KRKELKTHYQ ADIERMYGRK
//