ID   S27A2_RAT               Reviewed;         620 AA.
AC   P97524;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   24-JAN-2024, entry version 138.
DE   RecName: Full=Long-chain fatty acid transport protein 2 {ECO:0000305};
DE   AltName: Full=Arachidonate--CoA ligase;
DE            EC=6.2.1.15 {ECO:0000250|UniProtKB:O35488};
DE   AltName: Full=Fatty acid transport protein 2 {ECO:0000250|UniProtKB:O35488};
DE            Short=FATP-2 {ECO:0000250|UniProtKB:O35488};
DE   AltName: Full=Fatty-acid-coenzyme A ligase, very long-chain 1;
DE   AltName: Full=Long-chain-fatty-acid--CoA ligase;
DE            EC=6.2.1.3 {ECO:0000269|PubMed:8939997};
DE   AltName: Full=Phytanate--CoA ligase;
DE            EC=6.2.1.24 {ECO:0000250|UniProtKB:O14975};
DE   AltName: Full=Solute carrier family 27 member 2;
DE   AltName: Full=THCA-CoA ligase;
DE            EC=6.2.1.7 {ECO:0000250|UniProtKB:O14975};
DE   AltName: Full=Very long-chain acyl-CoA synthetase {ECO:0000303|PubMed:10640429, ECO:0000303|PubMed:8939997};
DE            Short=VLACS {ECO:0000303|PubMed:10640429, ECO:0000303|PubMed:8939997};
DE            Short=VLCS {ECO:0000250|UniProtKB:O14975};
DE            EC=6.2.1.- {ECO:0000269|PubMed:10640429, ECO:0000269|PubMed:8939997};
DE   AltName: Full=Very long-chain-fatty-acid-CoA ligase;
GN   Name=Slc27a2; Synonyms=Acsvl1, Facvl1, Fatp2, Vlacs, Vlcs;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP   ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   STRAIN=Wistar; TISSUE=Liver;
RX   PubMed=8939997; DOI=10.1074/jbc.271.48.30360;
RA   Uchiyama A., Aoyama T., Kamijo K., Uchida Y., Kondo N., Orii T.,
RA   Hashimoto T.;
RT   "Molecular cloning of cDNA encoding rat very long-chain acyl-CoA
RT   synthetase.";
RL   J. Biol. Chem. 271:30360-30365(1996).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX   PubMed=10640429; DOI=10.1006/excr.1999.4757;
RA   Smith B.T., Sengupta T.K., Singh I.;
RT   "Intraperoxisomal localization of very-long-chain fatty acyl-CoA
RT   synthetase: implication in X-adrenoleukodystrophy.";
RL   Exp. Cell Res. 254:309-320(2000).
CC   -!- FUNCTION: Mediates the import of long-chain fatty acids (LCFA) into the
CC       cell by facilitating their transport across cell membranes, playing an
CC       important role in hepatic fatty acid uptake (By similarity). Also
CC       functions as an acyl-CoA ligase catalyzing the ATP-dependent formation
CC       of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as
CC       substrates, which prevents fatty acid efflux from cells and might drive
CC       more fatty acid uptake (PubMed:8939997, PubMed:10640429). Plays a
CC       pivotal role in regulating available LCFA substrates from exogenous
CC       sources in tissues undergoing high levels of beta-oxidation or
CC       triglyceride synthesis (PubMed:8939997, PubMed:10640429). Can also
CC       activate branched-chain fatty acids such as phytanic acid and pristanic
CC       acid (By similarity). May contribute to the synthesis of sphingosine-1-
CC       phosphate (By similarity). Does not activate C24 bile acids, cholate
CC       and chenodeoxycholate. In vitro, activates 3-alpha,7-alpha,12-alpha-
CC       trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid
CC       deriving from the de novo synthesis from cholesterol. However, it is
CC       not critical for THCA activation and bile synthesis in vivo (By
CC       similarity). {ECO:0000250|UniProtKB:O14975,
CC       ECO:0000269|PubMed:10640429, ECO:0000269|PubMed:8939997}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a fatty acid(in) = a fatty acid(out); Xref=Rhea:RHEA:38879,
CC         ChEBI:CHEBI:28868; Evidence={ECO:0000250|UniProtKB:O14975};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z)-octadecenoate(out) = (9Z)-octadecenoate(in);
CC         Xref=Rhea:RHEA:33655, ChEBI:CHEBI:30823;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
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:8939997};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422;
CC         Evidence={ECO:0000305|PubMed:8939997};
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:O35488};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714;
CC         Evidence={ECO:0000250|UniProtKB:O35488};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z,15Z)-octadecatrienoate + ATP + CoA = (9Z,12Z,15Z)-
CC         octadecatrienoyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:44936,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:32387, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:74034, ChEBI:CHEBI:456215;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44937;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
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:8939997};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752;
CC         Evidence={ECO:0000305|PubMed:8939997};
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:0000250|UniProtKB:O14975};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
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:O14975};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47265;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
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:0000250|UniProtKB:O14975};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36140;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
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:O14975};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21381;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a very long-chain fatty acid + ATP + CoA = a very long-chain
CC         fatty acyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:54536,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:58950, ChEBI:CHEBI:138261, ChEBI:CHEBI:456215;
CC         Evidence={ECO:0000269|PubMed:8939997, ECO:0000305|PubMed:10640429};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54537;
CC         Evidence={ECO:0000305|PubMed:10640429, ECO:0000305|PubMed:8939997};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + CoA + tetracosanoate = AMP + diphosphate +
CC         tetracosanoyl-CoA; Xref=Rhea:RHEA:33639, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:31014, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:65052, ChEBI:CHEBI:456215;
CC         Evidence={ECO:0000269|PubMed:8939997, ECO:0000305|PubMed:10640429};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33640;
CC         Evidence={ECO:0000305|PubMed:10640429, ECO:0000305|PubMed:8939997};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA =
CC         (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate;
CC         Xref=Rhea:RHEA:44932, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:74298, ChEBI:CHEBI:77016,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:O14975};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44933;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate
CC         + ATP + CoA = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-
CC         26-oyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:22976,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:58677, ChEBI:CHEBI:58734, ChEBI:CHEBI:456215; EC=6.2.1.7;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22977;
CC         Evidence={ECO:0000250|UniProtKB:O14975};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:10640429}; Multi-pass membrane protein
CC       {ECO:0000255}. Peroxisome membrane {ECO:0000269|PubMed:10640429,
CC       ECO:0000269|PubMed:8939997}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:10640429}. Cell membrane
CC       {ECO:0000250|UniProtKB:O35488}; Multi-pass membrane protein
CC       {ECO:0000255}. Microsome {ECO:0000269|PubMed:10640429,
CC       ECO:0000269|PubMed:8939997}.
CC   -!- TISSUE SPECIFICITY: Liver and kidney (at protein level).
CC       {ECO:0000269|PubMed:8939997}.
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; D85100; BAA12722.1; -; mRNA.
DR   RefSeq; NP_113924.1; NM_031736.1.
DR   AlphaFoldDB; P97524; -.
DR   SMR; P97524; -.
DR   BioGRID; 249304; 1.
DR   IntAct; P97524; 1.
DR   STRING; 10116.ENSRNOP00000059771; -.
DR   iPTMnet; P97524; -.
DR   PhosphoSitePlus; P97524; -.
DR   Ensembl; ENSRNOT00055008357; ENSRNOP00055006326; ENSRNOG00055005204.
DR   Ensembl; ENSRNOT00060024150; ENSRNOP00060019266; ENSRNOG00060014106.
DR   Ensembl; ENSRNOT00065020888; ENSRNOP00065016092; ENSRNOG00065012788.
DR   GeneID; 65192; -.
DR   KEGG; rno:65192; -.
DR   UCSC; RGD:71103; rat.
DR   AGR; RGD:71103; -.
DR   CTD; 11001; -.
DR   RGD; 71103; Slc27a2.
DR   InParanoid; P97524; -.
DR   OrthoDB; 1650656at2759; -.
DR   PhylomeDB; P97524; -.
DR   Reactome; R-RNO-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR   Reactome; R-RNO-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR   Reactome; R-RNO-389599; Alpha-oxidation of phytanate.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-75105; Fatty acyl-CoA biosynthesis.
DR   Reactome; R-RNO-9033241; Peroxisomal protein import.
DR   PRO; PR:P97524; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD.
DR   GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
DR   GO; GO:0005777; C:peroxisome; IDA:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0047676; F:arachidonate-CoA ligase activity; IEA:UniProtKB-EC.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0047747; F:cholate-CoA ligase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR   GO; GO:0015245; F:fatty acid transmembrane transporter activity; ISO:RGD.
DR   GO; GO:0005324; F:long-chain fatty acid transporter activity; ISO:RGD.
DR   GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:RGD.
DR   GO; GO:1901480; F:oleate transmembrane transporter activity; IEA:RHEA.
DR   GO; GO:0050197; F:phytanate-CoA ligase activity; ISO:RGD.
DR   GO; GO:0070251; F:pristanate-CoA ligase activity; ISO:RGD.
DR   GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IMP:UniProtKB.
DR   GO; GO:0006699; P:bile acid biosynthetic process; ISO:RGD.
DR   GO; GO:0001561; P:fatty acid alpha-oxidation; ISO:RGD.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; ISO:RGD.
DR   GO; GO:0015908; P:fatty acid transport; ISO:RGD.
DR   GO; GO:0044539; P:long-chain fatty acid import into cell; ISO:RGD.
DR   GO; GO:0001676; P:long-chain fatty acid metabolic process; IMP:UniProtKB.
DR   GO; GO:0097089; P:methyl-branched fatty acid metabolic process; ISO:RGD.
DR   GO; GO:0042760; P:very long-chain fatty acid catabolic process; ISO:RGD.
DR   GO; GO:0000038; P:very long-chain fatty acid metabolic process; ISO:RGD.
DR   CDD; cd05938; hsFATP2a_ACSVL_like; 1.
DR   Gene3D; 3.30.300.30; -; 1.
DR   Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR   InterPro; IPR025110; AMP-bd_C.
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; PTHR43107; LONG-CHAIN FATTY ACID TRANSPORT PROTEIN; 1.
DR   PANTHER; PTHR43107:SF13; VERY LONG-CHAIN ACYL-COA SYNTHETASE; 1.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF13193; AMP-binding_C; 1.
DR   SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Cell membrane; Direct protein sequencing;
KW   Endoplasmic reticulum; Fatty acid metabolism; Ligase; Lipid metabolism;
KW   Lipid transport; Membrane; Microsome; Nucleotide-binding; Peroxisome;
KW   Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..620
FT                   /note="Long-chain fatty acid transport protein 2"
FT                   /id="PRO_0000193206"
FT   TOPO_DOM        1..4
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250|UniProtKB:O14975"
FT   TRANSMEM        5..27
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        28..106
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:O14975"
FT   TRANSMEM        107..127
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        128..267
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250|UniProtKB:O14975"
FT   TRANSMEM        268..288
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        289..620
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:O14975"
FT   BINDING         222..233
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         291
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O35488"
FT   MOD_RES         577
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:O14975"
SQ   SEQUENCE   620 AA;  70694 MW;  6CF9362DC3805526 CRC64;
     MLPVLYTGLA GLLLLPLLLT CCCPYLLQDV RFFLQLANMA RQVRSYRQRR PVRTILHVFL
     EQARKTPHKP FLLFRDETLT YAQVDRRSNQ VARALHDHLG LRQGDCVALF MGNEPAYVWL
     WLGLLKLGCP MACLNYNIRA KSLLHCFQCC GAKVLLASPE LHEAVEEVLP TLKKEGVSVF
     YVSRTSNTNG VDTVLDKVDG VSADPIPESW RSEVTFTTPA VYIYTSGTTG LPKAATINHH
     RLWYGTSLAL RSGIKAHDVI YTTMPLYHSA ALMIGLHGCI VVGATFALRS KFSASQFWDD
     CRKYNATVIQ YIGELLRYLC NTPQKPNDRD HKVKIALGNG LRGDVWREFI KRFGDIHIYE
     FYASTEGNIG FMNYPRKIGA VGRENYLQKK VVRHELIKYD VEKDEPVRDA NGYCIKVPKG
     EVGLLICKIT ELTPFFGYAG GKTQTEKKKL RDVFKKGDVY FNSGDLLMID RENFIYFHDR
     VGDTFRWKGE NVATTEVADI VGLVDFVEEV NVYGVPVPGH EGRIGMASIK MKENYEFNGK
     KLFQHISEYL PSYSRPRFLR IQDTIEITGT FKHRKVTLME EGFNPSVIKD TLYFMDDTEK
     TYVPMTEDIY NAIIDKTLKL
//