S27A2_RAT
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 03-AUG-2022, entry version 132.
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}.
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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 iPTMnet; P97524; -.
DR PhosphoSitePlus; P97524; -.
DR PRIDE; P97524; -.
DR GeneID; 65192; -.
DR KEGG; rno:65192; -.
DR UCSC; RGD:71103; rat.
DR CTD; 11001; -.
DR RGD; 71103; Slc27a2.
DR InParanoid; P97524; -.
DR OrthoDB; 298283at2759; -.
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-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:0030176; C:integral component of endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0005779; C:integral component of peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005778; C:peroxisomal membrane; IDA:HGNC-UCL.
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: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 Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 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.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR030305; FATP2.
DR PANTHER; PTHR43107:SF13; PTHR43107:SF13; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 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
