ID S27A2_HUMAN Reviewed; 620 AA. AC O14975; A8K2J7; Q53FY6; Q6PF09; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2010, sequence version 2. DT 27-MAR-2024, entry version 189. 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:0000303|PubMed:20530735}; DE Short=FATP-2 {ECO:0000303|PubMed:20530735}; 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:10198260, ECO:0000269|PubMed:10749848, ECO:0000269|PubMed:11980911}; DE AltName: Full=Phytanate--CoA ligase; DE EC=6.2.1.24 {ECO:0000269|PubMed:10198260}; DE AltName: Full=Solute carrier family 27 member 2; DE AltName: Full=THCA-CoA ligase; DE EC=6.2.1.7 {ECO:0000269|PubMed:11980911}; DE AltName: Full=Very long-chain acyl-CoA synthetase {ECO:0000303|PubMed:10198260, ECO:0000303|PubMed:10749848, ECO:0000303|PubMed:11980911}; DE Short=VLACS {ECO:0000303|PubMed:20530735}; DE Short=VLCS {ECO:0000303|PubMed:10198260, ECO:0000303|PubMed:10749848, ECO:0000303|PubMed:11980911}; DE EC=6.2.1.- {ECO:0000269|PubMed:10198260, ECO:0000269|PubMed:10749848, ECO:0000269|PubMed:11980911, ECO:0000269|PubMed:21768100}; DE AltName: Full=Very long-chain-fatty-acid-CoA ligase; GN Name=SLC27A2; Synonyms=ACSVL1, FACVL1, FATP2, VLACS; 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), AND VARIANT GLN-48. RC TISSUE=Liver; RA Uchiyama A., Aoyama T., Kamijo K., Wakui K., Fukushima Y., Shimozawa N., RA Suzuki Y., Kondo N., Orii T., Hashimoto T.; RT "Molecular cloning of a possible human homolog of the rat very-long-chain RT acyl-CoA synthetase cDNA and its chromosomal localization."; RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR RP LOCATION, FUNCTION, CATALYTIC ACTIVITY, AND VARIANT GLN-48. RX PubMed=10198260; DOI=10.1006/bbrc.1999.0510; RA Steinberg S.J., Wang S.J., Kim D.G., Mihalik S.J., Watkins P.A.; RT "Human very-long-chain acyl-CoA synthetase: cloning, topography, and RT relevance to branched-chain fatty acid metabolism."; RL Biochem. Biophys. Res. Commun. 257:615-621(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-48. RC TISSUE=Colon; 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 MRNA] (ISOFORM 1). RC TISSUE=Kidney; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLN-48. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; 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 [8] RP 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). RN [9] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=10749848; DOI=10.1074/jbc.c000015200; RA Steinberg S.J., Mihalik S.J., Kim D.G., Cuebas D.A., Watkins P.A.; RT "The human liver-specific homolog of very long-chain acyl-CoA synthetase is RT cholate:CoA ligase."; RL J. Biol. Chem. 275:15605-15608(2000). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=11980911; DOI=10.1074/jbc.m203295200; RA Mihalik S.J., Steinberg S.J., Pei Z., Park J., Kim do G., Heinzer A.K., RA Dacremont G., Wanders R.J., Cuebas D.A., Smith K.D., Watkins P.A.; RT "Participation of two members of the very long-chain acyl-CoA synthetase RT family in bile acid synthesis and recycling."; RL J. Biol. Chem. 277:24771-24779(2002). RN [11] 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 [12] RP FUNCTION, CATALYTIC ACTIVITY, TRANSPORT ACTIVITY, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RX PubMed=20530735; DOI=10.1152/ajpendo.00226.2010; RA Falcon A., Doege H., Fluitt A., Tsang B., Watson N., Kay M.A., Stahl A.; RT "FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain RT acyl-CoA synthetase."; RL Am. J. Physiol. 299:E384-393(2010). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-577, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, TRANSPORT ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=22022213; DOI=10.7150/ijms.8.599; RA Krammer J., Digel M., Ehehalt F., Stremmel W., Fuellekrug J., Ehehalt R.; RT "Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 RT increases fatty acid uptake in human hepatoma cells."; RL Int. J. Med. Sci. 8:599-614(2011). RN [15] 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 [16] RP FUNCTION (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY (ISOFORMS 1 AND 2), TISSUE RP SPECIFICITY (ISOFORMS 1 AND 2), AND TRANSPORT ACTIVITY (ISOFORMS 1 AND 2). RX PubMed=21768100; DOI=10.1074/jbc.m111.226316; RA Melton E.M., Cerny R.L., Watkins P.A., DiRusso C.C., Black P.N.; RT "Human fatty acid transport protein 2a/very long chain acyl-CoA synthetase RT 1 (FATP2a/Acsvl1) has a preference in mediating the channeling of exogenous RT n-3 fatty acids into phosphatidylinositol."; RL J. Biol. Chem. 286:30670-30679(2011). RN [17] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-577, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [19] RP IDENTIFICATION BY 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). 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 (PubMed:20530735, CC PubMed:22022213, PubMed:24269233, PubMed:10198260, PubMed:10749848, CC PubMed:11980911). Also functions as an acyl-CoA ligase catalyzing the CC ATP-dependent formation of fatty acyl-CoA using LCFA and very-long- CC chain fatty acids (VLCFA) as substrates, which prevents fatty acid CC efflux from cells and might drive more fatty acid uptake CC (PubMed:20530735, PubMed:22022213, PubMed:24269233, PubMed:10198260, CC PubMed:10749848, PubMed:11980911). Plays a pivotal role in regulating CC available LCFA substrates from exogenous sources in tissues undergoing CC high levels of beta-oxidation or triglyceride synthesis CC (PubMed:20530735). Can also activate branched-chain fatty acids such as CC phytanic acid and pristanic acid (PubMed:10198260). May contribute to CC the synthesis of sphingosine-1-phosphate (PubMed:24269233). Does not CC activate C24 bile acids, cholate and chenodeoxycholate CC (PubMed:11980911). 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 (PubMed:11980911). CC However, it is not critical for THCA activation and bile synthesis in CC vivo (PubMed:20530735). {ECO:0000269|PubMed:10198260, CC ECO:0000269|PubMed:10749848, ECO:0000269|PubMed:11980911, CC ECO:0000269|PubMed:20530735, ECO:0000269|PubMed:22022213, CC ECO:0000269|PubMed:24269233}. CC -!- FUNCTION: [Isoform 1]: Exhibits both long-chain fatty acids (LCFA) CC transport activity and acyl CoA synthetase towards very long-chain CC fatty acids (PubMed:21768100, PubMed:10198260). Shows a preference for CC generating CoA derivatives of n-3 fatty acids, which are preferentially CC trafficked into phosphatidylinositol (PubMed:21768100). CC {ECO:0000269|PubMed:10198260, ECO:0000269|PubMed:21768100}. CC -!- FUNCTION: [Isoform 2]: Exhibits long-chain fatty acids (LCFA) transport CC activity but lacks acyl CoA synthetase towards very long-chain fatty CC acids. {ECO:0000269|PubMed:21768100}. CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=a fatty acid(in) = a fatty acid(out); Xref=Rhea:RHEA:38879, CC ChEBI:CHEBI:28868; Evidence={ECO:0000269|PubMed:20530735, CC ECO:0000269|PubMed:21768100, ECO:0000269|PubMed:22022213}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38881; CC Evidence={ECO:0000305|PubMed:20530735, ECO:0000305|PubMed:21768100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=(9Z)-octadecenoate(out) = (9Z)-octadecenoate(in); CC Xref=Rhea:RHEA:33655, ChEBI:CHEBI:30823; CC Evidence={ECO:0000269|PubMed:22022213}; CC -!- CATALYTIC ACTIVITY: [Isoform 2]: CC Reaction=a fatty acid(in) = a fatty acid(out); Xref=Rhea:RHEA:38879, CC ChEBI:CHEBI:28868; Evidence={ECO:0000269|PubMed:21768100}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38881; CC Evidence={ECO:0000305|PubMed:21768100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:10198260, ECO:0000269|PubMed:10749848, CC ECO:0000269|PubMed:11980911, ECO:0000269|PubMed:22022213, CC ECO:0000305|PubMed:20530735}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422; CC Evidence={ECO:0000305|PubMed:10198260, ECO:0000305|PubMed:10749848, CC ECO:0000305|PubMed:11980911, ECO:0000305|PubMed:20530735, CC ECO:0000305|PubMed:22022213}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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: [Isoform 1]: 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:10198260, CC ECO:0000269|PubMed:10749848, ECO:0000269|PubMed:11980911, CC ECO:0000305|PubMed:20530735}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752; CC Evidence={ECO:0000305|PubMed:10198260, ECO:0000305|PubMed:10749848, CC ECO:0000305|PubMed:11980911, ECO:0000305|PubMed:20530735}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:22022213}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608; CC Evidence={ECO:0000305|PubMed:22022213}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:0000269|PubMed:10198260}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21381; CC Evidence={ECO:0000305|PubMed:10198260}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:0000269|PubMed:21768100}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44937; CC Evidence={ECO:0000305|PubMed:21768100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:0000269|PubMed:10198260}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47265; CC Evidence={ECO:0000305|PubMed:10198260}; 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:24269233}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36140; CC Evidence={ECO:0000305|PubMed:24269233}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:10198260, ECO:0000269|PubMed:10749848, CC ECO:0000269|PubMed:11980911, ECO:0000269|PubMed:21768100, CC ECO:0000305|PubMed:20530735}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54537; CC Evidence={ECO:0000305|PubMed:10198260, ECO:0000305|PubMed:10749848, CC ECO:0000305|PubMed:11980911, ECO:0000305|PubMed:20530735}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:10198260, ECO:0000269|PubMed:10749848, CC ECO:0000269|PubMed:21768100, ECO:0000305|PubMed:20530735}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33640; CC Evidence={ECO:0000305|PubMed:10198260, ECO:0000305|PubMed:10749848, CC ECO:0000305|PubMed:20530735, ECO:0000305|PubMed:21768100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:0000269|PubMed:21768100}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44933; CC Evidence={ECO:0000305|PubMed:21768100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: 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:0000269|PubMed:11980911}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22977; CC Evidence={ECO:0000305|PubMed:11980911}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=12 uM for hexadecanoate (palmitate) {ECO:0000269|PubMed:11980911}; CC Vmax=1.4 nmol/min/mg enzyme for hexadecanoyl-CoA (palmitoyl-CoA) CC synthesis {ECO:0000269|PubMed:11980911}; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:11980911, ECO:0000269|PubMed:22022213, CC ECO:0000269|PubMed:24269233}; Multi-pass membrane protein CC {ECO:0000255}. Peroxisome membrane {ECO:0000269|PubMed:10198260, CC ECO:0000269|PubMed:10640429}; Peripheral membrane protein CC {ECO:0000269|PubMed:10640429}. Cell membrane CC {ECO:0000269|PubMed:20530735}; Multi-pass membrane protein CC {ECO:0000255}. Microsome {ECO:0000269|PubMed:10640429}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=FATP2a {ECO:0000303|PubMed:21768100}; CC IsoId=O14975-1; Sequence=Displayed; CC Name=2; Synonyms=FATP2b {ECO:0000303|PubMed:21768100}; CC IsoId=O14975-2; Sequence=VSP_042726; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in liver, kidney, placenta, CC intestine, brain, heart, and colon (PubMed:10198260, PubMed:21768100, CC PubMed:24269233). Predominantly expressed in liver (PubMed:20530735). CC {ECO:0000269|PubMed:10198260, ECO:0000269|PubMed:20530735, CC ECO:0000269|PubMed:21768100, ECO:0000269|PubMed:24269233}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in liver, placenta, and CC intestine, but much lower relative to isoform 1. CC {ECO:0000269|PubMed:21768100}. 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; D88308; BAA23644.1; -; mRNA. DR EMBL; AF096290; AAC64973.1; -; mRNA. DR EMBL; AK223145; BAD96865.1; -; mRNA. DR EMBL; AK290262; BAF82951.1; -; mRNA. DR EMBL; AC009753; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471082; EAW77386.1; -; Genomic_DNA. DR EMBL; BC057770; AAH57770.1; -; mRNA. DR CCDS; CCDS10133.1; -. [O14975-1] DR CCDS; CCDS53943.1; -. [O14975-2] DR RefSeq; NP_001153101.1; NM_001159629.1. [O14975-2] DR RefSeq; NP_003636.2; NM_003645.3. [O14975-1] DR AlphaFoldDB; O14975; -. DR SMR; O14975; -. DR BioGRID; 116194; 170. DR IntAct; O14975; 40. DR MINT; O14975; -. DR STRING; 9606.ENSP00000267842; -. DR BindingDB; O14975; -. DR ChEMBL; CHEMBL4326; -. DR DrugBank; DB11936; Bempedoic acid. DR SwissLipids; SLP:000000428; -. DR SwissLipids; SLP:000000431; -. [O14975-2] DR SwissLipids; SLP:000000432; -. [O14975-1] DR TCDB; 4.C.1.1.5; the fatty acid group translocation (fat) family. DR GlyCosmos; O14975; 2 sites, 1 glycan. DR GlyGen; O14975; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O14975; -. DR MetOSite; O14975; -. DR PhosphoSitePlus; O14975; -. DR SwissPalm; O14975; -. DR BioMuta; SLC27A2; -. DR EPD; O14975; -. DR jPOST; O14975; -. DR MassIVE; O14975; -. DR MaxQB; O14975; -. DR PaxDb; 9606-ENSP00000267842; -. DR PeptideAtlas; O14975; -. DR ProteomicsDB; 48348; -. [O14975-1] DR ProteomicsDB; 48349; -. [O14975-2] DR Pumba; O14975; -. DR Antibodypedia; 12170; 217 antibodies from 28 providers. DR DNASU; 11001; -. DR Ensembl; ENST00000267842.10; ENSP00000267842.5; ENSG00000140284.11. [O14975-1] DR Ensembl; ENST00000380902.8; ENSP00000370289.4; ENSG00000140284.11. [O14975-2] DR GeneID; 11001; -. DR KEGG; hsa:11001; -. DR MANE-Select; ENST00000267842.10; ENSP00000267842.5; NM_003645.4; NP_003636.2. DR UCSC; uc001zxw.4; human. [O14975-1] DR AGR; HGNC:10996; -. DR CTD; 11001; -. DR DisGeNET; 11001; -. DR GeneCards; SLC27A2; -. DR HGNC; HGNC:10996; SLC27A2. DR HPA; ENSG00000140284; Tissue enhanced (kidney, liver). DR MIM; 603247; gene. DR neXtProt; NX_O14975; -. DR OpenTargets; ENSG00000140284; -. DR PharmGKB; PA27971; -. DR VEuPathDB; HostDB:ENSG00000140284; -. DR eggNOG; KOG1179; Eukaryota. DR GeneTree; ENSGT00940000161137; -. DR HOGENOM; CLU_000022_46_2_1; -. DR InParanoid; O14975; -. DR OMA; IIHELYA; -. DR OrthoDB; 1650656at2759; -. DR PhylomeDB; O14975; -. DR TreeFam; TF313430; -. DR BioCyc; MetaCyc:HS06695-MONOMER; -. DR PathwayCommons; O14975; -. DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol. DR Reactome; R-HSA-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol. DR Reactome; R-HSA-389599; Alpha-oxidation of phytanate. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR SignaLink; O14975; -. DR SIGNOR; O14975; -. DR BioGRID-ORCS; 11001; 12 hits in 1161 CRISPR screens. DR ChiTaRS; SLC27A2; human. DR GeneWiki; SLC27A2; -. DR GenomeRNAi; 11001; -. DR Pharos; O14975; Tbio. DR PRO; PR:O14975; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; O14975; Protein. DR Bgee; ENSG00000140284; Expressed in bronchial epithelial cell and 162 other cell types or tissues. DR ExpressionAtlas; O14975; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. 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; IPI:UniProtKB. DR GO; GO:0015245; F:fatty acid transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0005324; F:long-chain fatty acid transporter activity; IDA:UniProtKB. DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB. DR GO; GO:1901480; F:oleate transmembrane transporter activity; IEA:RHEA. DR GO; GO:0050197; F:phytanate-CoA ligase activity; IDA:UniProtKB. DR GO; GO:0070251; F:pristanate-CoA ligase activity; IDA:UniProtKB. DR GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IDA:UniProtKB. DR GO; GO:0006699; P:bile acid biosynthetic process; IDA:UniProtKB. DR GO; GO:0001561; P:fatty acid alpha-oxidation; IDA:UniProtKB. DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB. DR GO; GO:0046949; P:fatty-acyl-CoA biosynthetic process; TAS:Reactome. 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:0097089; P:methyl-branched fatty acid metabolic process; IDA:UniProtKB. DR GO; GO:0042760; P:very long-chain fatty acid catabolic process; IBA:GO_Central. 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. DR Genevisible; O14975; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Cell membrane; 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_0000193204" FT TOPO_DOM 1..4 FT /note="Lumenal" FT /evidence="ECO:0000305|PubMed:11980911" FT TRANSMEM 5..27 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 28..106 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:11980911" FT TRANSMEM 107..127 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 128..261 FT /note="Lumenal" FT /evidence="ECO:0000305|PubMed:11980911" FT TRANSMEM 262..282 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 283..620 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:11980911" 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:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 230..282 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042726" FT VARIANT 48 FT /note="K -> Q (in dbSNP:rs1648348)" FT /evidence="ECO:0000269|PubMed:10198260, FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1, FT ECO:0000269|Ref.6" FT /id="VAR_046533" SQ SEQUENCE 620 AA; 70312 MW; 752E2FFBB2E47C26 CRC64; MLSAIYTVLA GLLFLPLLVN LCCPYFFQDI GYFLKVAAVG RRVRSYGKRR PARTILRAFL EKARQTPHKP FLLFRDETLT YAQVDRRSNQ VARALHDHLG LRQGDCVALL MGNEPAYVWL WLGLVKLGCA MACLNYNIRA KSLLHCFQCC GAKVLLVSPE LQAAVEEILP SLKKDDVSIY YVSRTSNTDG IDSFLDKVDE VSTEPIPESW RSEVTFSTPA LYIYTSGTTG LPKAAMITHQ RIWYGTGLTF VSGLKADDVI YITLPFYHSA ALLIGIHGCI VAGATLALRT KFSASQFWDD CRKYNVTVIQ YIGELLRYLC NSPQKPNDRD HKVRLALGNG LRGDVWRQFV KRFGDICIYE FYAATEGNIG FMNYARKVGA VGRVNYLQKK IITYDLIKYD VEKDEPVRDE NGYCVRVPKG EVGLLVCKIT QLTPFNGYAG AKAQTEKKKL RDVFKKGDLY FNSGDLLMVD HENFIYFHDR VGDTFRWKGE NVATTEVADT VGLVDFVQEV NVYGVHVPDH EGRIGMASIK MKENHEFDGK KLFQHIADYL PSYARPRFLR IQDTIEITGT FKHRKMTLVE EGFNPAVIKD ALYFLDDTAK MYVPMTEDIY NAISAKTLKL //