S27A2_HUMAN
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 03-AUG-2022, entry version 180.
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}.
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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; 165.
DR IntAct; O14975; 39.
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 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; O14975; -.
DR PeptideAtlas; O14975; -.
DR PRIDE; O14975; -.
DR ProteomicsDB; 48348; -. [O14975-1]
DR ProteomicsDB; 48349; -. [O14975-2]
DR Antibodypedia; 12170; 195 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 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; LRSHETW; -.
DR OrthoDB; 298283at2759; -.
DR PhylomeDB; O14975; -.
DR TreeFam; TF313430; -.
DR BioCyc; MetaCyc:HS06695-MON; -.
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-9033241; Peroxisomal protein import.
DR SignaLink; O14975; -.
DR SIGNOR; O14975; -.
DR BioGRID-ORCS; 11001; 9 hits in 1081 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 160 other tissues.
DR ExpressionAtlas; O14975; baseline and differential.
DR Genevisible; O14975; HS.
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:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005779; C:integral component of peroxisomal membrane; IDA: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: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: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 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; 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
