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 11-NOV-2015, entry version 135. DE RecName: Full=Very long-chain acyl-CoA synthetase; DE Short=VLACS; DE Short=VLCS; DE EC=6.2.1.-; DE AltName: Full=Fatty acid transport protein 2; DE Short=FATP-2; 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; DE AltName: Full=Solute carrier family 27 member 2; DE AltName: Full=THCA-CoA ligase; 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Shimozawa N., Suzuki Y., Kondo N., Orii T., Hashimoto T.; RT "Molecular cloning of a possible human homolog of the rat very-long- RT chain 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, RP SUBCELLULAR LOCATION, 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 RP 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., RA Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human RT chromosome 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=11980911; DOI=10.1074/jbc.M203295200; RA Mihalik S.J., Steinberg S.J., Pei Z., Park J., Kim do G., RA Heinzer A.K., Dacremont G., Wanders R.J., Cuebas D.A., Smith K.D., RA Watkins P.A.; RT "Participation of two members of the very long-chain acyl-CoA RT synthetase family in bile acid synthesis and recycling."; RL J. Biol. Chem. 277:24771-24779(2002). RN [9] 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-577, AND IDENTIFICATION RP BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Acyl-CoA synthetase probably involved in bile acid CC metabolism. Proposed to activate C27 precurors of bile acids to CC their CoA thioesters derivatives before side chain cleavage via CC peroxisomal beta-oxidation occurs. In vitro, activates 3-alpha,7- CC alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 CC precursor of cholic acid deriving from the de novo synthesis from CC cholesterol. Does not utilize C24 bile acids as substrates. In CC vitro, also activates long- and branched-chain fatty acids and may CC have additional roles in fatty acid metabolism. May be involved in CC translocation of long-chain fatty acids (LFCA) across membranes CC (By similarity). {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: ATP + a long-chain fatty acid + CoA = AMP + CC diphosphate + an acyl-CoA. {ECO:0000269|PubMed:11980911}. CC -!- CATALYTIC ACTIVITY: ATP + a very-long-chain carboxylic acid + CoA CC = AMP + diphosphate + an acyl-CoA. {ECO:0000269|PubMed:11980911}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass CC membrane protein. Peroxisome membrane; Multi-pass membrane CC protein. Note=Peripheral membrane associated with the lumenal side CC of peroxisomes. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O14975-1; Sequence=Displayed; CC Name=2; CC IsoId=O14975-2; Sequence=VSP_042726; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney, placenta and CC pancreas. {ECO:0000269|PubMed:10198260}. CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme CC family. {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 UniGene; Hs.11729; -. DR ProteinModelPortal; O14975; -. DR SMR; O14975; 60-555. DR BioGrid; 116194; 34. DR IntAct; O14975; 2. DR MINT; MINT-2998454; -. DR STRING; 9606.ENSP00000267842; -. DR ChEMBL; CHEMBL4326; -. DR TCDB; 4.C.1.1.5; the proposed fatty acid transporter (fat) family. DR PhosphoSite; O14975; -. DR BioMuta; SLC27A2; -. DR MaxQB; O14975; -. DR PaxDb; O14975; -. DR PRIDE; O14975; -. DR Ensembl; ENST00000267842; ENSP00000267842; ENSG00000140284. [O14975-1] DR Ensembl; ENST00000380902; ENSP00000370289; ENSG00000140284. [O14975-2] DR GeneID; 11001; -. DR KEGG; hsa:11001; -. DR UCSC; uc001zxw.3; human. [O14975-1] DR UCSC; uc010bes.3; human. [O14975-2] DR CTD; 11001; -. DR GeneCards; SLC27A2; -. DR HGNC; HGNC:10996; SLC27A2. DR HPA; HPA026089; -. DR MIM; 603247; gene. DR neXtProt; NX_O14975; -. DR PharmGKB; PA27971; -. DR eggNOG; KOG1179; Eukaryota. DR eggNOG; ENOG410XQ8T; LUCA. DR GeneTree; ENSGT00550000074420; -. DR HOGENOM; HOG000044189; -. DR HOVERGEN; HBG005642; -. DR InParanoid; O14975; -. DR KO; K08746; -. DR OMA; HHRLWYG; -. DR OrthoDB; EOG7W6WKB; -. DR PhylomeDB; O14975; -. DR TreeFam; TF313430; -. DR BioCyc; MetaCyc:HS06695-MONOMER; -. 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 ChiTaRS; SLC27A2; human. DR GeneWiki; SLC27A2; -. DR GenomeRNAi; 11001; -. DR NextBio; 41795; -. DR PRO; PR:O14975; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; O14975; -. DR CleanEx; HS_SLC27A2; -. DR ExpressionAtlas; O14975; baseline and differential. DR Genevisible; O14975; HS. 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; IDA: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:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0015245; F:fatty acid transporter activity; IEA:Ensembl. 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:0005102; F:receptor binding; IPI: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:0008206; P:bile acid metabolic process; TAS:Reactome. DR GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome. 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; 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:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0042760; P:very long-chain fatty acid catabolic process; IEA:Ensembl. DR InterPro; IPR025110; AMP-bd_C. DR InterPro; IPR020845; AMP-binding_CS. DR InterPro; IPR000873; AMP-dep_Synth/Lig. DR InterPro; IPR030305; FATP2. DR PANTHER; PTHR24096:SF127; PTHR24096:SF127; 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; Complete proteome; KW Endoplasmic reticulum; Fatty acid metabolism; Ligase; KW Lipid metabolism; Membrane; Nucleotide-binding; Peroxisome; KW Phosphoprotein; Polymorphism; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1 620 Very long-chain acyl-CoA synthetase. FT /FTId=PRO_0000193204. FT TOPO_DOM 1 4 Lumenal. {ECO:0000305|PubMed:11980911}. FT TRANSMEM 5 27 Helical. {ECO:0000255}. FT TOPO_DOM 28 106 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 107 127 Helical. {ECO:0000255}. FT TOPO_DOM 128 261 Lumenal. {ECO:0000255}. FT TRANSMEM 262 282 Helical. {ECO:0000255}. FT TOPO_DOM 283 620 Cytoplasmic. {ECO:0000255}. FT NP_BIND 222 233 AMP. {ECO:0000255}. FT MOD_RES 291 291 N6-acetyllysine. FT {ECO:0000250|UniProtKB:O35488}. FT MOD_RES 577 577 Phosphothreonine. FT {ECO:0000244|PubMed:20068231}. FT VAR_SEQ 230 282 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_042726. FT VARIANT 48 48 K -> Q (in dbSNP:rs1648348). FT {ECO:0000269|PubMed:10198260, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|Ref.1, ECO:0000269|Ref.6}. FT /FTId=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 //