S27A6_HUMAN
ID S27A6_HUMAN Reviewed; 619 AA.
AC Q9Y2P4; Q6IAM5; Q7Z6E6; Q86YF6;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Long-chain fatty acid transport protein 6;
DE Short=FATP-6 {ECO:0000303|PubMed:12556534};
DE Short=Fatty acid transport protein 6;
DE AltName: Full=Arachidonate--CoA ligase {ECO:0000250|UniProtKB:E9Q9W4};
DE EC=6.2.1.15 {ECO:0000250|UniProtKB:E9Q9W4};
DE AltName: Full=Fatty-acid-coenzyme A ligase, very long-chain 2 {ECO:0000250|UniProtKB:E9Q9W4};
DE AltName: Full=Long-chain-fatty-acid--CoA ligase;
DE EC=6.2.1.3 {ECO:0000250|UniProtKB:E9Q9W4};
DE AltName: Full=Solute carrier family 27 member 6;
DE AltName: Full=Very long-chain acyl-CoA synthetase homolog 1;
DE Short=VLCSH1;
DE Short=hVLCS-H1;
DE EC=6.2.1.- {ECO:0000250|UniProtKB:E9Q9W4};
GN Name=SLC27A6; Synonyms=ACSVL2, FACVL2, FATP6;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND TRANSPORT ACTIVITY.
RX PubMed=12556534; DOI=10.1074/jbc.m211412200;
RA Gimeno R.E., Ortegon A.M., Patel S., Punreddy S., Ge P., Sun Y.,
RA Lodish H.F., Stahl A.;
RT "Characterization of a heart-specific fatty acid transport protein.";
RL J. Biol. Chem. 278:16039-16044(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Steinberg S.J., Watkins P.A.;
RT "Human very long-chain acyl-CoA synthetase homolog 1.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-19.
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Mediates the import of long-chain fatty acids (LCFA) into the
CC cell by facilitating their transport at the plasma membrane
CC (PubMed:12556534). 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 (By similarity). Plays a
CC pivotal role in regulating available LCFA substrates from exogenous
CC sources in tissues undergoing high levels of beta-oxidation such as the
CC heart (PubMed:12556534). {ECO:0000250|UniProtKB:E9Q9W4,
CC ECO:0000269|PubMed:12556534}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acid(in) = a fatty acid(out); Xref=Rhea:RHEA:38879,
CC ChEBI:CHEBI:28868; Evidence={ECO:0000269|PubMed:12556534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate(out) = hexadecanoate(in); Xref=Rhea:RHEA:45256,
CC ChEBI:CHEBI:7896; Evidence={ECO:0000269|PubMed:12556534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate(out) = (9Z)-octadecenoate(in);
CC Xref=Rhea:RHEA:33655, ChEBI:CHEBI:30823;
CC Evidence={ECO:0000269|PubMed:12556534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate(out) = (9Z,12Z)-
CC octadecadienoate(in); Xref=Rhea:RHEA:45264, ChEBI:CHEBI:30245;
CC Evidence={ECO:0000269|PubMed:12556534};
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:0000250|UniProtKB:E9Q9W4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54537;
CC Evidence={ECO:0000250|UniProtKB:E9Q9W4};
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:0000250|UniProtKB:E9Q9W4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33640;
CC Evidence={ECO:0000250|UniProtKB:E9Q9W4};
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:0000250|UniProtKB:E9Q9W4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422;
CC Evidence={ECO:0000250|UniProtKB:E9Q9W4};
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:E9Q9W4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714;
CC Evidence={ECO:0000250|UniProtKB:E9Q9W4};
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:E9Q9W4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608;
CC Evidence={ECO:0000250|UniProtKB:E9Q9W4};
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC {ECO:0000305|PubMed:12556534}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:E9Q9W4}; Multi-pass
CC membrane protein {ECO:0000255}. Note=In heart is exclusively located on
CC the sarcolemma in areas juxtaposed with small blood vessels where it
CC colocalizes CD36. {ECO:0000305|PubMed:12556534}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in heart and localizes to
CC cardiac myocytes (PubMed:12556534). Expressed at moderate levels in
CC placenta, testis, and adrenal glands. Expressed at very low levels in
CC kidney, bladder and uterus. {ECO:0000269|PubMed:12556534}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AF064254; AAD29443.1; -; mRNA.
DR EMBL; CR457129; CAG33410.1; -; mRNA.
DR EMBL; BX537383; CAD97625.1; -; mRNA.
DR EMBL; BC041945; AAH41945.1; -; mRNA.
DR CCDS; CCDS4145.1; -.
DR RefSeq; NP_001017372.1; NM_001017372.2.
DR RefSeq; NP_001304913.1; NM_001317984.1.
DR RefSeq; NP_054750.1; NM_014031.4.
DR AlphaFoldDB; Q9Y2P4; -.
DR SMR; Q9Y2P4; -.
DR BioGRID; 118790; 83.
DR IntAct; Q9Y2P4; 14.
DR STRING; 9606.ENSP00000262462; -.
DR SwissLipids; SLP:000001263; -.
DR TCDB; 4.C.1.1.11; the fatty acid group translocation (fat) family.
DR iPTMnet; Q9Y2P4; -.
DR PhosphoSitePlus; Q9Y2P4; -.
DR BioMuta; SLC27A6; -.
DR DMDM; 74725713; -.
DR EPD; Q9Y2P4; -.
DR jPOST; Q9Y2P4; -.
DR MassIVE; Q9Y2P4; -.
DR PaxDb; Q9Y2P4; -.
DR PeptideAtlas; Q9Y2P4; -.
DR PRIDE; Q9Y2P4; -.
DR ProteomicsDB; 85853; -.
DR Antibodypedia; 1944; 89 antibodies from 21 providers.
DR DNASU; 28965; -.
DR Ensembl; ENST00000262462.9; ENSP00000262462.4; ENSG00000113396.13.
DR Ensembl; ENST00000395266.5; ENSP00000378684.1; ENSG00000113396.13.
DR Ensembl; ENST00000506176.1; ENSP00000421024.1; ENSG00000113396.13.
DR GeneID; 28965; -.
DR KEGG; hsa:28965; -.
DR MANE-Select; ENST00000262462.9; ENSP00000262462.4; NM_001017372.3; NP_001017372.1.
DR UCSC; uc003kuy.3; human.
DR CTD; 28965; -.
DR DisGeNET; 28965; -.
DR GeneCards; SLC27A6; -.
DR HGNC; HGNC:11000; SLC27A6.
DR HPA; ENSG00000113396; Tissue enhanced (adrenal gland, brain, fallopian tube, heart muscle).
DR MIM; 604196; gene.
DR neXtProt; NX_Q9Y2P4; -.
DR OpenTargets; ENSG00000113396; -.
DR PharmGKB; PA35874; -.
DR VEuPathDB; HostDB:ENSG00000113396; -.
DR eggNOG; KOG1179; Eukaryota.
DR GeneTree; ENSGT00940000159700; -.
DR HOGENOM; CLU_000022_46_2_1; -.
DR InParanoid; Q9Y2P4; -.
DR OMA; NIKMCEF; -.
DR OrthoDB; 386992at2759; -.
DR PhylomeDB; Q9Y2P4; -.
DR TreeFam; TF313430; -.
DR PathwayCommons; Q9Y2P4; -.
DR Reactome; R-HSA-804914; Transport of fatty acids.
DR SignaLink; Q9Y2P4; -.
DR SIGNOR; Q9Y2P4; -.
DR BioGRID-ORCS; 28965; 13 hits in 1080 CRISPR screens.
DR ChiTaRS; SLC27A6; human.
DR GeneWiki; SLC27A6; -.
DR GenomeRNAi; 28965; -.
DR Pharos; Q9Y2P4; Tbio.
DR PRO; PR:Q9Y2P4; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9Y2P4; protein.
DR Bgee; ENSG00000113396; Expressed in secondary oocyte and 120 other tissues.
DR ExpressionAtlas; Q9Y2P4; baseline and differential.
DR Genevisible; Q9Y2P4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0047676; F:arachidonate-CoA ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0015245; F:fatty acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0005324; F:long-chain fatty acid transporter activity; IBA:GO_Central.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IBA:GO_Central.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:1901480; F:oleate transmembrane transporter activity; IEA:RHEA.
DR GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IEA:Ensembl.
DR GO; GO:0015909; P:long-chain fatty acid transport; TAS:Reactome.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; TAS:ProtInc.
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; IPR030309; FATP6.
DR PANTHER; PTHR43107:SF10; PTHR43107:SF10; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Fatty acid metabolism; Ligase; Lipid metabolism;
KW Lipid transport; Membrane; Nucleotide-binding; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..619
FT /note="Long-chain fatty acid transport protein 6"
FT /id="PRO_0000193216"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..139
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 221..232
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255"
FT VARIANT 19
FT /note="L -> V (in dbSNP:rs2526247)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_048245"
FT CONFLICT 25
FT /note="P -> T (in Ref. 5; AAH41945)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="R -> H (in Ref. 4; CAD97625)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="L -> I (in Ref. 5; AAH41945)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="P -> S (in Ref. 3; CAG33410)"
FT /evidence="ECO:0000305"
FT CONFLICT 432
FT /note="N -> S (in Ref. 4; CAD97625)"
FT /evidence="ECO:0000305"
FT CONFLICT 596
FT /note="N -> D (in Ref. 4; CAD97625)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="K -> N (in Ref. 3; CAG33410)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 619 AA; 70112 MW; 20264CE3FBB44FF5 CRC64;
MLLSWLTVLG AGMVVLHFLQ KLLFPYFWDD FWFVLKVVLI IIRLKKYEKR GELVTVLDKF
LSHAKRQPRK PFIIYEGDIY TYQDVDKRSS RVAHVFLNHS SLKKGDTVAL LMSNEPDFVH
VWFGLAKLGC VVAFLNTNIR SNSLLNCIRA CGPRALVVGA DLLGTVEEIL PSLSENISVW
GMKDSVPQGV ISLKEKLSTS PDEPVPRSHH VVSLLKSTCL YIFTSGTTGL PKAAVISQLQ
VLRGSAVLWA FGCTAHDIVY ITLPLYHSSA AILGISGCVE LGATCVLKKK FSASQFWSDC
KKYDVTVFQY IGELCRYLCK QSKREGEKDH KVRLAIGNGI RSDVWREFLD RFGNIKVCEL
YAATESSISF MNYTGRIGAI GRTNLFYKLL STFDLIKYDF QKDEPMRNEQ GWCIHVKKGE
PGLLISRVNA KNPFFGYAGP YKHTKDKLLC DVFKKGDVYL NTGDLIVQDQ DNFLYFWDRT
GDTFRWKGEN VATTEVADVI GMLDFIQEAN VYGVAISGYE GRAGMASIIL KPNTSLDLEK
VYEQVVTFLP AYACPRFLRI QEKMEATGTF KLLKHQLVED GFNPLKISEP LYFMDNLKKS
YVLLTRELYD QIMLGEIKL
