S27A4_HUMAN
ID S27A4_HUMAN Reviewed; 643 AA.
AC Q6P1M0; A8K2F7; O95186; Q96G53;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Long-chain fatty acid transport protein 4 {ECO:0000305};
DE Short=FATP-4 {ECO:0000303|PubMed:22022213};
DE Short=Fatty acid transport protein 4;
DE AltName: Full=Arachidonate--CoA ligase {ECO:0000250|UniProtKB:Q91VE0};
DE EC=6.2.1.15 {ECO:0000250|UniProtKB:Q91VE0};
DE AltName: Full=Long-chain-fatty-acid--CoA ligase {ECO:0000250|UniProtKB:Q91VE0};
DE EC=6.2.1.3 {ECO:0000269|PubMed:22022213, ECO:0000269|PubMed:24269233};
DE AltName: Full=Solute carrier family 27 member 4;
DE AltName: Full=Very long-chain acyl-CoA synthetase 4 {ECO:0000303|PubMed:24269233};
DE Short=ACSVL4 {ECO:0000303|PubMed:24269233};
DE EC=6.2.1.- {ECO:0000250|UniProtKB:Q91VE0};
GN Name=SLC27A4 {ECO:0000312|HGNC:HGNC:10998};
GN Synonyms=ACSVL4 {ECO:0000303|PubMed:24269233}, FATP4;
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 TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=9878842; DOI=10.1016/s0167-4781(98)00231-0;
RA Fitscher B.A., Riedel H.D., Young K.C., Stremmel W.;
RT "Tissue distribution and cDNA cloning of a human fatty acid transport
RT protein (hsFATP4).";
RL Biochim. Biophys. Acta 1443:381-385(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thalamus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
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 [6]
RP FUNCTION, AND TRANSPORT ACTIVITY.
RX PubMed=10518211; DOI=10.1016/s1097-2765(00)80332-9;
RA Stahl A., Hirsch D.J., Gimeno R.E., Punreddy S., Ge P., Watson N.,
RA Patel S., Kotler M., Raimondi A., Tartaglia L.A., Lodish H.F.;
RT "Identification of the major intestinal fatty acid transport protein.";
RL Mol. Cell 4:299-308(1999).
RN [7]
RP FUNCTION, 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 [8]
RP FUNCTION, AND TRANSPORT ACTIVITY.
RX PubMed=20448275; DOI=10.1177/1087057110369700;
RA Zhou W., Madrid P., Fluitt A., Stahl A., Xie X.S.;
RT "Development and validation of a high-throughput screening assay for human
RT long-chain fatty acid transport proteins 4 and 5.";
RL J. Biomol. Screen. 15:488-497(2010).
RN [9]
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 [10]
RP FUNCTION, TRANSPORT ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=21395585; DOI=10.1111/j.1471-4159.2011.07245.x;
RA Mitchell R.W., On N.H., Del Bigio M.R., Miller D.W., Hatch G.M.;
RT "Fatty acid transport protein expression in human brain and potential role
RT in fatty acid transport across human brain microvessel endothelial cells.";
RL J. Neurochem. 117:735-746(2011).
RN [11]
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 [12]
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 [13]
RP VARIANT SER-209.
RX PubMed=14715877; DOI=10.1210/jc.2003-030682;
RA Gertow K., Bellanda M., Eriksson P., Boquist S., Hamsten A.,
RA Sunnerhagen M., Fisher R.M.;
RT "Genetic and structural evaluation of fatty acid transport protein-4 in
RT relation to markers of the insulin resistance syndrome.";
RL J. Clin. Endocrinol. Metab. 89:392-399(2004).
RN [14]
RP VARIANTS IPS THR-92; PRO-247; ARG-300 AND HIS-583.
RX PubMed=19631310; DOI=10.1016/j.ajhg.2009.06.021;
RA Klar J., Schweiger M., Zimmerman R., Zechner R., Li H., Torma H.,
RA Vahlquist A., Bouadjar B., Dahl N., Fischer J.;
RT "Mutations in the fatty acid transport protein 4 gene cause the ichthyosis
RT prematurity syndrome.";
RL Am. J. Hum. Genet. 85:248-253(2009).
RN [15]
RP VARIANT IPS CYS-374.
RX PubMed=20815031; DOI=10.1002/ajmg.a.33648;
RA Morice-Picard F., Leaute-Labreze C., Decor A., Boralevi F., Lacombe D.,
RA Taieb A., Fischer J.;
RT "A novel mutation in the fatty acid transport protein 4 gene in a patient
RT initially described as affected by self-healing congenital verruciform
RT hyperkeratosis.";
RL Am. J. Med. Genet. A 152:2664-2665(2010).
CC -!- FUNCTION: Mediates the levels of long-chain fatty acids (LCFA) in the
CC cell by facilitating their transport across cell membranes
CC (PubMed:10518211, PubMed:12556534, PubMed:20448275, PubMed:21395585,
CC PubMed:22022213). Appears to be the principal fatty acid transporter in
CC small intestinal enterocytes (PubMed:20448275). Also functions as an
CC acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-
CC CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates,
CC which prevents fatty acid efflux from cells and might drive more fatty
CC acid uptake (PubMed:22022213, PubMed:24269233). Plays a role in the
CC formation of the epidermal barrier. Required for fat absorption in
CC early embryogenesis (By similarity). Probably involved in fatty acid
CC transport across the blood barrier (PubMed:21395585). Indirectly
CC inhibits RPE65 via substrate competition and via production of VLCFA
CC derivatives like lignoceroyl-CoA. Prevents light-induced degeneration
CC of rods and cones (By similarity). {ECO:0000250|UniProtKB:Q91VE0,
CC ECO:0000269|PubMed:10518211, ECO:0000269|PubMed:12556534,
CC ECO:0000269|PubMed:20448275, ECO:0000269|PubMed:21395585,
CC ECO:0000269|PubMed:22022213, ECO:0000269|PubMed:24269233}.
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:10518211,
CC ECO:0000269|PubMed:12556534, ECO:0000269|PubMed:20448275,
CC ECO:0000269|PubMed:21395585, ECO:0000269|PubMed:22022213};
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, ECO:0000269|PubMed:21395585};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate(out) = (9Z)-octadecenoate(in);
CC Xref=Rhea:RHEA:33655, ChEBI:CHEBI:30823;
CC Evidence={ECO:0000269|PubMed:10518211, ECO:0000269|PubMed:12556534,
CC ECO:0000269|PubMed:22022213};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate(out) = hexadecanoate(in); Xref=Rhea:RHEA:45256,
CC ChEBI:CHEBI:7896; Evidence={ECO:0000269|PubMed:10518211,
CC ECO:0000269|PubMed:12556534};
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:22022213, ECO:0000269|PubMed:24269233};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422;
CC Evidence={ECO:0000269|PubMed:24269233, ECO:0000305|PubMed:22022213};
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:24269233};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752;
CC Evidence={ECO:0000269|PubMed:24269233};
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:0000269|PubMed:24269233};
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:0000269|PubMed:22022213};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608;
CC Evidence={ECO:0000305|PubMed:22022213};
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:Q91VE0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19714;
CC Evidence={ECO:0000250|UniProtKB:Q91VE0};
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:Q91VE0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54537;
CC Evidence={ECO:0000250|UniProtKB:Q91VE0};
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:Q91VE0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33640;
CC Evidence={ECO:0000250|UniProtKB:Q91VE0};
CC -!- INTERACTION:
CC Q6P1M0-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12898981, EBI-5235340;
CC Q6P1M0-2; Q96A09: TENT5B; NbExp=3; IntAct=EBI-12898981, EBI-752030;
CC Q6P1M0-2; P54577: YARS1; NbExp=3; IntAct=EBI-12898981, EBI-1048893;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22022213, ECO:0000305|PubMed:24269233}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P1M0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P1M0-2; Sequence=VSP_055808, VSP_055809;
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in brain, testis, colon
CC and kidney. Expressed at medium levels in heart and liver, small
CC intestine and stomach. Expressed at low levels in peripheral
CC leukocytes, bone marrow, skeletal muscle and aorta. Expressed in
CC adipose tissue (PubMed:24269233, PubMed:9878842). Expressed in brain
CC gray matter (PubMed:21395585). {ECO:0000269|PubMed:21395585,
CC ECO:0000269|PubMed:24269233, ECO:0000269|PubMed:9878842}.
CC -!- DISEASE: Ichthyosis prematurity syndrome (IPS) [MIM:608649]: A
CC keratinization disorder characterized by complications in the second
CC trimester of pregnancy resulting from polyhydramnion, with premature
CC birth of a child with thick caseous desquamating epidermis, respiratory
CC complications and transient eosinophilia. After recovery during the
CC first months of life, the symptoms are relatively benign and the
CC patients suffer from a lifelong non-scaly ichthyosis with atopic
CC manifestations. {ECO:0000269|PubMed:19631310,
CC ECO:0000269|PubMed:20815031}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: SLC27A4/FATP4-mediated fatty acid uptake is associated
CC to paramaters related to insulin resistance, which is associated with
CC disturbed fatty acid metabolism and homeostasis, such as obesity.
CC SLC27A4/FATP4 expression is positively correlated with acquired
CC obesity.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD11623.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF055899; AAD11623.1; ALT_FRAME; mRNA.
DR EMBL; AK290222; BAF82911.1; -; mRNA.
DR EMBL; AL359091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87779.1; -; Genomic_DNA.
DR EMBL; BC009959; AAH09959.1; -; mRNA.
DR EMBL; BC065003; AAH65003.1; -; mRNA.
DR CCDS; CCDS6899.1; -. [Q6P1M0-1]
DR RefSeq; NP_005085.2; NM_005094.3. [Q6P1M0-1]
DR RefSeq; XP_016869711.1; XM_017014222.1. [Q6P1M0-1]
DR AlphaFoldDB; Q6P1M0; -.
DR SMR; Q6P1M0; -.
DR BioGRID; 116192; 139.
DR IntAct; Q6P1M0; 33.
DR MINT; Q6P1M0; -.
DR STRING; 9606.ENSP00000300456; -.
DR BindingDB; Q6P1M0; -.
DR ChEMBL; CHEMBL4327; -.
DR GuidetoPHARMACOLOGY; 1111; -.
DR SwissLipids; SLP:000000451; -.
DR TCDB; 4.C.1.1.10; the fatty acid group translocation (fat) family.
DR iPTMnet; Q6P1M0; -.
DR MetOSite; Q6P1M0; -.
DR PhosphoSitePlus; Q6P1M0; -.
DR SwissPalm; Q6P1M0; -.
DR BioMuta; SLC27A4; -.
DR DMDM; 74749065; -.
DR EPD; Q6P1M0; -.
DR jPOST; Q6P1M0; -.
DR MassIVE; Q6P1M0; -.
DR MaxQB; Q6P1M0; -.
DR PaxDb; Q6P1M0; -.
DR PeptideAtlas; Q6P1M0; -.
DR PRIDE; Q6P1M0; -.
DR ProteomicsDB; 66849; -. [Q6P1M0-1]
DR ProteomicsDB; 76596; -.
DR Antibodypedia; 1947; 159 antibodies from 31 providers.
DR DNASU; 10999; -.
DR Ensembl; ENST00000300456.5; ENSP00000300456.3; ENSG00000167114.13. [Q6P1M0-1]
DR Ensembl; ENST00000372870.5; ENSP00000361961.1; ENSG00000167114.13. [Q6P1M0-2]
DR GeneID; 10999; -.
DR KEGG; hsa:10999; -.
DR MANE-Select; ENST00000300456.5; ENSP00000300456.3; NM_005094.4; NP_005085.2.
DR UCSC; uc004but.4; human. [Q6P1M0-1]
DR CTD; 10999; -.
DR DisGeNET; 10999; -.
DR GeneCards; SLC27A4; -.
DR GeneReviews; SLC27A4; -.
DR HGNC; HGNC:10998; SLC27A4.
DR HPA; ENSG00000167114; Low tissue specificity.
DR MalaCards; SLC27A4; -.
DR MIM; 604194; gene.
DR MIM; 608649; phenotype.
DR neXtProt; NX_Q6P1M0; -.
DR OpenTargets; ENSG00000167114; -.
DR Orphanet; 88621; Ichthyosis-prematurity syndrome.
DR PharmGKB; PA35872; -.
DR VEuPathDB; HostDB:ENSG00000167114; -.
DR eggNOG; KOG1179; Eukaryota.
DR GeneTree; ENSGT00940000158646; -.
DR HOGENOM; CLU_1170347_0_0_1; -.
DR InParanoid; Q6P1M0; -.
DR OMA; IVGMGQC; -.
DR PhylomeDB; Q6P1M0; -.
DR TreeFam; TF313430; -.
DR BioCyc; MetaCyc:ENSG00000167114-MON; -.
DR BRENDA; 6.2.1.3; 2681.
DR PathwayCommons; Q6P1M0; -.
DR Reactome; R-HSA-5619108; Defective SLC27A4 causes ichthyosis prematurity syndrome (IPS).
DR Reactome; R-HSA-804914; Transport of fatty acids.
DR SignaLink; Q6P1M0; -.
DR SIGNOR; Q6P1M0; -.
DR BioGRID-ORCS; 10999; 8 hits in 1073 CRISPR screens.
DR ChiTaRS; SLC27A4; human.
DR GeneWiki; SLC27A4; -.
DR GenomeRNAi; 10999; -.
DR Pharos; Q6P1M0; Tchem.
DR PRO; PR:Q6P1M0; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q6P1M0; protein.
DR Bgee; ENSG00000167114; Expressed in mucosa of transverse colon and 152 other tissues.
DR ExpressionAtlas; Q6P1M0; baseline and differential.
DR Genevisible; Q6P1M0; HS.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ARUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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; IMP:ARUK-UCL.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:1901480; F:oleate transmembrane transporter activity; IEA:RHEA.
DR GO; GO:0090434; F:oleoyl-CoA ligase activity; IDA:ARUK-UCL.
DR GO; GO:0090433; F:palmitoyl-CoA ligase activity; IDA:ARUK-UCL.
DR GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IEA:Ensembl.
DR GO; GO:0090630; P:activation of GTPase activity; IDA:ARUK-UCL.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA:ARUK-UCL.
DR GO; GO:0015908; P:fatty acid transport; IMP:ARUK-UCL.
DR GO; GO:0044381; P:glucose import in response to insulin stimulus; ISS:ARUK-UCL.
DR GO; GO:1990379; P:lipid transport across blood-brain barrier; IMP:ARUK-UCL.
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:0015909; P:long-chain fatty acid transport; IMP:ARUK-UCL.
DR GO; GO:0001579; P:medium-chain fatty acid transport; IBA:GO_Central.
DR GO; GO:0062003; P:negative regulation of all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity; IEA:Ensembl.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ARUK-UCL.
DR GO; GO:0007584; P:response to nutrient; IBA:GO_Central.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
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; IPR030304; FATP4.
DR InterPro; IPR022272; Lipocalin_CS.
DR PANTHER; PTHR43107:SF11; PTHR43107:SF11; 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 Alternative splicing; Disease variant; Endoplasmic reticulum;
KW Fatty acid metabolism; Ichthyosis; Ligase; Lipid metabolism;
KW Lipid transport; Membrane; Nucleotide-binding; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..643
FT /note="Long-chain fatty acid transport protein 4"
FT /id="PRO_0000193209"
FT TRANSMEM 20..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 243..254
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..76
FT /note="MLLGASLVGVLLFSKLVLKLPWTQVGFSLLFLYLGSGGWRFIRVFIKTIRRD
FT IFGGLVLLKVKAKVRQCLQERRTV -> MPLTLSTLLQPGRIWTGRRAAEPTPGHNAAW
FT SLSGGGAAVLQAGAETALDPGGILPVVPLLGIWRLALHPGLHQDH (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055808"
FT VAR_SEQ 77..482
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055809"
FT VARIANT 92
FT /note="A -> T (in IPS; dbSNP:rs137853132)"
FT /evidence="ECO:0000269|PubMed:19631310"
FT /id="VAR_063192"
FT VARIANT 209
FT /note="G -> S (correlates with lower body mass index,
FT triglyceride concentrations, systolic blood pressure,
FT insulin concentrations and homeostasis model assessment
FT index; dbSNP:rs2240953)"
FT /evidence="ECO:0000269|PubMed:14715877"
FT /id="VAR_023783"
FT VARIANT 247
FT /note="S -> P (in IPS; dbSNP:rs137853133)"
FT /evidence="ECO:0000269|PubMed:19631310"
FT /id="VAR_063193"
FT VARIANT 300
FT /note="Q -> R (in IPS; dbSNP:rs137853134)"
FT /evidence="ECO:0000269|PubMed:19631310"
FT /id="VAR_063194"
FT VARIANT 374
FT /note="R -> C (in IPS; dbSNP:rs768495407)"
FT /evidence="ECO:0000269|PubMed:20815031"
FT /id="VAR_064500"
FT VARIANT 583
FT /note="R -> H (in IPS; dbSNP:rs137853135)"
FT /evidence="ECO:0000269|PubMed:19631310"
FT /id="VAR_063195"
FT CONFLICT 194
FT /note="L -> P (in Ref. 1; AAD11623)"
FT /evidence="ECO:0000305"
FT CONFLICT 605
FT /note="G -> A (in Ref. 1; AAD11623)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 643 AA; 72064 MW; 95E677DB3CEB9A14 CRC64;
MLLGASLVGV LLFSKLVLKL PWTQVGFSLL FLYLGSGGWR FIRVFIKTIR RDIFGGLVLL
KVKAKVRQCL QERRTVPILF ASTVRRHPDK TALIFEGTDT HWTFRQLDEY SSSVANFLQA
RGLASGDVAA IFMENRNEFV GLWLGMAKLG VEAALINTNL RRDALLHCLT TSRARALVFG
SEMASAICEV HASLDPSLSL FCSGSWEPGA VPPSTEHLDP LLKDAPKHLP SCPDKGFTDK
LFYIYTSGTT GLPKAAIVVH SRYYRMAALV YYGFRMRPND IVYDCLPLYH SAGNIVGIGQ
CLLHGMTVVI RKKFSASRFW DDCIKYNCTI VQYIGELCRY LLNQPPREAE NQHQVRMALG
NGLRQSIWTN FSSRFHIPQV AEFYGATECN CSLGNFDSQV GACGFNSRIL SFVYPIRLVR
VNEDTMELIR GPDGVCIPCQ PGEPGQLVGR IIQKDPLRRF DGYLNQGANN KKIAKDVFKK
GDQAYLTGDV LVMDELGYLY FRDRTGDTFR WKGENVSTTE VEGTLSRLLD MADVAVYGVE
VPGTEGRAGM AAVASPTGNC DLERFAQVLE KELPLYARPI FLRLLPELHK TGTYKFQKTE
LRKEGFDPAI VKDPLFYLDA QKGRYVPLDQ EAYSRIQAGE EKL
