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Q91VE0

- S27A4_MOUSE

UniProt

Q91VE0 - S27A4_MOUSE

Protein

Long-chain fatty acid transport protein 4

Gene

Slc27a4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Involved in translocation of long-chain fatty acids (LFCA) across the plasma membrane. Appears to be the principal fatty acid transporter in small intestinal enterocytes. Plays a role in the formation of the epidermal barrier. Required for fat absorption in early embryogenesis. Has acyl-CoA ligase activity for long-chain and very-long-chain fatty acids (VLCFAs). Indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Prevents light-induced degeneration of rods and cones.6 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi243 – 25412AMPSequence AnalysisAdd
    BLAST

    GO - Molecular functioni

    1. long-chain fatty acid-CoA ligase activity Source: MGI
    2. nucleotide binding Source: UniProtKB-KW
    3. very long-chain fatty acid-CoA ligase activity Source: MGI

    GO - Biological processi

    1. fatty acid metabolic process Source: MGI
    2. long-chain fatty acid import Source: Ensembl
    3. long-chain fatty acid metabolic process Source: MGI
    4. long-chain fatty acid transport Source: MGI
    5. medium-chain fatty acid transport Source: MGI
    6. response to nutrient Source: Ensembl
    7. skin development Source: MGI
    8. very long-chain fatty acid catabolic process Source: MGI
    9. very long-chain fatty acid metabolic process Source: MGI

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Fatty acid metabolism, Lipid metabolism, Lipid transport, Transport

    Keywords - Ligandi

    Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi6.2.1.3. 3474.
    ReactomeiREACT_198636. Transport of fatty acids.

    Protein family/group databases

    TCDBi4.C.1.1.1. the proposed fatty acid transporter (fat) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Long-chain fatty acid transport protein 4 (EC:6.2.1.-)
    Short name:
    FATP-4
    Short name:
    Fatty acid transport protein 4
    Alternative name(s):
    Solute carrier family 27 member 4
    Gene namesi
    Name:Slc27a4
    Synonyms:Acsvl4, Fatp4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:1347347. Slc27a4.

    Subcellular locationi

    GO - Cellular componenti

    1. brush border membrane Source: MGI
    2. endoplasmic reticulum Source: MGI
    3. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    4. integral component of membrane Source: UniProtKB-KW
    5. microvillus Source: MGI
    6. plasma membrane Source: MGI

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Defects in Slc27a4 are the cause of wrinkle-free (wrfr) phenotype. It is a spontaneous, autosomal recessive mutation resulting in very tight, thick skin and is secondary characterized by severe breathing difficulties. Mice die shortly after birth. This phenotype is similar to human restrictive dermopathy, a very rare human genetic disorder.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 643643Long-chain fatty acid transport protein 4PRO_0000193211Add
    BLAST

    Proteomic databases

    MaxQBiQ91VE0.
    PaxDbiQ91VE0.
    PRIDEiQ91VE0.

    PTM databases

    PhosphoSiteiQ91VE0.

    Expressioni

    Tissue specificityi

    Most abundantly expressed in small intestine, brain, kidney, liver, skin and heart. In small intestine, expressed at high levels on the apical side of mature enterocytes. Highly expressed by the epithelial cells of the visceral endoderm and localized to the brush-border membrane of extraembryonic endodermal cells (at protein level). Expressed in the retinal pigment epithelium and in the retina (at protein level). Expressed in the retinal pigment epithelium and in the retina.5 Publications

    Gene expression databases

    BgeeiQ91VE0.
    GenevestigatoriQ91VE0.

    Structurei

    3D structure databases

    ProteinModelPortaliQ91VE0.
    SMRiQ91VE0. Positions 74-607.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei20 – 4223HelicalSequence AnalysisAdd
    BLAST
    Transmembranei139 – 15618HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0318.
    GeneTreeiENSGT00550000074420.
    HOGENOMiHOG000044189.
    HOVERGENiHBG005642.
    InParanoidiQ91VE0.
    KOiK08745.
    OMAiNDIVYDC.
    OrthoDBiEOG7W6WKB.
    PhylomeDBiQ91VE0.
    TreeFamiTF313430.

    Family and domain databases

    InterProiIPR025110. AMP-bd_C.
    IPR020845. AMP-binding_CS.
    IPR000873. AMP-dep_Synth/Lig.
    IPR022272. Lipocalin_CS.
    [Graphical view]
    PfamiPF00501. AMP-binding. 1 hit.
    PF13193. AMP-binding_C. 1 hit.
    [Graphical view]
    PROSITEiPS00455. AMP_BINDING. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q91VE0-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLLGASLVGA LLFSKLVLKL PWTQVGFSLL LLYLGSGGWR FIRVFIKTVR    50
    RDIFGGMVLL KVKTKVRRYL QERKTVPLLF ASMVQRHPDK TALIFEGTDT 100
    HWTFRQLDEY SSSVANFLQA RGLASGNVVA LFMENRNEFV GLWLGMAKLG 150
    VEAALINTNL RRDALRHCLD TSKARALIFG SEMASAICEI HASLEPTLSL 200
    FCSGSWEPST VPVSTEHLDP LLEDAPKHLP SHPDKGFTDK LFYIYTSGTT 250
    GLPKAAIVVH SRYYRMASLV YYGFRMRPDD IVYDCLPLYH SAGNIVGIGQ 300
    CLLHGMTVVI RKKFSASRFW DDCIKYNCTI VQYIGELCRY LLNQPPREAE 350
    SRHKVRMALG NGLRQSIWTD FSSRFHIPQV AEFYGATECN CSLGNFDSRV 400
    GACGFNSRIL SFVYPIRLVR VNEDTMELIR GPDGVCIPCQ PGQPGQLVGR 450
    IIQQDPLRRF DGYLNQGANN KKIANDVFKK GDQAYLTGDV LVMDELGYLY 500
    FRDRTGDTFR WKGENVSTTE VEGTLSRLLH MADVAVYGVE VPGTEGRAGM 550
    AAVASPISNC DLESFAQTLK KELPLYARPI FLRFLPELHK TGTFKFQKTE 600
    LRKEGFDPSV VKDPLFYLDA RKGCYVALDQ EAYTRIQAGE EKL 643
    Length:643
    Mass (Da):72,319
    Last modified:December 1, 2001 - v1
    Checksum:i10B3E9730FDF586A
    GO

    Sequence cautioni

    The sequence AAC40188.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.
    The sequence AAC40188.1 differs from that shown. Reason: Frameshift at several positions.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti330 – 3301I → V in AAC40188. (PubMed:9671728)Curated
    Sequence conflicti542 – 5421P → S in BAE41756. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ251113 mRNA. Translation: CAC42082.1.
    AJ276492 Genomic DNA. Translation: CAC42083.1.
    AK036919 mRNA. Translation: BAC29639.1.
    AK155388 mRNA. Translation: BAE33236.1.
    AK170377 mRNA. Translation: BAE41756.1.
    CT010312 mRNA. Translation: CAJ18520.1.
    BC023114 mRNA. Translation: AAH23114.1.
    AF072759 mRNA. Translation: AAC40188.1. Sequence problems.
    CCDSiCCDS15858.1.
    RefSeqiNP_036119.1. NM_011989.4.
    UniGeneiMm.330113.

    Genome annotation databases

    EnsembliENSMUST00000080065; ENSMUSP00000078971; ENSMUSG00000059316.
    GeneIDi26569.
    KEGGimmu:26569.
    UCSCiuc008jaf.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ251113 mRNA. Translation: CAC42082.1 .
    AJ276492 Genomic DNA. Translation: CAC42083.1 .
    AK036919 mRNA. Translation: BAC29639.1 .
    AK155388 mRNA. Translation: BAE33236.1 .
    AK170377 mRNA. Translation: BAE41756.1 .
    CT010312 mRNA. Translation: CAJ18520.1 .
    BC023114 mRNA. Translation: AAH23114.1 .
    AF072759 mRNA. Translation: AAC40188.1 . Sequence problems.
    CCDSi CCDS15858.1.
    RefSeqi NP_036119.1. NM_011989.4.
    UniGenei Mm.330113.

    3D structure databases

    ProteinModelPortali Q91VE0.
    SMRi Q91VE0. Positions 74-607.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    TCDBi 4.C.1.1.1. the proposed fatty acid transporter (fat) family.

    PTM databases

    PhosphoSitei Q91VE0.

    Proteomic databases

    MaxQBi Q91VE0.
    PaxDbi Q91VE0.
    PRIDEi Q91VE0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000080065 ; ENSMUSP00000078971 ; ENSMUSG00000059316 .
    GeneIDi 26569.
    KEGGi mmu:26569.
    UCSCi uc008jaf.1. mouse.

    Organism-specific databases

    CTDi 10999.
    MGIi MGI:1347347. Slc27a4.

    Phylogenomic databases

    eggNOGi COG0318.
    GeneTreei ENSGT00550000074420.
    HOGENOMi HOG000044189.
    HOVERGENi HBG005642.
    InParanoidi Q91VE0.
    KOi K08745.
    OMAi NDIVYDC.
    OrthoDBi EOG7W6WKB.
    PhylomeDBi Q91VE0.
    TreeFami TF313430.

    Enzyme and pathway databases

    BRENDAi 6.2.1.3. 3474.
    Reactomei REACT_198636. Transport of fatty acids.

    Miscellaneous databases

    NextBioi 304651.
    PROi Q91VE0.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q91VE0.
    Genevestigatori Q91VE0.

    Family and domain databases

    InterProi IPR025110. AMP-bd_C.
    IPR020845. AMP-binding_CS.
    IPR000873. AMP-dep_Synth/Lig.
    IPR022272. Lipocalin_CS.
    [Graphical view ]
    Pfami PF00501. AMP-binding. 1 hit.
    PF13193. AMP-binding_C. 1 hit.
    [Graphical view ]
    PROSITEi PS00455. AMP_BINDING. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mouse fatty acid transport protein 4 (FATP4): characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase."
      Herrmann T., Buchkremer F., Gosch I., Hall A.M., Bernlohr D.A., Stremmel W.
      Gene 270:31-40(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE SPECIFICITY.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J and NOD.
      Tissue: Dendritic cell and Vagina.
    3. "Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)."
      Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Liver.
    5. "A family of fatty acid transporters conserved from mycobacterium to man."
      Hirsch D., Stahl A., Lodish H.F.
      Proc. Natl. Acad. Sci. U.S.A. 95:8625-8629(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 145-643, TISSUE SPECIFICITY.
    6. Cited for: FUNCTION IN FATTY ACID TRANSPORT, TISSUE SPECIFICITY.
    7. "Targeted deletion of fatty acid transport protein-4 results in early embryonic lethality."
      Gimeno R.E., Hirsch D.J., Punreddy S., Sun Y., Ortegon A.M., Wu H., Daniels T., Stricker-Krongrad A., Lodish H.F., Stahl A.
      J. Biol. Chem. 278:49512-49516(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    8. "Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy."
      Herrmann T., van der Hoeven F., Grone H.J., Stewart A.F., Langbein L., Kaiser I., Liebisch G., Gosch I., Buchkremer F., Drobnik W., Schmitz G., Stremmel W.
      J. Cell Biol. 161:1105-1115(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "Cloning of wrinkle-free, a previously uncharacterized mouse mutation, reveals crucial roles for fatty acid transport protein 4 in skin and hair development."
      Moulson C.L., Martin D.R., Lugus J.J., Schaffer J.E., Lind A.C., Miner J.H.
      Proc. Natl. Acad. Sci. U.S.A. 100:5274-5279(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISEASE.
    10. "Enzymatic properties of purified murine fatty acid transport protein 4 and analysis of acyl-CoA synthetase activities in tissues from FATP4 null mice."
      Hall A.M., Wiczer B.M., Herrmann T., Stremmel W., Bernlohr D.A.
      J. Biol. Chem. 280:11948-11954(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS AN ACYL-COA LIGASE.
    11. "Comparative biochemical studies of the murine fatty acid transport proteins (FATP) expressed in yeast."
      DiRusso C.C., Li H., Darwis D., Watkins P.A., Berger J., Black P.N.
      J. Biol. Chem. 280:16829-16837(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    12. "Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
      Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
      Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Brain.
    13. "Fatty acid transport protein 4 (FATP4) prevents light-induced degeneration of cone and rod photoreceptors by inhibiting RPE65 isomerase."
      Li S., Lee J., Zhou Y., Gordon W.C., Hill J.M., Bazan N.G., Miner J.H., Jin M.
      J. Neurosci. 33:3178-3189(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiS27A4_MOUSE
    AccessioniPrimary (citable) accession number: Q91VE0
    Secondary accession number(s): O88562, Q3TD48
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 6, 2005
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 114 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Slc27a4 deficient mice display features of a neonatally lethal restrictive dermopathy. Their skin is characterized by hyperproliferative hyperkeratosis with a disturbed epidermal barrier, a flat dermal-epidermal junction, a reduced number of pilo-sebaceous structures, and a compact dermis. The rigid skin consistency results in an altered body shape with facial dysmorphia, generalized joint flexion contractures and impaired movement including suckling and breathing deficiencies. Lipid analysis demonstrates a disturbed fatty acid composition of epidermal ceramides, in particular a decrease in the C26:0 and C26:0-OH fatty acid substitutes.
    Deletion of Slc27a4 results in embryonic lethality, which has been attributed to a requirement for fat absorption early in embryonic development across the visceral endoderm.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3