Q91VE0 (S27A4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Long-chain fatty acid transport protein 4
Short name=FATP-4
Short name=Fatty acid transport protein 4
EC=6.2.1.-

Alternative name(s):
Solute carrier family 27 member 4

Gene names

Name:	Slc27a4
Synonyms:	Acsvl4, Fatp4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	643 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.6 Ref.8 Ref.10 Ref.11
Subcellular location	Membrane; Multi-pass membrane protein Probable Ref.11.
Tissue specificity	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). Ref.1 Ref.5 Ref.6 Ref.7
Involvement in disease	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. Ref.9
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.
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family.
Sequence caution	The sequence AAC40188.1 differs from that shown. Reason: Frameshift at several positions. The sequence AAC40188.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism Lipid transport Transport
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Nucleotide-binding
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	long-chain fatty acid import Inferred from electronic annotation. Source: Compara long-chain fatty acid transport Inferred from mutant phenotype Ref.6Ref.7. Source: MGI medium-chain fatty acid transport Inferred from direct assay PubMed 17062637. Source: MGI skin development Inferred from mutant phenotype Ref.8PubMed 16354193PubMed 17401141. Source: MGI very long-chain fatty acid catabolic process Inferred from direct assay PubMed 17522045. Source: MGI
Cellular_component	brush border membrane Inferred from direct assay Ref.7. Source: MGI endoplasmic reticulum Inferred from direct assay PubMed 15496455PubMed 17062637. Source: MGI endoplasmic reticulum membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microvillus Inferred from direct assay Ref.6. Source: MGI
Molecular_function	long-chain fatty acid-CoA ligase activity Inferred from direct assay Ref.1Ref.10PubMed 17062637. Source: MGI nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW very long-chain fatty acid-CoA ligase activity Inferred from direct assay Ref.10PubMed 17522045PubMed 18258213. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 643	643	Long-chain fatty acid transport protein 4		PRO_0000193211
Regions
	Transmembrane	20 – 42	23	Helical; Potential
	Transmembrane	139 – 156	18	Helical; Potential
	Nucleotide binding	243 – 254	12	AMP Potential
Experimental info
	Sequence conflict	330	1	I → V in AAC40188. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q91VE0 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 10B3E9730FDF586A	FASTA	643	72,319
	10 20 30 40 50 60 MLLGASLVGA LLFSKLVLKL PWTQVGFSLL LLYLGSGGWR FIRVFIKTVR RDIFGGMVLL 70 80 90 100 110 120 KVKTKVRRYL QERKTVPLLF ASMVQRHPDK TALIFEGTDT HWTFRQLDEY SSSVANFLQA 130 140 150 160 170 180 RGLASGNVVA LFMENRNEFV GLWLGMAKLG VEAALINTNL RRDALRHCLD TSKARALIFG 190 200 210 220 230 240 SEMASAICEI HASLEPTLSL FCSGSWEPST VPVSTEHLDP LLEDAPKHLP SHPDKGFTDK 250 260 270 280 290 300 LFYIYTSGTT GLPKAAIVVH SRYYRMASLV YYGFRMRPDD IVYDCLPLYH SAGNIVGIGQ 310 320 330 340 350 360 CLLHGMTVVI RKKFSASRFW DDCIKYNCTI VQYIGELCRY LLNQPPREAE SRHKVRMALG 370 380 390 400 410 420 NGLRQSIWTD FSSRFHIPQV AEFYGATECN CSLGNFDSRV GACGFNSRIL SFVYPIRLVR 430 440 450 460 470 480 VNEDTMELIR GPDGVCIPCQ PGQPGQLVGR IIQQDPLRRF DGYLNQGANN KKIANDVFKK 490 500 510 520 530 540 GDQAYLTGDV LVMDELGYLY FRDRTGDTFR WKGENVSTTE VEGTLSRLLH MADVAVYGVE 550 560 570 580 590 600 VPGTEGRAGM AAVASPISNC DLESFAQTLK KELPLYARPI FLRFLPELHK TGTFKFQKTE 610 620 630 640 LRKEGFDPSV VKDPLFYLDA RKGCYVALDQ EAYTRIQAGE EKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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. Tissue: 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]	"Identification of the major intestinal fatty acid transport protein." Stahl A., Hirsch D.J., Gimeno R.E., Punreddy S., Ge P., Watson N., Patel S., Kotler M., Raimondi A., Tartaglia L.A., Lodish H.F. Mol. Cell 4:299-308(1999) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ251113 mRNA. Translation: CAC42082.1. AJ276492 Genomic DNA. Translation: CAC42083.1. AK036919 mRNA. Translation: BAC29639.1. AK155388 mRNA. Translation: BAE33236.1. CT010312 mRNA. Translation: CAJ18520.1. BC023114 mRNA. Translation: AAH23114.1. AF072759 mRNA. Translation: AAC40188.1. Sequence problems.
IPI	IPI00126796.
RefSeq	NP_036119.1. NM_011989.4.
UniGene	Mm.330113.
3D structure databases
ProteinModelPortal	Q91VE0.
SMR	Q91VE0. Positions 74-607.
ModBase	Search...
Protein family/group databases
TCDB	4.C.1.1.1. proposed fatty acid transporter (FAT) family.
PTM databases
PhosphoSite	Q91VE0.
Proteomic databases
PaxDb	Q91VE0.
PRIDE	Q91VE0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000080065; ENSMUSP00000078971; ENSMUSG00000059316.
GeneID	26569.
KEGG	mmu:26569.
Organism-specific databases
CTD	10999.
MGI	MGI:1347347. Slc27a4.
Phylogenomic databases
eggNOG	COG0318.
GeneTree	ENSGT00550000074420.
HOGENOM	HOG000044189.
HOVERGEN	HBG005642.
InParanoid	Q91VE0.
KO	K08745.
OMA	FIRVFIK.
OrthoDB	EOG473PQW.
Enzyme and pathway databases
BRENDA	6.2.1.3. 3474.
Gene expression databases
ArrayExpress	Q91VE0.
Bgee	Q91VE0.
Genevestigator	Q91VE0.
GermOnline	ENSMUSG00000059316. Mus musculus.
Family and domain databases
InterPro	IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. IPR022272. Lipocalin_CS. [Graphical view]
Pfam	PF00501. AMP-binding. 1 hit. [Graphical view]
PROSITE	PS00455. AMP_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	304651.
SOURCE	Search...

Entry information

Entry name

S27A4_MOUSE

Accession

Primary (citable) accession number: Q91VE0
Secondary accession number(s): O88562

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program