FAT1_YEAST
ID FAT1_YEAST Reviewed; 669 AA.
AC P38225; D6VQ41; O60021; Q86ZS3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Very long-chain fatty acid transport protein {ECO:0000305};
DE EC=6.2.1.- {ECO:0000269|PubMed:15699031};
DE AltName: Full=Very-long-chain acyl-CoA synthetase;
DE Short=VLCS;
GN Name=FAT1; OrderedLocusNames=YBR041W; ORFNames=YBR0411;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RC STRAIN=W303A;
RX PubMed=9079682; DOI=10.1074/jbc.272.13.8531;
RA Faergeman N.J., Dirusso C.C., Elberger A., Knudsen J., Black P.N.;
RT "Disruption of the Saccharomyces cerevisiae homologue to the murine fatty
RT acid transport protein impairs uptake and growth on long-chain fatty
RT acids.";
RL J. Biol. Chem. 272:8531-8538(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 590-639.
RC STRAIN=ATCC 204508 / S288c;
RA Zhang Z., Stuart L.T., Dietrich F.S.;
RT "Saccharomyces cerevisiae YBR041W sequence update.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=9660783; DOI=10.1074/jbc.273.29.18210;
RA Watkins P.A., Lu J.F., Steinberg S.J., Gould S.J., Smith K.D.,
RA Braiterman L.T.;
RT "Disruption of the Saccharomyces cerevisiae FAT1 gene decreases very long-
RT chain fatty acyl-CoA synthetase activity and elevates intracellular very
RT long-chain fatty acid concentrations.";
RL J. Biol. Chem. 273:18210-18219(1998).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=10515935; DOI=10.1128/jb.181.20.6441-6448.1999;
RA Athenstaedt K., Zweytick D., Jandrositz A., Kohlwein S.D., Daum G.;
RT "Identification and characterization of major lipid particle proteins of
RT the yeast Saccharomyces cerevisiae.";
RL J. Bacteriol. 181:6441-6448(1999).
RN [7]
RP FUNCTION.
RX PubMed=9988704; DOI=10.1074/jbc.274.8.4671;
RA Choi J.Y., Martin C.E.;
RT "The Saccharomyces cerevisiae FAT1 gene encodes an acyl-CoA synthetase that
RT is required for maintenance of very long chain fatty acid levels.";
RL J. Biol. Chem. 274:4671-4683(1999).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11330068; DOI=10.1385/cbb:32:1-3:333;
RA Watkins P.A., Lu J.F., Braiterman L.T., Steinberg S.J., Smith K.D.;
RT "Disruption of a yeast very-long-chain acyl-CoA synthetase gene simulates
RT the cellular phenotype of X-linked adrenoleukodystrophy.";
RL Cell Biochem. Biophys. 32:333-337(2000).
RN [9]
RP FUNCTION.
RX PubMed=12052836; DOI=10.1074/jbc.m205034200;
RA Zou Z., DiRusso C.C., Ctrnacta V., Black P.N.;
RT "Fatty acid transport in Saccharomyces cerevisiae. Directed mutagenesis of
RT FAT1 distinguishes the biochemical activities associated with Fat1p.";
RL J. Biol. Chem. 277:31062-31071(2002).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH FAA1 AND FAA4.
RX PubMed=12601005; DOI=10.1074/jbc.m210557200;
RA Zou Z., Tong F., Faergeman N.J., Boersting C., Black P.N., DiRusso C.C.;
RT "Vectorial acylation in Saccharomyces cerevisiae. Fat1p and fatty acyl-CoA
RT synthetase are interacting components of a fatty acid import complex.";
RL J. Biol. Chem. 278:16414-16422(2003).
RN [11]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [12]
RP CATALYTIC ACTIVITY.
RX PubMed=15699031; DOI=10.1074/jbc.m409598200;
RA DiRusso C.C., Li H., Darwis D., Watkins P.A., Berger J., Black P.N.;
RT "Comparative biochemical studies of the murine fatty acid transport
RT proteins (FATP) expressed in yeast.";
RL J. Biol. Chem. 280:16829-16837(2005).
RN [13]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=17679730; DOI=10.1194/jlr.m700300-jlr200;
RA Obermeyer T., Fraisl P., DiRusso C.C., Black P.N.;
RT "Topology of the yeast fatty acid transport protein Fat1p: mechanistic
RT implications for functional domains on the cytosolic surface of the plasma
RT membrane.";
RL J. Lipid Res. 48:2354-2364(2007).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=21820081; DOI=10.1016/j.bbalip.2011.07.015;
RA Grillitsch K., Connerth M., Kofeler H., Arrey T.N., Rietschel B.,
RA Wagner B., Karas M., Daum G.;
RT "Lipid particles/droplets of the yeast Saccharomyces cerevisiae revisited:
RT lipidome meets proteome.";
RL Biochim. Biophys. Acta 1811:1165-1176(2011).
RN [15]
RP FUNCTION.
RX PubMed=22493507; DOI=10.1074/jbc.m111.332833;
RA van Roermund C.W., Ijlst L., Majczak W., Waterham H.R., Folkerts H.,
RA Wanders R.J., Hellingwerf K.J.;
RT "Peroxisomal fatty acid uptake mechanism in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 287:20144-20153(2012).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=24868093; DOI=10.1194/jlr.m050229;
RA Currie E., Guo X., Christiano R., Chitraju C., Kory N., Harrison K.,
RA Haas J., Walther T.C., Farese R.V. Jr.;
RT "High-confidence proteomic analysis of yeast lipid droplets identifies
RT additional droplet proteins and reveals connections to dolichol synthesis
RT and sterol acetylation.";
RL J. Lipid Res. 55:1465-1477(2014).
CC -!- FUNCTION: Acyl-CoA synthetase required for both the import of long
CC chain fatty acids (LCFAs) (C14-C18) and the activation very long chain
CC fatty acids (VLCFAs) (C20-C26) by esterification of the fatty acids
CC into metabolically active CoA-thioesters for subsequent degradation or
CC incorporation into phospholipids (PubMed:9079682, PubMed:11330068,
CC PubMed:9988704, PubMed:12052836, PubMed:12601005). The transport and
CC fatty acyl-CoA synthetase activities are genetically separable and are
CC thus independent activities (PubMed:12052836). Esterifies VLCFAs in the
CC peroxisome matrix. The VLCFAs are actively transported into peroxisomes
CC by a PXA1-PXA2 heterodimeric transporter in the peroxisomal membrane
CC (PubMed:22493507). {ECO:0000269|PubMed:11330068,
CC ECO:0000269|PubMed:12052836, ECO:0000269|PubMed:12601005,
CC ECO:0000269|PubMed:22493507, ECO:0000269|PubMed:9079682,
CC ECO:0000269|PubMed:9988704}.
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:0000269|PubMed:15699031};
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:0000269|PubMed:12601005, ECO:0000269|PubMed:15699031};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33640;
CC Evidence={ECO:0000305|PubMed:12601005, ECO:0000305|PubMed:15699031};
CC -!- SUBUNIT: Interacts with fatty acyl-CoA synthetases FAA1 and FAA4.
CC {ECO:0000269|PubMed:12601005}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:10515935,
CC ECO:0000269|PubMed:21820081, ECO:0000269|PubMed:24868093}. Cell
CC membrane {ECO:0000269|PubMed:17679730}; Multi-pass membrane protein
CC {ECO:0000255}. Peroxisome membrane {ECO:0000269|PubMed:22493507};
CC Multi-pass membrane protein {ECO:0000255}. Peroxisome
CC {ECO:0000269|PubMed:11330068}.
CC -!- DOMAIN: The FACS motif is required for catalytic activity and substrate
CC specificity. {ECO:0000250|UniProtKB:P30624}.
CC -!- MISCELLANEOUS: Present with 16900 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA84983.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF065148; AAC17118.1; -; Genomic_DNA.
DR EMBL; Z35910; CAA84983.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AY260890; AAP21758.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07161.1; -; Genomic_DNA.
DR PIR; S45899; S45899.
DR RefSeq; NP_009597.2; NM_001178389.1.
DR AlphaFoldDB; P38225; -.
DR SMR; P38225; -.
DR BioGRID; 32742; 214.
DR DIP; DIP-5048N; -.
DR IntAct; P38225; 14.
DR MINT; P38225; -.
DR STRING; 4932.YBR041W; -.
DR SwissLipids; SLP:000000129; -.
DR TCDB; 4.C.1.1.2; the fatty acid group translocation (fat) family.
DR MaxQB; P38225; -.
DR PaxDb; P38225; -.
DR PRIDE; P38225; -.
DR EnsemblFungi; YBR041W_mRNA; YBR041W; YBR041W.
DR GeneID; 852329; -.
DR KEGG; sce:YBR041W; -.
DR SGD; S000000245; FAT1.
DR VEuPathDB; FungiDB:YBR041W; -.
DR eggNOG; KOG1179; Eukaryota.
DR GeneTree; ENSGT00940000169294; -.
DR HOGENOM; CLU_000022_46_3_1; -.
DR InParanoid; P38225; -.
DR OMA; IVGMGQC; -.
DR BioCyc; YEAST:YBR041W-MON; -.
DR BRENDA; 6.2.1.3; 984.
DR PRO; PR:P38225; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38225; protein.
DR GO; GO:0071944; C:cell periphery; HDA:SGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0000329; C:fungal-type vacuole membrane; HDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031235; C:intrinsic component of the cytoplasmic side of the plasma membrane; IDA:SGD.
DR GO; GO:0005811; C:lipid droplet; IDA:SGD.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005777; C:peroxisome; IMP:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005324; F:long-chain fatty acid transporter activity; IMP:SGD.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IBA:GO_Central.
DR GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IMP:SGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0044539; P:long-chain fatty acid import into cell; IMP:SGD.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:SGD.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IMP:SGD.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
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; IPR030310; FadD17/FadD6-like.
DR PANTHER; PTHR43107:SF15; PTHR43107:SF15; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Ligase; Lipid droplet; Lipid transport;
KW Membrane; Nucleotide-binding; Peroxisome; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..669
FT /note="Very long-chain fatty acid transport protein"
FT /id="PRO_0000193181"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:17679730"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..148
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:17679730"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:17679730"
FT INTRAMEM 271..339
FT /evidence="ECO:0000305|PubMed:17679730"
FT TOPO_DOM 340..669
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:17679730"
FT MOTIF 501..551
FT /note="FACS"
FT /evidence="ECO:0000250|UniProtKB:P30624"
FT MOTIF 667..669
FT /note="C-terminal peroxisome targeting signal (PTS1)"
FT /evidence="ECO:0000305|PubMed:22493507"
FT BINDING 256..267
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P69451"
SQ SEQUENCE 669 AA; 77141 MW; 509A5DEDDEE98823 CRC64;
MSPIQVVVFA LSRIFLLLFR LIKLIITPIQ KSLGYLFGNY FDELDRKYRY KEDWYIIPYF
LKSVFCYIID VRRHRFQNWY LFIKQVQQNG DHLAISYTRP MAEKGEFQLE TFTYIETYNI
VLRLSHILHF DYNVQAGDYV AIDCTNKPLF VFLWLSLWNI GAIPAFLNYN TKGTPLVHSL
KISNITQVFI DPDASNPIRE SEEEIKNALP DVKLNYLEEQ DLMHELLNSQ SPEFLQQDNV
RTPLGLTDFK PSMLIYTSGT TGLPKSAIMS WRKSSVGCQV FGHVLHMTNE STVFTAMPLF
HSTAALLGAC AILSHGGCLA LSHKFSASTF WKQVYLTGAT HIQYVGEVCR YLLHTPISKY
EKMHKVKVAY GNGLRPDIWQ DFRKRFNIEV IGEFYAATEA PFATTTFQKG DFGIGACRNY
GTIIQWFLSF QQTLVRMDPN DDSVIYRNSK GFCEVAPVGE PGEMLMRIFF PKKPETSFQG
YLGNAKETKS KVVRDVFRRG DAWYRCGDLL KADEYGLWYF LDRMGDTFRW KSENVSTTEV
EDQLTASNKE QYAQVLVVGI KVPKYEGRAG FAVIKLTDNS LDITAKTKLL NDSLSRLNLP
SYAMPLFVKF VDEIKMTDNH KILKKVYREQ KLPKGLDGND TIFWLKNYKR YEVLTAADWE
AIDAQTIKL
