FADS1_RAT
ID FADS1_RAT Reviewed; 447 AA.
AC Q920R3; Q9EPV4;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Acyl-CoA (8-3)-desaturase {ECO:0000305};
DE EC=1.14.19.44 {ECO:0000269|PubMed:24070791};
DE AltName: Full=Delta(5) fatty acid desaturase;
DE Short=D5D {ECO:0000250|UniProtKB:Q920L1};
DE Short=Delta(5) desaturase {ECO:0000250|UniProtKB:Q920L1};
DE Short=Delta-5 desaturase {ECO:0000303|PubMed:24070791};
DE AltName: Full=Fatty acid desaturase 1 {ECO:0000250|UniProtKB:O60427};
GN Name=Fads1 {ECO:0000303|PubMed:24070791};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Lewis; TISSUE=Liver;
RX PubMed=11414679; DOI=10.1006/abbi.2001.2361;
RA Zolfaghari R., Cifelli C.J., Banta M.D., Ross A.C.;
RT "Fatty acid Delta(5)-desaturase mRNA is regulated by dietary vitamin A and
RT exogenous retinoic acid in liver of adult rats.";
RL Arch. Biochem. Biophys. 391:8-15(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Inagaki K., Aki T., Shimada Y., Kawamoto S., Shigeta S., Ono K., Suzuki O.;
RT "Cloning and expression of rat liver delta-5 fatty acid desaturase.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24070791; DOI=10.1194/jlr.m042572;
RA Rioux V., Pedrono F., Blanchard H., Duby C., Boulier-Monthean N.,
RA Bernard L., Beauchamp E., Catheline D., Legrand P.;
RT "Trans-vaccenate is Delta13-desaturated by FADS3 in rodents.";
RL J. Lipid Res. 54:3438-3452(2013).
CC -!- FUNCTION: Acts as a front-end fatty acyl-coenzyme A (CoA) desaturase
CC that introduces a cis double bond at carbon 5 located between a
CC preexisting double bond and the carboxyl end of the fatty acyl chain.
CC Involved in biosynthesis of highly unsaturated fatty acids (HUFA) from
CC the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA)
CC (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors.
CC Specifically, desaturates dihomo-gamma-linoleoate (DGLA) (20:3n-6) and
CC eicosatetraenoate (ETA) (20:4n-3) to generate arachidonate (AA) (20:4n-
CC 6) and eicosapentaenoate (EPA) (20:5n-3), respectively
CC (PubMed:24070791). As a rate limiting enzyme for DGLA (20:3n-6) and AA
CC (20:4n-6)-derived eicosanoid biosynthesis, controls the metabolism of
CC inflammatory lipids like prostaglandin E2, critical for efficient acute
CC inflammatory response and maintenance of epithelium homeostasis.
CC Contributes to membrane phospholipid biosynthesis by providing AA
CC (20:4n-6) as a major acyl chain esterified into phospholipids. In
CC particular, regulates phosphatidylinositol-4,5-bisphosphate levels,
CC modulating inflammatory cytokine production in T-cells (By similarity).
CC Also desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a
CC metabolite in the biohydrogenation pathway of LA (18:2n-6)
CC (PubMed:24070791). {ECO:0000250|UniProtKB:Q920L1,
CC ECO:0000269|PubMed:24070791}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2
CC H(+) + O2 = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + 2 Fe(III)-
CC [cytochrome b5] + 2 H2O; Xref=Rhea:RHEA:46424, Rhea:RHEA-COMP:10438,
CC Rhea:RHEA-COMP:10439, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:57368, ChEBI:CHEBI:74264; EC=1.14.19.44;
CC Evidence={ECO:0000269|PubMed:24070791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46425;
CC Evidence={ECO:0000305|PubMed:24070791};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA + 2 Fe(II)-[cytochrome
CC b5] + 2 H(+) + O2 = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + 2
CC Fe(III)-[cytochrome b5] + 2 H2O; Xref=Rhea:RHEA:46420, Rhea:RHEA-
CC COMP:10438, Rhea:RHEA-COMP:10439, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:29034, ChEBI:CHEBI:73862, ChEBI:CHEBI:74265;
CC EC=1.14.19.44; Evidence={ECO:0000250|UniProtKB:O60427};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46421;
CC Evidence={ECO:0000250|UniProtKB:O60427};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) +
CC O2 = (5Z,11E)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2
CC H2O; Xref=Rhea:RHEA:46060, Rhea:RHEA-COMP:10438, Rhea:RHEA-
CC COMP:10439, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:74296,
CC ChEBI:CHEBI:85651; Evidence={ECO:0000269|PubMed:24070791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46061;
CC Evidence={ECO:0000305|PubMed:24070791};
CC -!- PATHWAY: Lipid metabolism; polyunsaturated fatty acid biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:A4UVI1}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:A4UVI1}. Mitochondrion
CC {ECO:0000250|UniProtKB:O60427}.
CC -!- TISSUE SPECIFICITY: Highly abundant in adrenal gland and mammary tissue
CC and moderately in liver, kidney, lung, spleen, thymus, brain, and eye.
CC {ECO:0000269|PubMed:11414679}.
CC -!- INDUCTION: Regulated by dietary vitamin A and exogenous retinoic acid
CC in liver. {ECO:0000269|PubMed:11414679}.
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family.
CC {ECO:0000305}.
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DR EMBL; AF320509; AAG35068.1; -; mRNA.
DR EMBL; AB052085; BAB69054.1; -; mRNA.
DR RefSeq; NP_445897.2; NM_053445.2.
DR AlphaFoldDB; Q920R3; -.
DR SMR; Q920R3; -.
DR STRING; 10116.ENSRNOP00000027834; -.
DR BindingDB; Q920R3; -.
DR ChEMBL; CHEMBL5727; -.
DR SwissLipids; SLP:000001191; -.
DR PhosphoSitePlus; Q920R3; -.
DR jPOST; Q920R3; -.
DR PaxDb; Q920R3; -.
DR PRIDE; Q920R3; -.
DR GeneID; 84575; -.
DR KEGG; rno:84575; -.
DR UCSC; RGD:621678; rat.
DR CTD; 3992; -.
DR RGD; 621678; Fads1.
DR VEuPathDB; HostDB:ENSRNOG00000020480; -.
DR eggNOG; KOG4232; Eukaryota.
DR HOGENOM; CLU_016265_0_1_1; -.
DR InParanoid; Q920R3; -.
DR OMA; MITFYIR; -.
DR OrthoDB; 1060606at2759; -.
DR PhylomeDB; Q920R3; -.
DR TreeFam; TF313604; -.
DR Reactome; R-RNO-2046105; Linoleic acid (LA) metabolism.
DR Reactome; R-RNO-2046106; alpha-linolenic acid (ALA) metabolism.
DR UniPathway; UPA00658; -.
DR PRO; PR:Q920R3; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020480; Expressed in liver and 19 other tissues.
DR Genevisible; Q920R3; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0062076; F:acyl-CoA delta5-desaturase activity; IDA:UniProtKB.
DR GO; GO:0016213; F:linoleoyl-CoA desaturase activity; ISO:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; ISO:RGD.
DR GO; GO:0016717; F:oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IMP:RGD.
DR GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0035900; P:response to isolation stress; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0009744; P:response to sucrose; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; IEP:RGD.
DR GO; GO:0006636; P:unsaturated fatty acid biosynthetic process; IDA:RGD.
DR Gene3D; 3.10.120.10; -; 1.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR InterPro; IPR005804; FA_desaturase_dom.
DR InterPro; IPR012171; Fatty_acid_desaturase.
DR PANTHER; PTHR19353; PTHR19353; 1.
DR Pfam; PF00173; Cyt-b5; 1.
DR Pfam; PF00487; FA_desaturase; 1.
DR PIRSF; PIRSF015921; FA_sphinglp_des; 1.
DR PRINTS; PR00363; CYTOCHROMEB5.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Electron transport; Endoplasmic reticulum;
KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..447
FT /note="Acyl-CoA (8-3)-desaturase"
FT /id="PRO_0000307099"
FT TOPO_DOM 1..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..161
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..308
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 309..329
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 330..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 19..97
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT MOTIF 182..186
FT /note="Histidine box-1"
FT MOTIF 219..223
FT /note="Histidine box-2"
FT MOTIF 385..389
FT /note="Histidine box-3"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O60427"
FT CONFLICT 73
FT /note="P -> R (in Ref. 1; AAG35068)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="R -> E (in Ref. 1; AAG35068)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="P -> S (in Ref. 1; AAG35068)"
FT /evidence="ECO:0000305"
FT CONFLICT 391
FT /note="F -> L (in Ref. 1; AAG35068)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 447 AA; 52482 MW; 764D7D7C9AA3F7BE CRC64;
MAPDPVQTPD PASAQLRQMR YFTWEEVAQR SGREKERWLV IDRKVYNISD FSRRHPGGSR
VISHYAGQDA TDPFVAFHIN KGLVRKYMNS LLIGELAPEQ PSFEPTKNKA LTDEFRELRA
TVERMGLMKA NHLFFLFYLL HILLLDVAAW LTLWIFGTSL VPFTLCAVLL STVQAQAGWL
QHDFGHLSVF STSTWNHLVH HFVIGHLKGA PASWWNHMHF QHHAKPNCFR KDPDINMHPL
FFALGKVLSV ELGKEKKKHM PYNHQHKYFF LIGPPALLPL YFQWYIFYFV VQRKKWVDLA
WMLSFYVRVF FTYMPLLGLK GLLCLFFIVR FLESNWFVWV TQMNHIPMHI DHDRNVDWVS
TQLQATCNVH QSAFNNWFSG HLNFQIEHHL FPTMPRHNYH KVAPLVQSLC AKYGIKYESK
PLLTAFADIV YSLKESGQLW LDAYLHQ
