FADS3_RAT
ID FADS3_RAT Reviewed; 449 AA.
AC Q8K1P9;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Fatty acid desaturase 3 {ECO:0000303|PubMed:19752397};
DE EC=1.14.19.- {ECO:0000269|PubMed:24070791};
DE AltName: Full=Delta(13) fatty acid desaturase {ECO:0000305|PubMed:24070791};
DE Short=Delta(13) desaturase {ECO:0000305|PubMed:24070791};
GN Name=Fads3 {ECO:0000303|PubMed:19752397, 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].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RA D'Andrea S., Guillou H., Jan S., Daval S., Rioux V., Legrand P.;
RT "Characterization of a novel putative fatty acid desaturase from rat.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=19752397; DOI=10.1194/jlr.m000588;
RA Pedrono F., Blanchard H., Kloareg M., D'andrea S., Daval S., Rioux V.,
RA Legrand P.;
RT "The fatty acid desaturase 3 gene encodes for different FADS3 protein
RT isoforms in mammalian tissues.";
RL J. Lipid Res. 51:472-479(2010).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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: Mammals have different sphingoid bases that differ in their
CC length and/or pattern of desaturation and hydroxyl groups. The
CC predominant sphingoid base in mammalian ceramides is sphing-4-enine
CC (sphingosine or SPH) which has a trans desaturation at carbon 4. FADS3
CC is a ceramide desaturase that introduces a cis double bond between
CC carbon 14 and carbon 15 of the SPH-containing ceramides, producing
CC sphinga-4,14-dienine-containing ceramides (SPD ceramides). SPD
CC ceramides occur widely in mammalian tissues and cells. Due to their
CC unusual structure containing a cis double bond, SPD ceramides may have
CC an opposite, negative role in lipid microdomain formation relative to
CC conventional ceramides (By similarity). FADS3 also acts as a methyl-end
CC fatty acyl coenzyme A (CoA) desaturase that introduces a cis double
CC bond between the preexisting double bond and the terminal methyl group
CC of the fatty acyl chain. Desaturates (11E)-octadecenoate (trans-
CC vaccenoate) at carbon 13 to generate (11E,13Z)-octadecadienoate (also
CC known as conjugated linoleic acid 11E,13Z-CLA) (PubMed:24070791).
CC {ECO:0000250|UniProtKB:Q9Y5Q0, ECO:0000269|PubMed:24070791}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + 2 Fe(II)-[cytochrome b5] + 2 H(+) +
CC O2 = an N-acyl-sphinga-4E,14Z-dienine + 2 Fe(III)-[cytochrome b5] + 2
CC H2O; Xref=Rhea:RHEA:63928, 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:52639,
CC ChEBI:CHEBI:139573; Evidence={ECO:0000250|UniProtKB:Q9Y5Q0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63929;
CC Evidence={ECO:0000250|UniProtKB:Q9Y5Q0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(II)-[cytochrome b5] + 2 H(+) + N-(hexanoyl)sphing-4-enine
CC + O2 = 2 Fe(III)-[cytochrome b5] + 2 H2O + N-hexanoyl-sphinga-4E,14Z-
CC dienine; Xref=Rhea:RHEA:63940, 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:63867,
CC ChEBI:CHEBI:149631; Evidence={ECO:0000250|UniProtKB:Q9Y5Q0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63941;
CC Evidence={ECO:0000250|UniProtKB:Q9Y5Q0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) +
CC O2 = (11E,13Z)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2
CC H2O; Xref=Rhea:RHEA:46056, 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:85650; Evidence={ECO:0000269|PubMed:24070791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46057;
CC Evidence={ECO:0000269|PubMed:24070791};
CC -!- PATHWAY: Lipid metabolism; polyunsaturated fatty acid biosynthesis.
CC {ECO:0000305|PubMed:24070791}.
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000250|UniProtKB:Q9Y5Q0}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9Y5Q0}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Essentially expressed in liver and kidney and to a
CC lesser extent in heart, adipose tissue, stomach and pancreas (at
CC protein level). {ECO:0000269|PubMed:19752397}.
CC -!- DOMAIN: The protein sequence includes a number of characteristic
CC features of microsomal fatty acid desaturases including the three
CC histidine boxes (these domains may contain the active site and/or be
CC involved in metal ion binding), and the N-terminal cytochrome b5 domain
CC containing the heme-binding motif, HPGG, similar to that of other fatty
CC acid desaturases. {ECO:0000250|UniProtKB:Q9Y5Q0}.
CC -!- MISCELLANEOUS: Two potential isoforms are detected in various tissues.
CC A 75 kDa isoform is expressed in lung, spleen and thymus. A 37 kDa
CC isoform is highly expressed in skeletal and abdominal muscles, brain
CC and ovary and to a lesser extent in heart, lung, brown adipose tissue
CC and eye. {ECO:0000269|PubMed:19752397}.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family.
CC {ECO:0000305}.
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DR EMBL; AJ494720; CAD38527.1; -; mRNA.
DR RefSeq; NP_775160.1; NM_173137.1.
DR AlphaFoldDB; Q8K1P9; -.
DR SMR; Q8K1P9; -.
DR STRING; 10116.ENSRNOP00000027693; -.
DR SwissLipids; SLP:000001192; -.
DR PaxDb; Q8K1P9; -.
DR Ensembl; ENSRNOT00000100217; ENSRNOP00000090422; ENSRNOG00000020385.
DR GeneID; 286922; -.
DR KEGG; rno:286922; -.
DR UCSC; RGD:628876; rat.
DR CTD; 3995; -.
DR RGD; 628876; Fads3.
DR eggNOG; KOG4232; Eukaryota.
DR GeneTree; ENSGT00950000182990; -.
DR HOGENOM; CLU_016265_0_1_1; -.
DR InParanoid; Q8K1P9; -.
DR OMA; WMHEAGH; -.
DR OrthoDB; 1060606at2759; -.
DR PhylomeDB; Q8K1P9; -.
DR TreeFam; TF313604; -.
DR UniPathway; UPA00222; -.
DR UniPathway; UPA00658; -.
DR PRO; PR:Q8K1P9; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020385; Expressed in lung and 18 other tissues.
DR ExpressionAtlas; Q8K1P9; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0006665; P:sphingolipid metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006636; P:unsaturated fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
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 Electron transport; Endoplasmic reticulum; Fatty acid biosynthesis;
KW Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..449
FT /note="Fatty acid desaturase 3"
FT /id="PRO_0000307110"
FT TOPO_DOM 1..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 159..163
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..310
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..449
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 24..101
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 186..190
FT /note="Histidine box-1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5Q0"
FT MOTIF 223..227
FT /note="Histidine box-2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5Q0"
FT MOTIF 387..391
FT /note="Histidine box-3"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5Q0"
SQ SEQUENCE 449 AA; 51467 MW; E2E33662095855AB CRC64;
MGGVGEPGGG PGPREGPAPL GAPLPIFRWE QIRQHDLPGD KWLVIERRVY DISRWAQRHP
GGSRLIGHHS AEDATDAFHA FHQDLHFVRK FLKPLLIGEL APEEPSQDGA QNAQLIEDFR
ALRQAAEDMK LFEADTTFFA LLLGHILAME LLAWLLVYLL GPGWVSSVLA ALILAISQAQ
CWCLQHDLGH ASIFPKSRWN HVAQQFVMGQ LKGFSAHWWN FRHFQHHAKP NIFHKDPDVT
VAPVFLLGES SVEYGKKKRR YLPYNHQHLY FFLIGPPLLT LVNFEVENLA YMLVCMQWTD
LLWAASFYSR FFLSYSPFYG ATGTLLLFVA VRVLESHWFV WITQMNHIPK EIGHEKHRDW
ASSQLAATCN VEPSLFIDWF SGHLNFQIEH HLFPTMPRHN YRRVAPLVKA FCAKHGLHYE
VKPFLTALVD IIGSLKKSGD IWLDAYLHQ
