FADS2_RAT
ID FADS2_RAT Reviewed; 444 AA.
AC Q9Z122; H2BF31;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Acyl-CoA 6-desaturase {ECO:0000305};
DE EC=1.14.19.3 {ECO:0000269|PubMed:11988075, ECO:0000269|PubMed:24070791};
DE AltName: Full=Delta(6) fatty acid desaturase;
DE Short=D6D {ECO:0000250|UniProtKB:Q9Z0R9};
DE Short=Delta(6) desaturase;
DE Short=Delta-6 desaturase {ECO:0000303|PubMed:11988075, ECO:0000303|PubMed:14563830};
DE AltName: Full=Fatty acid desaturase 2;
GN Name=Fads2; Synonyms=Fadsd6;
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], AND FUNCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=10049752; DOI=10.1006/bbrc.1999.0235;
RA Aki T., Shimada Y., Inagaki K., Higashimoto H., Kawamoto S., Shigeta S.,
RA Ono K., Suzuki O.;
RT "Molecular cloning and functional characterization of rat Delta-6 fatty
RT acid desaturase.";
RL Biochem. Biophys. Res. Commun. 255:575-579(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=Dark agouti;
RX PubMed=22216341; DOI=10.1371/journal.pone.0029662;
RA Gregory M.K., Gibson R.A., Cook-Johnson R.J., Cleland L.G., James M.J.;
RT "Elongase reactions as control points in long-chain polyunsaturated fatty
RT acid synthesis.";
RL PLoS ONE 6:E29662-E29662(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=5094766; DOI=10.1007/bf02531137;
RA Brenner R.R.;
RT "The desaturation step in the animal biosynthesis of polyunsaturated fatty
RT acids.";
RL Lipids 6:567-575(1971).
RN [5]
RP INDUCTION.
RX PubMed=12538079; DOI=10.1016/s0952-3278(02)00265-x;
RA Brenner R.R.;
RT "Hormonal modulation of delta-6 and delta-5 desaturases: case of
RT diabetes.";
RL Prostaglandins Leukot. Essent. Fatty Acids 68:151-162(2003).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11988075; DOI=10.1042/bj3640049;
RA D'andrea S., Guillou H., Jan S., Catheline D., Thibault J.N., Bouriel M.,
RA Rioux V., Legrand P.;
RT "The same rat Delta6-desaturase not only acts on 18- but also on 24-carbon
RT fatty acids in very-long-chain polyunsaturated fatty acid biosynthesis.";
RL Biochem. J. 364:49-55(2002).
RN [7]
RP FUNCTION.
RX PubMed=14563830; DOI=10.1194/jlr.m300339-jlr200;
RA Guillou H., D'Andrea S., Rioux V., Barnouin R., Dalaine S., Pedrono F.,
RA Jan S., Legrand P.;
RT "Distinct roles of endoplasmic reticulum cytochrome b5 and fused cytochrome
RT b5-like domain for rat delta-6-desaturase activity.";
RL J. Lipid Res. 45:32-40(2004).
RN [8]
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: Involved in the biosynthesis of highly unsaturated fatty
CC acids (HUFA) from the essential polyunsaturated fatty acids (PUFA)
CC linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3)
CC precursors, acting as a fatty acyl-coenzyme A (CoA) desaturase that
CC introduces a cis double bond at carbon 6 of the fatty acyl chain.
CC Catalyzes the first and rate limiting step in this pathway which is the
CC desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate
CC (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively
CC (PubMed:10049752, PubMed:22216341, PubMed:11988075, PubMed:14563830,
CC PubMed:24070791). Subsequently, in the biosynthetic pathway of HUFA n-3
CC series, it desaturates tetracosapentaenoate (24:5n-3) to
CC tetracosahexaenoate (24:6n-3), which is then converted to
CC docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system
CC function (PubMed:11988075). It can also desaturate (11E)-octadecenoate
CC (trans-vaccenoate) at carbon 6 generating (6Z,11E)-octadecadienoate
CC (PubMed:24070791). In addition to Delta-6 activity, this enzyme
CC exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA
CC substrates (By similarity). {ECO:0000250|UniProtKB:B8R1K0,
CC ECO:0000269|PubMed:10049752, ECO:0000269|PubMed:11988075,
CC ECO:0000269|PubMed:14563830, ECO:0000269|PubMed:22216341,
CC ECO:0000269|PubMed:24070791}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2
CC H(+) + O2 = (6Z,9Z,12Z)-octadecatrienoyl-CoA + 2 Fe(III)-[cytochrome
CC b5] + 2 H2O; Xref=Rhea:RHEA:47140, 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:57363,
CC ChEBI:CHEBI:57383; EC=1.14.19.3;
CC Evidence={ECO:0000250|UniProtKB:O95864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47141;
CC Evidence={ECO:0000250|UniProtKB:O95864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z)-octadecatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] +
CC 2 H(+) + O2 = (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + 2 Fe(III)-
CC [cytochrome b5] + 2 H2O; Xref=Rhea:RHEA:47144, 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:71489, ChEBI:CHEBI:74034; EC=1.14.19.3;
CC Evidence={ECO:0000269|PubMed:11988075, ECO:0000269|PubMed:24070791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47145;
CC Evidence={ECO:0000269|PubMed:11988075, ECO:0000269|PubMed:24070791};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA + 2 Fe(II)-
CC [cytochrome b5] + 2 H(+) + O2 = (6Z,9Z,12Z,15Z,18Z,21Z)-
CC tetracosahexaenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O;
CC Xref=Rhea:RHEA:36999, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:74083,
CC ChEBI:CHEBI:74086; Evidence={ECO:0000269|PubMed:11988075};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37000;
CC Evidence={ECO:0000269|PubMed:11988075};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) +
CC O2 = (6Z,11E)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2
CC H2O; Xref=Rhea:RHEA:46064, 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:85652; Evidence={ECO:0000269|PubMed:24070791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46065;
CC Evidence={ECO:0000269|PubMed:24070791};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11Z,14Z)-eicosadienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2
CC H(+) + O2 = (8Z,11Z,14Z)-eicosatrienoyl-CoA + 2 Fe(III)-[cytochrome
CC b5] + 2 H2O; Xref=Rhea:RHEA:39567, 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:74264,
CC ChEBI:CHEBI:76410; Evidence={ECO:0000250|UniProtKB:B8R1K0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39568;
CC Evidence={ECO:0000250|UniProtKB:B8R1K0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11Z,14Z,17Z)-eicosatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] +
CC 2 H(+) + O2 = (8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA + 2 Fe(III)-
CC [cytochrome b5] + 2 H2O; Xref=Rhea:RHEA:39571, 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:74265, ChEBI:CHEBI:74328;
CC Evidence={ECO:0000250|UniProtKB:B8R1K0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39572;
CC Evidence={ECO:0000250|UniProtKB:B8R1K0};
CC -!- PATHWAY: Lipid metabolism; polyunsaturated fatty acid biosynthesis.
CC {ECO:0000305|PubMed:11988075, ECO:0000305|PubMed:24070791}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}. Microsome membrane
CC {ECO:0000269|PubMed:11988075}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver and brain (at protein level)
CC (PubMed:11988075). Highest activity is found in the liver and adrenals
CC followed by the testes and other organs, absent in adipose tissue
CC (PubMed:5094766). {ECO:0000269|PubMed:11988075,
CC ECO:0000269|PubMed:5094766}.
CC -!- INDUCTION: Inhibited by a shortage of insulin and an increase of
CC glucagon. {ECO:0000269|PubMed:12538079}.
CC -!- DOMAIN: The protein sequence includes a number of characteristic
CC features of microsomal fatty acid desaturases including the three
CC histidine boxes HXXXH, HXXHH, and QXXHH (these domains may contain the
CC active site and/or be involved in metal ion binding), and the N-
CC terminal cytochrome b5 domain containing the heme-binding motif, HPGG,
CC similar to that of other fatty acid desaturases.
CC {ECO:0000250|UniProtKB:O95864}.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family.
CC {ECO:0000305}.
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DR EMBL; AB021980; BAA75496.1; -; mRNA.
DR EMBL; HQ909027; AEX15918.1; -; mRNA.
DR EMBL; BC081776; AAH81776.1; -; mRNA.
DR PIR; JG0180; JG0180.
DR RefSeq; NP_112634.1; NM_031344.2.
DR AlphaFoldDB; Q9Z122; -.
DR SMR; Q9Z122; -.
DR STRING; 10116.ENSRNOP00000027756; -.
DR BindingDB; Q9Z122; -.
DR ChEMBL; CHEMBL5088; -.
DR SwissLipids; SLP:000001190; -.
DR jPOST; Q9Z122; -.
DR PaxDb; Q9Z122; -.
DR Ensembl; ENSRNOT00000027756; ENSRNOP00000027756; ENSRNOG00000020440.
DR GeneID; 83512; -.
DR KEGG; rno:83512; -.
DR CTD; 9415; -.
DR RGD; 68339; Fads2.
DR eggNOG; KOG4232; Eukaryota.
DR GeneTree; ENSGT00950000182990; -.
DR HOGENOM; CLU_016265_0_1_1; -.
DR InParanoid; Q9Z122; -.
DR OrthoDB; 1060606at2759; -.
DR PhylomeDB; Q9Z122; -.
DR BRENDA; 1.14.19.3; 5301.
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:Q9Z122; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016213; F:linoleoyl-CoA desaturase activity; IEA:UniProtKB-EC.
DR GO; GO:0045485; F:omega-6 fatty acid desaturase activity; TAS:Reactome.
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:0004768; F:stearoyl-CoA 9-desaturase activity; ISO:RGD.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0006636; P:unsaturated fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0042761; P:very long-chain fatty acid biosynthetic process; TAS: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 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 Microsome; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..444
FT /note="Acyl-CoA 6-desaturase"
FT /id="PRO_0000307105"
FT TOPO_DOM 1..130
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 152..157
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..305
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 18..95
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT MOTIF 180..184
FT /note="Histidine box-1"
FT MOTIF 217..221
FT /note="Histidine box-2"
FT MOTIF 382..386
FT /note="Histidine box-3"
FT CONFLICT 101
FT /note="L -> M (in Ref. 2; AEX15918)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 444 AA; 52380 MW; D9AE0C7AE499A1AE CRC64;
MGKGGNQGEG STELQAPMPT FRWEEIQKHN LRTDRWLVID RKVYNVTKWS QRHPGGHRVI
GHYSGEDATD AFRAFHLDLD FVGKFLKPLL IGELAPEEPS LDRGKSSQIT EDFRALKKTA
EDMNLFKTNH LFFFLLLSHI IVMESIAWFI LSYFGNGWIP TVITAFVLAT SQAQAGWLQH
DYGHLSVYKK SIWNHIVHKF VIGHLKGASA NWWNHRHFQH HAKPNIFHKD PDIKSLHVFV
LGEWQPLEYG KKKLKYLPYN HQHEYFFLIG PPLLIPMYFQ YQIIMTMIRR RDWVDLAWAI
SYYARFFYTY IPFYGILGAL VFLNFIRFLE SHWFVWVTQM NHIVMEIDLD HYRDWFSSQL
AATCNVEQSF FNDWFSGHLN FQIEHHLFPT MPRHNLHKIA PLVKSLCAKH GIEYQEKPLL
RALLDIVSSL KKSGELWLDA YLHK
