FADS2_MOUSE
ID FADS2_MOUSE Reviewed; 444 AA.
AC Q9Z0R9;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Acyl-CoA 6-desaturase {ECO:0000305|PubMed:9867867};
DE EC=1.14.19.3 {ECO:0000269|PubMed:9867867};
DE AltName: Full=Delta(6) fatty acid desaturase;
DE Short=D6D {ECO:0000303|PubMed:11792729};
DE Short=Delta(6) desaturase;
DE Short=Delta-6 desaturase {ECO:0000303|PubMed:11792729, ECO:0000303|PubMed:9867867};
DE AltName: Full=Fatty acid desaturase 2;
GN Name=Fads2 {ECO:0000312|MGI:MGI:1930079}; Synonyms=Fadsd2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=9867867; DOI=10.1074/jbc.274.1.471;
RA Cho H.P., Nakamura M.T., Clarke S.D.;
RT "Cloning, expression, and nutritional regulation of the mammalian Delta-6
RT desaturase.";
RL J. Biol. Chem. 274:471-477(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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, AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=11792729;
RA Matsuzaka T., Shimano H., Yahagi N., Amemiya-Kudo M., Yoshikawa T.,
RA Hasty A.H., Tamura Y., Osuga J., Okazaki H., Iizuka Y., Takahashi A.,
RA Sone H., Gotoda T., Ishibashi S., Yamada N.;
RT "Dual regulation of mouse Delta(5)- and Delta(6)-desaturase gene expression
RT by SREBP-1 and PPARalpha.";
RL J. Lipid Res. 43:107-114(2002).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:9867867). 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 (By similarity). It can also desaturate (11E)-octadecenoate
CC (trans-vaccenoate) at carbon 6 generating (6Z,11E)-octadecadienoate (By
CC similarity). In addition to Delta-6 activity, this enzyme exhibits
CC Delta-8 activity with slight biases toward n-3 fatty acyl-CoA
CC substrates (By similarity). {ECO:0000250|UniProtKB:B8R1K0,
CC ECO:0000250|UniProtKB:Q9Z122, ECO:0000269|PubMed:9867867}.
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:0000269|PubMed:9867867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47141;
CC Evidence={ECO:0000269|PubMed:9867867};
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:9867867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47145;
CC Evidence={ECO:0000269|PubMed:9867867};
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:0000250|UniProtKB:Q9Z122};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37000;
CC Evidence={ECO:0000250|UniProtKB:Q9Z122};
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:0000250|UniProtKB:Q9Z122};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46065;
CC Evidence={ECO:0000250|UniProtKB:Q9Z122};
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:9867867}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the adrenal gland, liver,
CC brain, and testis, tissues where lipogenesis and steroidogenesis are
CC active. Also detected in lung, heart, and skeletal muscle.
CC {ECO:0000269|PubMed:11792729, ECO:0000269|PubMed:9867867}.
CC -!- DEVELOPMENTAL STAGE: Found in 13-day-old embryo heart.
CC -!- INDUCTION: Induced by dietary PUFA-deficient diet. Induced by a fat-
CC free diet and by a diet containing triolein (18:1n-9) as the only fat
CC source. Down-regulated in liver by dietary PUFA.
CC {ECO:0000269|PubMed:11792729, ECO:0000269|PubMed:9867867}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF126798; AAD20017.1; -; mRNA.
DR EMBL; AK143524; BAE25416.1; -; mRNA.
DR EMBL; BC057189; AAH57189.1; -; mRNA.
DR CCDS; CCDS29571.1; -.
DR RefSeq; NP_062673.1; NM_019699.1.
DR AlphaFoldDB; Q9Z0R9; -.
DR SMR; Q9Z0R9; -.
DR BioGRID; 208008; 3.
DR STRING; 10090.ENSMUSP00000025567; -.
DR BindingDB; Q9Z0R9; -.
DR ChEMBL; CHEMBL5087; -.
DR iPTMnet; Q9Z0R9; -.
DR PhosphoSitePlus; Q9Z0R9; -.
DR EPD; Q9Z0R9; -.
DR jPOST; Q9Z0R9; -.
DR MaxQB; Q9Z0R9; -.
DR PaxDb; Q9Z0R9; -.
DR PeptideAtlas; Q9Z0R9; -.
DR PRIDE; Q9Z0R9; -.
DR ProteomicsDB; 277036; -.
DR Antibodypedia; 1645; 186 antibodies from 25 providers.
DR DNASU; 56473; -.
DR Ensembl; ENSMUST00000025567; ENSMUSP00000025567; ENSMUSG00000024665.
DR GeneID; 56473; -.
DR KEGG; mmu:56473; -.
DR UCSC; uc008gpb.1; mouse.
DR CTD; 9415; -.
DR MGI; MGI:1930079; Fads2.
DR VEuPathDB; HostDB:ENSMUSG00000024665; -.
DR eggNOG; KOG4232; Eukaryota.
DR GeneTree; ENSGT00950000182990; -.
DR HOGENOM; CLU_016265_0_1_1; -.
DR InParanoid; Q9Z0R9; -.
DR OMA; QWWKNKH; -.
DR OrthoDB; 1060606at2759; -.
DR PhylomeDB; Q9Z0R9; -.
DR TreeFam; TF313604; -.
DR Reactome; R-MMU-2046105; Linoleic acid (LA) metabolism.
DR Reactome; R-MMU-2046106; alpha-linolenic acid (ALA) metabolism.
DR UniPathway; UPA00658; -.
DR BioGRID-ORCS; 56473; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Fads2; mouse.
DR PRO; PR:Q9Z0R9; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9Z0R9; protein.
DR Bgee; ENSMUSG00000024665; Expressed in ear vesicle and 235 other tissues.
DR ExpressionAtlas; Q9Z0R9; baseline and differential.
DR Genevisible; Q9Z0R9; MM.
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:0016020; C:membrane; TAS:MGI.
DR GO; GO:0016213; F:linoleoyl-CoA desaturase activity; IEA:UniProtKB-EC.
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; IDA:MGI.
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 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 Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..444
FT /note="Acyl-CoA 6-desaturase"
FT /id="PRO_0000307103"
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
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..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 REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
SQ SEQUENCE 444 AA; 52387 MW; 7615D17024D3B771 CRC64;
MGKGGNQGEG STERQAPMPT FRWEEIQKHN LRTDRWLVID RKVYNVTKWS QRHPGGHRVI
GHYSGEDATD AFRAFHLDLD FVGKFLKPLL IGELAPEEPS LDRGKSSQIT EDFRALKKTA
EDMNLFKTNH LFFFLLLSHI IVMESLAWFI LSYFGTGWIP TLVTAFVLAT SQAQAGWLQH
DYGHLSVYKK SIWNHVVHKF VIGHLKGASA NWWNHRHFQH HAKPNIFHKD PDIKSLHVFV
LGEWQPLEYG KKKLKYLPYN HQHEYFFLIG PPLLIPMYFQ YQIIMTMISR RDWVDLAWAI
SYYMRFFYTY IPFYGILGAL VFLNFIRFLE SHWFVWVTQM NHLVMEIDLD HYRDWFSSQL
AATCNVEQSF FNDWFSGHLN FQIEHHLFPT MPRHNLHKIA PLVKSLCAKH GIEYQEKPLL
RALIDIVSSL KKSGELWLDA YLHK
