FADS1_MOUSE
ID FADS1_MOUSE Reviewed; 447 AA.
AC Q920L1; Q3U494; Q8BZX7; Q8R0G8; Q8VC07;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Acyl-CoA (8-3)-desaturase {ECO:0000305};
DE EC=1.14.19.44 {ECO:0000305|PubMed:22534642};
DE AltName: Full=Delta(5) fatty acid desaturase;
DE Short=D5D {ECO:0000303|PubMed:11792729};
DE Short=Delta(5) desaturase {ECO:0000303|PubMed:11792729};
DE Short=Delta-5 desaturase {ECO:0000250|UniProtKB:O60427};
DE AltName: Full=Fatty acid desaturase 1 {ECO:0000303|PubMed:22534642};
GN Name=Fads1 {ECO:0000303|PubMed:22534642, ECO:0000312|MGI:MGI:1923517};
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], 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Spinal ganglion, and Testis;
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=C57BL/6J, and FVB/N; TISSUE=Brain, Kidney, and 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 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).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=22534642; DOI=10.1194/jlr.m024216;
RA Fan Y.Y., Monk J.M., Hou T.Y., Callway E., Vincent L., Weeks B., Yang P.,
RA Chapkin R.S.;
RT "Characterization of an arachidonic acid-deficient (Fads1 knockout) mouse
RT model.";
RL J. Lipid Res. 53:1287-1295(2012).
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 (Probable). As a
CC rate limiting enzyme for DGLA (20:3n-6) and AA (20:4n-6)-derived
CC eicosanoid biosynthesis, controls the metabolism of inflammatory lipids
CC like prostaglandin E2, critical for efficient acute inflammatory
CC response and maintenance of epithelium homeostasis. Contributes to
CC membrane phospholipid biosynthesis by providing AA (20:4n-6) as a major
CC acyl chain esterified into phospholipids. In particular, regulates
CC phosphatidylinositol-4,5-bisphosphate levels, modulating inflammatory
CC cytokine production in T-cells (PubMed:22534642). Also desaturates
CC (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the
CC biohydrogenation pathway of LA (18:2n-6) (By similarity).
CC {ECO:0000250|UniProtKB:Q920R3, ECO:0000269|PubMed:22534642,
CC ECO:0000305|PubMed:22534642}.
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:0000305|PubMed:22534642};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46425;
CC Evidence={ECO:0000305|PubMed:22534642};
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:0000250|UniProtKB:Q920R3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46061;
CC Evidence={ECO:0000250|UniProtKB:Q920R3};
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 expressed in the adrenal gland, liver,
CC brain, and testis, tissues where lipogenesis and steroidogenesis are
CC active (PubMed:11792729). Expressed in colonic mucosa
CC (PubMed:22534642). {ECO:0000269|PubMed:11792729,
CC ECO:0000269|PubMed:22534642}.
CC -!- INDUCTION: Expression in liver is down-regulated by dietary PUFA.
CC {ECO:0000269|PubMed:11792729}.
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding.
CC -!- DISRUPTION PHENOTYPE: Knockout mice die prematurely with no survivors
CC past 12 weeks of age. This phenotype can be rescued by adding
CC arachidonic acid (AA) to the diet. {ECO:0000269|PubMed:22534642}.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family.
CC {ECO:0000305}.
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DR EMBL; AB072976; BAB69894.1; -; mRNA.
DR EMBL; AK033308; BAC28228.1; -; mRNA.
DR EMBL; AK083959; BAC39079.1; -; mRNA.
DR EMBL; AK154367; BAE32539.1; -; mRNA.
DR EMBL; BC022139; AAH22139.1; -; mRNA.
DR EMBL; BC026831; AAH26831.1; -; mRNA.
DR EMBL; BC026848; AAH26848.1; -; mRNA.
DR EMBL; BC063053; AAH63053.1; -; mRNA.
DR CCDS; CCDS29572.1; -.
DR RefSeq; NP_666206.1; NM_146094.2.
DR AlphaFoldDB; Q920L1; -.
DR SMR; Q920L1; -.
DR BioGRID; 218056; 3.
DR IntAct; Q920L1; 1.
DR STRING; 10090.ENSMUSP00000010807; -.
DR BindingDB; Q920L1; -.
DR ChEMBL; CHEMBL5725; -.
DR iPTMnet; Q920L1; -.
DR PhosphoSitePlus; Q920L1; -.
DR EPD; Q920L1; -.
DR jPOST; Q920L1; -.
DR PaxDb; Q920L1; -.
DR PeptideAtlas; Q920L1; -.
DR PRIDE; Q920L1; -.
DR ProteomicsDB; 277035; -.
DR Antibodypedia; 21596; 276 antibodies from 36 providers.
DR DNASU; 76267; -.
DR Ensembl; ENSMUST00000010807; ENSMUSP00000010807; ENSMUSG00000010663.
DR GeneID; 76267; -.
DR KEGG; mmu:76267; -.
DR UCSC; uc008gpd.2; mouse.
DR CTD; 3992; -.
DR MGI; MGI:1923517; Fads1.
DR VEuPathDB; HostDB:ENSMUSG00000010663; -.
DR eggNOG; KOG4232; Eukaryota.
DR GeneTree; ENSGT00950000182990; -.
DR HOGENOM; CLU_016265_0_1_1; -.
DR InParanoid; Q920L1; -.
DR OMA; MITFYIR; -.
DR OrthoDB; 1060606at2759; -.
DR PhylomeDB; Q920L1; -.
DR TreeFam; TF313604; -.
DR BRENDA; 1.14.19.30; 3474.
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; 76267; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Fads1; mouse.
DR PRO; PR:Q920L1; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q920L1; protein.
DR Bgee; ENSMUSG00000010663; Expressed in adrenal gland and 254 other tissues.
DR ExpressionAtlas; Q920L1; baseline and differential.
DR Genevisible; Q920L1; MM.
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; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0062076; F:acyl-CoA delta5-desaturase activity; IMP:UniProtKB.
DR GO; GO:0016213; F:linoleoyl-CoA desaturase activity; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0019369; P:arachidonic acid metabolic process; ISO:MGI.
DR GO; GO:0009267; P:cellular response to starvation; ISO:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; ISO:MGI.
DR GO; GO:0006636; P:unsaturated fatty acid biosynthetic process; ISO:MGI.
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_0000307097"
FT TOPO_DOM 1..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 146..160
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 161..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 32
FT /note="G -> W (in Ref. 2; BAE32539)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="V -> L (in Ref. 3; AAH26848)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="V -> I (in Ref. 3; AAH26848/AAH22139/AAH26831)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 447 AA; 52323 MW; 1C69B61DF919A009 CRC64;
MAPDPVPTPG PASAQLRQTR YFTWEEVAQR SGREKERWLV IDRKVYNISD FSRRHPGGSR
VISHYAGQDA TDPFVAFHIN KGLVRKYMNS LLIGELAPEQ PSFEPTKNKA LTDEFRELRA
TVERMGLMKA NHLFFLVYLL HILLLDVAAW LTLWIFGTSL VPFILCAVLL STVQAQAGWL
QHDFGHLSVF GTSTWNHLLH HFVIGHLKGA PASWWNHMHF QHHAKPNCFR KDPDINMHPL
FFALGKVLPV ELGREKKKHM PYNHQHKYFF LIGPPALLPL YFQWYIFYFV VQRKKWVDLA
WMLSFYARIF FTYMPLLGLK GFLGLFFIVR FLESNWFVWV TQMNHIPMHI DHDRNVDWVS
TQLQATCNVH QSAFNNWFSG HLNFQIEHHL FPTMPRHNYH KVAPLVQSLC AKYGIKYESK
PLLTAFADIV YSLKESGQLW LDAYLHQ
