FADS1_PAPAN
ID FADS1_PAPAN Reviewed; 444 AA.
AC A4UVI1; F1CNE5; L7NWK4; L7NWR0; Q0PR60;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 25-MAY-2022, entry version 69.
DE RecName: Full=Acyl-CoA (8-3)-desaturase {ECO:0000305};
DE EC=1.14.19.44 {ECO:0000269|PubMed:22619218};
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:0000250|UniProtKB:O60427};
DE AltName: Full=Fatty acid desaturase 1 {ECO:0000250|UniProtKB:O60427};
GN Name=FADS1 {ECO:0000250|UniProtKB:O60427};
OS Papio anubis (Olive baboon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Papio.
OX NCBI_TaxID=9555;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=22619218; DOI=10.1194/jlr.m025312;
RA Park W.J., Kothapalli K.S., Reardon H.T., Lawrence P., Qian S.B.,
RA Brenna J.T.;
RT "A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid
RT precursor fatty acids.";
RL J. Lipid Res. 53:1502-1512(2012).
CC -!- FUNCTION: [Isoform 1]: Acts as a front-end fatty acyl-coenzyme A (CoA)
CC desaturase that introduces a cis double bond at carbon 5 located
CC between a preexisting double bond and the carboxyl end of the fatty
CC acyl chain. Involved in biosynthesis of highly unsaturated fatty acids
CC (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic
CC acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3)
CC precursors. Specifically, desaturates dihomo-gamma-linoleoate (DGLA)
CC (20:3n-6) and eicosatetraenoate (ETA) (20:4n-3) to generate
CC arachidonate (AA) (20:4n-6) and eicosapentaenoate (EPA) (20:5n-3),
CC respectively (Probable). As a rate limiting enzyme for DGLA (20:3n-6)
CC and AA (20:4n-6)-derived eicosanoid biosynthesis, controls the
CC metabolism of inflammatory lipids like prostaglandin E2, critical for
CC efficient acute inflammatory response and maintenance of epithelium
CC homeostasis. Contributes to membrane phospholipid biosynthesis by
CC providing AA (20:4n-6) as a major acyl chain esterified into
CC phospholipids. In particular, regulates phosphatidylinositol-4,5-
CC bisphosphate levels, modulating inflammatory cytokine production in T-
CC cells (By similarity). Also desaturates (11E)-octadecenoate (trans-
CC vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathway of
CC LA (18:2n-6) (By similarity). {ECO:0000250|UniProtKB:Q920L1,
CC ECO:0000250|UniProtKB:Q920R3, ECO:0000305|PubMed:22619218}.
CC -!- FUNCTION: [Isoform 2]: Does not exhibit any catalytic activity toward
CC 20:3n-6, but it may enhance FADS2 activity.
CC {ECO:0000269|PubMed:22619218}.
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:22619218};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46425;
CC Evidence={ECO:0000305|PubMed:22619218};
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 ECO:0000305|PubMed:22619218};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46421;
CC Evidence={ECO:0000305|PubMed:22619218};
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: [Isoform 1]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22619218}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:22619218}. Mitochondrion
CC {ECO:0000269|PubMed:22619218}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22619218}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:22619218}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=FADS1CS;
CC IsoId=A4UVI1-1; Sequence=Displayed;
CC Name=2; Synonyms=FADS1AT1;
CC IsoId=A4UVI1-2; Sequence=VSP_053444;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in brain, liver and
CC thymus (at protein level). Isoform 1 seems to be more abundant than
CC isoform 2. Expression of isoform 2 is very low in spleen and not
CC detectable in skeletal muscle. {ECO:0000269|PubMed:22619218}.
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; DQ779578; ABG77281.1; -; mRNA.
DR EMBL; EF531577; ABP06289.1; -; mRNA.
DR EMBL; HQ440212; ADQ89961.1; -; mRNA.
DR EMBL; JF518968; AFC78250.1; -; mRNA.
DR EMBL; JF518969; AFC78251.1; -; mRNA.
DR EMBL; JF518970; AFC78252.1; -; mRNA.
DR EMBL; JF518971; AFC78253.1; -; mRNA.
DR EMBL; JF518972; AFC78254.1; -; mRNA.
DR EMBL; JF518974; AFC78256.1; -; mRNA.
DR RefSeq; NP_001106097.1; NM_001112627.1. [A4UVI1-1]
DR AlphaFoldDB; A4UVI1; -.
DR SMR; A4UVI1; -.
DR STRING; 9555.ENSPANP00000011222; -.
DR GeneID; 100126707; -.
DR KEGG; panu:100126707; -.
DR CTD; 3992; -.
DR eggNOG; KOG4232; Eukaryota.
DR OrthoDB; 1060606at2759; -.
DR UniPathway; UPA00658; -.
DR Proteomes; UP000028761; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0062076; F:acyl-CoA delta5-desaturase activity; IDA:UniProtKB.
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 Acetylation; Alternative splicing; Electron transport;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Mitochondrion;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..444
FT /note="Acyl-CoA (8-3)-desaturase"
FT /id="PRO_0000307098"
FT TOPO_DOM 1..121
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..146
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168..267
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..305
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 17..94
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT MOTIF 179..183
FT /note="Histidine box-1"
FT MOTIF 216..220
FT /note="Histidine box-2"
FT MOTIF 382..386
FT /note="Histidine box-3"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O60427"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:22619218"
FT /id="VSP_053444"
FT CONFLICT 425
FT /note="D -> N (in Ref. 1; AFC78250)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 444 AA; 51869 MW; 6D2BDD805FB38A8A CRC64;
MAPDPVAAKT PVQGPTPRYF TWDEVAQRSG CEERWLVIDR KVYDISEFTR RHPGGSRVIS
HYAGQDATDP FVAFHSNKGL VKKYMNSLLI GELSPEQPSF EPTKNKELTD EFRELRATVE
QMGLMKANHV FFLLYLLHIL LLDGAAWLTL WIFGTSFLPF LLCAVLLTAA QIQAGWLQHD
LGHLSVFSTS KWNHLVHHFV IGHLKGVPAS WWNHMHFQHH AKPNCFGKDP DINMHPFFFA
LGKILSVELG KQKKKYMPYN HQHKYFFLIG PPALVPFFFQ WYVFYFVIQR KKWVDLAWMI
TFYIRLLLTY VPLLGLKAFL GLYFIVRFLE SNWFVWVTQM NHIPMHIDHD RNMDWVSTQL
QATCNVHKSA FNDWFSGHLN FQIEHHLFPM MPRHNYHKVA PLVQSLCAKH GIEYQSKPLL
SAFADIIHSL KESGQLWLDA YLHQ
