FADS3_HUMAN
ID FADS3_HUMAN Reviewed; 445 AA.
AC Q9Y5Q0; O60426;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Fatty acid desaturase 3 {ECO:0000250|UniProtKB:Q8K1P9};
DE EC=1.14.19.- {ECO:0000269|PubMed:31916624};
DE AltName: Full=Delta(13) fatty acid desaturase {ECO:0000250|UniProtKB:Q8K1P9};
DE Short=Delta(13) desaturase {ECO:0000250|UniProtKB:Q8K1P9};
GN Name=FADS3 {ECO:0000303|PubMed:19752397, ECO:0000312|HGNC:HGNC:3576};
GN Synonyms=CYB5RP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10860662; DOI=10.1006/geno.2000.6196;
RA Marquardt A., Stoehr H., White K., Weber B.H.;
RT "cDNA cloning, genomic structure, and chromosomal localization of three
RT members of the human fatty acid desaturase family.";
RL Genomics 66:175-183(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Li W., Metzker M.L., Caskey C.T., Petrukhin K.;
RT "Human retina-specific delta 6 fatty acid desaturase.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=31916624; DOI=10.1096/fj.201902645r;
RA Jojima K., Edagawa M., Sawai M., Ohno Y., Kihara A.;
RT "Biosynthesis of the anti-lipid-microdomain sphingoid base 4,14-
RT sphingadiene by the ceramide desaturase FADS3.";
RL FASEB J. 34:3318-3335(2020).
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 (PubMed:31916624). FADS3 also acts as a methyl-
CC end 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, the predominant trans fatty acid in human milk) at carbon
CC 13 to generate (11E,13Z)-octadecadienoate (also known as conjugated
CC linoleic acid 11E,13Z-CLA). {ECO:0000250|UniProtKB:Q8K1P9,
CC ECO:0000269|PubMed:31916624}.
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:0000269|PubMed:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63929;
CC Evidence={ECO:0000269|PubMed:31916624};
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:0000269|PubMed:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63941;
CC Evidence={ECO:0000269|PubMed:31916624};
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:0000250|UniProtKB:Q8K1P9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46057;
CC Evidence={ECO:0000250|UniProtKB:Q8K1P9};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000305|PubMed:31916624}.
CC -!- PATHWAY: Lipid metabolism; polyunsaturated fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q8K1P9}.
CC -!- INTERACTION:
CC Q9Y5Q0; Q8N5I4: DHRSX; NbExp=3; IntAct=EBI-17548630, EBI-3923585;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:31916624}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in various organs and tissues
CC including liver, kidney, brain, lung, pancreas, testis, ovary and
CC skeletal muscle (at 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:0000303|PubMed:10860662}.
CC -!- MISCELLANEOUS: A 28 kDa isoform is expressed in lung, kidney, pancreas
CC and ovary (at protein level). {ECO:0000269|PubMed:19752397}.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC23396.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF084560; AAG23122.1; -; mRNA.
DR EMBL; AF134404; AAD31282.1; -; mRNA.
DR EMBL; AC004770; AAC23396.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AP006260; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004901; AAH04901.1; -; mRNA.
DR CCDS; CCDS8013.1; -.
DR RefSeq; NP_068373.1; NM_021727.4.
DR AlphaFoldDB; Q9Y5Q0; -.
DR SMR; Q9Y5Q0; -.
DR BioGRID; 110182; 44.
DR IntAct; Q9Y5Q0; 19.
DR STRING; 9606.ENSP00000278829; -.
DR SwissLipids; SLP:000000278; -.
DR iPTMnet; Q9Y5Q0; -.
DR PhosphoSitePlus; Q9Y5Q0; -.
DR BioMuta; FADS3; -.
DR DMDM; 74762790; -.
DR EPD; Q9Y5Q0; -.
DR jPOST; Q9Y5Q0; -.
DR MassIVE; Q9Y5Q0; -.
DR MaxQB; Q9Y5Q0; -.
DR PaxDb; Q9Y5Q0; -.
DR PeptideAtlas; Q9Y5Q0; -.
DR PRIDE; Q9Y5Q0; -.
DR ProteomicsDB; 86470; -.
DR Antibodypedia; 28347; 157 antibodies from 22 providers.
DR DNASU; 3995; -.
DR Ensembl; ENST00000278829.7; ENSP00000278829.2; ENSG00000221968.9.
DR GeneID; 3995; -.
DR KEGG; hsa:3995; -.
DR MANE-Select; ENST00000278829.7; ENSP00000278829.2; NM_021727.5; NP_068373.1.
DR UCSC; uc001nsm.5; human.
DR CTD; 3995; -.
DR DisGeNET; 3995; -.
DR GeneCards; FADS3; -.
DR HGNC; HGNC:3576; FADS3.
DR HPA; ENSG00000221968; Low tissue specificity.
DR MIM; 606150; gene.
DR neXtProt; NX_Q9Y5Q0; -.
DR OpenTargets; ENSG00000221968; -.
DR PharmGKB; PA27975; -.
DR VEuPathDB; HostDB:ENSG00000221968; -.
DR eggNOG; KOG4232; Eukaryota.
DR GeneTree; ENSGT00950000182990; -.
DR InParanoid; Q9Y5Q0; -.
DR OMA; WMHEAGH; -.
DR OrthoDB; 1060606at2759; -.
DR PhylomeDB; Q9Y5Q0; -.
DR TreeFam; TF313604; -.
DR BRENDA; 1.14.19.30; 2681.
DR PathwayCommons; Q9Y5Q0; -.
DR SignaLink; Q9Y5Q0; -.
DR SIGNOR; Q9Y5Q0; -.
DR UniPathway; UPA00222; -.
DR UniPathway; UPA00658; -.
DR BioGRID-ORCS; 3995; 9 hits in 1075 CRISPR screens.
DR ChiTaRS; FADS3; human.
DR GenomeRNAi; 3995; -.
DR Pharos; Q9Y5Q0; Tbio.
DR PRO; PR:Q9Y5Q0; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y5Q0; protein.
DR Bgee; ENSG00000221968; Expressed in tibial nerve and 213 other tissues.
DR ExpressionAtlas; Q9Y5Q0; baseline and differential.
DR Genevisible; Q9Y5Q0; HS.
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; NAS:UniProtKB.
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; NAS:UniProtKB.
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..445
FT /note="Fatty acid desaturase 3"
FT /id="PRO_0000307108"
FT TOPO_DOM 1..133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155..159
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..306
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 307..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 328..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 20..97
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 182..186
FT /note="Histidine box-1"
FT /evidence="ECO:0000303|PubMed:10860662"
FT MOTIF 219..223
FT /note="Histidine box-2"
FT /evidence="ECO:0000303|PubMed:10860662"
FT MOTIF 383..387
FT /note="Histidine box-3"
FT /evidence="ECO:0000303|PubMed:10860662"
FT VARIANT 192
FT /note="K -> N (in dbSNP:rs35479241)"
FT /id="VAR_035341"
FT VARIANT 216
FT /note="N -> K (in dbSNP:rs34511441)"
FT /id="VAR_035342"
SQ SEQUENCE 445 AA; 51145 MW; 7840EF6BE055111D CRC64;
MGGVGEPGPR EGPAQPGAPL PTFCWEQIRA HDQPGDKWLV IERRVYDISR WAQRHPGGSR
LIGHHGAEDA TDAFRAFHQD LNFVRKFLQP LLIGELAPEE PSQDGPLNAQ LVEDFRALHQ
AAEDMKLFDA SPTFFAFLLG HILAMEVLAW LLIYLLGPGW VPSALAAFIL AISQAQSWCL
QHDLGHASIF KKSWWNHVAQ KFVMGQLKGF SAHWWNFRHF QHHAKPNIFH KDPDVTVAPV
FLLGESSVEY GKKKRRYLPY NQQHLYFFLI GPPLLTLVNF EVENLAYMLV CMQWADLLWA
ASFYARFFLS YLPFYGVPGV LLFFVAVRVL ESHWFVWITQ MNHIPKEIGH EKHRDWVSSQ
LAATCNVEPS LFTNWFSGHL NFQIEHHLFP RMPRHNYSRV APLVKSLCAK HGLSYEVKPF
LTALVDIVRS LKKSGDIWLD AYLHQ
