ELOV3_MOUSE
ID ELOV3_MOUSE Reviewed; 271 AA.
AC O35949;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Elongation of very long chain fatty acids protein 3 {ECO:0000255|HAMAP-Rule:MF_03203, ECO:0000305};
DE EC=2.3.1.199 {ECO:0000250|UniProtKB:Q9HB03, ECO:0000255|HAMAP-Rule:MF_03203};
DE AltName: Full=3-keto acyl-CoA synthase Elovl3 {ECO:0000255|HAMAP-Rule:MF_03203};
DE AltName: Full=CIN-2;
DE AltName: Full=Cold-inducible glycoprotein of 30 kDa;
DE AltName: Full=ELOVL fatty acid elongase 3 {ECO:0000255|HAMAP-Rule:MF_03203};
DE Short=ELOVL FA elongase 3 {ECO:0000255|HAMAP-Rule:MF_03203};
DE AltName: Full=Very long chain 3-ketoacyl-CoA synthase 3 {ECO:0000255|HAMAP-Rule:MF_03203};
DE AltName: Full=Very long chain 3-oxoacyl-CoA synthase 3 {ECO:0000255|HAMAP-Rule:MF_03203};
GN Name=Elovl3 {ECO:0000255|HAMAP-Rule:MF_03203}; Synonyms=Cig30;
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], GLYCOSYLATION AT ASN-6, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Brown adipose tissue;
RX PubMed=9395518; DOI=10.1074/jbc.272.50.31738;
RA Tvrdik P., Asadi A., Kozak L.P., Nedergaard J., Cannon B., Jacobsson A.;
RT "Cig30, a mouse member of a novel membrane protein gene family, is involved
RT in the recruitment of brown adipose tissue.";
RL J. Biol. Chem. 272:31738-31746(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=10473596; DOI=10.1074/jbc.274.37.26387;
RA Tvrdik P., Asadi A., Kozak L.P., Nuglozeh E., Parente F., Nedergaard J.,
RA Jacobsson A.;
RT "Cig30 and Pitx3 genes are arranged in a partially overlapping tail-to-tail
RT array resulting in complementary transcripts.";
RL J. Biol. Chem. 274:26387-26392(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 GLYCOSYLATION AT ASN-6, AND SUBCELLULAR LOCATION.
RX PubMed=10429212; DOI=10.1046/j.1432-1327.1999.00498.x;
RA Monne M., Gafvelin G., Nilsson R., von Heijne G.;
RT "N-tail translocation in a eukaryotic polytopic membrane protein: synergy
RT between neighboring transmembrane segments.";
RL Eur. J. Biochem. 263:264-269(1999).
RN [5]
RP FUNCTION.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=10791983; DOI=10.1083/jcb.149.3.707;
RA Tvrdik P., Westerberg R., Silve S., Asadi A., Jakobsson A., Cannon B.,
RA Loison G., Jacobsson A.;
RT "Role of a new mammalian gene family in the biosynthesis of very long chain
RT fatty acids and sphingolipids.";
RL J. Cell Biol. 149:707-718(2000).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=14581464; DOI=10.1074/jbc.m310529200;
RA Westerberg R., Tvrdik P., Unden A.B., Mansson J.E., Norlen L.,
RA Jakobsson A., Holleran W.H., Elias P.M., Asadi A., Flodby P., Toftgard R.,
RA Capecchi M.R., Jacobsson A.;
RT "Role for ELOVL3 and fatty acid chain length in development of hair and
RT skin function.";
RL J. Biol. Chem. 279:5621-5629(2004).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16326704; DOI=10.1074/jbc.m511588200;
RA Westerberg R., Mansson J.E., Golozoubova V., Shabalina I.G., Backlund E.C.,
RA Tvrdik P., Retterstol K., Capecchi M.R., Jacobsson A.;
RT "ELOVL3 is an important component for early onset of lipid recruitment in
RT brown adipose tissue.";
RL J. Biol. Chem. 281:4958-4968(2006).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20605947; DOI=10.1096/fj.09-152298;
RA Zadravec D., Brolinson A., Fisher R.M., Carneheim C., Csikasz R.I.,
RA Bertrand-Michel J., Boren J., Guillou H., Rudling M., Jacobsso A.;
RT "Ablation of the very-long-chain fatty acid elongase ELOVL3 in mice leads
RT to constrained lipid storage and resistance to diet-induced obesity.";
RL FASEB J. 24:4366-4377(2010).
CC -!- FUNCTION: Catalyzes the first and rate-limiting reaction of the four
CC reactions that constitute the long-chain fatty acids elongation cycle.
CC This endoplasmic reticulum-bound enzymatic process allows the addition
CC of 2 carbons to the chain of long- and very long-chain fatty acids
CC (VLCFAs) per cycle. Condensing enzyme that exhibits activity toward
CC saturated and unsaturated acyl-CoA substrates with higher activity
CC toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. May participate in
CC the production of saturated and monounsaturated VLCFAs of different
CC chain lengths that are involved in multiple biological processes as
CC precursors of membrane lipids and lipid mediators. Participates in the
CC formation of certain VLCFA and triglycerides in certain cells of the
CC hair follicles and the sebaceous glands, required for skin barrier
CC function. Critical enzyme for lipid accumulation and metabolic activity
CC in brown adipocytes during the early phase of the tissue recruitment.
CC Plays a role in lipid storage and in resistance to diet-induced
CC obesity. {ECO:0000255|HAMAP-Rule:MF_03203, ECO:0000269|PubMed:10791983,
CC ECO:0000269|PubMed:14581464, ECO:0000269|PubMed:16326704,
CC ECO:0000269|PubMed:20605947}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-
CC chain 3-oxoacyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:32727,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:90725, ChEBI:CHEBI:90736;
CC EC=2.3.1.199; Evidence={ECO:0000255|HAMAP-Rule:MF_03203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32728;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + H(+) + malonyl-CoA = 3-oxodocosanoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:35327, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57380,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:71451;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35328;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + malonyl-CoA = 3-oxooctadecanoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:35315, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:71407;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35316;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA + octadecanoyl-CoA = 3-oxoeicosanoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:35319, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57394, ChEBI:CHEBI:65115;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35320;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + H(+) + malonyl-CoA = (11Z)-3-
CC oxoicosenoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36511,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57387, ChEBI:CHEBI:74011;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36512;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + H(+) + malonyl-CoA = (11Z,14Z)-
CC 3-oxoicosa-11,14-dienoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36503,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57383, ChEBI:CHEBI:57384, ChEBI:CHEBI:74012;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36504;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z)-octadecatrienoyl-CoA + H(+) + malonyl-CoA =
CC (11Z,14Z,17Z)-3-oxoeicosatrienoyl-CoA + CO2 + CoA;
CC Xref=Rhea:RHEA:36523, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74034,
CC ChEBI:CHEBI:74054; Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36524;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=docosanoyl-CoA + H(+) + malonyl-CoA = 3-oxotetracosanoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:36507, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:65059, ChEBI:CHEBI:73977;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36508;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA + tetradecanoyl-CoA = 3-oxohexadecanoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:39167, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57349,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57385;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39168;
CC Evidence={ECO:0000250|UniProtKB:Q9HB03};
CC -!- PATHWAY: Lipid metabolism; polyunsaturated fatty acid biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_03203}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03203, ECO:0000269|PubMed:10429212}; Multi-
CC pass membrane protein {ECO:0000255|HAMAP-Rule:MF_03203}.
CC -!- TISSUE SPECIFICITY: Expressed in brown adipose tissue and liver. In the
CC skin, strong expressed in the cells of the inner layer of the outer
CC root sheath of the hair follicles and in the sebocytes of the sebaceous
CC glands. Hardly detectable in the epidermis and not at all in
CC fibroblasts. {ECO:0000269|PubMed:14581464, ECO:0000269|PubMed:9395518}.
CC -!- INDUCTION: Strongly up-regulated in brown adipose tissue in conditions
CC of brown fat recruitment, such as cold stress, perinatal development
CC and after diet-induced thermogenesis. A synergistic action of both
CC catecholamines and glucocorticoids is required for the induction.
CC -!- PTM: N-Glycosylated. {ECO:0000255|HAMAP-Rule:MF_03203,
CC ECO:0000269|PubMed:10429212}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice grow normally and are fertile. They
CC display a sparse hair coat, a hyperplastic pilosebaceous system and
CC their hair lipid content is disturbed with exceptionally high levels of
CC eicosenoic acid (20:1). In the triglyceride fraction, fatty acids
CC longer than 20 carbon atoms are almost undetectable. As a result, mice
CC exhibited a severe defect in water repulsion and increased trans-
CC epidermal water loss. When exposed to cold stress, mutants exhibit a
CC significantly reduced VLCFA elongation activity in brown adipose
CC tissue, but only during the initial phase. Cold-acclimated mutants are
CC equally efficient as normal mice at elongating fatty acids. Mutant mice
CC are lean and resistant to diet-induced weight gain, they show normal
CC food intake but increased metabolic rate, and show reduced hepatic
CC lipogenesis and triglycerides synthesis. {ECO:0000269|PubMed:14581464,
CC ECO:0000269|PubMed:16326704, ECO:0000269|PubMed:20605947}.
CC -!- SIMILARITY: Belongs to the ELO family. ELOVL3 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03203}.
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DR EMBL; U97107; AAC06127.1; -; mRNA.
DR EMBL; AF054504; AAD51088.1; -; Genomic_DNA.
DR EMBL; BC016468; AAH16468.1; -; mRNA.
DR CCDS; CCDS29871.1; -.
DR RefSeq; NP_031729.1; NM_007703.2.
DR AlphaFoldDB; O35949; -.
DR SMR; O35949; -.
DR STRING; 10090.ENSMUSP00000036357; -.
DR BindingDB; O35949; -.
DR ChEMBL; CHEMBL5775; -.
DR GlyGen; O35949; 1 site.
DR iPTMnet; O35949; -.
DR PhosphoSitePlus; O35949; -.
DR jPOST; O35949; -.
DR MaxQB; O35949; -.
DR PaxDb; O35949; -.
DR PRIDE; O35949; -.
DR ProteomicsDB; 277787; -.
DR Antibodypedia; 31401; 195 antibodies from 24 providers.
DR DNASU; 12686; -.
DR Ensembl; ENSMUST00000237098; ENSMUSP00000157465; ENSMUSG00000038754.
DR GeneID; 12686; -.
DR KEGG; mmu:12686; -.
DR UCSC; uc008hsk.1; mouse.
DR CTD; 83401; -.
DR MGI; MGI:1195976; Elovl3.
DR VEuPathDB; HostDB:ENSMUSG00000038754; -.
DR eggNOG; KOG3072; Eukaryota.
DR GeneTree; ENSGT01050000244965; -.
DR HOGENOM; CLU_048483_1_1_1; -.
DR InParanoid; O35949; -.
DR OMA; QILQMFM; -.
DR OrthoDB; 1094172at2759; -.
DR PhylomeDB; O35949; -.
DR TreeFam; TF106467; -.
DR Reactome; R-MMU-2046105; Linoleic acid (LA) metabolism.
DR Reactome; R-MMU-2046106; alpha-linolenic acid (ALA) metabolism.
DR Reactome; R-MMU-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00658; -.
DR BioGRID-ORCS; 12686; 1 hit in 72 CRISPR screens.
DR PRO; PR:O35949; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; O35949; protein.
DR Bgee; ENSMUSG00000038754; Expressed in lip and 55 other tissues.
DR ExpressionAtlas; O35949; baseline and differential.
DR Genevisible; O35949; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0102336; F:3-oxo-arachidoyl-CoA synthase activity; IEA:RHEA.
DR GO; GO:0102338; F:3-oxo-lignoceronyl-CoA synthase activity; IEA:RHEA.
DR GO; GO:0009922; F:fatty acid elongase activity; ISO:MGI.
DR GO; GO:0102756; F:very-long-chain 3-ketoacyl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0034625; P:fatty acid elongation, monounsaturated fatty acid; IMP:UniProtKB.
DR GO; GO:0034626; P:fatty acid elongation, polyunsaturated fatty acid; ISO:MGI.
DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; IMP:UniProtKB.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006636; P:unsaturated fatty acid biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0042761; P:very long-chain fatty acid biosynthetic process; IMP:UniProtKB.
DR HAMAP; MF_03203; VLCF_elongase_3; 1.
DR InterPro; IPR030457; ELO_CS.
DR InterPro; IPR002076; ELO_fam.
DR InterPro; IPR033679; ELOVL3.
DR PANTHER; PTHR11157; PTHR11157; 1.
DR PANTHER; PTHR11157:SF68; PTHR11157:SF68; 1.
DR Pfam; PF01151; ELO; 1.
DR PROSITE; PS01188; ELO; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..271
FT /note="Elongation of very long chain fatty acids protein 3"
FT /id="PRO_0000207541"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203"
FT TRANSMEM 67..87
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203"
FT TRANSMEM 165..187
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203"
FT TRANSMEM 199..219
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203"
FT CARBOHYD 6
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03203,
FT ECO:0000269|PubMed:10429212, ECO:0000269|PubMed:9395518"
SQ SEQUENCE 271 AA; 32060 MW; F7CA96199BE89401 CRC64;
MDTSMNFSRG LKMDLMQPYD FETFQDLRPF LEEYWVSSFL IVVVYLLLIV VGQTYMRTRK
SFSLQRPLIL WSFFLAIFSI LGTLRMWKFM ATVMFTVGLK QTVCFAIYTD DAVVRFWSFL
FLLSKVVELG DTAFIILRKR PLIFVHWYHH STVLLFTSFG YKNKVPSGGW FMTMNFGVHS
VMYTYYTMKA AKLKHPNLLP MVITSLQILQ MVLGTIFGIL NYIWRQEKGC HTTTEHFFWS
FMLYGTYFIL FAHFFHRAYL RPKGKVASKS Q
