ELOV4_MOUSE
ID ELOV4_MOUSE Reviewed; 312 AA.
AC Q9EQC4; Q8JZV3;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Elongation of very long chain fatty acids protein 4 {ECO:0000255|HAMAP-Rule:MF_03204, ECO:0000305};
DE EC=2.3.1.199 {ECO:0000255|HAMAP-Rule:MF_03204, ECO:0000269|PubMed:18728184, ECO:0000269|PubMed:22158834, ECO:0000269|PubMed:22199362, ECO:0000269|PubMed:23479632, ECO:0000269|PubMed:23509295, ECO:0000269|PubMed:24569140};
DE AltName: Full=3-keto acyl-CoA synthase Elovl4 {ECO:0000255|HAMAP-Rule:MF_03204};
DE AltName: Full=ELOVL fatty acid elongase 4 {ECO:0000255|HAMAP-Rule:MF_03204};
DE Short=ELOVL FA elongase 4 {ECO:0000255|HAMAP-Rule:MF_03204};
DE AltName: Full=Very long chain 3-ketoacyl-CoA synthase 4 {ECO:0000255|HAMAP-Rule:MF_03204};
DE AltName: Full=Very long chain 3-oxoacyl-CoA synthase 4 {ECO:0000255|HAMAP-Rule:MF_03204};
GN Name=Elovl4 {ECO:0000255|HAMAP-Rule:MF_03204};
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].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=11138005; DOI=10.1038/83817;
RA Zhang K., Kniazeva M., Han M., Li W., Yu Z., Yang Z., Li Y., Metzker M.L.,
RA Allikmets R., Zack D.J., Kakuk L.E., Lagali P.S., Wong P.W., McDonald I.M.,
RA Sieving P.A., Figueroa D.J., Austin C.P., Gould R.J., Ayyagari R.,
RA Petrukhin K.;
RT "A 5-bp deletion in ELOVL4 is associated with two related forms of
RT autosomal dominant macular dystrophy.";
RL Nat. Genet. 27:89-93(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15028285; DOI=10.1016/j.ygeno.2003.09.020;
RA Mandal M.N., Ambasudhan R., Wong P.W., Gage P.J., Sieving P.A.,
RA Ayyagari R.;
RT "Characterization of mouse orthologue of ELOVL4: genomic organization and
RT spatial and temporal expression.";
RL Genomics 83:626-635(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=18728184; DOI=10.1073/pnas.0802607105;
RA Agbaga M.P., Brush R.S., Mandal M.N., Henry K., Elliott M.H.,
RA Anderson R.E.;
RT "Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis
RT of very long chain fatty acids.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12843-12848(2008).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22199362; DOI=10.1074/jbc.m111.256073;
RA Harkewicz R., Du H., Tong Z., Alkuraya H., Bedell M., Sun W., Wang X.,
RA Hsu Y.H., Esteve-Rudd J., Hughes G., Su Z., Zhang M., Lopes V.S.,
RA Molday R.S., Williams D.S., Dennis E.A., Zhang K.;
RT "Essential role of ELOVL4 protein in very long chain fatty acid synthesis
RT and retinal function.";
RL J. Biol. Chem. 287:11469-11480(2012).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22158834; DOI=10.1194/jlr.m021386;
RA Yu M., Benham A., Logan S., Brush R.S., Mandal M.N., Anderson R.E.,
RA Agbaga M.P.;
RT "ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs
RT over 20:4n6 and 22:6n3.";
RL J. Lipid Res. 53:494-504(2012).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=23479632; DOI=10.1073/pnas.1214707110;
RA Barabas P., Liu A., Xing W., Chen C.K., Tong Z., Watt C.B., Jones B.W.,
RA Bernstein P.S., Krizaj D.;
RT "Role of ELOVL4 and very long-chain polyunsaturated fatty acids in mouse
RT models of Stargardt type 3 retinal degeneration.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:5181-5186(2013).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=23509295; DOI=10.1073/pnas.1217251110;
RA Logan S., Agbaga M.P., Chan M.D., Kabir N., Mandal N.A., Brush R.S.,
RA Anderson R.E.;
RT "Deciphering mutant ELOVL4 activity in autosomal-dominant Stargardt macular
RT dystrophy.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:5446-5451(2013).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, MUTAGENESIS OF THR-22; HIS-158;
RP HIS-161; HIS-162 AND 308-LYS--LYS-310, SUBCELLULAR LOCATION, GLYCOSYLATION,
RP AND MOTIF.
RX PubMed=24569140; DOI=10.1194/jlr.m045443;
RA Logan S., Agbaga M.P., Chan M.D., Brush R.S., Anderson R.E.;
RT "Endoplasmic reticulum microenvironment and conserved histidines govern
RT ELOVL4 fatty acid elongase activity.";
RL J. Lipid Res. 55:698-708(2014).
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 catalyzes the synthesis of
CC very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty
CC acids that are involved in multiple biological processes as precursors
CC of membrane lipids and lipid mediators. May play a critical role in
CC early brain and skin development. {ECO:0000255|HAMAP-Rule:MF_03204,
CC ECO:0000269|PubMed:18728184, ECO:0000269|PubMed:22158834,
CC ECO:0000269|PubMed:22199362, ECO:0000269|PubMed:23479632,
CC ECO:0000269|PubMed:23509295, ECO:0000269|PubMed:24569140}.
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_03204,
CC ECO:0000269|PubMed:18728184, ECO:0000269|PubMed:22158834,
CC ECO:0000269|PubMed:22199362, ECO:0000269|PubMed:23479632,
CC ECO:0000269|PubMed:23509295, ECO:0000269|PubMed:24569140};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32728;
CC Evidence={ECO:0000269|PubMed:18728184};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexacosanoyl-CoA + malonyl-CoA = 3-oxooctacosanyol-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:36519, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:64868, ChEBI:CHEBI:73976;
CC Evidence={ECO:0000269|PubMed:18728184, ECO:0000269|PubMed:24569140};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36520;
CC Evidence={ECO:0000269|PubMed:24569140};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA + octacosanoyl-CoA = 3-oxo-triacontanoyl-
CC CoA + CO2 + CoA; Xref=Rhea:RHEA:36807, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74141, ChEBI:CHEBI:74228;
CC Evidence={ECO:0000269|PubMed:24569140};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36808;
CC Evidence={ECO:0000269|PubMed:24569140};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA + triacontanoyl-CoA = 3-oxo-
CC dotriacontanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:43852,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:76386, ChEBI:CHEBI:83795;
CC Evidence={ECO:0000269|PubMed:24569140};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43853;
CC Evidence={ECO:0000269|PubMed:24569140};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(19Z,22Z,25Z,28Z,31Z)-tetratriacontapentaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(21Z,24Z,27Z,30Z,33Z)-hexatriacontapentaenoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:36871, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74260, ChEBI:CHEBI:74261;
CC Evidence={ECO:0000269|PubMed:23509295};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36872;
CC Evidence={ECO:0000269|PubMed:23509295};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + H(+) + malonyl-
CC CoA = 3-oxo-(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + CO2 +
CC CoA; Xref=Rhea:RHEA:36943, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74298,
CC ChEBI:CHEBI:74304; Evidence={ECO:0000269|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36944;
CC Evidence={ECO:0000269|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + H(+) + malonyl-CoA =
CC (9Z,12Z,15Z,18Z)-3-oxotetracosatetraenoyl-CoA + CO2 + CoA;
CC Xref=Rhea:RHEA:36479, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:73856,
CC ChEBI:CHEBI:73857; Evidence={ECO:0000269|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36480;
CC Evidence={ECO:0000269|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11Z,14Z,17Z,20Z,23Z)-hexacosapentaenoyl-CoA + H(+) + malonyl-
CC CoA = 3-oxo-(13Z,16Z,19Z,22Z,25Z)-octacosapentaenoyl-CoA + CO2 + CoA;
CC Xref=Rhea:RHEA:36819, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74229,
CC ChEBI:CHEBI:74230; Evidence={ECO:0000305|PubMed:18728184};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36820;
CC Evidence={ECO:0000305|PubMed:18728184};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(13Z,16Z,19Z,22Z,25Z)-octacosapentaenoyl-CoA + H(+) + malonyl-
CC CoA = 3-oxo-(15Z,18Z,21Z,24Z,27Z)-triacontapentaenoyl-CoA + CO2 +
CC CoA; Xref=Rhea:RHEA:36843, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74233,
CC ChEBI:CHEBI:74246; Evidence={ECO:0000305|PubMed:18728184};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36844;
CC Evidence={ECO:0000305|PubMed:18728184};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15Z,18Z,21Z,24Z,27Z)-triacontapentaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(17Z,20Z,23Z,26Z,29Z)-dotriacontapentaenoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:36851, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74247, ChEBI:CHEBI:74254;
CC Evidence={ECO:0000305|PubMed:18728184};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36852;
CC Evidence={ECO:0000305|PubMed:18728184};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17Z,20Z,23Z,26Z,29Z)-dotriacontapentaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(19Z,22Z,25Z,28Z,31Z)-tetratriacontapentaenoyl-
CC CoA + CO2 + CoA; Xref=Rhea:RHEA:36859, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74249, ChEBI:CHEBI:74259;
CC Evidence={ECO:0000305|PubMed:18728184};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36860;
CC Evidence={ECO:0000305|PubMed:18728184};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(21Z,24Z,27Z,30Z,33Z)-hexatriacontapentaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(23Z,26Z,29Z,32Z,35Z)-octatriacontapentaenoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:36875, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74262, ChEBI:CHEBI:74263;
CC Evidence={ECO:0000305|PubMed:18728184};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36876;
CC Evidence={ECO:0000305|PubMed:18728184};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11Z,14Z,17Z,20Z)-hexacosatetraenoyl-CoA + H(+) + malonyl-CoA
CC = (13Z,16Z,19Z,22Z)-3-oxooctacosatetraenoyl-CoA + CO2 + CoA;
CC Xref=Rhea:RHEA:36907, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74282,
CC ChEBI:CHEBI:74283; Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36908;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(13Z,16Z,19Z,22Z)-octacosatetraenoyl-CoA + H(+) + malonyl-CoA
CC = 3-oxo-(15Z,18Z,21Z,24Z)-triacontatetraenoyl-CoA + CO2 + CoA;
CC Xref=Rhea:RHEA:36911, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74285,
CC ChEBI:CHEBI:74286; Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36912;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15Z,18Z,21Z,24Z)-triacontatetraenoyl-CoA + H(+) + malonyl-CoA
CC = 3-oxo-(17Z,20Z,23Z,26Z)-dotriacontatetraenoyl-CoA + CO2 + CoA;
CC Xref=Rhea:RHEA:36915, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74287,
CC ChEBI:CHEBI:74288; Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36916;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17Z,20Z,23Z,26Z)-dotriacontatetraenoyl-CoA + H(+) + malonyl-
CC CoA = 3-oxo-(19Z,22Z,25Z,28Z)-tetratriacontatetraenoyl-CoA + CO2 +
CC CoA; Xref=Rhea:RHEA:36919, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74289,
CC ChEBI:CHEBI:74290; Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36920;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(19Z,22Z,25Z,28Z)-tetratriacontatetraenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(21Z,24Z,27Z,30Z)-hexatriacontatetraenoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:36923, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74291, ChEBI:CHEBI:74292;
CC Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36924;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(21Z,24Z,27Z,30Z)-hexatriacontatetraenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(23Z,26Z,29Z,32Z)-octatriacontatetraenoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:36927, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74293, ChEBI:CHEBI:74294;
CC Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36928;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(8Z,11Z,14Z,17Z,20Z,23Z)-hexacosahexaenoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:36947, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74086, ChEBI:CHEBI:74305;
CC Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36948;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z,17Z,20Z,23Z)-hexacosahexaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(10Z,13Z,16Z,19Z,22Z,25Z)-octacosahexaenoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:36963, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74306, ChEBI:CHEBI:74311;
CC Evidence={ECO:0000305|PubMed:22199362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36964;
CC Evidence={ECO:0000305|PubMed:22199362};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(10Z,13Z,16Z,19Z,22Z,25Z)-octacosahexaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(12Z,15Z,18Z,21Z,24Z,27Z)-triacontahexaenoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:36967, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74312, ChEBI:CHEBI:74313;
CC Evidence={ECO:0000305|PubMed:22199362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36968;
CC Evidence={ECO:0000305|PubMed:22199362};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(12Z,15Z,18Z,21Z,24Z,27Z)-triacontahexaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(14Z,17Z,20Z,23Z,26Z,29Z)-dotriacontahexaenoyl-
CC CoA + CO2 + CoA; Xref=Rhea:RHEA:36979, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74315, ChEBI:CHEBI:74316;
CC Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36980;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14Z,17Z,20Z,23Z,26Z,29Z)-dotriacontahexaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(16Z,19Z,22Z,25Z,28Z,31Z)-
CC tetratriacontahexaenoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36983,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:74317, ChEBI:CHEBI:74318;
CC Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36984;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(16Z,19Z,22Z,25Z,28Z,31Z)-tetratriacontahexaenoyl-CoA + H(+) +
CC malonyl-CoA = 3-oxo-(18Z,21Z,24Z,27Z,30Z,33Z)-hexatriacontahexaenoyl-
CC CoA + CO2 + CoA; Xref=Rhea:RHEA:36995, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:74319, ChEBI:CHEBI:74320;
CC Evidence={ECO:0000305|PubMed:22158834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36996;
CC Evidence={ECO:0000305|PubMed:22158834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA + H(+) + malonyl-
CC CoA = 3-oxo-(11Z,14Z,17Z,20Z,23Z)-hexacosapentaenoyl-CoA + CO2 + CoA;
CC Xref=Rhea:RHEA:37243, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74083,
CC ChEBI:CHEBI:74663; Evidence={ECO:0000305|PubMed:22199362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37244;
CC Evidence={ECO:0000305|PubMed:22199362};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_03204, ECO:0000269|PubMed:18728184,
CC ECO:0000269|PubMed:22158834, ECO:0000269|PubMed:22199362,
CC ECO:0000269|PubMed:23479632, ECO:0000269|PubMed:23509295,
CC ECO:0000269|PubMed:24569140}.
CC -!- SUBUNIT: Oligomer. {ECO:0000255|HAMAP-Rule:MF_03204}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03204, ECO:0000269|PubMed:23509295,
CC ECO:0000269|PubMed:24569140}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03204}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina, exclusively in
CC photoreceptor cells and in the brain, skin, testis and lens.
CC {ECO:0000269|PubMed:15028285}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the ocular tissues of the retina at
CC 10.5 dpc and becomes restricted predominantly to the photoreceptor
CC layer in the mature retina (at protein level). Expressed in the embryo
CC at 7 dpc. {ECO:0000269|PubMed:15028285}.
CC -!- DOMAIN: The C-terminal di-lysine motif confers endoplasmic reticulum
CC localization. {ECO:0000255|HAMAP-Rule:MF_03204,
CC ECO:0000269|PubMed:24569140}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:23509295,
CC ECO:0000269|PubMed:24569140}.
CC -!- DISRUPTION PHENOTYPE: Rod or cone-specific conditional knockout of
CC Elovl4 results in a decrease in very long chain (C30-C34)
CC polyunsaturated fatty acids in the retina, but has no effect on
CC photoreceptors survival, phototransduction, synaptic transmission or
CC visual behavior. {ECO:0000269|PubMed:23479632}.
CC -!- SIMILARITY: Belongs to the ELO family. ELOVL4 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03204}.
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DR EMBL; AF277093; AAG47667.1; -; mRNA.
DR EMBL; AJ550628; CAD80158.4; -; Genomic_DNA.
DR EMBL; AJ550629; CAD80158.4; JOINED; Genomic_DNA.
DR EMBL; AJ550630; CAD80158.4; JOINED; Genomic_DNA.
DR EMBL; AJ550631; CAD80158.4; JOINED; Genomic_DNA.
DR EMBL; AJ550632; CAD80158.4; JOINED; Genomic_DNA.
DR EMBL; AJ550633; CAD80158.4; JOINED; Genomic_DNA.
DR EMBL; AK029065; BAC26274.1; -; mRNA.
DR EMBL; CH466522; EDL26470.1; -; Genomic_DNA.
DR EMBL; BC037030; AAH37030.1; -; mRNA.
DR CCDS; CCDS23376.1; -.
DR RefSeq; NP_683743.2; NM_148941.2.
DR AlphaFoldDB; Q9EQC4; -.
DR SMR; Q9EQC4; -.
DR STRING; 10090.ENSMUSP00000034796; -.
DR SwissLipids; SLP:000000264; -.
DR GlyConnect; 2280; 1 N-Linked glycan (1 site).
DR GlyGen; Q9EQC4; 2 sites, 1 N-linked glycan (1 site).
DR PhosphoSitePlus; Q9EQC4; -.
DR PaxDb; Q9EQC4; -.
DR PRIDE; Q9EQC4; -.
DR ProteomicsDB; 275454; -.
DR Antibodypedia; 31608; 261 antibodies from 26 providers.
DR Ensembl; ENSMUST00000034796; ENSMUSP00000034796; ENSMUSG00000032262.
DR GeneID; 83603; -.
DR KEGG; mmu:83603; -.
DR UCSC; uc012gxk.1; mouse.
DR CTD; 6785; -.
DR MGI; MGI:1933331; Elovl4.
DR VEuPathDB; HostDB:ENSMUSG00000032262; -.
DR eggNOG; KOG3071; Eukaryota.
DR GeneTree; ENSGT01050000244838; -.
DR HOGENOM; CLU_048483_0_1_1; -.
DR InParanoid; Q9EQC4; -.
DR OMA; AACGPKF; -.
DR OrthoDB; 1094172at2759; -.
DR PhylomeDB; Q9EQC4; -.
DR TreeFam; TF323454; -.
DR UniPathway; UPA00094; -.
DR BioGRID-ORCS; 83603; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Elovl4; mouse.
DR PRO; PR:Q9EQC4; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9EQC4; protein.
DR Bgee; ENSMUSG00000032262; Expressed in skin of external ear and 192 other tissues.
DR ExpressionAtlas; Q9EQC4; baseline and differential.
DR Genevisible; Q9EQC4; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0009922; F:fatty acid elongase activity; IMP:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0034626; P:fatty acid elongation, polyunsaturated fatty acid; IMP:UniProtKB.
DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; ISS:UniProtKB.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; IEA:UniProtKB-UniRule.
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; ISS:UniProtKB.
DR HAMAP; MF_03204; VLCF_elongase_4; 1.
DR InterPro; IPR030457; ELO_CS.
DR InterPro; IPR002076; ELO_fam.
DR InterPro; IPR033678; ELOVL4.
DR PANTHER; PTHR11157; PTHR11157; 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..312
FT /note="Elongation of very long chain fatty acids protein 4"
FT /id="PRO_0000207545"
FT TRANSMEM 42..62
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT TRANSMEM 78..98
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT REGION 273..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 308..312
FT /note="Di-lysine motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204,
FT ECO:0000269|PubMed:24569140"
FT COMPBIAS 273..295
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..312
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT MUTAGEN 22
FT /note="T->A: Loss of N-glycosylation. No effect on fatty
FT acid elongase activity."
FT /evidence="ECO:0000269|PubMed:24569140"
FT MUTAGEN 158
FT /note="H->Q: Loss of fatty acid elongase activity."
FT /evidence="ECO:0000269|PubMed:24569140"
FT MUTAGEN 161
FT /note="H->Q: Loss of fatty acid elongase activity."
FT /evidence="ECO:0000269|PubMed:24569140"
FT MUTAGEN 162
FT /note="H->Q: Loss of fatty acid elongase activity."
FT /evidence="ECO:0000269|PubMed:24569140"
FT MUTAGEN 308..310
FT /note="KPK->RKR: Loss of localization to the endoplasmic
FT reticulum. Loss of fatty acid elongase activity."
FT /evidence="ECO:0000269|PubMed:24569140"
FT CONFLICT 126
FT /note="G -> A (in Ref. 1; AAG47667)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 312 AA; 36506 MW; B049772627D28294 CRC64;
MGLLDSEPGS VLNAMSTAFN DTVEFYRWTW TIADKRVADW PLMQSPWPTI SISTLYLLFV
WLGPKWMKDR EPFQMRLVLI IYNFGMVLLN LFIFRELFMG SYNAGYSYIC QSVDYSNDVN
EVRIAGALWW YFVSKGVEYL DTVFFILRKK NNQVSFLHVY HHCTMFTLWW IGIKWVAGGQ
AFFGAQMNSF IHVIMYSYYG LTAFGPWIQK YLWWKRYLTM LQLVQFHVTI GHTALSLYTD
CPFPKWMHWA LIAYAISFIF LFLNFYTRTY NEPKQSKTGK TATNGISSNG VNKSEKALEN
GKPQKNGKPK GE
