ELOV4_HUMAN
ID ELOV4_HUMAN Reviewed; 314 AA.
AC Q9GZR5; B2R6B5; Q5TCS2; Q86YJ1; Q9H139;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
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:20937905, ECO:0000269|PubMed:23479632};
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 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 [GENOMIC DNA / MRNA], VARIANT VAL-299, AND DISEASE.
RC TISSUE=Retina;
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 [MRNA], AND INVOLVEMENT IN STGD3.
RX PubMed=11581213;
RA Edwards A.O., Donoso L.A., Ritter R. III;
RT "A novel gene for autosomal dominant Stargardt-like macular dystrophy with
RT homology to the SUR4 protein family.";
RL Invest. Ophthalmol. Vis. Sci. 42:2652-2663(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [7]
RP SUBCELLULAR LOCATION, OLIGOMERIZATION, AND GLYCOSYLATION AT ASN-20.
RX PubMed=16036915; DOI=10.1074/jbc.m503411200;
RA Grayson C., Molday R.S.;
RT "Dominant negative mechanism underlies autosomal dominant Stargardt-like
RT macular dystrophy linked to mutations in ELOVL4.";
RL J. Biol. Chem. 280:32521-32530(2005).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=20937905; DOI=10.1073/pnas.1005572107;
RA Ohno Y., Suto S., Yamanaka M., Mizutani Y., Mitsutake S., Igarashi Y.,
RA Sassa T., Kihara A.;
RT "ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid
RT synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18439-18444(2010).
RN [9]
RP PROBABLE ROLE IN BRAIN AND SKIN DEVELOPMENT, AND INVOLVEMENT IN ISQMR.
RX PubMed=22100072; DOI=10.1016/j.ajhg.2011.10.011;
RA Aldahmesh M.A., Mohamed J.Y., Alkuraya H.S., Verma I.C., Puri R.D.,
RA Alaiya A.A., Rizzo W.B., Alkuraya F.S.;
RT "Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability,
RT and spastic quadriplegia.";
RL Am. J. Hum. Genet. 89:745-750(2011).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 [11]
RP VARIANTS THR-267 AND VAL-299.
RX PubMed=12592226;
RA Rivolta C., Ayyagari R., Sieving P.A., Berson E.L., Dryja T.P.;
RT "Evaluation of the ELOVL4 gene in patients with autosomal recessive
RT retinitis pigmentosa and Leber congenital amaurosis.";
RL Mol. Vis. 9:49-51(2003).
RN [12]
RP INVOLVEMENT IN SCA34, AND VARIANT SCA34 PHE-168.
RX PubMed=24566826; DOI=10.1001/jamaneurol.2013.6337;
RA Cadieux-Dion M., Turcotte-Gauthier M., Noreau A., Martin C., Meloche C.,
RA Gravel M., Drouin C.A., Rouleau G.A., Nguyen D.K., Cossette P.;
RT "Expanding the clinical phenotype associated with ELOVL4 mutation: study of
RT a large French-Canadian family with autosomal dominant spinocerebellar
RT ataxia and erythrokeratodermia.";
RL JAMA Neurol. 71:470-475(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:20937905, ECO:0000269|PubMed:23479632}.
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:20937905};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32728;
CC Evidence={ECO:0000305|PubMed:20937905};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA + tetracosanoyl-CoA = 3-oxohexacosanoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:36515, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:65052, ChEBI:CHEBI:73980;
CC Evidence={ECO:0000269|PubMed:20937905};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36516;
CC Evidence={ECO:0000305|PubMed:20937905};
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:20937905};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36520;
CC Evidence={ECO:0000305|PubMed:20937905};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36808;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43853;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36872;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36944;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36480;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36820;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36844;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:23479632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36852;
CC Evidence={ECO:0000305|PubMed:23479632};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36860;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36876;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36908;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36912;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:23479632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36916;
CC Evidence={ECO:0000305|PubMed:23479632};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36920;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36924;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36928;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36948;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36964;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36968;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:23479632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36980;
CC Evidence={ECO:0000305|PubMed:23479632};
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:23479632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36984;
CC Evidence={ECO:0000305|PubMed:23479632};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36996;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
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:0000250|UniProtKB:Q9EQC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37244;
CC Evidence={ECO:0000250|UniProtKB:Q9EQC4};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_03204, ECO:0000269|PubMed:20937905,
CC ECO:0000269|PubMed:23479632}.
CC -!- SUBUNIT: Oligomer. {ECO:0000255|HAMAP-Rule:MF_03204,
CC ECO:0000269|PubMed:16036915}.
CC -!- INTERACTION:
CC Q9GZR5; Q9UHX3: ADGRE2; NbExp=3; IntAct=EBI-18535450, EBI-11277970;
CC Q9GZR5; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-18535450, EBI-12109402;
CC Q9GZR5; O95236-2: APOL3; NbExp=3; IntAct=EBI-18535450, EBI-11976321;
CC Q9GZR5; Q9HD20-3: ATP13A1; NbExp=3; IntAct=EBI-18535450, EBI-12069500;
CC Q9GZR5; Q07817: BCL2L1; NbExp=3; IntAct=EBI-18535450, EBI-78035;
CC Q9GZR5; O15155: BET1; NbExp=3; IntAct=EBI-18535450, EBI-749204;
CC Q9GZR5; Q13323: BIK; NbExp=3; IntAct=EBI-18535450, EBI-700794;
CC Q9GZR5; Q12981: BNIP1; NbExp=3; IntAct=EBI-18535450, EBI-4402847;
CC Q9GZR5; Q12983: BNIP3; NbExp=3; IntAct=EBI-18535450, EBI-749464;
CC Q9GZR5; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-18535450, EBI-8648738;
CC Q9GZR5; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-18535450, EBI-9083477;
CC Q9GZR5; Q8NHW4: CCL4L2; NbExp=3; IntAct=EBI-18535450, EBI-10271156;
CC Q9GZR5; P32970: CD70; NbExp=3; IntAct=EBI-18535450, EBI-18539709;
CC Q9GZR5; Q8NHS1: CLDND2; NbExp=3; IntAct=EBI-18535450, EBI-11959453;
CC Q9GZR5; Q96MX0: CMTM3; NbExp=3; IntAct=EBI-18535450, EBI-7247651;
CC Q9GZR5; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-18535450, EBI-11522780;
CC Q9GZR5; Q96FZ5: CMTM7; NbExp=3; IntAct=EBI-18535450, EBI-2807956;
CC Q9GZR5; P29400-2: COL4A5; NbExp=3; IntAct=EBI-18535450, EBI-12211159;
CC Q9GZR5; P00387: CYB5R3; NbExp=3; IntAct=EBI-18535450, EBI-1046040;
CC Q9GZR5; P78329: CYP4F2; NbExp=3; IntAct=EBI-18535450, EBI-1752413;
CC Q9GZR5; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-18535450, EBI-711490;
CC Q9GZR5; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-18535450, EBI-11337888;
CC Q9GZR5; Q8N128-2: FAM177A1; NbExp=3; IntAct=EBI-18535450, EBI-12201693;
CC Q9GZR5; Q92520: FAM3C; NbExp=3; IntAct=EBI-18535450, EBI-2876774;
CC Q9GZR5; Q96IV6: FAXDC2; NbExp=3; IntAct=EBI-18535450, EBI-12142299;
CC Q9GZR5; P37268: FDFT1; NbExp=3; IntAct=EBI-18535450, EBI-714550;
CC Q9GZR5; Q14318: FKBP8; NbExp=3; IntAct=EBI-18535450, EBI-724839;
CC Q9GZR5; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-18535450, EBI-713304;
CC Q9GZR5; Q8WWP7: GIMAP1; NbExp=3; IntAct=EBI-18535450, EBI-11991950;
CC Q9GZR5; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-18535450, EBI-6166686;
CC Q9GZR5; O14653: GOSR2; NbExp=3; IntAct=EBI-18535450, EBI-4401517;
CC Q9GZR5; O60883: GPR37L1; NbExp=3; IntAct=EBI-18535450, EBI-2927498;
CC Q9GZR5; P02724: GYPA; NbExp=3; IntAct=EBI-18535450, EBI-702665;
CC Q9GZR5; P09601: HMOX1; NbExp=3; IntAct=EBI-18535450, EBI-2806151;
CC Q9GZR5; P30519: HMOX2; NbExp=3; IntAct=EBI-18535450, EBI-712096;
CC Q9GZR5; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-18535450, EBI-3918847;
CC Q9GZR5; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-18535450, EBI-725665;
CC Q9GZR5; P11215: ITGAM; NbExp=3; IntAct=EBI-18535450, EBI-2568251;
CC Q9GZR5; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-18535450, EBI-10266796;
CC Q9GZR5; O95214: LEPROTL1; NbExp=3; IntAct=EBI-18535450, EBI-750776;
CC Q9GZR5; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-18535450, EBI-2820517;
CC Q9GZR5; Q14210: LY6D; NbExp=3; IntAct=EBI-18535450, EBI-1965225;
CC Q9GZR5; Q13021: MALL; NbExp=3; IntAct=EBI-18535450, EBI-750078;
CC Q9GZR5; P50281: MMP14; NbExp=3; IntAct=EBI-18535450, EBI-992788;
CC Q9GZR5; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-18535450, EBI-10317425;
CC Q9GZR5; Q53FV1: ORMDL2; NbExp=3; IntAct=EBI-18535450, EBI-11075081;
CC Q9GZR5; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-18535450, EBI-721750;
CC Q9GZR5; Q99640-2: PKMYT1; NbExp=3; IntAct=EBI-18535450, EBI-12257782;
CC Q9GZR5; Q9Y342: PLLP; NbExp=3; IntAct=EBI-18535450, EBI-3919291;
CC Q9GZR5; P26678: PLN; NbExp=3; IntAct=EBI-18535450, EBI-692836;
CC Q9GZR5; P60201-2: PLP1; NbExp=3; IntAct=EBI-18535450, EBI-12188331;
CC Q9GZR5; P18031: PTPN1; NbExp=3; IntAct=EBI-18535450, EBI-968788;
CC Q9GZR5; Q9NP72: RAB18; NbExp=3; IntAct=EBI-18535450, EBI-722247;
CC Q9GZR5; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-18535450, EBI-10244780;
CC Q9GZR5; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-18535450, EBI-8652744;
CC Q9GZR5; O75396: SEC22B; NbExp=3; IntAct=EBI-18535450, EBI-1058865;
CC Q9GZR5; O75920: SERF1B; NbExp=3; IntAct=EBI-18535450, EBI-2115181;
CC Q9GZR5; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-18535450, EBI-749270;
CC Q9GZR5; O95562: SFT2D2; NbExp=3; IntAct=EBI-18535450, EBI-4402330;
CC Q9GZR5; Q99726: SLC30A3; NbExp=3; IntAct=EBI-18535450, EBI-10294651;
CC Q9GZR5; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-18535450, EBI-10262251;
CC Q9GZR5; Q6UX34: SNORC; NbExp=3; IntAct=EBI-18535450, EBI-11957067;
CC Q9GZR5; Q13277: STX3; NbExp=3; IntAct=EBI-18535450, EBI-1394295;
CC Q9GZR5; Q9H7V2: SYNDIG1; NbExp=3; IntAct=EBI-18535450, EBI-726331;
CC Q9GZR5; Q9NZ01: TECR; NbExp=3; IntAct=EBI-18535450, EBI-2877718;
CC Q9GZR5; P02787: TF; NbExp=3; IntAct=EBI-18535450, EBI-714319;
CC Q9GZR5; P17152: TMEM11; NbExp=3; IntAct=EBI-18535450, EBI-723946;
CC Q9GZR5; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-18535450, EBI-10694905;
CC Q9GZR5; Q96HH6: TMEM19; NbExp=3; IntAct=EBI-18535450, EBI-741829;
CC Q9GZR5; Q8N511: TMEM199; NbExp=3; IntAct=EBI-18535450, EBI-10265825;
CC Q9GZR5; Q969S6: TMEM203; NbExp=3; IntAct=EBI-18535450, EBI-12274070;
CC Q9GZR5; A2RU14: TMEM218; NbExp=3; IntAct=EBI-18535450, EBI-10173151;
CC Q9GZR5; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-18535450, EBI-347385;
CC Q9GZR5; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-18535450, EBI-10315004;
CC Q9GZR5; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-18535450, EBI-12887458;
CC Q9GZR5; Q8TBM7: TMEM254; NbExp=3; IntAct=EBI-18535450, EBI-11956809;
CC Q9GZR5; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-18535450, EBI-12038591;
CC Q9GZR5; Q2T9K0-2: TMEM44; NbExp=3; IntAct=EBI-18535450, EBI-13076526;
CC Q9GZR5; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-18535450, EBI-16746122;
CC Q9GZR5; A0AVG3: TSNARE1; NbExp=3; IntAct=EBI-18535450, EBI-12003468;
CC Q9GZR5; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-18535450, EBI-11988865;
CC Q9GZR5; Q9Y385: UBE2J1; NbExp=3; IntAct=EBI-18535450, EBI-988826;
CC Q9GZR5; Q53HI1: UNC50; NbExp=3; IntAct=EBI-18535450, EBI-7601760;
CC Q9GZR5; P23763-3: VAMP1; NbExp=3; IntAct=EBI-18535450, EBI-12097582;
CC Q9GZR5; Q15836: VAMP3; NbExp=3; IntAct=EBI-18535450, EBI-722343;
CC Q9GZR5; O75379: VAMP4; NbExp=3; IntAct=EBI-18535450, EBI-744953;
CC Q9GZR5; O95183: VAMP5; NbExp=3; IntAct=EBI-18535450, EBI-10191195;
CC Q9GZR5; O95292: VAPB; NbExp=3; IntAct=EBI-18535450, EBI-1188298;
CC Q9GZR5; O95070: YIF1A; NbExp=3; IntAct=EBI-18535450, EBI-2799703;
CC Q9GZR5; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-18535450, EBI-751210;
CC Q9GZR5; Q8IVQ6: ZDHHC21; NbExp=3; IntAct=EBI-18535450, EBI-2849773;
CC Q9GZR5; O95159: ZFPL1; NbExp=3; IntAct=EBI-18535450, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03204, ECO:0000269|PubMed:16036915,
CC ECO:0000269|PubMed:20937905}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03204}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina and at much lower level in
CC the brain. Ubiquitous, highest expression in thymus, followed by
CC testis, small intestine, ovary, and prostate. Little or no expression
CC in heart, lung, liver, or leukocates. {ECO:0000269|PubMed:20937905}.
CC -!- DOMAIN: The C-terminal di-lysine motif confers endoplasmic reticulum
CC localization. {ECO:0000255|HAMAP-Rule:MF_03204}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9EQC4}.
CC -!- DISEASE: Stargardt disease 3 (STGD3) [MIM:600110]: A common hereditary
CC macular degeneration. It is characterized by decreased central vision,
CC atrophy of the macula and underlying retinal pigment epithelium, and
CC frequent presence of prominent flecks in the posterior pole of the
CC retina. {ECO:0000269|PubMed:11138005, ECO:0000269|PubMed:11581213}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Ichthyosis, spastic quadriplegia, and intellectual disability
CC (ISQMR) [MIM:614457]: A severe autosomal recessive disorder
CC characterized by ichthyosis apparent from birth, profound psychomotor
CC retardation with essentially no development, spastic quadriplegia, and
CC seizures. {ECO:0000269|PubMed:22100072}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Spinocerebellar ataxia 34 (SCA34) [MIM:133190]: A form of
CC spinocerebellar ataxia, a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA34 is an autosomal dominant form
CC characterized by the association of progressive cerebellar ataxia with
CC erythrokeratodermia variabilis. {ECO:0000269|PubMed:24566826}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the ELO family. ELOVL4 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03204}.
CC -!- WEB RESOURCE: Name=Mutations of the ELOVL4 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/elovlmut.htm";
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DR EMBL; AF279654; AAG47669.1; -; Genomic_DNA.
DR EMBL; AF279649; AAG47669.1; JOINED; Genomic_DNA.
DR EMBL; AF279650; AAG47669.1; JOINED; Genomic_DNA.
DR EMBL; AF279651; AAG47669.1; JOINED; Genomic_DNA.
DR EMBL; AF279652; AAG47669.1; JOINED; Genomic_DNA.
DR EMBL; AF279653; AAG47669.1; JOINED; Genomic_DNA.
DR EMBL; AF277094; AAG47668.1; -; mRNA.
DR EMBL; AY037298; AAK68639.1; -; mRNA.
DR EMBL; AK055277; BAB70895.1; -; mRNA.
DR EMBL; AK312511; BAG35412.1; -; mRNA.
DR EMBL; AL133475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL132875; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48701.1; -; Genomic_DNA.
DR EMBL; BC038506; AAH38506.1; -; mRNA.
DR CCDS; CCDS4992.1; -.
DR RefSeq; NP_073563.1; NM_022726.3.
DR AlphaFoldDB; Q9GZR5; -.
DR SMR; Q9GZR5; -.
DR BioGRID; 112661; 125.
DR IntAct; Q9GZR5; 94.
DR STRING; 9606.ENSP00000358831; -.
DR DrugBank; DB09568; Omega-3-carboxylic acids.
DR DrugBank; DB09328; Vayarin.
DR SwissLipids; SLP:000000255; -.
DR GlyGen; Q9GZR5; 1 site.
DR iPTMnet; Q9GZR5; -.
DR PhosphoSitePlus; Q9GZR5; -.
DR SwissPalm; Q9GZR5; -.
DR BioMuta; ELOVL4; -.
DR DMDM; 20137966; -.
DR EPD; Q9GZR5; -.
DR MassIVE; Q9GZR5; -.
DR PaxDb; Q9GZR5; -.
DR PeptideAtlas; Q9GZR5; -.
DR PRIDE; Q9GZR5; -.
DR ProteomicsDB; 80120; -.
DR Antibodypedia; 31608; 261 antibodies from 26 providers.
DR DNASU; 6785; -.
DR Ensembl; ENST00000369816.5; ENSP00000358831.4; ENSG00000118402.6.
DR GeneID; 6785; -.
DR KEGG; hsa:6785; -.
DR MANE-Select; ENST00000369816.5; ENSP00000358831.4; NM_022726.4; NP_073563.1.
DR UCSC; uc003pja.5; human.
DR CTD; 6785; -.
DR DisGeNET; 6785; -.
DR GeneCards; ELOVL4; -.
DR HGNC; HGNC:14415; ELOVL4.
DR HPA; ENSG00000118402; Tissue enhanced (lymphoid tissue, retina).
DR MalaCards; ELOVL4; -.
DR MIM; 133190; phenotype.
DR MIM; 600110; phenotype.
DR MIM; 605512; gene.
DR MIM; 614457; phenotype.
DR neXtProt; NX_Q9GZR5; -.
DR OpenTargets; ENSG00000118402; -.
DR Orphanet; 352333; Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome.
DR Orphanet; 1955; Spinocerebellar ataxia type 34.
DR Orphanet; 827; Stargardt disease.
DR PharmGKB; PA27763; -.
DR VEuPathDB; HostDB:ENSG00000118402; -.
DR eggNOG; KOG3071; Eukaryota.
DR GeneTree; ENSGT01050000244838; -.
DR HOGENOM; CLU_048483_0_1_1; -.
DR InParanoid; Q9GZR5; -.
DR OMA; AACGPKF; -.
DR OrthoDB; 1094172at2759; -.
DR PhylomeDB; Q9GZR5; -.
DR TreeFam; TF323454; -.
DR BioCyc; MetaCyc:ENSG00000118402-MON; -.
DR PathwayCommons; Q9GZR5; -.
DR Reactome; R-HSA-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR SignaLink; Q9GZR5; -.
DR SIGNOR; Q9GZR5; -.
DR UniPathway; UPA00094; -.
DR BioGRID-ORCS; 6785; 32 hits in 1070 CRISPR screens.
DR GeneWiki; ELOVL4; -.
DR GenomeRNAi; 6785; -.
DR Pharos; Q9GZR5; Tbio.
DR PRO; PR:Q9GZR5; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9GZR5; protein.
DR Bgee; ENSG00000118402; Expressed in upper leg skin and 151 other tissues.
DR Genevisible; Q9GZR5; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0102337; F:3-oxo-cerotoyl-CoA synthase activity; IEA:RHEA.
DR GO; GO:0009922; F:fatty acid elongase activity; ISS:UniProtKB.
DR GO; GO:0008020; F:G protein-coupled photoreceptor activity; NAS:UniProtKB.
DR GO; GO:0102756; F:very-long-chain 3-ketoacyl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006633; P:fatty acid biosynthetic process; NAS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; IDA: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; IDA: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 Disease variant; Endoplasmic reticulum; Fatty acid biosynthesis;
KW Fatty acid metabolism; Glycoprotein; Ichthyosis; Intellectual disability;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Neurodegeneration;
KW Reference proteome; Spinocerebellar ataxia; Stargardt disease; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..314
FT /note="Elongation of very long chain fatty acids protein 4"
FT /id="PRO_0000207542"
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 247..267
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT REGION 275..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 310..314
FT /note="Di-lysine motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03204"
FT COMPBIAS 298..314
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 ECO:0000269|PubMed:16036915"
FT VARIANT 168
FT /note="L -> F (in SCA34; dbSNP:rs587777598)"
FT /evidence="ECO:0000269|PubMed:24566826"
FT /id="VAR_072565"
FT VARIANT 267
FT /note="I -> T (in dbSNP:rs148594713)"
FT /evidence="ECO:0000269|PubMed:12592226"
FT /id="VAR_017043"
FT VARIANT 299
FT /note="M -> V (in dbSNP:rs3812153)"
FT /evidence="ECO:0000269|PubMed:11138005,
FT ECO:0000269|PubMed:12592226"
FT /id="VAR_012492"
FT CONFLICT 44
FT /note="Q -> R (in Ref. 6; AAH38506)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 36829 MW; B2EBCE54D868E96E CRC64;
MGLLDSEPGS VLNVVSTALN DTVEFYRWTW SIADKRVENW PLMQSPWPTL SISTLYLLFV
WLGPKWMKDR EPFQMRLVLI IYNFGMVLLN LFIFRELFMG SYNAGYSYIC QSVDYSNNVH
EVRIAAALWW YFVSKGVEYL DTVFFILRKK NNQVSFLHVY HHCTMFTLWW IGIKWVAGGQ
AFFGAQLNSF IHVIMYSYYG LTAFGPWIQK YLWWKRYLTM LQLIQFHVTI GHTALSLYTD
CPFPKWMHWA LIAYAISFIF LFLNFYIRTY KEPKKPKAGK TAMNGISANG VSKSEKQLMI
ENGKKQKNGK AKGD
