Q9GZR5 (ELOV4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Elongation of very long chain fatty acids protein 4
EC=2.3.1.n8

Alternative name(s):
3-keto acyl-CoA synthase ELOVL4

Gene names

Name:

ELOVL4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Condensing enzyme that elongates saturated and monounsaturated very long chain fatty acids (VLCFAs). Elongates C24:0 and C26:0 acyl-CoAs. Seems to represent a photoreceptor-specific component of the fatty acid elongation system residing on the endoplasmic reticulum. May be implicated in docosahexaenoic acid (DHA) biosynthesis, which requires dietary consumption of the essential alpha-linolenic acid and a subsequent series of three elongation steps. Ref.8
Catalytic activity	Acyl-CoA + malonyl-CoA = 3-oxoacyl-CoA + CoA + CO2.
Subunit structure	Oligomer. Ref.7
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.7 Ref.8.
Tissue specificity	Expressed in the retina and at much lower level in the brain. Ubiquitous, highest expression in thymus, followed by testis, small intestine, ovary, and prostate. Little or no espression in heart, lung, liver, or leukocates. Ref.8
Domain	The di-lysine motif may confer endoplasmic reticulum localization By similarity.
Involvement in disease	Defects in ELOVL4 are the cause of Stargardt disease type 3 (STGD3) [MIM:600110]. STGD is one of the most frequent causes of macular degeneration in childhood. It is characterized by macular dystrophy with juvenile-onset, rapidly progressive course, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. STGD3 inheritance is autosomal dominant. Ref.1
Sequence similarities	Belongs to the ELO family.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid synthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Stargardt disease
Domain	Transmembrane Transmembrane helix
Molecular function	Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	fatty acid elongation, saturated fatty acid Inferred from direct assay Ref.8. Source: UniProtKB long-chain fatty-acyl-CoA biosynthetic process Traceable author statement. Source: Reactome triglyceride biosynthetic process Traceable author statement. Source: Reactome very long-chain fatty acid biosynthetic process Inferred from direct assay Ref.8. Source: UniProtKB
Cellular component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular function	G-protein coupled photoreceptor activity Non-traceable author statement Ref.1. Source: UniProtKB protein binding Inferred from physical interaction Ref.8. Source: UniProtKB transferase activity, transferring acyl groups other than amino-acyl groups Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 314	314	Elongation of very long chain fatty acids protein 4		PRO_0000207542
Regions
	Transmembrane	42 – 62	21	Helical; Potential
	Transmembrane	78 – 98	21	Helical; Potential
	Transmembrane	165 – 185	21	Helical; Potential
	Transmembrane	188 – 208	21	Helical; Potential
	Transmembrane	247 – 267	21	Helical; Potential
	Motif	310 – 314	5	Di-lysine motif Potential
Amino acid modifications
	Glycosylation	20	1	N-linked (GlcNAc...) Ref.7
Natural variations
	Natural variant	267	1	I → T. Ref.9		VAR_017043
	Natural variant	299	1	M → V. Ref.1 Ref.9 Corresponds to variant rs3812153 [ dbSNP | Ensembl ].		VAR_012492
Experimental info
	Sequence conflict	44	1	Q → R in AAH38506. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q9GZR5 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: B2EBCE54D868E96E	FASTA	314	36,829
	10 20 30 40 50 60 MGLLDSEPGS VLNVVSTALN DTVEFYRWTW SIADKRVENW PLMQSPWPTL SISTLYLLFV 70 80 90 100 110 120 WLGPKWMKDR EPFQMRLVLI IYNFGMVLLN LFIFRELFMG SYNAGYSYIC QSVDYSNNVH 130 140 150 160 170 180 EVRIAAALWW YFVSKGVEYL DTVFFILRKK NNQVSFLHVY HHCTMFTLWW IGIKWVAGGQ 190 200 210 220 230 240 AFFGAQLNSF IHVIMYSYYG LTAFGPWIQK YLWWKRYLTM LQLIQFHVTI GHTALSLYTD 250 260 270 280 290 300 CPFPKWMHWA LIAYAISFIF LFLNFYIRTY KEPKKPKAGK TAMNGISANG VSKSEKQLMI 310 ENGKKQKNGK AKGD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy." Zhang K., Kniazeva M., Han M., Li W., Yu Z., Yang Z., Li Y., Metzker M.L., Allikmets R., Zack D.J., Kakuk L.E., Lagali P.S., Wong P.W., McDonald I.M., Sieving P.A., Figueroa D.J., Austin C.P., Gould R.J., Ayyagari R., Petrukhin K. Nat. Genet. 27:89-93(2001) [PubMed: 11138005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT VAL-299, DISEASE. Tissue: Retina.
[2]	"A novel gene for autosomal dominant Stargardt-like macular dystrophy with homology to the SUR4 protein family." Edwards A.O., Donoso L.A., Ritter R. III Invest. Ophthalmol. Vis. Sci. 42:2652-2663(2001) [PubMed: 11581213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Thalamus.
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Dominant negative mechanism underlies autosomal dominant Stargardt-like macular dystrophy linked to mutations in ELOVL4." Grayson C., Molday R.S. J. Biol. Chem. 280:32521-32530(2005) [PubMed: 16036915] [Abstract] Cited for: SUBCELLULAR LOCATION, OLIGOMERIZATION, GLYCOSYLATION AT ASN-20.
[8]	"ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis." Ohno Y., Suto S., Yamanaka M., Mizutani Y., Mitsutake S., Igarashi Y., Sassa T., Kihara A. Proc. Natl. Acad. Sci. U.S.A. 107:18439-18444(2010) [PubMed: 20937905] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"Evaluation of the ELOVL4 gene in patients with autosomal recessive retinitis pigmentosa and Leber congenital amaurosis." Rivolta C., Ayyagari R., Sieving P.A., Berson E.L., Dryja T.P. Mol. Vis. 9:49-51(2003) [PubMed: 12592226] [Abstract] Cited for: VARIANTS THR-267 AND VAL-299.
+	Additional computationally mapped references.

Web resources

Mutations of the ELOVL4 gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF279654 , AF279649, AF279650, AF279651, AF279652, AF279653 Genomic DNA. Translation: AAG47669.1. AF277094 mRNA. Translation: AAG47668.1. AY037298 mRNA. Translation: AAK68639.1. AK055277 mRNA. Translation: BAB70895.1. AK312511 mRNA. Translation: BAG35412.1. AL133475, AL132875 Genomic DNA. Translation: CAI20320.1. AL132875, AL133475 Genomic DNA. Translation: CAI23374.1. CH471051 Genomic DNA. Translation: EAW48701.1. BC038506 mRNA. Translation: AAH38506.1.
IPI	IPI00009295.
RefSeq	NP_073563.1. NM_022726.3.
UniGene	Hs.101915.
3D structure databases
ProteinModelPortal	Q9GZR5.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9GZR5.
Polymorphism databases
DMDM	20137966.
Proteomic databases
PRIDE	Q9GZR5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000369816; ENSP00000358831; ENSG00000118402.
GeneID	6785.
KEGG	hsa:6785.
NMPDR	fig|9606.3.peg.27447.
UCSC	uc003pja.2. human.
Organism-specific databases
CTD	6785.
GeneCards	GC06M080624.
H-InvDB	HIX0006027.
HGNC	HGNC:14415. ELOVL4.
MIM	600110. phenotype. 605512. gene.
neXtProt	NX_Q9GZR5.
Orphanet	827. Stargardt disease.
PharmGKB	PA27763.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17677.
GeneTree	ENSGT00550000074145.
HOGENOM	HBG315669.
HOVERGEN	HBG051468.
InParanoid	Q9GZR5.
OMA	FYVRTYK.
OrthoDB	EOG4N5VX9.
PhylomeDB	Q9GZR5.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000118402-MONOMER.
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q9GZR5.
Bgee	Q9GZR5.
CleanEx	HS_ELOVL4.
Genevestigator	Q9GZR5.
GermOnline	ENSG00000118402. Homo sapiens.
Family and domain databases
InterPro	IPR002076. GNS1_SUR4. [Graphical view]
KO	K10249.
PANTHER	PTHR11157. GNS1_SUR4. 1 hit.
Pfam	PF01151. ELO. 1 hit. [Graphical view]
PROSITE	PS01188. ELO. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00132. Alpha-Linolenic Acid.
NextBio	26492.
SOURCE	Search...

Entry information

Entry name

ELOV4_HUMAN

Accession

Primary (citable) accession number: Q9GZR5
Secondary accession number(s): B2R6B5 , Q5TCS2, Q86YJ1, Q9H139

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2002
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.