Q91ZQ5 (RPE65_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Retinoid isomerohydrolase
EC=3.1.1.64

Alternative name(s):
All-trans-retinyl-palmitate hydrolase
Retinal pigment epithelium-specific 65 kDa protein
Retinol isomerase

Gene names

Name:

Rpe65

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	533 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays important roles in the production of 11-cis retinal and in visual pigment regeneration. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT. The enzymatic activity is linearly dependent of the expression levels and membrane association By similarity.
Catalytic activity	An all-trans-retinyl ester + H2O = 11-cis-retinol + a fatty acid.
Cofactor	Binds 1 Fe2+ ion per subunit By similarity.
Subunit structure	Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65 By similarity.
Subcellular location	Cytoplasm By similarity. Cell membrane; Lipid-anchor By similarity. Microsome membrane By similarity. Note: Attached to the membrane by a lipid anchor when palmitoylated (membrane form), soluble when unpalmitoylated. Undergoes light-dependent intracellular transport to become more concentrated in the central region of the retina pigment epithelium cells By similarity.
Tissue specificity	Retinal pigment epithelium specific.
Post-translational modification	Palmitoylation by LRAT regulates ligand binding specificity; the palmitoylated form (membrane form) specifically binds all-trans-retinyl-palmitate, while the soluble unpalmitoylated form binds all-trans-retinol (vitamin A) By similarity.
Involvement in disease	Defects in Rpe65 are the cause of light damage susceptibility (LDS) of the retina. Ref.4
Sequence similarities	Belongs to the carotenoid oxygenase family.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Cell membrane Cytoplasm Endoplasmic reticulum Membrane Microsome
Disease	Disease mutation
Ligand	Iron Metal-binding
Molecular function	Hydrolase Isomerase
PTM	Acetylation Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to electrical stimulus Inferred from mutant phenotype PubMed 21052544. Source: MGI insulin receptor signaling pathway Inferred from mutant phenotype PubMed 17272282. Source: MGI regulation of rhodopsin gene expression Inferred from mutant phenotype PubMed 11897783. Source: MGI retina morphogenesis in camera-type eye Inferred from mutant phenotype PubMed 21052544. Source: MGI retinal metabolic process Inferred from mutant phenotype PubMed 11897783. Source: MGI visual perception Inferred from mutant phenotype PubMed 11897783. Source: MGI
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW organelle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity Inferred from electronic annotation. Source: EC all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW retinal isomerase activity Inferred from mutant phenotype PubMed 18195010. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 533	532	Retinoid isomerohydrolase		PRO_0000143944
Sites
	Metal binding	180	1	Iron; catalytic By similarity
	Metal binding	241	1	Iron; catalytic By similarity
	Metal binding	313	1	Iron; catalytic By similarity
	Metal binding	527	1	Iron; catalytic By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	101	1	Phosphothreonine By similarity
	Modified residue	105	1	Phosphothreonine By similarity
	Modified residue	113	1	N6-acetyllysine By similarity
	Modified residue	117	1	Phosphoserine By similarity
	Lipidation	112	1	S-palmitoyl cysteine; in membrane form By similarity
	Lipidation	231	1	S-palmitoyl cysteine; in membrane form By similarity
	Lipidation	329	1	S-palmitoyl cysteine; in membrane form By similarity
	Lipidation	330	1	S-palmitoyl cysteine; in membrane form By similarity
Natural variations
	Natural variant	450	1	L → M in LDS. Ref.2 Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q91ZQ5 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 5ACB3EBC2F1CD438	FASTA	533	61,067
	10 20 30 40 50 60 MSIQIEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF EVGSEPFYHL 70 80 90 100 110 120 FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI TEFGTCAFPD PCKNIFSRFF 130 140 150 160 170 180 SYFKGVEVTD NALVNIYPVG EDYYACTETN FITKINPETL ETIKQVDLCN YISVNGATAH 190 200 210 220 230 240 PHIESDGTVY NIGNCFGKNF TVAYNIIKIP PLKADKEDPI NKSEVVVQFP CSDRFKPSYV 250 260 270 280 290 300 HSFGLTPNYI VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNESMGVWLH VADKKRRKYF 310 320 330 340 350 360 NNKYRTSPFN LFHHINTYED NGFLIVDLCC WKGFEFVYNY LYLANLRENW EEVKRNAMKA 370 380 390 400 410 420 PQPEVRRYVL PLTIDKVDTG RNLVTLPHTT ATATLRSDET IWLEPEVLFS GPRQAFEFPQ 430 440 450 460 470 480 INYQKFGGKP YTYAYGLGLN HFVPDKLCKL NVKTKEIWMW QEPDSYPSEP IFVSQPDALE 490 500 510 520 530 EDDGVVLSVV VSPGAGQKPA YLLVLNAKDL SEIARAEVET NIPVTFHGLF KRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A point mutation in Rpe65 gene causes retinal degeneration (rd12) in mice." Chang B., Hawes N.L., Hurd R.E., Davisson M.T., Heckenlively J. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6J. Tissue: Retina.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT MET-450. Strain: C57BL/6J.
[3]	"Sequence and structure of the mouse gene for RPE65." Boulanger A., Liu S., Yu S., Redmond T.M. Mol. Vis. 7:283-287(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-483. Strain: 129/Sv.
[4]	"The Rpe65 Leu450Met variation increases retinal resistance against light-induced degeneration by slowing rhodopsin regeneration." Wenzel A., Reme C.E., Williams T.P., Hafezi F., Grimm C. J. Neurosci. 21:53-58(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LDS MET-450.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF410461 mRNA. Translation: AAL01119.1. AC163272 Genomic DNA. No translation available. AH011240 Genomic DNA. Translation: AAL39096.1.
IPI	IPI00131304.
UniGene	Mm.131708.
3D structure databases
ProteinModelPortal	Q91ZQ5.
SMR	Q91ZQ5. Positions 4-533.
ModBase	Search...
PTM databases
PhosphoSite	Q91ZQ5.
Proteomic databases
PRIDE	Q91ZQ5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:98001. Rpe65.
Phylogenomic databases
eggNOG	COG3670.
HOGENOM	HOG000232156.
HOVERGEN	HBG050679.
InParanoid	Q91ZQ5.
OrthoDB	EOG47M1XK.
Gene expression databases
CleanEx	MM_RPE65.
Genevestigator	Q91ZQ5.
GermOnline	ENSMUSG00000028174. Mus musculus.
Family and domain databases
InterPro	IPR004294. Carotenoid_Oase. [Graphical view]
PANTHER	PTHR10543. PTHR10543. 1 hit.
Pfam	PF03055. RPE65. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

RPE65_MOUSE

Accession

Primary (citable) accession number: Q91ZQ5
Secondary accession number(s): E9QNS6, Q8VHP2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 74 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program