Q9TVB8 · RPE65_CANLF

Function

function

Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. Catalyzes the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore. Essential for the production of 11-cis retinal for both rod and cone photoreceptors. Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid. 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.

Catalytic activity

Cofactor

Fe2+ (UniProtKB | Rhea| CHEBI:29033 )

Note: Binds 1 Fe2+ ion per subunit.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site180Fe cation (UniProtKB | ChEBI); catalytic
Binding site241Fe cation (UniProtKB | ChEBI); catalytic
Binding site313Fe cation (UniProtKB | ChEBI); catalytic
Binding site527Fe cation (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmembrane
Cellular Componentplasma membrane
Molecular Functionall-trans-retinyl-ester hydrolase, 11-cis retinol forming activity
Molecular Functionall-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity
Molecular Functionbeta-carotene 15,15'-dioxygenase activity
Molecular Functioncardiolipin binding
Molecular Functionisomerase activity
Molecular Functionmetal ion binding
Molecular Functionphosphatidylcholine binding
Molecular Functionphosphatidylserine binding
Molecular Functionretinol isomerase activity
Biological Processretinal metabolic process
Biological Processretinoid metabolic process
Biological Processvisual perception
Biological Processzeaxanthin biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Retinoid isomerohydrolase
  • EC number
  • Alternative names
    • All-trans-retinyl-palmitate hydrolase
    • Lutein isomerase
    • Meso-zeaxanthin isomerase (EC:5.3.3.22
      ) . EC:5.3.3.22 (UniProtKB | ENZYME | Rhea)
    • Retinal pigment epithelium-specific 65 kDa protein
    • Retinol isomerase

Gene names

    • Name
      RPE65

Organism names

Accessions

  • Primary accession
    Q9TVB8
  • Secondary accessions
    • O97623
    • Q8MJY9

Proteomes

Subcellular Location

Cytoplasm
Cell membrane
; Lipid-anchor
Microsome membrane
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).

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis180Loss of enzymatic activity.
Mutagenesis231Does not affect isomerization activity.
Mutagenesis241Loss of isomerohydrolase activity.
Mutagenesis313Loss of isomerohydrolase activity.
Mutagenesis329Decreasing protein levels. isomerohydrolase activity.
Mutagenesis329-330Decreasing protein levels. Loss of isomerohydrolase activity.
Mutagenesis330Does not affect isomerohydrolase activity.
Mutagenesis417Loss of enzymatic isomerohydrolase.
Mutagenesis477Does not affect isomerohydrolase activity.
Mutagenesis527Loss of isomerohydrolase activity.

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, lipidation.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylserine
ChainPRO_00001439412-533Retinoid isomerohydrolase
Modified residue101Phosphothreonine
Modified residue105Phosphothreonine
Lipidation112S-palmitoyl cysteine; in membrane form
Modified residue113N6-acetyllysine
Modified residue117Phosphoserine
Lipidation231S-palmitoyl cysteine; in membrane form
Lipidation329S-palmitoyl cysteine; in membrane form
Lipidation330S-palmitoyl cysteine; in membrane form

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).

Keywords

Proteomic databases

Expression

Tissue specificity

Retinal pigment epithelium specific.

Interaction

Subunit

Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Belongs to the carotenoid oxygenase family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    533
  • Mass (Da)
    60,880
  • Last updated
    2007-01-23 v3
  • Checksum
    EBEC87458BA4C91B
MSIQVEHPAGGYKKLFETVEELSSPLTAHVTGRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRRFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQVDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQADKEDPISKSEVVVQFPCSDRFKPSYVHSFGLTPNYIVFVETPVKINLLKFLSSWSLWGANYMDCFESNETMGVWLHIADKKRKKYLNNKYRTSSFNLFHHINTYEDNEFLIVDLCCWKGFEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDKADTGKNLVTLPNTTATATLRSDETIWLEPEVLFSGPRQAFEFPQINYQKSGGKPYTYAYGLGLNHFVPDRLCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict368in Ref. 1; AAC72356
Sequence conflict426in Ref. 1; AAC72356

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF084537
EMBL· GenBank· DDBJ
AAC72356.1
EMBL· GenBank· DDBJ
mRNA
Y16567
EMBL· GenBank· DDBJ
CAA76290.1
EMBL· GenBank· DDBJ
mRNA
AJ506754
EMBL· GenBank· DDBJ
CAD45010.1
EMBL· GenBank· DDBJ
Genomic DNA
AJ506755
EMBL· GenBank· DDBJ
CAD45010.1
EMBL· GenBank· DDBJ
Genomic DNA
AJ506756
EMBL· GenBank· DDBJ
CAD45010.1
EMBL· GenBank· DDBJ
Genomic DNA
AJ506757
EMBL· GenBank· DDBJ
CAD45010.1
EMBL· GenBank· DDBJ
Genomic DNA
AJ251207
EMBL· GenBank· DDBJ
CAD45010.1
EMBL· GenBank· DDBJ
Genomic DNA
AJ506759
EMBL· GenBank· DDBJ
CAD45010.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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