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FLASH GENE
Symbol PRPH2 contributors: shn - updated : 02-02-2017
HGNC name peripherin 2 (retinal degeneration, slow)
HGNC id 9942
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 3027 39 346 in the rims of rod and cone outer segment discs 1991 1986774
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Visualeyeretina  specific
cells
SystemCellPubmedSpeciesStageRna symbol
Visualcone photoreceptor
Visualrod photoreceptor
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four putative transmembrane domains, and the fourth transmembrane domain (TM4) of PRPH2 is required for the interaction with rhodopsin
  • twelve cysteine residues
  • two possible sites for N-linked glycosylation
  • two intradiscal loop region, and integrity of the second intradiscal domain is critical for normal macular cone structure
  • conjugated GlycoP
    mono polymer tetramer
    HOMOLOGY
    interspecies ortholog to Prph2, mouse
    ortholog to PRPH2, Pan troglodytes
    ortholog to Prph2, Rattus norvegicus
    ortholog to zgc:56548, danio rerio
    Homologene
    FAMILY
  • tetraspanin family
  • transmembrane 4 superfamily
  • CATEGORY adhesion , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,membrane
    text detected exclusively in the distal tip of the connecting cilium in advance of outer segment formation
    basic FUNCTION
  • involved in stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim
  • RDS protein functions as an adhesion molecule for stabilization of the outer segment discs
  • RDS is essential for disk morphogenesis of cone and rod outer segments
  • couples rhodopsin to the CNG channel in outer segments of rod photoreceptors
  • is a critical component of the machinery necessary for the formation of rod and cone outer segments
  • role for PRPH2 as the core component of a multiprotein plasma membrane-rim-disc complex that has both a structural role in photoreceptor OS formation and maintenance and a functional role in orienting proteins for optimal signal transduction
  • photoreceptor tetraspanin, having a role as a functional protein key for organizing membrane domains for cellular signalling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
  • homodimer disulfide-linked
  • PRPH2 forms a complex with melanoregulin (MREG)
  • INTERACTION
    DNA
    RNA
    small molecule cofactor,
    protein
  • cGMP-gated channel - Na/Ca-K exchanger complex and soluble GARP proteins
  • assembles into heterotetrameric complexes with rod outer segment membrane protein 1, Rom1
  • cell & other
    REGULATION
    Other glycosylation of PRPH2 is required for its function or stability in cones, a difference that may be due to extracellular versus intradiscal localization of the PRPH2 glycan in cones versus rods
    ASSOCIATED DISORDERS
    corresponding disease(s) MDBS1 , RP7 , CACD2 , AVMD , CORD23 , LCA18
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in severe retinitis pigmentosa (rarely acting in a digenic mode of inheritance with ROM1)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • knockout mice carrying a homozygous null mutation in perhipherin/rds fail to develop photoreceptor outer segments
  • an insertion of a 9.2-kb repetitive genomic element into rds exon 2 is responsible for the murine Mouse "retinal degeneration, slow (rds)" defect
  • transgenic/knockout mice that duplicate the amino acid substitutions and predicted levels of rds and rom1 in patients with RDS-mediated digenic and dominant RP display a faster photoreceptor degeneration
  • transgenic/knockout mice that duplicate the amino acid substitutions and predicted levels of rds and rom1 in patients with RDS-mediated digenic and dominant RP exhibit photoreceptor degeneration by outer segment disorganization
  • Mice homozygous for the retinal degeneration slow (rds) mutation exhibit abnormal development of photoreceptor cells, followed by their slow degeneration
  • single base deletion at codon 307 of the rds-peripherin gene in mice have a more rapid retinopathy than that in the naturally occurring null mutant rds(-/-) mouse
  • R172W/rds(-/-) mice display cone-rod dystrophy
  • rhodopsin-knockout mice failed to create normal rod outer segments and instead, elaborated membranous protrusions at the distal cilium tip
  • subretinal injection of recombinant adeno-associated virus (AAV) encoding a Prph2 transgene in rds mice results in stable generation of outer segment structures and formation of new stacks of discs containing both perpherin-2 and rhodopsin