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FLASH GENE
Symbol PRPH2 contributors: shn - updated : 02-02-2017
HGNC name peripherin 2 (retinal degeneration, slow)
HGNC id 9942
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