Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol CRB1 contributors: mct/shn - updated : 14-03-2017
HGNC name crumbs homolog 1 (Drosophila)
HGNC id 2343
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon moderately Homo sapiens
Nervousbrain   highly Homo sapiens
Respiratorylung   moderately Homo sapiens
Skin/Tegumentskin   moderately Homo sapiens
Urinarykidney   moderately Homo sapiens
Visualeyeretina  highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Visualcone photoreceptor Homo sapiens
VisualMuller cell Homo sapiens
Visualrod photoreceptor Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal, pregnancy
Text brain, eye
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a signal sequence
  • 28 EGF-like-domains contained in four clusters
  • four laminin AG-like repeats or ALPS (agrin, laminin, perlecan slit) in its extracellular domain
  • a short intracellular domain including a juxtamembrane FERM-binding motif (FBM (FERM: 4.1, ezrin, radixin, moesin; Glu, glutamic acid)
  • a transmembrane domain
  • a C-terminal PDZ-binding motif (PBM) (Ling 2010)
  • N-linked glycosylation motifs in the extracellular domain
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to crumbs 1, Drosophila
    ortholog to Crb1, Mus musculus
    ortholog to CRB1, Pan troglodytes
    ortholog to crb1, Danio rerio
    ortholog to Crb1, Rattus norvegicus
    intraspecies paralog to CRB2 and CRB3
    Homologene
    FAMILY
  • CRUMBS family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm
    text
  • internal fragment of the photoreceptors
  • location in the retina to be adjacent to the outer limiting membrane, bordering on the subretinal space
  • apical transmembrane protein (Ling 2010)
  • basic FUNCTION
  • involved in the normal development of the retina through cell-cell interactions and in the regulation of apoptosis
  • maintenance of cell polarity in the retina (de Hollander 1999)
  • central regulator of stalk membrane biogenesis, potentially involved in the organization or polarity of retinal cells and required to maintaining integrity of the rapidly expanding zonula adherens during photoreceptor morphogenesis
  • a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain and essential for photoreceptor morphogenesis (Pellikka 2002)
  • essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina (Mehalow 2003)
  • maintenance of photoreceptor cell polarization and adhesion (van de Pavert 2004)
  • intracellular domain of CRB1 has a highly conserved role in organizing a macromolecular protein scaffold (Richard 2006)
  • required to regulate number and size of these Muller glia cell villi (van de Pavert 2007)
  • required for rhabdomere elongation and stalk membrane formation during photoreceptor morphogenesis (Ling 2010)
  • CRB1 and CRB2 suppress late progenitor pool expansion by regulating multiple proliferative signaling pathways
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text apical-basal cell polarity
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    upstream component of the Hippo signaling pathway (Ling 2010)
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associated with Lin-7 (Pals1 or Mpp5) and Mpp4 at the outer limiting membrane in the retina (van de Pavert 2004)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) LCA8 , RP12
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Crb1 natural mouse model (rd8) harbouring the deletion del35-39 display moderate rods an cones degeneration (Mehalow et al, 2003)
  • Crb1(-/-) mice completely lacking any functional Crb1 develop localized lesions where the integrity of the outer limiting membrane is lost and giant half rosettes are formed and exhibit delamination of the photoreceptor layer followed by neuronal cell death in the inner and outer nuclear layers of the retina (van de Pavert et al, 2004)
  • Loss of Crb1 in Mu¨ ller glia cells of Crb1-/- mice resulted in an irregular number and size of their apical villi (van de Pavert et al, 2007)
  • Crb1(C249W) mice showed loss of photoreceptors in the retina, relatively late compared with mice lacking Crb1 (van de Pavert et al, 2007)
  • Crb1-/- mouse retinae develop localized lesions, particularly in the inferior temporal quadrant of the mouse eye, after retinal development
  • spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia type 2 (MacTel 2), with a mutation in the Crb1 gene