CRB2
Function
Apical polarity protein that plays a central role during the epithelial-to-mesenchymal transition (EMT) at gastrulation, when newly specified mesodermal cells move inside the embryo (By similarity). Acts by promoting cell ingression, the process by which cells leave the epithelial epiblast and move inside the embryo to form a new tissue layer (By similarity). The anisotropic distribution of CRB2 and MYH10/myosin-IIB at cell edges define which cells will ingress: cells with high apical CRB2 are probably extruded from the epiblast by neighboring cells with high levels of apical MYH10/myosin-IIB (By similarity). Plays a role in the maintenance of retinal neuroepithelium organization, structural integrity, adhesion, photoreceptor polarity and retinal photoreceptor layer thickness (By similarity). May play a role in determining the length of cone photoreceptor outer segments and proliferation of late-born progenitor cells (By similarity). Also required for maintenance of the apical polarity complex during development of the cortex (By similarity). Inhibits gamma-secretase-dependent cleavage of APP and secretion of amyloid-beta peptide 40 and amyloid-beta peptide 42, and thereby inhibits gamma-secretase-dependent Notch transcription (PubMed:20299451).
Involvement in disease
Focal segmental glomerulosclerosis 9
FSGS9
A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.
None
The disease is caused by variants affecting the gene represented in this entry.
Retinitis pigmentosa
RP
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Retinitis pigmentosa can be inherited as an autosomal dominant, autosomal recessive or X-linked condition.
None
Disease susceptibility may be associated with variants affecting the gene represented in this entry.
Ventriculomegaly with cystic kidney disease
VMCKD
A severe autosomal recessive developmental disorder manifesting in utero. It is characterized by cerebral ventriculomegaly, echogenic kidneys, microscopic renal tubular cysts and findings of congenital nephrosis.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
O-glucosylated by POGLUT1 at Ser-267; consists of an O-glucose trisaccharide, in which the O-glucose is elongated by the addition of two xylose residues. O-glucosylation is required for localization at the plasma membrane.
N-glycosylated.
Sequence Similarities
Belongs to the Crumbs protein family.
Tissue Specificity
Expressed in glomeruli, podocytes of the glomerular capillary loops, and parietal glomerular epithelial cells in the kidney (at protein level) (PubMed:27942854, PubMed:29473663). Expressed in retina, fetal eye and brain (PubMed:15851977). Also expressed in kidney, RPE/choroid, and at low levels in lung, placenta, and heart (PubMed:15851977).
Cellular localization
- Isoform 1
- Apical cell membrane
- Single-pass type I membrane protein
- Cytoplasm
- Cell junction
- O-glucosylation is required for localization at the apical plasma membrane (By similarity). Distributed in a complex anisotropic pattern on apical cell edges: the level of CRB2 on a cell edge is inversely correlated with the level of MYH10/myosin-IIB (By similarity).
- Isoform 2
- Secreted
Alternative names
Protein crumbs homolog 2, Crumbs-like protein 2, CRB2