SCRIB
Function
Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:16965391, PubMed:18641685, PubMed:18716323, PubMed:19041750, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Plays a role in cell directional movement, cell orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May regulate cell invasion via MAPK-mediated cell migration and adhesion (PubMed:18641685, PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity (PubMed:15182672).
Involvement in disease
Neural tube defects
NTD
Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated; targeted for UBE3A-dependent multiubiquitination in the presence of high-risk HPV E6 proteins and degraded.
Palmitoylated (PubMed:27380321). Could be depalmitoylated by LYPLA1 and/or LYPLA2 (PubMed:27380321). Palmitoylation of SCRIB by ZDHHC7 is required for its localization to cell-cell junctions, function in the establishement of epithelial cell polarity and the regulation of downstream signaling pathways important for epithelial cell differentiation (PubMed:27380321).
Sequence Similarities
Belongs to the LAP (LRR and PDZ) protein family.
Tissue Specificity
Expressed in kidney, skeletal muscles, liver, lung, breast, intestine, placenta and skin mainly in epithelial cells (at protein level).
Cellular localization
- Cell membrane
- Peripheral membrane protein
- Cell junction
- Cell junction
- Adherens junction
- Cell projection
- Lamellipodium
- Cytoplasm
- Postsynapse
- Presynapse
- Targeting to cell-cell junctions which is CDH1-dependent is required for the pro-apoptotic activity. In a subset of CD4+ T-cells, colocalizes with CRTAM at the immunological synapse during the late phase of T-cell activation (By similarity). Localized to small puncta throughout the cytoplasm and cell membrane when in the presence of SNAIL1 (By similarity). Localized along the length of perinuclear emanating vimentin bundles and at vimentin-positive fibrils at the cell periphery (PubMed:19386766). Localized to the lateral plasma membrane during the establishment and maturation of cell-cell contacts (PubMed:19386766).
Alternative names
CRIB1, KIAA0147, LAP4, SCRB1, VARTUL, SCRIB, Protein scribble homolog, Scribble, hScrib, Protein LAP4