ITGA6
The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
Full Name
Integrin Subunit Alpha 6
Function
Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (By similarity).
Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity).
Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity).
ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778).
ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760).
ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464).
Biological Process
Cell-substrate adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Cell-substrate junction assemblyManual Assertion Based On ExperimentTAS:ProtInc
Ectodermal cell differentiationManual Assertion Based On ExperimentIEP:UniProtKB
Integrin-mediated signaling pathwayIEA:UniProtKB-KW
Nail developmentManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of apoptotic processManual Assertion Based On ExperimentIGI:MGI
Positive regulation of cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of GTPase activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of neuron projection developmentISS:UniProtKB
Positive regulation of phosphorylationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:BHF-UCL
Skin morphogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Cellular Location
Cell membrane; Cell membrane
Involvement in disease
Epidermolysis bullosa letalis, with pyloric atresia (EB-PA):
An autosomal recessive, frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa.
Topology
Extracellular: 24-1050
Helical: 1051-1076
Cytoplasmic: 1077-1130
PTM
Isoforms containing segment A, but not segment B, are the major targets for PMA-induced phosphorylation. Phosphorylation occurs on 'Ser-1103' of isoform alpha-6X1X2A. Phosphorylation is not required for the induction of integrin alpha-6A/beta-1 high affinity but may reduce the affinity for ligand.
Undergoes PLAU-mediated cleavage at residues Arg-634-635-Arg in a time-dependent manner to produce processed integrin alpha-6 (alpha6p) (PubMed:11359780, PubMed:15023541, PubMed:17303120).
Production of alpha6p enhances prostate cancer cell invasion and migration (PubMed:17303120).
Palmitoylation by DHHC3 enhances stability and cell surface expression.
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Datasheet