Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development. Interacts with EGFR (By similarity). Interacts with ERBB2. Associated with the plasma membrane of basal skin keratinocytes. Translocates into the nucleus of differentiating suprabasal keratinocytes. Detected in lung, in airway epithelial cells and alveolar type 2 cells (at protein level). Detected in uterus stroma, luminal epithelium and glandular epithelium. Detected at low levels during embryogenesis. Strongly up-regulated during the first days after birth. Levels are increased on the first day after birth, and culminate three days after birth. Detected at low levels four days after birth, and throughout the remaining life span. Up-regulated by lysophosphatidic acid (LPA) and sphingosine 1-phosphate. Up-regulated by globular actin monomers, via MKL1 signaling. Up-regulated in uterus in response to progesterone. Up-regulated in uterus in response to estrogen. Up-regulated in pregnant uterus. The EGFR-binding region prevents binding of a cyclin-like activator to the EGFR kinase domain, and thereby keeps EGFR in an inactive conformation. Also maintains EGFR in an inactive conformation by preventing formation of an asymmetric homodimer (By similarity). Embryos are present at the expected Mendelian ratio, but half of the mice die before adolescence, due to defects in prenatal and perinatal lung development. In the 15.5 dpc embryo, lungs are smaller, have a less complex structure than normal, and present fewer blood vessels. Lungs in newborns present abnormal patterns of cell proliferation and apoptosis. Adults develop chronic obstructive pulmonary disease (COPD). Mice present epidermal hyperplasia with thickening and flaking skin and ulcerations on tail and footpads. Papillomas develop at sites of wounding. Mice are highly susceptible to chemical carcinogens and develop melanomas and/or papillomas after application of a carcinogen. They have a high incidence of spontaneous hyperplastic and neoplastic lesions, such as adenocarcinomas or squamous cell carcinomas. They present bone and cartilage hyperplasia, leading to fixed joints. Mice have altered response to progesterone in the uterus, resulting in endometrial epithelial hyperplasia and complete loss of fertility. Mice have a shortened life span and die prematurely at an age of five to seven months. Belongs to the MIG6 family.