機能Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex.
組織特異性Widely expressed. Isoform 1 and isoform 3 are predominant. Isoform 4, isoform 5 and isoform 6 are expressed moderately. Isoform 8 is found at low frequency. Isoform 7, isoform 9 and isoform 10 are not expressed in adult tissues, with the exception of adult retina expressing isoform 10. Isoform 9 is faintly expressed in fetal brain, heart, lung, skeletal muscle and spleen. Fetal thymus expresses isoforms 1, 7, 9 and 10 at similar levels.
関連疾患Defects in NF2 are the cause of neurofibromatosis 2 (NF2) [MIM:101000]; also known as central neurofibromatosis. NF2 is a genetic disorder characterized by bilateral vestibular schwannomas (formerly called acoustic neuromas), schwannomas of other cranial and peripheral nerves, meningiomas, and ependymomas. It is inherited in an autosomal dominant fashion with full penetrance. Affected individuals generally develop symptoms of eighth-nerve dysfunction in early adulthood, including deafness and balance disorder. Although the tumors of NF2 are histologically benign, their anatomic location makes management difficult, and patients suffer great morbidity and mortality. Defects in NF2 are a cause of schwannomatosis (SCHWA) [MIM:162091]; also known as congenital cutaneous neurilemmomatosis. Schwannomas are benign tumors of the peripheral nerve sheath that usually occur singly in otherwise normal individuals. Multiple schwannomas in the same individual suggest an underlying tumor-predisposition syndrome. The most common such syndrome is NF2. The hallmark of NF2 is the development of bilateral vestibular-nerve schwannomas; but two-thirds or more of all NF2-affected individuals develop schwannomas in other locations, and dermal schwannomas may precede vestibular tumors in NF2-affected children. There have been several reports of individuals with multiple schwannomas who do not show evidence of vestibular schwannoma. Clinical report suggests that schwannomatosis is a clinical entity distinct from other forms of neurofibromatosis.
配列類似性Contains 1 FERM domain.
翻訳後修飾Phosphorylation of Ser-518 inhibits nuclear localization by disrupting the intramolecular association of the FERM domain with the C-terminal tail. Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-protein ligase complex for ubiquitination and subsequent proteasome-dependent degradation.
細胞内局在Cytoplasm > perinuclear region. Cytoplasmic granule. Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia; Cytoplasm > perinuclear region. Cytoplasmic granule. Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia; Nucleus. Cell projection > filopodium membrane. Cell projection > ruffle membrane. Cytoplasm > perinuclear region. Cytoplasmic granule. Cytoplasm > cytoskeleton. In a fibroblastic cell line, isoform 10 is found homogeneously distributed over the entire cell, with a particularly strong staining in ruffling membranes and filopodia and Cell projection > filopodium membrane. Cell projection > ruffle membrane. Nucleus. In a fibroblastic cell line, isoform 1 is found homogeneously distributed over the entire cell, with a particularly strong staining in ruffling membranes and filopodia. Colocalizes with MPP1 in non-myelin-forming Schwann cells. Binds with VPRBP in the nucleus. The intramolecular association of the FERM domain with the C-terminal tail promotes nuclear accumulation. The unphosphorylated form accumulates predominantly in the nucleus while the phosphorylated form is largely confined to the non-nuclear fractions.
Western blot - Anti-NF2 / Merlin antibody [EPR2573(2)] (ab109244)
Predicted band size : 70 kDa Additional bands at : 70 kDa. We are unsure as to the identity of these extra bands.
Lane 1: Wild-type HAP1 cell lysate (20 µg) Lane 2: NF2 / Merlin knockout HAP1 cell lysate (20 µg) Lane 3: MCF7 cell lysate (20 µg) Lane 4: Jurkat cell lysate(20 µg) Lanes 1 - 4: Merged signal (red and green). Green - ab109244 observed at 70 kDa. Red - loading control, ab2XXX, observed at 37 kDa.
ab109244 was shown to specifically react with NF2 / Merlin when NF2 / Merlin knockout samples were used. Wild-type and NF2 / Merlin knockout samples were subjected to SDS-PAGE. ab109244 and ab8245 (loading control to GAPDH) were diluted to 1/50000 and 1/10000 respectively and incubated overnight at 4°C. Blots were developed with goat anti-rabbit IgG (H + L) and goat anti-mouse IgG (H + L) secondary antibodies at 1/10000 dilution for 1 hour at room temperature before imaging.
Western blot - NF2 / Merlin antibody [EPR2573(2)] (ab109244)
All lanes : Anti-NF2 / Merlin antibody [EPR2573(2)] (ab109244) at 1/50000 dilution
Lane 1 : HeLa cell lysate Lane 2 : MCF7 cell lysate Lane 3 : Jurkat cell lysate Lane 4 : PC3 cell lysate