Homo sapiens Protein: NF2 | |||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||
InnateDB Protein | IDBP-371161.5 | ||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||
Gene Symbol | NF2 | ||||||||||||||||||||||||
Protein Name | neurofibromin 2 (merlin) | ||||||||||||||||||||||||
Synonyms | ACN; BANF; SCH; | ||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||
Ensembl Protein | ENSP00000409921 | ||||||||||||||||||||||||
InnateDB Gene | IDBG-3678 (NF2) | ||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||
Function | 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. {ECO:0000269PubMed:20159598, ECO:0000269PubMed:20178741}. | ||||||||||||||||||||||||
Subcellular Localization | Isoform 1: Cell projection, filopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. Note=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.Isoform 7: Cytoplasm, perinuclear region. Cytoplasmic granule. Note=Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia.Isoform 9: Cytoplasm, perinuclear region. Cytoplasmic granule. Note=Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia.Isoform 10: Nucleus. Cell projection, filopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, perinuclear region. Cytoplasmic granule. Cytoplasm, cytoskeleton. Note=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. | ||||||||||||||||||||||||
Disease Associations | Neurofibromatosis 2 (NF2) [MIM:101000]: 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. {ECO:0000269PubMed:10090912, ECO:0000269PubMed:10790209, ECO:0000269PubMed:12709270, ECO:0000269PubMed:20445339, ECO:0000269PubMed:7666400, ECO:0000269PubMed:7759081, ECO:0000269PubMed:7913580, ECO:0000269PubMed:8081368, ECO:0000269PubMed:8230593, ECO:0000269PubMed:8566958, ECO:0000269PubMed:8698340, ECO:0000269PubMed:9643284}. Note=The disease is caused by mutations affecting the gene represented in this entry.Schwannomatosis 1 (SWNTS1) [MIM:162091]: A cancer syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves. {ECO:0000269PubMed:18072270}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle- shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. {ECO:0000269PubMed:12136076}. Note=The disease may be caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||||
Tissue Specificity | 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. | ||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 65 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||
InterPro |
IPR000299
FERM domain IPR000798 Ezrin/radixin/moesin like IPR018979 FERM, N-terminal IPR019748 FERM central domain IPR019749 Band 4.1 domain IPR019750 Band 4.1 family IPR029071 Ubiquitin-related domain |
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PFAM |
PF09379
PF00373 |
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PRINTS |
PR00661
PR00935 |
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PIRSF | |||||||||||||||||||||||||
SMART |
SM00295
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TIGRFAMs | |||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||
SwissProt | P35240 | ||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P35240 | ||||||||||||||||||||||||
TrEMBL | Q9NRW8 | ||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||
Entrez Gene | 4771 | ||||||||||||||||||||||||
UniGene | Hs.628119 | ||||||||||||||||||||||||
RefSeq | NP_861971 | ||||||||||||||||||||||||
HUGO | HGNC:7773 | ||||||||||||||||||||||||
OMIM | 607379 | ||||||||||||||||||||||||
CCDS | CCDS54516 | ||||||||||||||||||||||||
HPRD | 06980 | ||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||
EMBL | AF122827 AF122828 AF123570 AF165426 AF369657 AF369658 AF369661 AF369662 AF369663 AF369664 AF369665 AF369700 AF369701 BC003112 BC020257 CR456530 L11353 X72655 X72656 X72657 X72658 X72659 X72660 X72661 X72662 X72663 X72664 X72665 X72666 X72667 X72668 X72669 X72670 Y18000 Z22664 | ||||||||||||||||||||||||
GenPept | AAA36212 AAD48752 AAD48753 AAD48754 AAF80764 AAH03112 AAH20257 AAK54160 AAK54161 AAK54162 AAK54163 AAK54164 AAK54165 AAK54166 AAK54195 AAK54196 CAA51220 CAA76992 CAA76993 CAA80377 CAG30416 | ||||||||||||||||||||||||