InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NF2

Summary

InnateDB Protein

IDBP-3682.6

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

ENSP00000344666

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.

Experimentally validated
Total	65 [view]
Protein-Protein	64 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0005515	protein binding
GO:0008092	cytoskeletal protein binding

Biological Process

GO:0001707	mesoderm formation
GO:0001953	negative regulation of cell-matrix adhesion
GO:0006469	negative regulation of protein kinase activity
GO:0007398	ectoderm development
GO:0007420	brain development
GO:0008156	negative regulation of DNA replication
GO:0008285	negative regulation of cell proliferation
GO:0014010	Schwann cell proliferation
GO:0021766	hippocampus development
GO:0022408	negative regulation of cell-cell adhesion
GO:0030036	actin cytoskeleton organization
GO:0030336	negative regulation of cell migration
GO:0031647	regulation of protein stability
GO:0035330	regulation of hippo signaling
GO:0042127	regulation of cell proliferation
GO:0042475	odontogenesis of dentin-containing tooth
GO:0042518	negative regulation of tyrosine phosphorylation of Stat3 protein
GO:0042524	negative regulation of tyrosine phosphorylation of Stat5 protein
GO:0043409	negative regulation of MAPK cascade
GO:0045216	cell-cell junction organization
GO:0045597	positive regulation of cell differentiation
GO:0046426	negative regulation of JAK-STAT cascade
GO:0051496	positive regulation of stress fiber assembly
GO:0070306	lens fiber cell differentiation
GO:1900180	regulation of protein localization to nucleus
GO:2000177	regulation of neural precursor cell proliferation

Cellular Component

GO:0001726	ruffle
GO:0005634	nucleus
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005769	early endosome
GO:0005856	cytoskeleton
GO:0005886	plasma membrane
GO:0005912	adherens junction
GO:0016020	membrane
GO:0019898	extrinsic component of membrane
GO:0030027	lamellipodium
GO:0030175	filopodium
GO:0030864	cortical actin cytoskeleton
GO:0031527	filopodium membrane
GO:0032154	cleavage furrow
GO:0032587	ruffle membrane
GO:0045177	apical part of cell
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000299 FERM domain
IPR000533 Tropomyosin
IPR000798 Ezrin/radixin/moesin like
IPR008954 Moesin tail domain
IPR011174 Ezrin/radixin/moesin
IPR011259 Ezrin/radixin/moesin, C-terminal
IPR018979 FERM, N-terminal
IPR018980 FERM, C-terminal PH-like domain
IPR019748 FERM central domain
IPR019749 Band 4.1 domain
IPR019750 Band 4.1 family
IPR029071 Ubiquitin-related domain

PFAM

PF00261
PF12718
PF00769
PF09379
PF09380
PF00373

PRINTS

PR00194
PR00661
PR00935

PIRSF

PIRSF002305

SMART

SM00295

TIGRFAMs

Post-translational Modifications

Modification

Cross-References