UniProt:P35240 NF2

chain
  • chain:1-595
checksum B1A1BF2BD5DA561C
comment
  • 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.SUBUNIT Interacts with NHERF1, HGS and AGAP2. Interacts with LAYN (By similarity). Interacts with SGSM3. Interacts (via FERM domain) with MPP1. Interacts with WWC1. Interacts with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. The unphosphorylated form interacts (via FERM domain) with VPRBP/DCAF1. Interacts (via FERM domain) with NOP53; the interaction is direct (PubMed:21167305). Interacts with SCHIP1; the interaction is direct (PubMed:10669747).INTERACTION 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 DCAF1 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.SUBCELLULAR LOCATION Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia.SUBCELLULAR LOCATION Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia.SUBCELLULAR LOCATION 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.ALTERNATIVE PRODUCTS 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.PTM Phosphorylation of Ser-518 inhibits nuclear localization by disrupting the intramolecular association of the FERM domain with the C-terminal tail (PubMed:20178741). The dephosphorylation of Ser-518 favors the interaction with NOP53 (PubMed:21167305).PTM Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-protein ligase complex for ubiquitination and subsequent proteasome-dependent degradation.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease may be caused by variants affecting the gene represented in this entry.
crossReference
databaseName UniProt
dbId 59165
description
  • recommendedName: Merlin alternativeName: Moesin-ezrin-radixin-like protein alternativeName: Neurofibromin-2 alternativeName: Schwannomerlin alternativeName: Schwannomin
displayName UniProt:P35240 NF2
geneName
  • NF2
  • SCH
identifier P35240
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Cell membrane
  • Cell projection
  • Cytoplasm
  • Cytoskeleton
  • Deafness
  • Disease variant
  • Membrane
  • Nucleus
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Tumor suppressor
  • Ubl conjugation
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • NF2
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • MERL_HUMAN
  • O95683
  • Q8WUJ2
  • Q969N0
  • Q969Q3
  • Q96T30
  • Q96T31
  • Q96T32
  • Q96T33
  • Q9BTW3
  • Q9UNG9
  • Q9UNH3
  • Q9UNH4
sequenceLength 595
species [Species:48887] Homo sapiens
stId uniprot:P35240
url http://purl.uniprot.org/uniprot/P35240

Referrals

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