MERL_HUMAN
Source:
PM23856902
PM22954596
Marked as 'Membrane associated protein'
Confidence:
medium (present in either hRBCD or BSc_CH or PM22954596)
Search PubMed for
(RBC AND this entry)
Gene names:
NF2
, SCH
Protein names and data:
MERL_HUMAN
, Merlin
, Moesin-ezrin-radixin-like protein; Neurofibromin-2; Schwannomerlin; Schwannomin
Lenght: 595 a.a.
Mass: 69690 Da
fasta formatted sequence
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.
Disease:
( OMIM:
101000
156240
162091
607379
)
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. Note=The disease is caused by mutations affecting the gene represented in this entry. Schwannomatosis (SCHWA) [MIM:162091]: 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. 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. Note=The disease may be caused by mutations affecting the gene represented in this entry.
Cellular location:
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.
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.
Genetic variants
46 - 46
L -> R (in vestibular schwannoma; loss of ability to interact with the CUL4A-RBX1- DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex). VAR_000809
62 - 62
F -> S (in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/ DCAF1 E3 ubiquitin-protein ligase complex). VAR_000810
77 - 77
M -> V (in NF2). VAR_043011
79 - 79
K -> E (in vestibular schwannoma). VAR_000811
96 - 96
Missing (in NF2 and in sporadic meningioma). VAR_000812
106 - 106
E -> G (in NF2). VAR_000813
117 - 117
L -> I (in sporadic meningioma). VAR_000814
119 - 119
Missing (in sporadic meningioma). VAR_000815
122 - 129
Missing (in sporadic meningioma). VAR_000816
133 - 133
C -> R (in NF2). VAR_065227
141 - 141
L -> P (in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/ DCAF1 E3 ubiquitin-protein ligase complex). VAR_043012
197 - 197
G -> C (in NF2). VAR_043013
219 - 219
V -> M (in vestibular schwannoma). VAR_000817
220 - 220
N -> Y (in NF2). VAR_000818
234 - 234
L -> R (in NF2 and in retinal hamartoma; severe). VAR_009123
273 - 273
I -> F (in breast ductal carcinoma). VAR_000819
339 - 339
L -> F (in sporadic meningioma). VAR_000820
344 - 344
Q -> H (in dbSNP:rs2229064). VAR_048358
2229064
351 - 351
R -> H. VAR_029041
352 - 352
T -> M (in NF2). VAR_000821
360 - 360
L -> P (in NF2). VAR_000822
364 - 364
K -> I (in melanoma). VAR_000823
413 - 413
K -> E (in NF2). VAR_043014
418 - 418
R -> C (in vestibular schwannoma). VAR_000824
463 - 463
E -> K (in a breast cancer sample; somatic mutation). VAR_035848
533 - 533
K -> T (in NF2). VAR_043015
535 - 535
L -> P (in NF2; late onset). VAR_000825
538 - 538
Q -> P (in NF2; mild). VAR_000826
539 - 539
L -> H (in NF2). VAR_043016
579 - 579
K -> M (in NF2). VAR_043017
Database cross-references
UniProt:
P35240
Ensembl:
ENST00000334961
Ensembl:
ENST00000338641
Ensembl:
ENST00000347330
Ensembl:
ENST00000353887
Ensembl:
ENST00000361166
Ensembl:
ENST00000361452
Ensembl:
ENST00000361676
Ensembl:
ENST00000397789
Ensembl:
ENST00000403435
Ensembl:
ENST00000403999
Ensembl:
ENST00000413209
Ensembl:
ENST00000432151
MIM:
101000
MIM:
156240
MIM:
162091
MIM:
607379
neXtProt:
NX_P35240
Antibodypedia:
P35240
(may not find the protein thus also not any antibody)
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