Merlin (NF2)
The protein contains 595 amino acids for an estimated molecular weight of 69690 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton organization
Cell-cell junction organization
Ectoderm development
Hippocampus development
Lens fiber cell differentiation
Mesoderm formation
Negative regulation of cell migration
Negative regulation of cell population proliferation
Negative regulation of cell-cell adhesion
Negative regulation of cell-matrix adhesion
Negative regulation of DNA replication
Negative regulation of MAPK cascade
Negative regulation of protein kinase activity
Negative regulation of receptor signaling pathway via JAK-STAT
Negative regulation of tyrosine phosphorylation of STAT protein
Negative regulation of tyrosine phosphorylation of Stat3 protein
Negative regulation of tyrosine phosphorylation of Stat5 protein
Odontogenesis of dentin-containing tooth
Positive regulation of cell differentiation
Positive regulation of stress fiber assembly
Regulation of apoptotic process
Regulation of cell cycle
Regulation of gliogenesis
Regulation of hippo signaling
Regulation of neural precursor cell proliferation
Regulation of protein localization to nucleus
Regulation of protein stability
Regulation of stem cell proliferation
Schwann cell proliferation
Cellular Component
Adherens junction
Apical part of cell
Cell body
Cleavage furrow
Cortical actin cytoskeleton
Cytoplasm
Cytoskeleton
Cytosol
Early endosome
Extrinsic component of membrane
Filopodium membrane
Lamellipodium
Membrane
Neuron projection
Nucleolus
Nucleus
Perinuclear region of cytoplasm
Plasma membrane
Ruffle membrane
The reference OMIM entry for this protein is 101000
Neurofibromatosis, type ii; nf2
Neurofibromatosis, central type
Acoustic schwannomas, bilateral
Bilateral acoustic neurofibromatosis; banf
Acoustic neurinoma, bilateral; acn
A number sign (#) is used with this entry because neurofibromatosis type II is caused by mutation in the gene encoding neurofibromin-2 (NF2; 607379), which is also called merlin, on chromosome 22q12.2.
DESCRIPTION
The central or type II form of neurofibromatosis (NF2) is an autosomal dominant multiple neoplasia syndrome characterized by tumors of the eighth cranial nerve (usually bilateral), meningiomas of the brain, and schwannomas of the dorsal roots of the spinal cord. The incidence of neurofibromatosis type II is 1 in 25,000 live births (Asthagiri et al., 2009). NF2 has few of the hallmarks of the peripheral or type I form of neurofibromatosis (NF1; 162200), also known as von Recklinghausen disease. Asthagiri et al. (2009) provided a detailed review of neurofibromatosis type II.CLINICAL FEATURES
Gardner and Frazier (1933) reported a family of 5 generations in which 38 members were deaf because of bilateral acoustic neuromas; of these, 15 later became blind. The average age at onset of deafness was 20 years. The average age at death of affected persons in the second generation was 72, in the third generation 63, in the fourth 42, and in the fifth 28. Follow-up of this family (Gardner and Turner, 1940; Young et al., 1970) revealed no evidence of the systemic manifestations of neurofibromatosis I (NF1; 162200), also known as von Recklinghausen disease. Other families with no evidence of the latter disease were reported by Worster-Drought et al. (1937), Feiling and Ward (1920), and Moyes (1968). Worster-Drought et al. (1937) pointed out that Wishart (1822) was the first to report a case of bilateral acoustic neuroma. Wishart's patient, Michael Blair, was 21 years old when he consulted Mr. Wishart, president of the Royal College of Surgeons of Edinburgh, because of bilateral deafness. He had a peculiarly shaped head from infancy, and blindness in the right eye was discovered at about 4 months after birth. He became completely blind and deaf toward the end of his life. Autopsy revealed tumors of the dura mater and brain and also a 'tumour of the size of a small nut, and very hard, being attached to each of them (auditory nerves), just where they enter the meatus auditorius internus.' Nager (1969) showed that in about 4% of cases acoustic neuroma is bilateral. In addition to their autosomal dominant inheritance and association with neurofibromatosis, bilateral tumors differ from unilateral ones in that they can reach a remarkably large size with extensive involvement of the temporal bone and the nerves therein. Fabricant et al. (1979) reported that more than 30 kindreds with 'central neurofibromatosis' had been described. Most patients with the central form (NF2) have no cafe-au-lait spots or peripheral neurofibromata, and no patients in one large series had 6 or more cafe-au-lait spots (Eldridge, 1981). Kanter et al. (1980), who reviewed 9 personally studied kindreds and 15 reported ones, with a total of 130 cases, showed an increase only in antigenic activity of nerve growth factor (NGF; 162030) in central neurofibromatosis and only in functional activity in peripheral neurofibromatosis. In a series reported by Mrazek et al. (1988), 1 of 41 acoustic neurinoma cases was bilateral. This was in a 10-year-old girl with von Recklinghausen neurofibromatosis, whose first tumor had been diagnosed at age 6. Mayfrank et al. (1990) studied 10 patients with NF2 and found that all were sporadic cases, each presumably the result ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 101000 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed