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P35240 (MERL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Merlin
Alternative name(s):
Moesin-ezrin-radixin-like protein
Neurofibromin-2
Schwannomerlin
Schwannomin
Gene names
Name:NF2
Synonyms:SCH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length595 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.18 Ref.19

Subunit structure

Interacts with SLC9A3R1, 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. Ref.9 Ref.10 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.20

Subcellular location

Isoform 1: Cell projectionfilopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projectionruffle 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. Ref.4 Ref.17 Ref.18

Isoform 7: Cytoplasmperinuclear region. Cytoplasmic granule. Note: Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia. Ref.4 Ref.17 Ref.18

Isoform 9: Cytoplasmperinuclear region. Cytoplasmic granule. Note: Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia. Ref.4 Ref.17 Ref.18

Isoform 10: Nucleus. Cell projectionfilopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projectionruffle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmperinuclear region. Cytoplasmic granule. Cytoplasmcytoskeleton. 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. Ref.4 Ref.17 Ref.18

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.

Post-translational modification

Phosphorylation of Ser-518 inhibits nuclear localization by disrupting the intramolecular association of the FERM domain with the C-terminal tail.

Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-protein ligase complex for ubiquitination and subsequent proteasome-dependent degradation. Ref.15

Involvement in disease

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. Ref.18 Ref.23 Ref.24 Ref.27 Ref.30 Ref.31 Ref.32 Ref.34 Ref.35 Ref.37 Ref.38 Ref.39 Ref.42

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. Ref.41

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. Ref.11

Sequence similarities

Contains 1 FERM domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDeafness
Disease mutation
Tumor suppressor
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSchwann cell proliferation

Inferred from mutant phenotype PubMed 17353411. Source: HGNC

actin cytoskeleton organization

Inferred from mutant phenotype PubMed 9537418. Source: HGNC

cell-cell junction organization

Inferred from electronic annotation. Source: Ensembl

ectoderm development

Inferred from electronic annotation. Source: Ensembl

lens fiber cell differentiation

Inferred from electronic annotation. Source: Ensembl

mesoderm formation

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA replication

Inferred from mutant phenotype PubMed 17210637. Source: HGNC

negative regulation of JAK-STAT cascade

Inferred from direct assay PubMed 12444102. Source: HGNC

negative regulation of MAPK cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell migration

Traceable author statement PubMed 17210637. Source: HGNC

negative regulation of cell proliferation

Inferred from direct assay Ref.18. Source: UniProtKB

negative regulation of cell-cell adhesion

Inferred from direct assay PubMed 17210637. Source: HGNC

negative regulation of cell-matrix adhesion

Traceable author statement PubMed 17210637. Source: HGNC

negative regulation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of tyrosine phosphorylation of Stat3 protein

Inferred from direct assay PubMed 12444102. Source: HGNC

negative regulation of tyrosine phosphorylation of Stat5 protein

Inferred from direct assay PubMed 12444102. Source: HGNC

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

positive regulation of stress fiber assembly

Inferred from mutant phenotype PubMed 9537418. Source: HGNC

regulation of hippo signaling

Inferred from mutant phenotype Ref.19. Source: UniProtKB

   Cellular_componentadherens junction

Inferred from electronic annotation. Source: Ensembl

cleavage furrow

Inferred from electronic annotation. Source: Ensembl

cortical actin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 9537418. Source: HGNC

cytoskeleton

Traceable author statement Ref.2. Source: ProtInc

early endosome

Inferred from direct assay Ref.10. Source: HGNC

extrinsic component of membrane

Inferred from electronic annotation. Source: InterPro

filopodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lamellipodium

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from direct assay PubMed 9537418. Source: HGNC

nucleus

Inferred from direct assay Ref.4Ref.18. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay PubMed 17210637. Source: HGNC

plasma membrane

Inferred from direct assay Ref.4. Source: UniProtKB

ruffle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Alternative products

This entry describes 10 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P35240-1)

Also known as: I;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P35240-2)

The sequence of this isoform differs from the canonical sequence as follows:
     580-595: LTLQSAKSRVAFFEEL → SSPRQKTYLHLSPQSRLFPGTLYVVMLYVVMVLPSVILTRA
Isoform 3 (identifier: P35240-3)

Also known as: II;

The sequence of this isoform differs from the canonical sequence as follows:
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.
Isoform 4 (identifier: P35240-4)

Also known as: delE2/3;

The sequence of this isoform differs from the canonical sequence as follows:
     39-121: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.
Isoform 5 (identifier: P35240-5)

Also known as: delE3;

The sequence of this isoform differs from the canonical sequence as follows:
     81-121: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.
Isoform 6 (identifier: P35240-6)

Also known as: delE2;

The sequence of this isoform differs from the canonical sequence as follows:
     39-80: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.
Isoform 7 (identifier: P35240-7)

Also known as: MER150;

The sequence of this isoform differs from the canonical sequence as follows:
     259-259: N → R
     260-595: Missing.
Isoform 8 (identifier: P35240-8)

The sequence of this isoform differs from the canonical sequence as follows:
     335-363: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.
Isoform 9 (identifier: P35240-9)

Also known as: MER162;

The sequence of this isoform differs from the canonical sequence as follows:
     150-579: Missing.
Isoform 10 (identifier: P35240-10)

Also known as: MER151;

The sequence of this isoform differs from the canonical sequence as follows:
     39-121: Missing.
     150-225: Missing.
     334-379: MERQRLAREK...ANEALMRSEE → GQRGRSAEAG...HEPNSSTVAS
     380-595: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 595595Merlin
PRO_0000219412

Regions

Domain22 – 311290FERM
Compositional bias327 – 465139Glu-rich

Amino acid modifications

Modified residue5181Phosphoserine; by PAK Ref.14

Natural variations

Alternative sequence39 – 12183Missing in isoform 4 and isoform 10.
VSP_007041
Alternative sequence39 – 8042Missing in isoform 6.
VSP_007040
Alternative sequence81 – 12141Missing in isoform 5.
VSP_007042
Alternative sequence150 – 579430Missing in isoform 9.
VSP_007044
Alternative sequence150 – 22576Missing in isoform 10.
VSP_007043
Alternative sequence2591N → R in isoform 7.
VSP_007045
Alternative sequence260 – 595336Missing in isoform 7.
VSP_007046
Alternative sequence334 – 37946MERQR…MRSEE → GQRGRSAEAGPAGSTRGGAK SQAEAPGDCHQAHVPAHEPN SSTVAS in isoform 10.
VSP_007047
Alternative sequence335 – 36329Missing in isoform 8.
VSP_007048
Alternative sequence380 – 595216Missing in isoform 10.
VSP_007049
Alternative sequence580 – 59516LTLQS…FFEEL → SSPRQKTYLHLSPQSRLFPG TLYVVMLYVVMVLPSVILTR A in isoform 2.
VSP_000492
Alternative sequence580 – 59011LTLQSAKSRVA → PQAQGRRPICI in isoform 3, isoform 4, isoform 5, isoform 6 and isoform 8.
VSP_007050
Alternative sequence591 – 5955Missing in isoform 3, isoform 4, isoform 5, isoform 6 and isoform 8.
VSP_007051
Natural variant461L → R in vestibular schwannoma; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. Ref.18 Ref.25
VAR_000809
Natural variant621F → S in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. Ref.18 Ref.27 Ref.35 Ref.38
VAR_000810
Natural variant771M → V in NF2. Ref.35
VAR_043011
Natural variant791K → E in vestibular schwannoma. Ref.28
VAR_000811
Natural variant961Missing in NF2 and in sporadic meningioma. Ref.24 Ref.33
VAR_000812
Natural variant1061E → G in NF2. Ref.27 Ref.35
VAR_000813
Natural variant1171L → I in sporadic meningioma.
VAR_000814
Natural variant1191Missing in sporadic meningioma.
VAR_000815
Natural variant122 – 1298Missing in sporadic meningioma.
VAR_000816
Natural variant1331C → R in NF2. Ref.42
VAR_065227
Natural variant1411L → P in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. Ref.18 Ref.39
VAR_043012
Natural variant1971G → C in NF2. Ref.34
VAR_043013
Natural variant2191V → M in vestibular schwannoma. Ref.26
VAR_000817
Natural variant2201N → Y in NF2. Ref.23
VAR_000818
Natural variant2341L → R in NF2 and in retinal hamartoma; severe. Ref.37
VAR_009123
Natural variant2731I → F in breast ductal carcinoma. Ref.29
VAR_000819
Natural variant3391L → F in sporadic meningioma.
VAR_000820
Natural variant3441Q → H.
Corresponds to variant rs2229064 [ dbSNP | Ensembl ].
VAR_048358
Natural variant3511R → H. Ref.28
VAR_029041
Natural variant3521T → M in NF2. Ref.27 Ref.35
VAR_000821
Natural variant3601L → P in NF2.
VAR_000822
Natural variant3641K → I in melanoma. Ref.29
VAR_000823
Natural variant4131K → E in NF2. Ref.30 Ref.35
VAR_043014
Natural variant4181R → C in vestibular schwannoma. Ref.26
VAR_000824
Natural variant4631E → K in a breast cancer sample; somatic mutation. Ref.40
VAR_035848
Natural variant5331K → T in NF2. Ref.38
VAR_043015
Natural variant5351L → P in NF2; late onset. Ref.30 Ref.31 Ref.35
VAR_000825
Natural variant5381Q → P in NF2; mild. Ref.32
VAR_000826
Natural variant5391L → H in NF2. Ref.34
VAR_043016
Natural variant5791K → M in NF2. Ref.38
VAR_043017

Experimental info

Mutagenesis641L → P: Abolishes binding to AGAP2 and interaction with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. Ref.13 Ref.18
Mutagenesis5181S → A: Loss of phosphorylation. Significant accumulation in the nucleus and no effect on binding to VPRBP. Ref.18
Mutagenesis5181S → D: No effect on phosphorylation. Defective nuclear accumulation. Significant decrease in binding to VPRBP and in ability to inhibit cell proliferation. Ref.18
Sequence conflict771M → I in AAH20257. Ref.7
Sequence conflict5811T → P in AAK54160. Ref.5
Sequence conflict5811T → P in AAK54162. Ref.5

Secondary structure

...................................................... 595
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (I) [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: B1A1BF2BD5DA561C

FASTA59569,690
        10         20         30         40         50         60 
MAGAIASRMS FSSLKRKQPK TFTVRIVTMD AEMEFNCEMK WKGKDLFDLV CRTLGLRETW 

        70         80         90        100        110        120 
FFGLQYTIKD TVAWLKMDKK VLDHDVSKEE PVTFHFLAKF YPENAEEELV QEITQHLFFL 

       130        140        150        160        170        180 
QVKKQILDEK IYCPPEASVL LASYAVQAKY GDYDPSVHKR GFLAQEELLP KRVINLYQMT 

       190        200        210        220        230        240 
PEMWEERITA WYAEHRGRAR DEAEMEYLKI AQDLEMYGVN YFAIRNKKGT ELLLGVDALG 

       250        260        270        280        290        300 
LHIYDPENRL TPKISFPWNE IRNISYSDKE FTIKPLDKKI DVFKFNSSKL RVNKLILQLC 

       310        320        330        340        350        360 
IGNHDLFMRR RKADSLEVQQ MKAQAREEKA RKQMERQRLA REKQMREEAE RTRDELERRL 

       370        380        390        400        410        420 
LQMKEEATMA NEALMRSEET ADLLAEKAQI TEEEAKLLAQ KAAEAEQEMQ RIKATAIRTE 

       430        440        450        460        470        480 
EEKRLMEQKV LEAEVLALKM AEESERRAKE ADQLKQDLQE AREAERRAKQ KLLEIATKPT 

       490        500        510        520        530        540 
YPPMNPIPAP LPPDIPSFNL IGDSLSFDFK DTDMKRLSME IEKEKVEYME KSKHLQEQLN 

       550        560        570        580        590 
ELKTEIEALK LKERETALDI LHNENSDRGG SSKHNTIKKL TLQSAKSRVA FFEEL 

« Hide

Isoform 2 [UniParc].

Checksum: 6A462A3A113A6C28
Show »

FASTA62072,514
Isoform 3 (II) [UniParc].

Checksum: 99B732B48367D22A
Show »

FASTA59069,090
Isoform 4 (delE2/3) [UniParc].

Checksum: DD8162ABBC9EA4CA
Show »

FASTA50759,096
Isoform 5 (delE3) [UniParc].

Checksum: 905559E6F72D3F4C
Show »

FASTA54964,189
Isoform 6 (delE2) [UniParc].

Checksum: 58E15B35515C10EE
Show »

FASTA54863,996
Isoform 7 (MER150) [UniParc].

Checksum: 3C7B9CDBC884CDF6
Show »

FASTA25930,454
Isoform 8 [UniParc].

Checksum: 371C417ABDB68D02
Show »

FASTA56165,350
Isoform 9 (MER162) [UniParc].

Checksum: 01B92CD1AFEEB202
Show »

FASTA16519,215
Isoform 10 (MER151) [UniParc].

Checksum: 05961D105F94276E
Show »

FASTA22024,515

References

« Hide 'large scale' references
[1]"A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor."
Trofatter J.A., Maccollin M.M., Rutter J.L., Murrell J.R., Duyao M.P., Parry D.N., Eldridge R., Kley N., Menon A.G., Pulaski K., Haase V.H., Ambrose C.M., Munroe D., Bove C., Haines J.L., Martuza R.L., Macdonald M.E., Seizinger B.R. expand/collapse author list , Short M.P., Buckler A.J., Gusella J.F.
Cell 72:791-800(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2."
Rouleau G.A., Merel P., Lutchman M., Sanson M., Zucman J., Marineau C., Hoang-Xuan K., Demczuk S., Desmaze C., Plougastel B., Pulst S., Lenoir G., Bijlsma E., Fashold R., Dumanski J.P., de Jong P., Parry D., Eldrige R. expand/collapse author list , Aurias A., Delattre O., Thomas G.
Nature 363:515-521(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"NF2 gene in neurofibromatosis type 2 patients."
Zucman-Rossi J., Legoix P., Der Sarjussian H., Cheret G., Sor F., Bernardi A., Cazes L., Giraud S., Lenoir G., Thomas G.
Hum. Mol. Genet. 7:2095-2101(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[4]"Novel alternatively spliced isoforms of the neurofibromatosis type 2 tumor suppressor are targeted to the nucleus and cytoplasmic granules."
Schmucker B., Tang Y., Kressel M.
Hum. Mol. Genet. 8:1561-1570(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 7; 9 AND 10), SUBCELLULAR LOCATION.
[5]"Multiple transcription initiation sites, alternative splicing, and differential polyadenylation contribute to the complexity of human neurofibromatosis 2 transcripts."
Chang L.-S., Akhmametyeva E.M., Wu Y., Zhu L., Welling D.B.
Genomics 79:63-76(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4; 5; 6 AND 8).
[6]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
Tissue: Lung and Skin.
[8]"The gene of neurofibromatosis type 2."
Marineau C., Merel P., Rouleau G.A., Thomas G.
Medecine/Sciences 11:35-42(1995)
Cited for: REVIEW.
[9]"NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins."
Murthy A., Gonzalez-Agosti C., Cordero E., Pinney D., Candia C., Solomon F., Gusella J., Ramesh V.
J. Biol. Chem. 273:1273-1276(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC9A3R1.
[10]"The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate."
Scoles D.R., Huynh D.P., Chen M.S., Burke S.P., Gutmann D.H., Pulst S.-M.
Hum. Mol. Genet. 9:1567-1574(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HGS.
[11]"Neurofibromatosis 2 and malignant mesothelioma."
Baser M.E., De Rienzo A., Altomare D., Balsara B.R., Hedrick N.M., Gutmann D.H., Pitts L.H., Jackler R.K., Testa J.R.
Neurology 59:290-291(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MESOM.
[12]"MAP, a protein interacting with a tumor suppressor, merlin, through the run domain."
Lee I.K., Kim K.-S., Kim H., Lee J.Y., Ryu C.H., Chun H.J., Lee K.-U., Lim Y., Kim Y.H., Huh P.-W., Lee K.-H., Han S.-I., Jun T.-Y., Rha H.K.
Biochem. Biophys. Res. Commun. 325:774-783(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SGSM3.
[13]"Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L."
Rong R., Tang X., Gutmann D.H., Ye K.
Proc. Natl. Acad. Sci. U.S.A. 101:18200-18205(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AGAP2, MUTAGENESIS OF LEU-64.
[14]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation."
Huang J., Chen J.
Oncogene 27:4056-4064(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DCAF1, UBIQUITINATION.
[16]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Identification of erythrocyte p55/MPP1 as a binding partner of NF2 tumor suppressor protein/Merlin."
Seo P.-S., Quinn B.J., Khan A.A., Zeng L., Takoudis C.G., Hanada T., Bolis A., Bolino A., Chishti A.H.
Exp. Biol. Med. 234:255-262(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MPP1, SUBCELLULAR LOCATION.
[18]"Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus."
Li W., You L., Cooper J., Schiavon G., Pepe-Caprio A., Zhou L., Ishii R., Giovannini M., Hanemann C.O., Long S.B., Erdjument-Bromage H., Zhou P., Tempst P., Giancotti F.G.
Cell 140:477-490(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VPRBP AND THE CUL4A-RBX1-DDB1-VPRBP/DCAF1 E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, PHOSPHORYLATION, MUTAGENESIS OF LEU-64 AND SER-518, CHARACTERIZATION OF VARIANT ARG-46, CHARACTERIZATION OF VARIANTS NF2 SER-62 AND PRO-141.
[19]"Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded."
Yu J., Zheng Y., Dong J., Klusza S., Deng W.-M., Pan D.
Dev. Cell 18:288-299(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Kibra Is a regulator of the Salvador/Warts/Hippo signaling network."
Genevet A., Wehr M.C., Brain R., Thompson B.J., Tapon N.
Dev. Cell 18:300-308(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WWC1.
[21]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product."
Kang B.S., Cooper D.R., Devedjiev Y., Derewenda U., Derewenda Z.S.
Acta Crystallogr. D 58:381-391(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-313.
[23]"DNA diagnosis of neurofibromatosis 2. Altered coding sequence of the merlin tumor suppressor in an extended pedigree."
Maccollin M.M., Mohney T., Trofatter J.A., Wertelecki W., Ramesh V., Gusella J.F.
JAMA 270:2316-2320(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NF2 TYR-220.
[24]"Mutational analysis of patients with neurofibromatosis 2."
Maccollin M.M., Ramesh V., Jacoby L.B., Louis D.N., Rubio M.-P., Pulaski K., Trofatter J.A., Short M.P., Bove C., Eldridge R., Parry D.M., Gusella J.F.
Am. J. Hum. Genet. 55:314-320(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NF2 PHE-96 DEL.
[25]"Somatic NF2 gene mutations in familial and non-familial vestibular schwannoma."
Irving R.M., Moffat D.A., Hardy D.G., Barton D.E., Xuereb J.H., Maher E.R.
Hum. Mol. Genet. 3:347-350(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-46.
[26]"Exon scanning for mutation of the NF2 gene in schwannomas."
Jacoby L.B., Maccollin M.M., Louis D.N., Mohney T., Rubio M.-P., Pulaski K., Trofatter J.A., Kley N., Seizinger B.R., Ramesh V., Gusella J.F.
Hum. Mol. Genet. 3:413-419(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MET-219 AND CYS-418.
[27]"Germline mutations in the neurofibromatosis type 2 tumour suppressor gene."
Bourn D., Carter S.A., Mason S., Gareth D., Evans R., Strachan T.
Hum. Mol. Genet. 3:813-816(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NF2 SER-62; GLY-106 AND MET-352.
[28]"Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas."
Sainz J., Huynh D.P., Figueroa K., Ragge N.K., Baser M.E., Pulst S.M.
Hum. Mol. Genet. 3:885-891(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLU-79 AND HIS-351.
[29]"Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types."
Bianchi A.B., Hara T., Ramesh V., Gao J., Klein Szanto A.J., Morin F., Menon A.G., Trofatter J.A., Gusella J.F., Seizinger B.R., Kley N.
Nat. Genet. 6:185-192(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHE-273 AND ILE-364.
[30]"Eleven novel mutations in the NF2 tumour suppressor gene."
Bourn D., Evans G., Mason S., Tekes S., Trueman L., Strachan T.
Hum. Genet. 95:572-574(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NF2 PHE-119 DEL; GLU-413 AND PRO-535.
[31]"Diagnostic issues in a family with late onset type 2 neurofibromatosis."
Evans D.G.R., Bourn D., Wallace A., Ramsden R.T., Mitchell J.D., Strachan T.
J. Med. Genet. 32:470-474(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NF2 PRO-535.
[32]"A missense mutation in the NF2 gene results in moderate and mild clinical phenotypes of neurofibromatosis type 2."
Kluwe L., Mautner V.-F.
Hum. Genet. 97:224-227(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NF2 PRO-538.
[33]"Screening for mutations in the neurofibromatosis type 2 (NF2) gene in sporadic meningiomas."
de Vitis L.R., Tedde A., Vitelli F., Ammannati F., Mennonna P., Bigozzi U., Montali E., Papi L.
Hum. Genet. 97:632-637(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHE-96 DEL; ILE-117; PHE-119 DEL; 122-VAL--GLU-129 DEL AND PHE-339.
[34]"Mutational spectrum in the neurofibromatosis type 2 gene in sporadic and familial schwannomas."
Welling D.B., Guida M., Goll F., Pearl D.K., Glasscock M.E., Pappas D.G., Linthicum F.H., Rogers D., Prior T.W.
Hum. Genet. 98:189-193(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NF2 CYS-197 AND HIS-539.
[35]"Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations."
Evans D.G.R., Trueman L., Wallace A., Collins S., Strachan T.
J. Med. Genet. 35:450-455(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NF2 SER-62; VAL-77; GLY-106; MET-352; GLU-413 AND PRO-535.
[36]Erratum
Evans D.G., Trueman L., Wallace A., Collins S., Strachan T.
J. Med. Genet. 36:87-87(1999)
[37]"Germ-line NF2 mutations and disease severity in neurofibromatosis type 2 patients with retinal abnormalities."
Baser M.E., Kluwe L., Mautner V.-F.
Am. J. Hum. Genet. 64:1230-1233(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NF2 ARG-234.
[38]"Detection of novel NF2 mutations by an RNA mismatch cleavage method."
Faudoa R., Xue Z., Lee F., Baser M.E., Hung G.
Hum. Mutat. 15:474-478(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NF2 SER-62; THR-533 AND MET-579.
[39]"Preimplantation diagnosis for neurofibromatosis."
Verlinsky Y., Rechitsky S., Verlinsky O., Chistokhina A., Sharapova T., Masciangelo C., Levy M., Kaplan B., Lederer K., Kuliev A.
Reprod. BioMed. Online 4:218-222(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NF2 PRO-141.
[40]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-463.
[41]"Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas."
Sestini R., Bacci C., Provenzano A., Genuardi M., Papi L.
Hum. Mutat. 29:227-231(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SCHWA.
[42]"Molecular characterization of the NF2 gene in Korean patients with neurofibromatosis type 2: a report of four novel mutations."
Seong M.W., Yeo I.K., Cho S.I., Park C.K., Kim S.K., Paek S.H., Kim D.G., Jung H.W., Park H., Kim S.Y., Kim J.Y., Park S.S.
Korean J. Lab. Med. 30:190-194(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NF2 ARG-133.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L11353 mRNA. Translation: AAA36212.1.
X72655 expand/collapse EMBL AC list , X72656, X72657, X72658, X72659, X72660, X72661, X72662, X72663, X72664, X72665, X72666, X72667, X72668, X72669, X72670 Genomic DNA. Translation: CAA51220.1.
Z22664 mRNA. Translation: CAA80377.1.
Y18000 Genomic DNA. Translation: CAA76992.1.
Y18000 Genomic DNA. Translation: CAA76993.1.
AF122827 mRNA. Translation: AAD48752.1.
AF122828 mRNA. Translation: AAD48753.1.
AF123570 mRNA. Translation: AAD48754.1.
AF369657 mRNA. Translation: AAK54160.1.
AF369658 mRNA. Translation: AAK54161.1.
AF369661 mRNA. Translation: AAK54162.1.
AF369662 mRNA. Translation: AAK54163.1.
AF369663 mRNA. Translation: AAK54164.1.
AF369664 mRNA. Translation: AAK54165.1.
AF369665 mRNA. Translation: AAK54166.1.
AF369700 mRNA. Translation: AAK54195.1.
AF369701 mRNA. Translation: AAK54196.1.
CR456530 mRNA. Translation: CAG30416.1.
BC003112 mRNA. Translation: AAH03112.2.
BC020257 mRNA. Translation: AAH20257.1.
PIRS33809.
RefSeqNP_000259.1. NM_000268.3.
NP_057502.2. NM_016418.5.
NP_861546.1. NM_181825.2.
NP_861966.1. NM_181828.2.
NP_861967.1. NM_181829.2.
NP_861968.1. NM_181830.2.
NP_861969.1. NM_181831.2.
NP_861970.1. NM_181832.2.
NP_861971.1. NM_181833.2.
UniGeneHs.187898.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H4RX-ray1.80A/B1-313[»]
3U8ZX-ray2.64A/B/C/D18-312[»]
ProteinModelPortalP35240.
SMRP35240. Positions 18-595.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110844. 32 interactions.
IntActP35240. 25 interactions.

PTM databases

PhosphoSiteP35240.

Polymorphism databases

DMDM462594.

Proteomic databases

PaxDbP35240.
PRIDEP35240.

Protocols and materials databases

DNASU4771.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334961; ENSP00000335652; ENSG00000186575. [P35240-4]
ENST00000338641; ENSP00000344666; ENSG00000186575. [P35240-1]
ENST00000347330; ENSP00000335160; ENSG00000186575. [P35240-10]
ENST00000353887; ENSP00000340626; ENSG00000186575. [P35240-4]
ENST00000361166; ENSP00000354529; ENSG00000186575. [P35240-3]
ENST00000361452; ENSP00000354897; ENSG00000186575. [P35240-5]
ENST00000361676; ENSP00000355183; ENSG00000186575. [P35240-6]
ENST00000397789; ENSP00000380891; ENSG00000186575. [P35240-3]
ENST00000403435; ENSP00000384029; ENSG00000186575. [P35240-8]
ENST00000403999; ENSP00000384797; ENSG00000186575. [P35240-3]
ENST00000413209; ENSP00000409921; ENSG00000186575. [P35240-9]
ENST00000432151; ENSP00000395885; ENSG00000186575. [P35240-10]
GeneID4771.
KEGGhsa:4771.
UCSCuc003afy.4. human. [P35240-3]
uc003afz.4. human. [P35240-4]
uc003aga.4. human. [P35240-6]
uc003age.4. human. [P35240-1]
uc003agh.4. human. [P35240-5]
uc003agj.4. human. [P35240-9]

Organism-specific databases

CTD4771.
GeneCardsGC22P029999.
HGNCHGNC:7773. NF2.
HPACAB005385.
HPA003097.
MIM101000. phenotype.
156240. phenotype.
162091. phenotype.
607379. gene.
neXtProtNX_P35240.
Orphanet637. Neurofibromatosis type 2.
93921. Neurofibromatosis type 3.
PharmGKBPA31580.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG328202.
HOVERGENHBG002185.
InParanoidP35240.
KOK16684.
OMAITNEMER.
OrthoDBEOG7BGHK6.
PhylomeDBP35240.
TreeFamTF313935.

Enzyme and pathway databases

SignaLinkP35240.

Gene expression databases

ArrayExpressP35240.
BgeeP35240.
GenevestigatorP35240.

Family and domain databases

Gene3D1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
InterProIPR019749. Band_41_domain.
IPR019750. Band_41_fam.
IPR015788. EMR2/Merlin.
IPR011174. ERM.
IPR011259. ERM_C_dom.
IPR000798. Ez/rad/moesin_like.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR018979. FERM_N.
IPR018980. FERM_PH-like_C.
IPR008954. Moesin_tail.
IPR011993. PH_like_dom.
[Graphical view]
PANTHERPTHR23281:SF4. PTHR23281:SF4. 1 hit.
PfamPF00769. ERM. 1 hit.
PF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]
PIRSFPIRSF002305. ERM. 1 hit.
PRINTSPR00935. BAND41.
PR00661. ERMFAMILY.
SMARTSM00295. B41. 1 hit.
[Graphical view]
SUPFAMSSF47031. SSF47031. 1 hit.
SSF48678. SSF48678. 1 hit.
PROSITEPS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP35240.
GeneWikiMerlin_(protein).
GenomeRNAi4771.
NextBio18368.
PMAP-CutDBP35240.
PROP35240.
SOURCESearch...

Entry information

Entry nameMERL_HUMAN
AccessionPrimary (citable) accession number: P35240
Secondary accession number(s): O95683 expand/collapse secondary AC list , Q8WUJ2, Q969N0, Q969Q3, Q96T30, Q96T31, Q96T32, Q96T33, Q9BTW3, Q9UNG9, Q9UNH3, Q9UNH4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 169 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM