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P46662 (MERL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Merlin
Alternative name(s):
Moesin-ezrin-radixin-like protein
Neurofibromin-2
Schwannomin
Gene names
Name:Nf2
Synonyms:Nf-2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length596 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 By similarity. Plays a role in lens development and is required for complete fiber cell terminal differentiation, maintenance of cell polarity and separation of the lens vesicle from the corneal epithelium. Ref.6

Subunit structure

Interacts with SLC9A3R1, HGS and AGAP2. Interacts with SGSM3. Interacts (via FERM domain) with MPP1 By similarity. Interacts with LAYN and WWC1. Interacts with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. The unphosphorylated form interacts (via FERM domain) with VPRBP/DCAF1 By similarity. Ref.5

Subcellular location

Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cell projection By similarity. Cytoplasmcytoskeleton By similarity. Nucleus By similarity. Note: 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 By similarity.

Post-translational modification

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

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

Disruption phenotype

Mice are born with abnormally small lenses with serious structural defects. Failure of lens vesicle separation and the resulting changes in cell organization causes lenses to herniate, leading to expulsion of lens fiber cells through a perforation in the cornea. Developing lenses show loss of cell apical-basal polarity, failure of the lens vesicle to separate from the surface ectoderm, failure to properly exit the cell cycle during fiber cell differentiation and incomplete terminal differentiation of fiber cells. Ref.6

Sequence similarities

Contains 1 FERM domain.

Ontologies

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

Inferred from electronic annotation. Source: Ensembl

actin cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

cell-cell junction organization

Inferred from mutant phenotype PubMed 12695331. Source: MGI

ectoderm development

Inferred from mutant phenotype PubMed 9171370. Source: MGI

lens fiber cell differentiation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

mesoderm formation

Inferred from mutant phenotype PubMed 9171370. Source: MGI

negative regulation of DNA replication

Inferred from electronic annotation. Source: Ensembl

negative regulation of MAPK cascade

Inferred from mutant phenotype PubMed 16405865. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 10887156PubMed 9553042. Source: MGI

negative regulation of cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein kinase activity

Inferred from direct assay PubMed 14580336. Source: MGI

negative regulation of tyrosine phosphorylation of Stat3 protein

Inferred from electronic annotation. Source: Ensembl

negative regulation of tyrosine phosphorylation of Stat5 protein

Inferred from electronic annotation. Source: Ensembl

odontogenesis of dentin-containing tooth

Inferred from mutant phenotype PubMed 10887156. Source: MGI

positive regulation of stress fiber assembly

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from mutant phenotype PubMed 12695331. Source: MGI

regulation of hippo signaling

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentadherens junction

Inferred from mutant phenotype PubMed 12695331. Source: MGI

cleavage furrow

Inferred from direct assay PubMed 9631655. Source: MGI

cortical actin cytoskeleton

Inferred from direct assay PubMed 15467741. Source: MGI

cytoplasm

Inferred from direct assay PubMed 15133494PubMed 8547603. Source: MGI

cytoskeleton

Inferred from direct assay PubMed 15467741. Source: MGI

early endosome

Inferred from electronic annotation. Source: Ensembl

extrinsic component of membrane

Inferred from electronic annotation. Source: InterPro

filopodium

Inferred from direct assay PubMed 9563848. Source: MGI

lamellipodium

Inferred from direct assay PubMed 9563848. Source: MGI

nucleolus

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 15133494. Source: MGI

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

ruffle

Inferred from direct assay PubMed 9563848. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P46662-1)

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: P46662-2)

The sequence of this isoform differs from the canonical sequence as follows:
     581-596: LTLQSAKSRVAFFEEL → PQAQGRRPICI

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 596596Merlin
PRO_0000219413

Regions

Domain22 – 311290FERM
Compositional bias327 – 465139Glu-rich

Amino acid modifications

Modified residue5181Phosphoserine; by PAK By similarity

Natural variations

Alternative sequence581 – 59616LTLQS…FFEEL → PQAQGRRPICI in isoform 2.
VSP_000493

Experimental info

Sequence conflict4751I → T in AAA39808. Ref.2
Sequence conflict5541R → A in AAA39807. Ref.1
Sequence conflict5541R → A in AAA63648. Ref.1
Sequence conflict5701G → A in AAA39808. Ref.2

Secondary structure

........................................................ 596
Helix Strand Turn

Details...

Sequences

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

Last modified June 27, 2003. Version 2.
Checksum: 8D06F557E3435851

FASTA59669,776
        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 VYCPPEASVL LASYAVQAKY GDYDPSVHKR GFLAQEELLP KRVINLYQMT 

       190        200        210        220        230        240 
PEMWEERITA WYAEHRGRAR DEAEMEYLKI AQDLEMYGVN YFTIRNKKGT 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 
YPPMNPIPPP LPPDIPSFDI IADSLSFDFK DTDMKRLSME IEKEKVEYME KSKHLQEQLN 

       550        560        570        580        590 
ELKTEIEALK LKERETALDV LHSESSDRGG PSSKHNTIKK LTLQSAKSRV AFFEEL 

« Hide

Isoform 2 [UniParc].

Checksum: 20B97F99EBF87184
Show »

FASTA59169,176

References

« Hide 'large scale' references
[1]"The murine NF2 homologue encodes a highly conserved merlin protein with alternative forms."
Haase V.H., Trofatter J.A., Maccollin M., Tarttelin E., Gusella J.F., Ramesh V.
Hum. Mol. Genet. 3:407-411(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Alternative transcripts in the mouse neurofibromatosis type 2 (NF2) gene are conserved and code for schwannomins with distinct C-terminal domains."
Huynh D.P., Nechiporuk T., Pulst S.M.
Hum. Mol. Genet. 3:1075-1079(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Brain.
[4]"The mouse neurofibromatosis type 2 gene maps to chromosome 11."
Claudio J.O., Marineau C., Rouleau G.A.
Genomics 21:437-439(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 400-596.
Tissue: Brain.
[5]"Layilin, a cell surface hyaluronan receptor, interacts with merlin and radixin."
Bono P., Cordero E., Johnson K., Borowsky M., Ramesh V., Jacks T., Hynes R.O.
Exp. Cell Res. 308:177-187(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LAYN.
[6]"The tumor suppressor merlin is required for cell cycle exit, terminal differentiation, and cell polarity in the developing murine lens."
Wiley L.A., Dattilo L.K., Kang K.B., Giovannini M., Beebe D.C.
Invest. Ophthalmol. Vis. Sci. 51:3611-3618(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X74671 mRNA. Translation: CAA52737.1.
L27105 mRNA. Translation: AAA39807.1.
L27090 mRNA. Translation: AAA63648.1.
L28176 mRNA. Translation: AAA39808.1.
AK045998 mRNA. Translation: BAC32567.1.
X75759 mRNA. Translation: CAA53386.1.
PIRI48683.
I54368.
I68664.
RefSeqNP_001239179.1. NM_001252250.1.
NP_001239180.1. NM_001252251.1.
NP_001239181.1. NM_001252252.1.
NP_001239182.1. NM_001252253.1.
NP_035028.2. NM_010898.4.
XP_006514633.1. XM_006514570.1.
UniGeneMm.297109.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ISNX-ray2.90A18-340[»]
ProteinModelPortalP46662.
SMRP46662. Positions 18-596.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201737. 3 interactions.
IntActP46662. 5 interactions.
MINTMINT-242068.

PTM databases

PhosphoSiteP46662.

Proteomic databases

PaxDbP46662.
PRIDEP46662.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000053079; ENSMUSP00000055033; ENSMUSG00000009073. [P46662-2]
ENSMUST00000056290; ENSMUSP00000055061; ENSMUSG00000009073. [P46662-2]
ENSMUST00000109910; ENSMUSP00000105536; ENSMUSG00000009073. [P46662-1]
GeneID18016.
KEGGmmu:18016.
UCSCuc007hvf.2. mouse. [P46662-1]

Organism-specific databases

CTD4771.
MGIMGI:97307. Nf2.

Phylogenomic databases

eggNOGNOG328202.
GeneTreeENSGT00650000092953.
HOGENOMHOG000007113.
HOVERGENHBG002185.
InParanoidP46662.
KOK16684.
OMAITNEMER.
OrthoDBEOG7BGHK6.
PhylomeDBP46662.
TreeFamTF313935.

Gene expression databases

ArrayExpressP46662.
BgeeP46662.
CleanExMM_NF2.
GenevestigatorP46662.

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

ChiTaRSNF2. mouse.
EvolutionaryTraceP46662.
NextBio293053.
PROP46662.
SOURCESearch...

Entry information

Entry nameMERL_MOUSE
AccessionPrimary (citable) accession number: P46662
Secondary accession number(s): Q8BR03
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: June 27, 2003
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot