P46662 (MERL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Merlin

Alternative name(s):
Moesin-ezrin-radixin-like protein
Neurofibromin-2
Schwannomin

Gene names

Name:	Nf2
Synonyms:	Nf-2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	596 AA.
Sequence status	Complete.
Protein existence	Evidence 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.7
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. Cytoplasm › cytoskeleton 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.7
Sequence similarities	Contains 1 FERM domain.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane Nucleus
Coding sequence diversity	Alternative splicing
Disease	Tumor suppressor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Schwann cell proliferation Inferred from electronic annotation. Source: Compara actin cytoskeleton organization Inferred from electronic annotation. Source: Compara 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.7. Source: UniProtKB mesoderm formation Inferred from mutant phenotype PubMed 9171370. Source: MGI negative regulation of DNA replication Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara negative regulation of tyrosine phosphorylation of Stat5 protein Inferred from electronic annotation. Source: Compara odontogenesis of dentin-containing tooth Inferred from mutant phenotype PubMed 10887156. Source: MGI positive regulation of stress fiber assembly Inferred from electronic annotation. Source: Compara regulation of hippo signaling cascade Inferred from electronic annotation. Source: Compara
Cellular_component	adherens 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 early endosome Inferred from electronic annotation. Source: Compara extrinsic to 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: Compara nucleus Inferred from direct assay PubMed 15133494. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 596

596

Merlin

PRO_0000219413

Regions

Domain

22 – 311

290

FERM

Compositional bias

327 – 465

139

Glu-rich

Amino acid modifications

Modified residue

518

1

Phosphoserine; by PAK By similarity

Natural variations

Alternative sequence

581 – 596

16

LTLQS…FFEEL → PQAQGRRPICI in isoform 2.

VSP_000493

Experimental info

Sequence conflict

475

1

I → T in AAA39808. Ref.2

Sequence conflict

554

1

R → A in AAA39807. Ref.1

Sequence conflict

554

1

R → A in AAA63648. Ref.1

Sequence conflict

570

1

G → A in AAA39808. Ref.2

Secondary structure

1

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596

Helix Strand Turn

Details...

Beta strand

21 – 27

7

Beta strand

32 – 38

7

Helix

43 – 54

12

Helix

59 – 61

3

Beta strand

62 – 67

6

Beta strand

69 – 74

6

Beta strand

77 – 80

4

Turn

81 – 83

3

Beta strand

89 – 98

10

Helix

105 – 108

4

Helix

112 – 127

16

Helix

135 – 150

16

Turn

155 – 157

3

Turn

160 – 163

4

Beta strand

164 – 166

3

Helix

171 – 174

4

Helix

181 – 194

14

Turn

195 – 197

3

Helix

200 – 212

13

Turn

215 – 218

4

Beta strand

220 – 222

3

Beta strand

233 – 236

4

Beta strand

238 – 245

8

Beta strand

248 – 251

4

Beta strand

253 – 257

5

Turn

258 – 260

3

Beta strand

261 – 267

7

Beta strand

270 – 277

8

Turn

278 – 280

3

Helix

292 – 311

20

Helix

316 – 337

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 27, 2003. Version 2. Checksum: 8D06F557E3435851	FASTA	596	69,776
	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
	Isoform 2 [UniParc]. Checksum: 20B97F99EBF87184	FASTA	591	69,176
	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 PQAQGRRPIC I

References

	« Hide 'large scale' referencesShow '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. , 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]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518, MASS SPECTROMETRY. Tissue: Melanoma.
[7]	"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.

IPI

IPI00135968.
IPI00228063.

PIR

I48683.
I54368.
I68664.

RefSeq

NP_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.

UniGene

Mm.297109.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ISN	X-ray	2.90	A	18-340	[»]

ProteinModelPortal

P46662.

SMR

P46662. Positions 18-382.

ModBase

Search...

Protein-protein interaction databases

IntAct

P46662. 5 interactions.

PTM databases

PhosphoSite

P46662.

Proteomic databases

PaxDb

P46662.

PRIDE

P46662.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000053079; ENSMUSP00000055033; ENSMUSG00000009073.
ENSMUST00000056290; ENSMUSP00000055061; ENSMUSG00000009073.
ENSMUST00000109910; ENSMUSP00000105536; ENSMUSG00000009073.

GeneID

18016.

KEGG

mmu:18016.

Organism-specific databases

CTD

4771.

MGI

MGI:97307. Nf2.

Phylogenomic databases

eggNOG

NOG328202.

GeneTree

ENSGT00650000092953.

HOGENOM

HOG000007113.

HOVERGEN

HBG002185.

InParanoid

P46662.

KO

K16684.

OMA

DITQHLF.

OrthoDB

EOG4NVZK5.

Gene expression databases

ArrayExpress

P46662.

Bgee

P46662.

CleanEx

MM_NF2.

Genevestigator

P46662.

GermOnline

ENSMUSG00000009073. Mus musculus.

Family and domain databases

Gene3D

1.20.80.10. 1 hit.
2.30.29.30. 1 hit.

InterPro

IPR019749. Band_41_domain.
IPR019750. Band_41_fam.
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.
IPR011993. PH_like_dom.
[Graphical view]

Pfam

PF00769. ERM. 1 hit.
PF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]

PIRSF

PIRSF002305. ERM. 1 hit.

PRINTS

PR00935. BAND41.
PR00661. ERMFAMILY.

SMART

SM00295. B41. 1 hit.
[Graphical view]

SUPFAM

SSF47031. FERM_3-hlx. 1 hit.
SSF48678. Moesin. 1 hit.

PROSITE

PS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NF2. mouse.

EvolutionaryTrace

P46662.

NextBio

293053.

SOURCE

Search...

Entry information

Entry name

MERL_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program