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Protein

Merlin

Gene

Nf2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

GO - Biological processi

  • actin cytoskeleton organization Source: MGI
  • brain development Source: MGI
  • cell-cell junction organization Source: MGI
  • ectoderm development Source: MGI
  • hippocampus development Source: MGI
  • lens fiber cell differentiation Source: UniProtKB
  • mesoderm formation Source: MGI
  • negative regulation of cell-cell adhesion Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of DNA replication Source: MGI
  • negative regulation of JAK-STAT cascade Source: MGI
  • negative regulation of MAPK cascade Source: MGI
  • negative regulation of protein kinase activity Source: MGI
  • negative regulation of tyrosine phosphorylation of Stat3 protein Source: MGI
  • negative regulation of tyrosine phosphorylation of Stat5 protein Source: MGI
  • odontogenesis of dentin-containing tooth Source: MGI
  • positive regulation of cell differentiation Source: MGI
  • positive regulation of stress fiber assembly Source: MGI
  • regulation of cell proliferation Source: MGI
  • regulation of gliogenesis Source: MGI
  • regulation of hippo signaling Source: MGI
  • regulation of neural precursor cell proliferation Source: MGI
  • regulation of neurogenesis Source: MGI
  • regulation of protein localization to nucleus Source: MGI
  • regulation of protein stability Source: MGI
  • regulation of stem cell proliferation Source: MGI
  • Schwann cell proliferation Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-5627123. RHO GTPases activate PAKs.

Names & Taxonomyi

Protein namesi
Recommended name:
Merlin
Alternative name(s):
Moesin-ezrin-radixin-like protein
Neurofibromin-2
Schwannomin
Gene namesi
Name:Nf2
Synonyms:Nf-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:97307. Nf2.

Subcellular locationi

  • Cell membrane By similarity; Peripheral membrane protein By similarity; 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).By similarity

GO - Cellular componenti

  • adherens junction Source: MGI
  • apical part of cell Source: MGI
  • cell body Source: MGI
  • cleavage furrow Source: MGI
  • cortical actin cytoskeleton Source: MGI
  • cytoplasm Source: MGI
  • cytoskeleton Source: MGI
  • early endosome Source: MGI
  • extrinsic component of membrane Source: InterPro
  • filopodium Source: MGI
  • lamellipodium Source: MGI
  • membrane Source: MGI
  • neuron projection Source: MGI
  • nucleolus Source: MGI
  • nucleus Source: MGI
  • perinuclear region of cytoplasm Source: MGI
  • plasma membrane Source: MGI
  • ruffle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002194131 – 596MerlinAdd BLAST596

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphoserineBy similarity1
Modified residuei518Phosphoserine; by PAKBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP46662.
PaxDbiP46662.
PRIDEiP46662.

PTM databases

iPTMnetiP46662.
PhosphoSitePlusiP46662.

Expressioni

Gene expression databases

BgeeiENSMUSG00000009073.
CleanExiMM_NF2.
ExpressionAtlasiP46662. baseline and differential.
GenevisibleiP46662. MM.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
AMOTQ4VCS52EBI-644586,EBI-2511319From a different organism.
LATS1O958355EBI-644586,EBI-444209From a different organism.

Protein-protein interaction databases

BioGridi201737. 5 interactors.
IntActiP46662. 9 interactors.
MINTiMINT-242068.
STRINGi10090.ENSMUSP00000105536.

Structurei

Secondary structure

1596
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi25 – 27Combined sources3
Beta strandi32 – 34Combined sources3
Helixi43 – 54Combined sources12
Helixi59 – 61Combined sources3
Beta strandi62 – 68Combined sources7
Beta strandi71 – 74Combined sources4
Beta strandi77 – 80Combined sources4
Helixi81 – 83Combined sources3
Beta strandi84 – 86Combined sources3
Beta strandi89 – 91Combined sources3
Beta strandi93 – 100Combined sources8
Helixi105 – 108Combined sources4
Helixi112 – 127Combined sources16
Helixi135 – 150Combined sources16
Turni155 – 157Combined sources3
Turni160 – 165Combined sources6
Helixi171 – 175Combined sources5
Helixi181 – 193Combined sources13
Turni194 – 197Combined sources4
Helixi200 – 211Combined sources12
Turni215 – 218Combined sources4
Beta strandi220 – 226Combined sources7
Beta strandi231 – 237Combined sources7
Beta strandi240 – 244Combined sources5
Beta strandi249 – 251Combined sources3
Beta strandi253 – 257Combined sources5
Helixi258 – 260Combined sources3
Beta strandi261 – 267Combined sources7
Beta strandi270 – 277Combined sources8
Turni278 – 280Combined sources3
Beta strandi283 – 286Combined sources4
Helixi290 – 310Combined sources21
Helixi316 – 337Combined sources22

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ISNX-ray2.90A18-340[»]
3WA0X-ray2.31A/B/C/D/E/F19-314[»]
4P7IX-ray2.60A/B1-313[»]
4ZRKX-ray2.32A/B/C/D1-320[»]
ProteinModelPortaliP46662.
SMRiP46662.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46662.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 311FERMPROSITE-ProRule annotationAdd BLAST290

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi327 – 465Glu-richAdd BLAST139

Sequence similaritiesi

Contains 1 FERM domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3529. Eukaryota.
ENOG410XQFP. LUCA.
GeneTreeiENSGT00860000133686.
HOGENOMiHOG000007113.
HOVERGENiHBG002185.
InParanoidiP46662.
KOiK16684.
OMAiACYAEHR.
OrthoDBiEOG091G06UO.
PhylomeDBiP46662.
TreeFamiTF313935.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR019749. Band_41_domain.
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_dom-like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00769. ERM. 1 hit.
PF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]
PIRSFiPIRSF002305. ERM. 1 hit.
PRINTSiPR00935. BAND41.
PR00661. ERMFAMILY.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF48678. SSF48678. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P46662-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAGAIASRMS FSSLKRKQPK TFTVRIVTMD AEMEFNCEMK WKGKDLFDLV
60 70 80 90 100
CRTLGLRETW FFGLQYTIKD TVAWLKMDKK VLDHDVSKEE PVTFHFLAKF
110 120 130 140 150
YPENAEEELV QEITQHLFFL QVKKQILDEK VYCPPEASVL LASYAVQAKY
160 170 180 190 200
GDYDPSVHKR GFLAQEELLP KRVINLYQMT PEMWEERITA WYAEHRGRAR
210 220 230 240 250
DEAEMEYLKI AQDLEMYGVN YFTIRNKKGT ELLLGVDALG LHIYDPENRL
260 270 280 290 300
TPKISFPWNE IRNISYSDKE FTIKPLDKKI DVFKFNSSKL RVNKLILQLC
310 320 330 340 350
IGNHDLFMRR RKADSLEVQQ MKAQAREEKA RKQMERQRLA REKQMREEAE
360 370 380 390 400
RTRDELERRL LQMKEEATMA NEALMRSEET ADLLAEKAQI TEEEAKLLAQ
410 420 430 440 450
KAAEAEQEMQ RIKATAIRTE EEKRLMEQKV LEAEVLALKM AEESERRAKE
460 470 480 490 500
ADQLKQDLQE AREAERRAKQ KLLEIATKPT YPPMNPIPPP LPPDIPSFDI
510 520 530 540 550
IADSLSFDFK DTDMKRLSME IEKEKVEYME KSKHLQEQLN ELKTEIEALK
560 570 580 590
LKERETALDV LHSESSDRGG PSSKHNTIKK LTLQSAKSRV AFFEEL
Length:596
Mass (Da):69,776
Last modified:June 27, 2003 - v2
Checksum:i8D06F557E3435851
GO
Isoform 2 (identifier: P46662-2) [UniParc]FASTAAdd to basket

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

Show »
Length:591
Mass (Da):69,176
Checksum:i20B97F99EBF87184
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti475I → T in AAA39808 (PubMed:7981675).Curated1
Sequence conflicti554R → A in AAA39807 (PubMed:8012352).Curated1
Sequence conflicti554R → A in AAA63648 (PubMed:8012352).Curated1
Sequence conflicti570G → A in AAA39808 (PubMed:7981675).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000493581 – 596LTLQS…FFEEL → PQAQGRRPICI in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24391.1. [P46662-1]
CCDS56757.1. [P46662-2]
PIRiI48683.
I54368.
I68664.
RefSeqiNP_001239179.1. NM_001252250.1. [P46662-2]
NP_001239180.1. NM_001252251.1. [P46662-2]
NP_001239181.1. NM_001252252.1.
NP_001239182.1. NM_001252253.1.
NP_035028.2. NM_010898.4. [P46662-1]
XP_006514633.1. XM_006514570.2. [P46662-2]
XP_011241971.1. XM_011243669.2. [P46662-2]
UniGeneiMm.297109.

Genome annotation databases

EnsembliENSMUST00000053079; ENSMUSP00000055033; ENSMUSG00000009073. [P46662-2]
ENSMUST00000056290; ENSMUSP00000055061; ENSMUSG00000009073. [P46662-2]
ENSMUST00000109910; ENSMUSP00000105536; ENSMUSG00000009073. [P46662-1]
GeneIDi18016.
KEGGimmu:18016.
UCSCiuc007hvf.2. mouse. [P46662-1]
uc007hvg.2. mouse. [P46662-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24391.1. [P46662-1]
CCDS56757.1. [P46662-2]
PIRiI48683.
I54368.
I68664.
RefSeqiNP_001239179.1. NM_001252250.1. [P46662-2]
NP_001239180.1. NM_001252251.1. [P46662-2]
NP_001239181.1. NM_001252252.1.
NP_001239182.1. NM_001252253.1.
NP_035028.2. NM_010898.4. [P46662-1]
XP_006514633.1. XM_006514570.2. [P46662-2]
XP_011241971.1. XM_011243669.2. [P46662-2]
UniGeneiMm.297109.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ISNX-ray2.90A18-340[»]
3WA0X-ray2.31A/B/C/D/E/F19-314[»]
4P7IX-ray2.60A/B1-313[»]
4ZRKX-ray2.32A/B/C/D1-320[»]
ProteinModelPortaliP46662.
SMRiP46662.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201737. 5 interactors.
IntActiP46662. 9 interactors.
MINTiMINT-242068.
STRINGi10090.ENSMUSP00000105536.

PTM databases

iPTMnetiP46662.
PhosphoSitePlusiP46662.

Proteomic databases

EPDiP46662.
PaxDbiP46662.
PRIDEiP46662.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053079; ENSMUSP00000055033; ENSMUSG00000009073. [P46662-2]
ENSMUST00000056290; ENSMUSP00000055061; ENSMUSG00000009073. [P46662-2]
ENSMUST00000109910; ENSMUSP00000105536; ENSMUSG00000009073. [P46662-1]
GeneIDi18016.
KEGGimmu:18016.
UCSCiuc007hvf.2. mouse. [P46662-1]
uc007hvg.2. mouse. [P46662-2]

Organism-specific databases

CTDi4771.
MGIiMGI:97307. Nf2.

Phylogenomic databases

eggNOGiKOG3529. Eukaryota.
ENOG410XQFP. LUCA.
GeneTreeiENSGT00860000133686.
HOGENOMiHOG000007113.
HOVERGENiHBG002185.
InParanoidiP46662.
KOiK16684.
OMAiACYAEHR.
OrthoDBiEOG091G06UO.
PhylomeDBiP46662.
TreeFamiTF313935.

Enzyme and pathway databases

ReactomeiR-MMU-5627123. RHO GTPases activate PAKs.

Miscellaneous databases

ChiTaRSiNf2. mouse.
EvolutionaryTraceiP46662.
PROiP46662.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000009073.
CleanExiMM_NF2.
ExpressionAtlasiP46662. baseline and differential.
GenevisibleiP46662. MM.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR019749. Band_41_domain.
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_dom-like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00769. ERM. 1 hit.
PF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]
PIRSFiPIRSF002305. ERM. 1 hit.
PRINTSiPR00935. BAND41.
PR00661. ERMFAMILY.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF48678. SSF48678. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMERL_MOUSE
AccessioniPrimary (citable) accession number: P46662
Secondary accession number(s): Q8BR03
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: June 27, 2003
Last modified: November 30, 2016
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.