ID  P35240;
PN  Merlin;
GN  NF2;
OS  9606;
SL  Nucleus Position: SL-0198;
SL  Comments: [Isoform 1]: Cell projection, filopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle 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 DCAF1 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. [Isoform 7]: Cytoplasm, perinuclear region. Cytoplasmic granule. Note=Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia. [Isoform 9]: Cytoplasm, perinuclear region. Cytoplasmic granule. Note=Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia. [Isoform 10]: Nucleus. Cell projection, filopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, perinuclear region. Cytoplasmic granule. Cytoplasm, cytoskeleton. 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.
DR  UNIPROT: P35240;
DR  UNIPROT: O95683;
DR  UNIPROT: Q8WUJ2;
DR  UNIPROT: Q969N0;
DR  UNIPROT: Q969Q3;
DR  UNIPROT: Q96T30;
DR  UNIPROT: Q96T31;
DR  UNIPROT: Q96T32;
DR  UNIPROT: Q96T33;
DR  UNIPROT: Q9BTW3;
DR  UNIPROT: Q9UNG9;
DR  UNIPROT: Q9UNH3;
DR  UNIPROT: Q9UNH4;
DR  PDB: 1H4R;
DR  PDB: 3U8Z;
DR  PDB: 4ZRI;
DR  PDB: 4ZRJ;
DR  PDB: 6CDS;
DR  PDB: 7LWH;
DR  Pfam: PF09380;
DR  Pfam: PF00373;
DR  Pfam: PF09379;
DR  PROSITE: PS00660;
DR  PROSITE: PS00661;
DR  PROSITE: PS50057;
DR  OMIM: 101000;
DR  OMIM: 156240;
DR  OMIM: 162091;
DR  OMIM: 607379;
DR  DisGeNET: 4771;
DE  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. {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}.
DE  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. {ECO:0000269|PubMed:10090912, ECO:0000269|PubMed:10669747, ECO:0000269|PubMed:10790209, ECO:0000269|PubMed:12709270, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:20445339, ECO:0000269|PubMed:7666400, ECO:0000269|PubMed:7759081, ECO:0000269|PubMed:7913580, ECO:0000269|PubMed:8081368, ECO:0000269|PubMed:8230593, ECO:0000269|PubMed:8566958, ECO:0000269|PubMed:8698340, ECO:0000269|PubMed:9643284}. Note=The disease is caused by variants affecting the gene represented in this entry. Schwannomatosis 1 (SWNTS1) [MIM:162091]: A cancer syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves. {ECO:0000269|PubMed:18072270}. Note=The disease is caused by variants affecting the gene represented in this entry. 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. {ECO:0000269|PubMed:12136076}. Note=The disease may be caused by variants affecting the gene represented in this entry.
DE  Reference Proteome: Yes;
DE  Interaction: P00533; IntAct: EBI-32720286; Score: 0.27
DE  Interaction: P01112; IntAct: EBI-27045317; Score: 0.27
DE  Interaction: P31689; IntAct: EBI-6911783; Score: 0.35
DE  Interaction: Q10728; IntAct: EBI-1014791; Score: 0.52
DE  Interaction: Q9H204; IntAct: EBI-1206136; Score: 0.58
DE  Interaction: O14745; IntAct: EBI-2527605; Score: 0.54
DE  Interaction: Q9BZE4; IntAct: EBI-1388499; Score: 0.61
DE  Interaction: P0DPB4; IntAct: EBI-1397471; Score: 0.51
DE  Interaction: P0DPB3; IntAct: EBI-1397568; Score: 0.40
DE  Interaction: Q4VCS5; IntAct: EBI-2513986; Score: 0.85
DE  Interaction: Q68EM7; IntAct: EBI-3892049; Score: 0.35
DE  Interaction: Q8NI35; IntAct: EBI-3957523; Score: 0.50
DE  Interaction: Q8N3R9; IntAct: EBI-3957573; Score: 0.35
DE  Interaction: Q13153; IntAct: EBI-3957588; Score: 0.40
DE  Interaction: A0A0G2JX94; IntAct: EBI-3892269; Score: 0.40
DE  Interaction: Q8IY63; IntAct: EBI-3957317; Score: 0.64
DE  Interaction: Q9Y2J4; IntAct: EBI-24403805; Score: 0.56
DE  Interaction: Q16584; IntAct: EBI-3990627; Score: 0.65
DE  Interaction: Q14324; IntAct: EBI-5661239; Score: 0.00
DE  Interaction: O60341; IntAct: EBI-8476950; Score: 0.67
DE  Interaction: O60884; IntAct: EBI-6911783; Score: 0.35
DE  Interaction: Q9BQE3; IntAct: EBI-6911783; Score: 0.35
DE  Interaction: P34932; IntAct: EBI-6911783; Score: 0.35
DE  Interaction: Q92598; IntAct: EBI-6911783; Score: 0.35
DE  Interaction: P63167; IntAct: EBI-6911783; Score: 0.35
DE  Interaction: P46937; IntAct: EBI-6912563; Score: 0.53
DE  Interaction: O95835; IntAct: EBI-9005158; Score: 0.56
DE  Interaction: P35240; IntAct: EBI-22185197; Score: 0.55
DE  Interaction: P57078; IntAct: EBI-12503575; Score: 0.35
DE  Interaction: O08917; IntAct: EBI-11025136; Score: 0.35
DE  Interaction: Q3UES3; IntAct: EBI-11025889; Score: 0.35
DE  Interaction: Q9WUM4; IntAct: EBI-11065690; Score: 0.35
DE  Interaction: O88952; IntAct: EBI-11079007; Score: 0.35
DE  Interaction: Q16643; IntAct: EBI-11080402; Score: 0.35
DE  Interaction: Q8VDD5; IntAct: EBI-11095050; Score: 0.35
DE  Interaction: O00400; IntAct: EBI-11135399; Score: 0.35
DE  Interaction: P46938; IntAct: EBI-11138299; Score: 0.35
DE  Interaction: Q13895; IntAct: EBI-24689238; Score: 0.56
DE  Interaction: Q8N3L3; IntAct: EBI-24702144; Score: 0.56
DE  Interaction: A2BDD9; IntAct: EBI-24715409; Score: 0.56
DE  Interaction: P50402; IntAct: EBI-23824818; Score: 0.56
DE  Interaction: Q96A37; IntAct: EBI-21627270; Score: 0.35
DE  Interaction: Q96S94; IntAct: EBI-21750627; Score: 0.35
DE  Interaction: Q13371; IntAct: EBI-21883365; Score: 0.35
DE  Interaction: Q9UJ04; IntAct: EBI-21883365; Score: 0.35
DE  Interaction: Q13136; IntAct: EBI-21883365; Score: 0.35
DE  Interaction: Q9Y4B6; IntAct: EBI-21912146; Score: 0.35
DE  Interaction: P48668; IntAct: EBI-21912146; Score: 0.35
DE  Interaction: P31431; IntAct: EBI-21912146; Score: 0.35
DE  Interaction: Q9Y2T2; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: Q9UQ35; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: Q9BW61; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: P78347; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: P18827; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: O95218; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: O14646; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: O00629; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: O00468; IntAct: EBI-21912201; Score: 0.35
DE  Interaction: P20719; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: Q9NP74; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: Q9H307; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: Q96HR8; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: Q8TBK6; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: Q3YEC7; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: P98160; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: O00422; IntAct: EBI-21912280; Score: 0.35
DE  Interaction: Q9HCG8; IntAct: EBI-21912397; Score: 0.35
DE  Interaction: Q3L8U1; IntAct: EBI-21912397; Score: 0.35
DE  Interaction: A0A8C0SSK1; IntAct: EBI-16145904; Score: 0.50
DE  Interaction: A0A8I3RSA7; IntAct: EBI-16145960; Score: 0.50
DE  Interaction: Q08345; IntAct: EBI-22227061; Score: 0.35
DE  Interaction: P11279; IntAct: EBI-16795491; Score: 0.27
DE  Interaction: P46663; IntAct: EBI-20803223; Score: 0.37
DE  Interaction: O14964; IntAct: EBI-22184874; Score: 0.63
DE  Interaction: Q9Y6K9; IntAct: EBI-20737021; Score: 0.35
DE  Interaction: Q92844; IntAct: EBI-20737201; Score: 0.35
DE  Interaction: Q8NFZ5; IntAct: EBI-20737410; Score: 0.35
DE  Interaction: P52272; IntAct: EBI-20927432; Score: 0.40
DE  Interaction: Q99613; IntAct: EBI-22185149; Score: 0.37
DE  Interaction: Q01082; IntAct: EBI-25396800; Score: 0.65
DE  Interaction: Q92918; IntAct: EBI-25393102; Score: 0.35
DE  Interaction: P62750; IntAct: EBI-25481947; Score: 0.35
DE  Interaction: Q9H7H0; IntAct: EBI-25481947; Score: 0.35
DE  Interaction: Q969Q0; IntAct: EBI-25481947; Score: 0.35
DE  Interaction: P60896; IntAct: EBI-25878246; Score: 0.56
DE  Interaction: Q15776; IntAct: EBI-25878230; Score: 0.56
DE  Interaction: P17024; IntAct: EBI-25878222; Score: 0.56
DE  Interaction: P40337; IntAct: EBI-25878214; Score: 0.56
DE  Interaction: Q99598; IntAct: EBI-25878206; Score: 0.56
DE  Interaction: P54274; IntAct: EBI-25878198; Score: 0.56
DE  Interaction: O15381; IntAct: EBI-25878188; Score: 0.56
DE  Interaction: O75530; IntAct: EBI-25878294; Score: 0.56
DE  Interaction: O00303; IntAct: EBI-25878286; Score: 0.56
DE  Interaction: O75925; IntAct: EBI-25878278; Score: 0.56
DE  Interaction: Q9UNS2; IntAct: EBI-25878254; Score: 0.56
DE  Interaction: Q14525; IntAct: EBI-25878172; Score: 0.56
DE  Interaction: P48730; IntAct: EBI-25878153; Score: 0.56
DE  Interaction: Q13191; IntAct: EBI-25878145; Score: 0.56
DE  Interaction: Q5H9J7; IntAct: EBI-25878632; Score: 0.56
DE  Interaction: P58304; IntAct: EBI-25878624; Score: 0.56
DE  Interaction: Q6ZR37; IntAct: EBI-25878616; Score: 0.56
DE  Interaction: Q6ZNE9; IntAct: EBI-25878606; Score: 0.56
DE  Interaction: Q8IZU1; IntAct: EBI-25878598; Score: 0.56
DE  Interaction: Q6ZNH5; IntAct: EBI-25878582; Score: 0.56
DE  Interaction: Q86WT6; IntAct: EBI-25878574; Score: 0.56
DE  Interaction: Q96DX5; IntAct: EBI-25878566; Score: 0.56
DE  Interaction: Q96D59; IntAct: EBI-25878550; Score: 0.56
DE  Interaction: Q8NEZ2; IntAct: EBI-25878542; Score: 0.56
DE  Interaction: Q7Z3I7; IntAct: EBI-25878526; Score: 0.56
DE  Interaction: Q8WWB5; IntAct: EBI-25878518; Score: 0.56
DE  Interaction: Q8N594; IntAct: EBI-25878510; Score: 0.56
DE  Interaction: Q8TBB1; IntAct: EBI-25878502; Score: 0.56
DE  Interaction: Q8NHS9; IntAct: EBI-25878494; Score: 0.56
DE  Interaction: Q6H8Q1; IntAct: EBI-25878486; Score: 0.56
DE  Interaction: Q9C0F3; IntAct: EBI-25878462; Score: 0.56
DE  Interaction: Q96KP6; IntAct: EBI-25878446; Score: 0.56
DE  Interaction: Q5VYS8; IntAct: EBI-25878438; Score: 0.56
DE  Interaction: Q6GQQ9; IntAct: EBI-25878428; Score: 0.56
DE  Interaction: Q96FW1; IntAct: EBI-25878420; Score: 0.56
DE  Interaction: Q8WVD3; IntAct: EBI-25878412; Score: 0.56
DE  Interaction: Q8WXF7; IntAct: EBI-25878396; Score: 0.56
DE  Interaction: Q5TAQ9; IntAct: EBI-25878388; Score: 0.56
DE  Interaction: Q9BY12; IntAct: EBI-25878378; Score: 0.56
DE  Interaction: Q6X4W1; IntAct: EBI-25878370; Score: 0.56
DE  Interaction: Q8N488; IntAct: EBI-25878352; Score: 0.56
DE  Interaction: Q13573; IntAct: EBI-25878334; Score: 0.56
DE  Interaction: Q9Y6C2; IntAct: EBI-25878318; Score: 0.56
DE  Interaction: O76041; IntAct: EBI-25878310; Score: 0.56
DE  Interaction: Q9UNE7; IntAct: EBI-25878302; Score: 0.56
DE  Interaction: P01116; IntAct: EBI-27041844; Score: 0.27
DE  Interaction: P01111; IntAct: EBI-27042293; Score: 0.27
DE  Interaction: Q13363; IntAct: EBI-27044482; Score: 0.35
DE  Interaction: F1PAA9; IntAct: EBI-27079701; Score: 0.27
DE  Interaction: P63252; IntAct: EBI-28956270; Score: 0.27
DE  Interaction: O15194; IntAct: EBI-27115784; Score: 0.27
DE  Interaction: P18433; IntAct: EBI-27116377; Score: 0.27
DE  Interaction: P23470; IntAct: EBI-27116482; Score: 0.27
DE  Interaction: P29323; IntAct: EBI-32721290; Score: 0.27
DE  Interaction: P11362; IntAct: EBI-32721578; Score: 0.27
DE  Interaction: P22455; IntAct: EBI-32722168; Score: 0.27
DE  Interaction: Q16288; IntAct: EBI-32724526; Score: 0.27
GO  GO:0005912;
GO  GO:0045177;
GO  GO:0044297;
GO  GO:0032154;
GO  GO:0030864;
GO  GO:0005737;
GO  GO:0005856;
GO  GO:0005829;
GO  GO:0005769;
GO  GO:0031527;
GO  GO:0030027;
GO  GO:0016020;
GO  GO:0043005;
GO  GO:0005730;
GO  GO:0005634;
GO  GO:0048471;
GO  GO:0005886;
GO  GO:0032587;
GO  GO:0003779;
GO  GO:0005178;
GO  GO:0030036;
GO  GO:0045216;
GO  GO:0007398;
GO  GO:0021766;
GO  GO:0070306;
GO  GO:0000165;
GO  GO:0001707;
GO  GO:0030336;
GO  GO:0008285;
GO  GO:0022408;
GO  GO:0001953;
GO  GO:0043409;
GO  GO:0033689;
GO  GO:0006469;
GO  GO:0046426;
GO  GO:0010626;
GO  GO:0042532;
GO  GO:0042475;
GO  GO:0033687;
GO  GO:0045597;
GO  GO:0051496;
GO  GO:0042981;
GO  GO:0051726;
GO  GO:0014013;
GO  GO:0035330;
GO  GO:2000177;
GO  GO:1900180;
GO  GO:0031647;
GO  GO:0072091;
GO  GO:0014010;
TP  Membrane Topology: Peripheral; Source: UniProt - Sequence Analysis;
SQ  MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKK
SQ  VLDHDVSKEEPVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKR
SQ  GFLAQEELLPKRVINLYQMTPEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALG
SQ  LHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQ
SQ  MKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQ
SQ  KAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPT
SQ  YPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDI
SQ  LHNENSDRGGSSKHNTIKKLTLQSAKSRVAFFEEL
//