MERL_RAT
ID MERL_RAT Reviewed; 586 AA.
AC Q63648;
DT 27-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Merlin;
DE AltName: Full=Moesin-ezrin-radixin-like protein;
DE AltName: Full=Neurofibromin-2;
DE AltName: Full=Schwannomin;
DE Flags: Fragment;
GN Name=Nf2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer; TISSUE=Heart, and Liver;
RX PubMed=9022813;
RX DOI=10.1002/(sici)1098-2744(199701)18:1<54::aid-mc7>3.0.co;2-r;
RA Kleymenova E.V., Bianchi A.A., Kley N., Pylev L.N., Walker C.L.;
RT "Characterization of the rat neurofibromatosis 2 gene and its involvement
RT in asbestos-induced mesothelioma.";
RL Mol. Carcinog. 18:54-60(1997).
CC -!- FUNCTION: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling
CC pathway, a signaling pathway that plays a pivotal role in tumor
CC suppression by restricting proliferation and promoting apoptosis. Along
CC with WWC1 can synergistically induce the phosphorylation of LATS1 and
CC LATS2 and can probably function in the regulation of the Hippo/SWH
CC (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing
CC protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its
CC stimulating activity. Suppresses cell proliferation and tumorigenesis
CC by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein
CC ligase complex Plays a role in lens development and is required for
CC complete fiber cell terminal differentiation, maintenance of cell
CC polarity and separation of the lens vesicle from the corneal
CC epithelium. {ECO:0000250|UniProtKB:P35240}.
CC -!- SUBUNIT: Interacts with SLC9A3R1, HGS and AGAP2. Interacts with SGSM3.
CC Interacts (via FERM domain) with MPP1. Interacts with LAYN and WWC1.
CC Interacts with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein
CC ligase complex. The unphosphorylated form interacts (via FERM domain)
CC with VPRBP/DCAF1. Interacts (via FERM domain) with NOP53; the
CC interaction is direct. Interacts with SCHIP1; the interaction is
CC direct. {ECO:0000250|UniProtKB:P35240}.
CC -!- INTERACTION:
CC Q63648; D4A9Q2: Amot; NbExp=4; IntAct=EBI-1013682, EBI-3892226;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cell projection
CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Colocalizes with MPP1 in non-myelin-forming Schwann
CC cells. Binds with DCAF1 in the nucleus. The intramolecular association
CC of the FERM domain with the C-terminal tail promotes nuclear
CC accumulation. The unphosphorylated form accumulates predominantly in
CC the nucleus while the phosphorylated form is largely confined to the
CC non-nuclear fractions (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-
CC protein ligase complex for ubiquitination and subsequent proteasome-
CC dependent degradation. {ECO:0000250}.
CC -!- PTM: Phosphorylation of Ser-514 inhibits nuclear localization by
CC disrupting the intramolecular association of the FERM domain with the
CC C-terminal tail. The dephosphorylation of Ser-514 favors the
CC interaction with NOP53. {ECO:0000250|UniProtKB:P35240}.
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DR EMBL; U61772; AAC13318.1; -; mRNA.
DR RefSeq; NP_037325.1; NM_013193.1.
DR AlphaFoldDB; Q63648; -.
DR SMR; Q63648; -.
DR CORUM; Q63648; -.
DR IntAct; Q63648; 3.
DR STRING; 10116.ENSRNOP00000010690; -.
DR iPTMnet; Q63648; -.
DR PhosphoSitePlus; Q63648; -.
DR PaxDb; Q63648; -.
DR PRIDE; Q63648; -.
DR GeneID; 25744; -.
DR KEGG; rno:25744; -.
DR UCSC; RGD:3169; rat.
DR CTD; 4771; -.
DR RGD; 3169; Nf2.
DR eggNOG; KOG3529; Eukaryota.
DR InParanoid; Q63648; -.
DR OrthoDB; 627741at2759; -.
DR PhylomeDB; Q63648; -.
DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-RNO-5627123; RHO GTPases activate PAKs.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005912; C:adherens junction; ISO:RGD.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0044297; C:cell body; ISO:RGD.
DR GO; GO:0032154; C:cleavage furrow; ISO:RGD.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005856; C:cytoskeleton; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0030175; C:filopodium; ISO:RGD.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0001726; C:ruffle; ISO:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0008013; F:beta-catenin binding; IPI:RGD.
DR GO; GO:0005178; F:integrin binding; IPI:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0048513; P:animal organ development; IEP:RGD.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0045216; P:cell-cell junction organization; ISO:RGD.
DR GO; GO:0007398; P:ectoderm development; ISO:RGD.
DR GO; GO:0021766; P:hippocampus development; ISO:RGD.
DR GO; GO:0070306; P:lens fiber cell differentiation; ISO:RGD.
DR GO; GO:0001707; P:mesoderm formation; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISO:RGD.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; ISO:RGD.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0014013; P:regulation of gliogenesis; ISO:RGD.
DR GO; GO:0035330; P:regulation of hippo signaling; ISO:RGD.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; ISO:RGD.
DR GO; GO:0050767; P:regulation of neurogenesis; ISO:RGD.
DR GO; GO:1900180; P:regulation of protein localization to nucleus; ISO:RGD.
DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
DR GO; GO:0072091; P:regulation of stem cell proliferation; ISO:RGD.
DR GO; GO:0014010; P:Schwann cell proliferation; ISO:RGD.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13194; FERM_C_ERM; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 6.10.360.10; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR011174; ERM.
DR InterPro; IPR041789; ERM_FERM_C.
DR InterPro; IPR000798; Ez/rad/moesin-like.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR019747; FERM_CS.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR018979; FERM_N.
DR InterPro; IPR018980; FERM_PH-like_C.
DR InterPro; IPR008954; Moesin_tail_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR23281; PTHR23281; 1.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR PIRSF; PIRSF002305; ERM; 1.
DR PRINTS; PR00935; BAND41.
DR PRINTS; PR00661; ERMFAMILY.
DR SMART; SM00295; B41; 1.
DR SMART; SM01196; FERM_C; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF48678; SSF48678; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Tumor suppressor; Ubl conjugation.
FT CHAIN <1..586
FT /note="Merlin"
FT /id="PRO_0000219415"
FT DOMAIN 18..307
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 325..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 557..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35240"
FT MOD_RES 514
FT /note="Phosphoserine; by PAK"
FT /evidence="ECO:0000250|UniProtKB:P35240"
FT NON_TER 1
SQ SEQUENCE 586 AA; 68712 MW; 2385AF8461407B24 CRC64;
IASRMSFSSL KRKQPKTFTV RIVTMDAEME FNCEMKWKGK DLFDLVCRTL GLRETWFFGL
QYTIKDTVAW LKMDKKVLDH DVSKEEPVTF HFLAKFYPEN AEEELVQEIT QHLFFLQVKK
QILDEKVYCP PEASVLLASY AVQAKYGDYD PSVHKRGFLA QEELLPKRVI NLYQMTPEMW
EERITAWYAE HRGRARDEAE MEYLKIAQDL EMYGVNYFTI RNKKGTELLL GVDALGLHIY
DPENRLTPKI SFPWNEIRNI SYSDKEFTIK PLDKKIDVFK FNSSKLRVNK LILQLCIGNH
DLFMRRRKAD SLEVQQMKAQ AREEKARKQM ERQRLAREKQ MREEAERSRD EPERRVLHMK
EEATMANEAL MRSEETADLL AEKAQITEEE AKLLAQKAAE AEQEMQRIKA TAIRTEEEKR
LMEQKVLEAE VLALKMAEES ERRAKEADQL KQDLQEAREA ERRAKQKLLE IATKPTYPPM
NPIPAPLPPD IPSFDIIGDS LSFDFKDTDM KRLSMEIEKE KVEYMEKSKH LQEQLNELKT
EIEALKLKER ETALDILHSE HSDSGTSSKH NTIKKPQAQG RRPICI
