MERL_PAPAN
ID MERL_PAPAN Reviewed; 595 AA.
AC P59750; Q866X1;
DT 27-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Merlin;
DE AltName: Full=Moesin-ezrin-radixin-like protein;
DE AltName: Full=Neurofibromin-2;
DE AltName: Full=Schwannomin;
GN Name=NF2;
OS Papio anubis (Olive baboon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Papio.
OX NCBI_TaxID=9555;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12925885; DOI=10.1007/s00335-003-3011-3;
RA Hansson C.M., Ali H., Bruder C.E., Fransson I., Kluge S., Andersson B.,
RA Roe B.A., Menzel U., Dumanski J.P.;
RT "Strong conservation of the human NF2 locus based on sequence comparison in
RT five species.";
RL Mamm. Genome 14:526-536(2003).
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 (By similarity). {ECO:0000250|UniProtKB:P35240}.
CC -!- SUBUNIT: Interacts with SLC9A3R1, HGS and AGAP2. Interacts with SGSM3.
CC Interacts (via FERM domain) with MPP1 (By similarity). Interacts with
CC LAYN and WWC1. Interacts with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3
CC ubiquitin-protein ligase complex. The unphosphorylated form interacts
CC (via FERM domain) with VPRBP/DCAF1. Interacts (via FERM domain) with
CC NOP53; the interaction is direct. Interacts with SCHIP1; the
CC interaction is direct. {ECO:0000250|UniProtKB:P35240}.
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: Phosphorylation of Ser-518 inhibits nuclear localization by
CC disrupting the intramolecular association of the FERM domain with the
CC C-terminal tail. {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-518 inhibits nuclear localization by
CC disrupting the intramolecular association of the FERM domain with the
CC C-terminal tail. The dephosphorylation of Ser-518 favors the
CC interaction with NOP53. {ECO:0000250|UniProtKB:P35240}.
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DR EMBL; AY123429; AAO23133.1; -; Genomic_DNA.
DR EMBL; AY123428; AAO23133.1; JOINED; Genomic_DNA.
DR RefSeq; XP_003905442.1; XM_003905393.3.
DR AlphaFoldDB; P59750; -.
DR SMR; P59750; -.
DR STRING; 9555.ENSPANP00000013097; -.
DR Ensembl; ENSPANT00000019023; ENSPANP00000013097; ENSPANG00000008277.
DR GeneID; 101024601; -.
DR KEGG; panu:101024601; -.
DR CTD; 4771; -.
DR eggNOG; KOG3529; Eukaryota.
DR GeneTree; ENSGT01020000230354; -.
DR HOGENOM; CLU_003623_6_1_1; -.
DR OMA; KERVDYW; -.
DR OrthoDB; 627741at2759; -.
DR Proteomes; UP000028761; Chromosome 16.
DR Bgee; ENSPANG00000008277; Expressed in postnatal subventricular zone and 68 other tissues.
DR ExpressionAtlas; P59750; baseline.
DR GO; GO:0005912; C:adherens junction; IEA:Ensembl.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0032154; C:cleavage furrow; IEA:Ensembl.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0030175; C:filopodium; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0001726; C:ruffle; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0045216; P:cell-cell junction organization; IEA:Ensembl.
DR GO; GO:0007398; P:ectoderm development; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0010626; P:negative regulation of Schwann cell proliferation; IEA:Ensembl.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0033687; P:osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
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:0035330; P:regulation of hippo signaling; IEA:Ensembl.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; IEA:Ensembl.
DR GO; GO:1900180; P:regulation of protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0014010; P:Schwann cell proliferation; IEA:Ensembl.
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 3: Inferred from homology;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Tumor suppressor; Ubl conjugation.
FT CHAIN 1..595
FT /note="Merlin"
FT /id="PRO_0000219414"
FT DOMAIN 22..311
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35240"
FT MOD_RES 518
FT /note="Phosphoserine; by PAK"
FT /evidence="ECO:0000250|UniProtKB:P35240"
SQ SEQUENCE 595 AA; 69663 MW; A15F5FC5DB3AA8EC CRC64;
MAGAIASRMS FSSLKRKQPK TFTVRIVTMD AEMEFNCEMK WKGKDLFDLV CRTLGLRETW
FFGLQYTIKD TVAWLKMDKK VLDHDVSKEE PVTFHFLAKF YPENAEEELV QEITQHLFFL
QVKKQILDEK IYCPPEASVL LASYAVQAKY GDYDPSVHKR GFLAQEELLP KRVINLYQMT
PEMWEERITA WYAEHRGRAR DEAEMEYLKI AQDLEMYGVN YFAIRNKKGT ELLLGVDALG
LHIYDPENRL TPKISFPWNE IRNISYSDKE FTIKPLDKKI DVFKFNSSKL RVNKLILQLC
IGNHDLFMRR RKADSLEVQQ MKAQAREEKA RKQMERQRLA REKQMREEAE RTRDELERRL
LQMKEEATMA NEALMRSEET ADLLAEKAQI TEEEAKLLAQ KAAEAEQEMQ RIKATAIRTE
EEKRLMEQKV LEAEVLALKM AEESERRAKE ADQLKQDLQE AREAERRAKQ KLLEIATKPT
YPPMNPIPAP LPPDIPSFSL IGDSLSFDFK DTDMKRLSME IEKEKVEYME KSKHLQEQLN
ELKTEIEALK LKERETALDI LHNENSDRGG SSKHNTIKKL TLQSAKSRVA FFEEL
