(data stored in ACNUC9306 zone)


ID   HS22_PE925                           STANDARD;      PRT;   595 AA.
AC   HS22_PE925;
DT   00-JAN-0000 (Rel. 1, Created)
DT   00-JAN-0000 (Rel. 2, Last sequence update)
DT   00-JAN-0000 (Rel. 3, Last annotation update)
DE   RecName: Full=Merlin;AltName: Full=Moesin-ezrin-radixin-like
DE   protein;AltName: Full=Neurofibromin-2;AltName:
DE   Full=Schwannomerlin;AltName: Full=Schwannomin; (HS22.PE925).
GN   Name=NF2; Synonyms=SCH;
OC   Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC   Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC   Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC   Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini;
OC   Hominoidea; Hominidae; Homininae; Homo.
OX   NCBI_TaxID=9606;
RN   [0]
RP   -.;
RG   -.;
RL   -.;
CC   -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS HS22.PE925.
CC       Homo sapiens chromosome 22 GRCh37  sequence 1..51244566 annotated by
CC       Ensembl
CC   -!- FUNCTION: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo)
CC       signaling pathway, a signaling pathway that plays a pivotal role
CC       in tumor suppression by restricting proliferation and promoting
CC       apoptosis. Along with WWC1 can synergistically induce the
CC       phosphorylation of LATS1 and LATS2 and can probably function in
CC       the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway.
CC       May act as a membrane stabilizing protein. May inhibit PI3 kinase
CC       by binding to AGAP2 and impairing its stimulating activity.
CC       Suppresses cell proliferation and tumorigenesis by inhibiting the
CC       CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex.
CC   -!- SUBUNIT: Interacts with SLC9A3R1, HGS and AGAP2. Interacts with
CC       LAYN (By similarity). Interacts with SGSM3. Interacts (via FERM
CC       domain) with MPP1. Interacts with WWC1. Interacts with the CUL4A-
CC       RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. The
CC       unphosphorylated form interacts (via FERM domain) with
CC       Q9BZE4:GTPBP4; NbExp=9; IntAct=EBI-1014472, EBI-1056249;
CC       Q9H204:MED28; NbExp=4; IntAct=EBI-1014472, EBI-514199;
CC       Q10728:Ppp1r12a (xeno); NbExp=2; IntAct=EBI-1014472, EBI-918263;
CC       Q3TI53:Schip1 (xeno); NbExp=2; IntAct=EBI-1014472, EBI-1397475;
CC       O14745:SLC9A3R1; NbExp=4; IntAct=EBI-1014500, EBI-349787;
CC   -!- SUBCELLULAR LOCATION: Isoform 1: Cell projection, filopodium
CC       membrane; Peripheral membrane protein; Cytoplasmic side. Cell
CC       projection, ruffle membrane; Peripheral membrane protein;
CC       Cytoplasmic side. Nucleus. Note=In a fibroblastic cell line,
CC       isoform 1 is found homogeneously distributed over the entire cell,
CC       with a particularly strong staining in ruffling membranes and
CC       filopodia. Colocalizes with MPP1 in non-myelin-forming Schwann
CC       cells. Binds with VPRBP in the nucleus. The intramolecular
CC       association of the FERM domain with the C-terminal tail promotes
CC       nuclear accumulation. The unphosphorylated form accumulates
CC       predominantly in the nucleus while the phosphorylated form is
CC       largely confined to the non-nuclear fractions.
CC   -!- SUBCELLULAR LOCATION: Isoform 7: Cytoplasm, perinuclear region.
CC       Cytoplasmic granule. Note=Observed in cytoplasmic granules
CC       concentrated in a perinuclear location. Isoform 7 is absent from
CC       ruffling membranes and filopodia.
CC   -!- SUBCELLULAR LOCATION: Isoform 9: Cytoplasm, perinuclear region.
CC       Cytoplasmic granule. Note=Observed in cytoplasmic granules
CC       concentrated in a perinuclear location. Isoform 9 is absent from
CC       ruffling membranes and filopodia.
CC   -!- SUBCELLULAR LOCATION: Isoform 10: Nucleus. Cell projection,
CC       filopodium membrane; Peripheral membrane protein; Cytoplasmic
CC       side. Cell projection, ruffle membrane; Peripheral membrane
CC       protein; Cytoplasmic side. Cytoplasm, perinuclear region.
CC       Cytoplasmic granule. Cytoplasm, cytoskeleton. Note=In a
CC       fibroblastic cell line, isoform 10 is found homogeneously
CC       distributed over the entire cell, with a particularly strong
CC       staining in ruffling membranes and filopodia.
CC       Event=Alternative splicing; Named isoforms=10;
CC       Name=1; Synonyms=I;
CC         IsoId=P35240-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P35240-2; Sequence=VSP_000492;
CC       Name=3; Synonyms=II;
CC         IsoId=P35240-3; Sequence=VSP_007050, VSP_007051;
CC       Name=4; Synonyms=delE2/3;
CC         IsoId=P35240-4; Sequence=VSP_007041, VSP_007050, VSP_007051;
CC       Name=5; Synonyms=delE3;
CC         IsoId=P35240-5; Sequence=VSP_007042, VSP_007050, VSP_007051;
CC       Name=6; Synonyms=delE2;
CC         IsoId=P35240-6; Sequence=VSP_007040, VSP_007050, VSP_007051;
CC       Name=7; Synonyms=MER150;
CC         IsoId=P35240-7; Sequence=VSP_007045, VSP_007046;
CC       Name=8;
CC         IsoId=P35240-8; Sequence=VSP_007048, VSP_007050, VSP_007051;
CC       Name=9; Synonyms=MER162;
CC         IsoId=P35240-9; Sequence=VSP_007044;
CC       Name=10; Synonyms=MER151;
CC         IsoId=P35240-10; Sequence=VSP_007041, VSP_007043, VSP_007047,
CC                                   VSP_007049;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Isoform 1 and isoform 3 are
CC       predominant. Isoform 4, isoform 5 and isoform 6 are expressed
CC       moderately. Isoform 8 is found at low frequency. Isoform 7,
CC       isoform 9 and isoform 10 are not expressed in adult tissues, with
CC       the exception of adult retina expressing isoform 10. Isoform 9 is
CC       faintly expressed in fetal brain, heart, lung, skeletal muscle and
CC       spleen. Fetal thymus expresses isoforms 1, 7, 9 and 10 at similar
CC       levels.
CC   -!- PTM: Phosphorylation of Ser-518 inhibits nuclear localization by
CC       disrupting the intramolecular association of the FERM domain with
CC       the C-terminal tail.
CC   -!- PTM: Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3
CC       ubiquitin-protein ligase complex for ubiquitination and subsequent
CC       proteasome-dependent degradation.
CC   -!- DISEASE: Defects in NF2 are the cause of neurofibromatosis 2 (NF2)
CC       [MIM:101000]; also known as central neurofibromatosis. NF2 is a
CC       genetic disorder characterized by bilateral vestibular schwannomas
CC       (formerly called acoustic neuromas), schwannomas of other cranial
CC       and peripheral nerves, meningiomas, and ependymomas. It is
CC       inherited in an autosomal dominant fashion with full penetrance.
CC       Affected individuals generally develop symptoms of eighth-nerve
CC       dysfunction in early adulthood, including deafness and balance
CC       disorder. Although the tumors of NF2 are histologically benign,
CC       their anatomic location makes management difficult, and patients
CC       suffer great morbidity and mortality.
CC   -!- DISEASE: Defects in NF2 are a cause of schwannomatosis (SCHWA)
CC       [MIM:162091]; also known as congenital cutaneous
CC       neurilemmomatosis. Schwannomas are benign tumors of the peripheral
CC       nerve sheath that usually occur singly in otherwise normal
CC       individuals. Multiple schwannomas in the same individual suggest
CC       an underlying tumor-predisposition syndrome. The most common such
CC       syndrome is NF2. The hallmark of NF2 is the development of
CC       bilateral vestibular-nerve schwannomas; but two-thirds or more of
CC       all NF2-affected individuals develop schwannomas in other
CC       locations, and dermal schwannomas may precede vestibular tumors in
CC       NF2-affected children. There have been several reports of
CC       individuals with multiple schwannomas who do not show evidence of
CC       vestibular schwannoma. Clinical report suggests that
CC       schwannomatosis is a clinical entity distinct from other forms of
CC       neurofibromatosis.
CC   -!- SIMILARITY: Contains 1 FERM domain.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/NF2117.html";
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NF2";
CC   -!- GENE_FAMILY: HOG000007113 [ FAMILY / ALN / TREE ]
DR   HOGENOM:Homo_sapiens;ENSG00000186575;ENST00000338641;ENSP00000344666.
DR   EMBL; AF122827; - ;
DR   EMBL; AF122828; - ;
DR   EMBL; AF123570; - ;
DR   EMBL; AF165426; - ;
DR   EMBL; AF369657; - ;
DR   EMBL; AF369658; - ;
DR   EMBL; AF369661; - ;
DR   EMBL; AF369662; - ;
DR   EMBL; AF369663; - ;
DR   EMBL; AF369664; - ;
DR   EMBL; AF369665; - ;
DR   EMBL; AF369700; - ;
DR   EMBL; AF369701; - ;
DR   EMBL; BC003112; - ;
DR   EMBL; BC020257; - ;
DR   EMBL; CR456530; - ;
DR   EMBL; L11353; - ;
DR   EMBL; X72655; - ;
DR   EMBL; X72656; - ;
DR   EMBL; X72657; - ;
DR   EMBL; X72658; - ;
DR   EMBL; X72659; - ;
DR   EMBL; X72660; - ;
DR   EMBL; X72661; - ;
DR   EMBL; X72662; - ;
DR   EMBL; X72663; - ;
DR   EMBL; X72664; - ;
DR   EMBL; X72665; - ;
DR   EMBL; X72666; - ;
DR   EMBL; X72667; - ;
DR   EMBL; X72668; - ;
DR   EMBL; X72669; - ;
DR   EMBL; X72670; - ;
DR   EMBL; Y18000; - ;
DR   EMBL; Z22664; - ;
DR   UniProtKB/Swiss-Prot; P35240; O95683; Q8WUJ2; Q969N0; Q969Q3; Q96T30; Q96T31; Q96T32; -.
DR   UniProtKB/Swiss-Prot; Q96T33; Q9BTW3; Q9UNG9; Q9UNH3; Q9UNH4; -.
DR   EMBL; L11353; AAA36212.1; -; mRNA.
DR   EMBL; X72655; CAA51220.1; -; Genomic_DNA.
DR   EMBL; X72656; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72657; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72658; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72659; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72660; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72661; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72662; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72663; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72664; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72665; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72666; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72667; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72668; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72669; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; X72670; CAA51220.1; JOINED; Genomic_DNA.
DR   EMBL; Z22664; CAA80377.1; -; mRNA.
DR   EMBL; Y18000; CAA76992.1; -; Genomic_DNA.
DR   EMBL; Y18000; CAA76993.1; -; Genomic_DNA.
DR   EMBL; AF122827; AAD48752.1; -; mRNA.
DR   EMBL; AF122828; AAD48753.1; -; mRNA.
DR   EMBL; AF123570; AAD48754.1; -; mRNA.
DR   EMBL; AF369657; AAK54160.1; -; mRNA.
DR   EMBL; AF369658; AAK54161.1; -; mRNA.
DR   EMBL; AF369661; AAK54162.1; -; mRNA.
DR   EMBL; AF369662; AAK54163.1; -; mRNA.
DR   EMBL; AF369663; AAK54164.1; -; mRNA.
DR   EMBL; AF369664; AAK54165.1; -; mRNA.
DR   EMBL; AF369665; AAK54166.1; -; mRNA.
DR   EMBL; AF369700; AAK54195.1; -; mRNA.
DR   EMBL; AF369701; AAK54196.1; -; mRNA.
DR   EMBL; CR456530; CAG30416.1; -; mRNA.
DR   EMBL; BC003112; AAH03112.2; -; mRNA.
DR   EMBL; BC020257; AAH20257.1; -; mRNA.
DR   IPI; IPI00216128; -.
DR   IPI; IPI00220308; -.
DR   IPI; IPI00220310; -.
DR   IPI; IPI00220311; -.
DR   IPI; IPI00220312; -.
DR   IPI; IPI00220314; -.
DR   IPI; IPI00220315; -.
DR   IPI; IPI00304755; -.
DR   IPI; IPI00414202; -.
DR   IPI; IPI00414431; -.
DR   PIR; S33809; S33809.
DR   RefSeq; NP_000259.1; NM_000268.3.
DR   RefSeq; NP_057502.2; NM_016418.5.
DR   RefSeq; NP_861546.1; NM_181825.2.
DR   RefSeq; NP_861966.1; NM_181828.2.
DR   RefSeq; NP_861967.1; NM_181829.2.
DR   RefSeq; NP_861968.1; NM_181830.2.
DR   RefSeq; NP_861969.1; NM_181831.2.
DR   RefSeq; NP_861970.1; NM_181832.2.
DR   RefSeq; NP_861971.1; NM_181833.2.
DR   UniGene; Hs.187898; -.
DR   PDB; 1H4R; X-ray; 1.80 A; A/B=1-313.
DR   PDBsum; 1H4R; -.
DR   ProteinModelPortal; P35240; -.
DR   SMR; P35240; 18-595.
DR   IntAct; P35240; 15.
DR   STRING; P35240; -.
DR   PhosphoSite; P35240; -.
DR   PRIDE; P35240; -.
DR   Ensembl; ENST00000338641; ENSP00000344666; ENSG00000186575.
DR   GeneID; 4771; -.
DR   KEGG; hsa:4771; -.
DR   UCSC; uc003afy.2; human.
DR   UCSC; uc003afz.2; human.
DR   UCSC; uc003aga.2; human.
DR   UCSC; uc003age.2; human.
DR   UCSC; uc003agh.2; human.
DR   UCSC; uc003agj.2; human.
DR   CTD; 4771; -.
DR   GeneCards; GC22P012962; -.
DR   HGNC; HGNC:7773; NF2.
DR   HPA; CAB005385; -.
DR   HPA; HPA003097; -.
DR   MIM; 101000; phenotype.
DR   MIM; 162091; phenotype.
DR   MIM; 607379; gene.
DR   neXtProt; NX_P35240; -.
DR   Orphanet; 637; Neurofibromatosis type 2.
DR   Orphanet; 93921; Neurofibromatosis type 3.
DR   PharmGKB; PA31580; -.
DR   eggNOG; prNOG08794; -.
DR   InParanoid; P35240; -.
DR   OrthoDB; EOG4NVZK5; -.
DR   NextBio; 18368; -.
DR   PMAP-CutDB; P35240; -.
DR   ArrayExpress; P35240; -.
DR   Bgee; P35240; -.
DR   Genevestigator; P35240; -.
DR   GermOnline; ENSG00000186575; Homo sapiens.
DR   GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR   GO; GO:0005769; C:early endosome; IDA:HGNC.
DR   GO; GO:0019898; C:extrinsic to membrane; IEA:InterPro.
DR   GO; GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005730; C:nucleolus; IDA:HGNC.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:HGNC.
DR   GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008092; F:cytoskeletal protein binding; IEA:InterPro.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IMP:HGNC.
DR   GO; GO:0030336; P:negative regulation of cell migration; TAS:HGNC.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
DR   GO; GO:0022408; P:negative regulation of cell-cell adhesion; IDA:HGNC.
DR   GO; GO:0001953; P:negative regulation of cell-matrix adhesion; TAS:HGNC.
DR   GO; GO:0008156; P:negative regulation of DNA replication; IMP:HGNC.
DR   GO; GO:0042518; P:negative regulation of tyrosine phosphorylation of Stat3 protein; IDA:HGNC.
DR   GO; GO:0042524; P:negative regulation of tyrosine phosphorylation of Stat5 protein; IDA:HGNC.
DR   GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:HGNC.
DR   GO; GO:0035330; P:regulation of hippo signaling cascade; IMP:UniProtKB.
DR   GO; GO:0014010; P:Schwann cell proliferation; IMP:HGNC.
DR   InterPro; IPR019749; Band_41_domain.
DR   InterPro; IPR019750; Band_41_fam.
DR   InterPro; IPR011174; ERM.
DR   InterPro; IPR011259; ERM_C.
DR   InterPro; IPR000798; Ez/rad/moesin.
DR   InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
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.
DR   InterPro; IPR011993; PH_type.
DR   Gene3D; G3DSA:; ACBP; 1.
DR   Gene3D; G3DSA:; PH_type; 1.
DR   Pfam; PF00769; ERM; 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   SMART; SM00295; B41; 1.
DR   SUPFAM; SSF47031; FERM_3-hlx; 1.
DR   SUPFAM; SSF48678; Moesin; 1.
DR   PROSITE; PS00660; FERM_1; 1.
DR   PROSITE; PS00661; FERM_2; 1.
DR   PROSITE; PS50057; FERM_3; 1.
KW   ENSG000001865751755old_1320000031; ENSP000003446667901old_1320000031;
KW   Q9NRW8_HUMAN; AF122827; AF122828; AF123570; AF165426; AF369657; AF369658;
KW   AF369662; AF369663; AF369664; AF369665; AF369700; AF369701; BC003112;
KW   CR456530; L11353; X72655; X72656; X72657; X72658; X72659; X72660; X72661;
KW   X72663; X72664; X72665; X72666; X72667; X72668; X72669; X72670; Y18000;
KW   Z22664;
KW   3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW   Complete proteome; Cytoplasm; Cytoskeleton; Deafness;
KW   Disease mutation; Membrane; Nucleus; Phosphoprotein; Polymorphism;
KW   Reference proteome; Tumor suppressor; Ubl conjugation.

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