UniProt Accession

 MERL_HUMAN; P35240; O95683; Q8WUJ2; Q969N0; Q969Q3; Q96T30; Q96T31; Q96T32; Q96T33; Q9BTW3; Q9UNG9; Q9UNH3; Q9UNH4 

Genbank Protein ID

 L11353; X72655; X72656; X72657; X72658; X72659; X72660; X72661; X72662; X72663; X72664; X72665; X72666; X72667; X72668; X72669; X72670; Z22664; Y18000; Y18000; AF122827; AF122828; AF123570; AF369657; AF369658; AF369661; AF369662; AF369663; AF369664; AF369665; AF369700; AF369701; CR456530; BC003112; BC020257 

Genbank Nucleotide ID

 AAA36212.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA51220.1; CAA80377.1; CAA76992.1; CAA76993.1; AAD48752.1; AAD48753.1; AAD48754.1; AAK54160.1; AAK54161.1; AAK54162.1; AAK54163.1; AAK54164.1; AAK54165.1; AAK54166.1; AAK54195.1; AAK54196.1; CAG30416.1; AAH03112.2; AAH20257.1 

Protein Name

 Merlin 

Protein Synonyms/Alias

 Moesin-ezrin-radixin-like protein; Neurofibromin-2; Schwannomerlin; Schwannomin 

Gene Name

 NF2 

Gene Synonyms/Alias

 SCH 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
159	DYDPSVHKRGFLAQE	ubiquitination	[1, 2, 3]
171	AQEELLPKRVINLYQ	ubiquitination	[4]
253	PENRLTPKISFPWNE	ubiquitination	[2]
269	RNISYSDKEFTIKPL	ubiquitination	[5]
279	TIKPLDKKIDVFKFN	acetylation	[6]
364	ERRLLQMKEEATMAN	ubiquitination	[1, 2, 7]
387	TADLLAEKAQITEEE	ubiquitination	[1, 3]
396	QITEEEAKLLAQKAA	ubiquitination	[1, 2, 3, 4, 5, 7, 8]
401	EAKLLAQKAAEAEQE	ubiquitination	[1, 2]
449	EESERRAKEADQLKQ	ubiquitination	[2]
533	VEYMEKSKHLQEQLN	ubiquitination	[2, 3, 7]
573	SDRGGSSKHNTIKKL	ubiquitination	[7]
579	SKHNTIKKLTLQSAK	ubiquitination	[2]
586	KLTLQSAKSRVAFFE	ubiquitination	[2]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [7] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [8] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 22 311 FERM.
 MOD_RES 518 518 Phosphoserine; by PAK.  

Keyword

 3D-structure; Alternative splicing; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Cytoskeleton; Deafness; Disease mutation; Membrane; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Tumor suppressor; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 595 AA 

Protein Sequence

Gene Ontology

 GO:0005912; C:adherens junction; IEA:Compara.
 GO:0032154; C:cleavage furrow; IEA:Compara.
 GO:0030864; C:cortical actin cytoskeleton; IEA:Compara.
 GO:0005856; C:cytoskeleton; TAS:ProtInc.
 GO:0005769; C:early endosome; IDA:HGNC.
 GO:0019898; C:extrinsic to membrane; IEA:InterPro.
 GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
 GO:0030027; C:lamellipodium; IEA:Compara.
 GO:0005730; C:nucleolus; IDA:HGNC.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:HGNC.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
 GO:0030036; P:actin cytoskeleton organization; IMP:HGNC.
 GO:0045216; P:cell-cell junction organization; IEA:Compara.
 GO:0007398; P:ectoderm development; IEA:Compara.
 GO:0070306; P:lens fiber cell differentiation; IEA:Compara.
 GO:0001707; P:mesoderm formation; IEA:Compara.
 GO:0030336; P:negative regulation of cell migration; TAS:HGNC.
 GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
 GO:0022408; P:negative regulation of cell-cell adhesion; IDA:HGNC.
 GO:0001953; P:negative regulation of cell-matrix adhesion; TAS:HGNC.
 GO:0008156; P:negative regulation of DNA replication; IMP:HGNC.
 GO:0043409; P:negative regulation of MAPK cascade; IEA:Compara.
 GO:0006469; P:negative regulation of protein kinase activity; IEA:Compara.
 GO:0042518; P:negative regulation of tyrosine phosphorylation of Stat3 protein; IDA:HGNC.
 GO:0042524; P:negative regulation of tyrosine phosphorylation of Stat5 protein; IDA:HGNC.
 GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Compara.
 GO:0051496; P:positive regulation of stress fiber assembly; IMP:HGNC.
 GO:0035330; P:regulation of hippo signaling cascade; IMP:UniProtKB.
 GO:0014010; P:Schwann cell proliferation; IMP:HGNC. 

Interpro

 IPR019749; Band_41_domain.
 IPR019750; Band_41_fam.
 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.
 IPR011993; PH_like_dom. 

Pfam

 PF00769; ERM
 PF09380; FERM_C
 PF00373; FERM_M
 PF09379; FERM_N 

SMART

 SM00295; B41 

PROSITE

 PS00660; FERM_1
 PS00661; FERM_2
 PS50057; FERM_3 

PRINTS

 PR00935; BAND41.
 PR00661; ERMFAMILY.