CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004324
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ezrin 
Protein Synonyms/Alias
 Cytovillin; Villin-2; p81 
Gene Name
 EZR 
Gene Synonyms/Alias
 VIL2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
3*****MPKPINVRVTubiquitination[1]
27IQPNTTGKQLFDQVVubiquitination[2]
35QLFDQVVKTIGLREVacetylation[3, 4, 5, 6]
35QLFDQVVKTIGLREVubiquitination[1, 2, 6, 7, 8, 9, 10]
60KGFPTWLKLDKKVSAacetylation[3, 4, 5, 6]
60KGFPTWLKLDKKVSAubiquitination[1]
72VSAQEVRKENPLQFKubiquitination[1, 8]
79KENPLQFKFRAKFYPacetylation[3]
79KENPLQFKFRAKFYPubiquitination[1, 2, 8, 10, 11, 12]
83LQFKFRAKFYPEDVAubiquitination[1, 2, 8, 11]
139AKFGDYNKEVHKSGYacetylation[3]
139AKFGDYNKEVHKSGYubiquitination[1, 2, 8, 10]
143DYNKEVHKSGYLSSEubiquitination[1, 2, 8, 10]
162QRVMDQHKLTRDQWEubiquitination[1, 2, 8, 10]
184AEHRGMLKDNAMLEYubiquitination[1, 2, 8]
209GINYFEIKNKKGTDLubiquitination[2, 8]
211NYFEIKNKKGTDLWLubiquitination[2]
212YFEIKNKKGTDLWLGubiquitination[2]
230LGLNIYEKDDKLTPKubiquitination[2]
233NIYEKDDKLTPKIGFubiquitination[8]
237KDDKLTPKIGFPWSEubiquitination[1, 2, 8, 10]
253RNISFNDKKFVIKPIacetylation[3]
253RNISFNDKKFVIKPIubiquitination[1, 2, 8]
254NISFNDKKFVIKPIDubiquitination[1, 10]
258NDKKFVIKPIDKKAPacetylation[3]
258NDKKFVIKPIDKKAPubiquitination[1]
262FVIKPIDKKAPDFVFubiquitination[2, 8]
263VIKPIDKKAPDFVFYacetylation[3]
263VIKPIDKKAPDFVFYubiquitination[1, 2, 8, 10]
296ELYMRRRKPDTIEVQubiquitination[1, 2, 8]
306TIEVQQMKAQAREEKubiquitination[2, 8]
337RETVEREKEQMMREKubiquitination[8]
344KEQMMREKEELMLRLacetylation[13]
344KEQMMREKEELMLRLubiquitination[1, 2, 7, 8]
357RLQDYEEKTKKAEREubiquitination[2, 8]
359QDYEEKTKKAERELSubiquitination[1]
412RQAVDQIKSQEQLAAubiquitination[2, 8]
427ELAEYTAKIALLEEAubiquitination[2, 8]
438LEEARRRKEDEVEEWubiquitination[2, 8]
450EEWQHRAKEAQDDLVubiquitination[1, 2, 8]
458EAQDDLVKTKEELHLubiquitination[1, 2, 8]
523KRITEAEKNERVQRQubiquitination[2, 8]
546SQARDENKRTHNDIIubiquitination[2]
Reference
 [1] 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]
 [2] 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]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [5] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [10] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [11] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [12] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [13] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
 Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
 J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330
Functional Description
 Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. 
Sequence Annotation
 DOMAIN 2 295 FERM.
 REGION 244 586 Interaction with SCYL3.
 MOD_RES 60 60 N6-acetyllysine.
 MOD_RES 146 146 Phosphotyrosine; by PDGFR.
 MOD_RES 354 354 Phosphotyrosine; by PDGFR.
 MOD_RES 535 535 Phosphoserine.
 MOD_RES 567 567 Phosphothreonine; by ROCK2 and PKC/PRKCI  
Keyword
 3D-structure; Acetylation; Cell membrane; Cell projection; Cell shape; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Membrane; Phosphoprotein; Polymorphism; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 586 AA 
Protein Sequence
MPKPINVRVT TMDAELEFAI QPNTTGKQLF DQVVKTIGLR EVWYFGLHYV DNKGFPTWLK 60
LDKKVSAQEV RKENPLQFKF RAKFYPEDVA EELIQDITQK LFFLQVKEGI LSDEIYCPPE 120
TAVLLGSYAV QAKFGDYNKE VHKSGYLSSE RLIPQRVMDQ HKLTRDQWED RIQVWHAEHR 180
GMLKDNAMLE YLKIAQDLEM YGINYFEIKN KKGTDLWLGV DALGLNIYEK DDKLTPKIGF 240
PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LQLCMGNHEL YMRRRKPDTI 300
EVQQMKAQAR EEKHQKQLER QQLETEKKRR ETVEREKEQM MREKEELMLR LQDYEEKTKK 360
AERELSEQIQ RALQLEEERK RAQEEAERLE ADRMAALRAK EELERQAVDQ IKSQEQLAAE 420
LAEYTAKIAL LEEARRRKED EVEEWQHRAK EAQDDLVKTK EELHLVMTAP PPPPPPVYEP 480
VSYHVQESLQ DEGAEPTGYS AELSSEGIRD DRNEEKRITE AEKNERVQRQ LLTLSSELSQ 540
ARDENKRTHN DIIHNENMRQ GRDKYKTLRQ IRQGNTKQRI DEFEAL 586 
Gene Ontology
 GO:0005884; C:actin filament; IDA:HGNC.
 GO:0045177; C:apical part of cell; IDA:BHF-UCL.
 GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
 GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
 GO:0030863; C:cortical cytoskeleton; TAS:HGNC.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0019898; C:extrinsic to membrane; IDA:UniProtKB.
 GO:0030175; C:filopodium; IDA:BHF-UCL.
 GO:0005932; C:microtubule basal body; IEA:Compara.
 GO:0005902; C:microvillus; IDA:BHF-UCL.
 GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0001726; C:ruffle; IDA:UniProtKB.
 GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
 GO:0001931; C:uropod; IEA:Compara.
 GO:0051015; F:actin filament binding; IDA:UniProtKB.
 GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007016; P:cytoskeletal anchoring at plasma membrane; NAS:UniProtKB.
 GO:0030855; P:epithelial cell differentiation; IEA:Compara.
 GO:0035088; P:establishment or maintenance of apical/basal cell polarity; IEA:Compara.
 GO:0007159; P:leukocyte cell-cell adhesion; IEP:BHF-UCL.
 GO:0022614; P:membrane to membrane docking; IEP:BHF-UCL.
 GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW. 
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.