CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-016344
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase MIB1 
Protein Synonyms/Alias
 DAPK-interacting protein 1; DIP-1; Mind bomb homolog 1; Zinc finger ZZ type with ankyrin repeat domain protein 2 
Gene Name
 MIB1 
Gene Synonyms/Alias
 DIP1; KIAA1323; ZZANK2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
25VVRGPDWKWGKQDGGubiquitination[1]
28GPDWKWGKQDGGEGHubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]
79DSAPTGIKHDGTMCDubiquitination[1, 5, 13, 14]
202VLWDNGAKNLYRVGFubiquitination[1, 5, 6, 7, 11, 12, 13, 14]
222LKCVQDAKGGSFYRDubiquitination[1, 5, 10, 12, 13, 14]
313FNPAVLTKANIVRSGubiquitination[5, 13]
368AMLPTLGKVGRVQQIubiquitination[1, 5, 6, 12, 13, 14]
399YNPAAVSKVASAGSAubiquitination[1, 5, 13]
420ERLSQLLKKLFETQEubiquitination[1, 6]
421RLSQLLKKLFETQESubiquitination[1, 2, 4, 5, 6, 9, 10, 11, 12, 13, 14]
437DLNEELVKAAANGDVubiquitination[1, 5, 6, 12, 13, 14]
452AKVEDLLKRPDVDVNubiquitination[1]
485DILKLLLKQNVDVEAubiquitination[1, 5, 6, 7, 10, 12, 13, 14]
495VDVEAEDKDGDRAVHubiquitination[6, 12, 14]
540PLHIAVNKGHLQVVKubiquitination[5, 13]
618AMRVLLSKLPRPWIVubiquitination[1, 5, 6, 12, 13]
691LLVRAGAKLDIQDKDubiquitination[1, 9, 14]
726QDMQDVGKVDAAWEPubiquitination[1, 5, 6, 12, 13, 14]
735DAAWEPSKNTLIMGLubiquitination[1, 5, 6, 12, 13, 14]
749LGTQGAEKKSAASIAubiquitination[1, 5, 6, 12, 13]
750GTQGAEKKSAASIACubiquitination[1, 14]
771ADLSIRNKKGQSPLDubiquitination[1, 10]
772DLSIRNKKGQSPLDLubiquitination[1, 10, 14]
787CPDPNLCKALAKCHKubiquitination[1, 5, 6, 7, 13, 14]
791NLCKALAKCHKEKVSubiquitination[14]
796LAKCHKEKVSGQVGSubiquitination[6, 9, 14]
826CMVCSDMKRDTLFGPubiquitination[6]
854VKKCLICKEQVQSRTubiquitination[1, 12, 14]
872ECVVCSDKKAAVLFQubiquitination[6, 14]
873CVVCSDKKAAVLFQPubiquitination[1, 14]
895ENCANLMKKCVQCRAubiquitination[7, 10, 14]
917FIMCCGGKSSEDATDubiquitination[1, 12, 14]
936GNIPVLQKDKDNTNVubiquitination[1, 5, 6, 12, 13, 14]
938IPVLQKDKDNTNVNAubiquitination[1, 6, 12, 14]
949NVNADVQKLQQQLQDubiquitination[1, 5, 6, 12, 13, 14]
958QQQLQDIKEQTMCPVubiquitination[1]
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] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [3] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [4] 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]
 [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] 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]
 [7] 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]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] 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]
 [13] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [14] 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] 
Functional Description
 E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF- induced apoptosis (By similarity). Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation. 
Sequence Annotation
 DOMAIN 6 74 MIB/HERC2 1.
 DOMAIN 143 221 MIB/HERC2 2.
 REPEAT 430 460 ANK 1.
 REPEAT 463 492 ANK 2.
 REPEAT 496 525 ANK 3.
 REPEAT 529 558 ANK 4.
 REPEAT 562 591 ANK 5.
 REPEAT 595 627 ANK 6.
 REPEAT 631 661 ANK 7.
 REPEAT 665 694 ANK 8.
 REPEAT 698 729 ANK 9.
 ZN_FING 79 126 ZZ-type.
 ZN_FING 819 854 RING-type 1.
 ZN_FING 866 901 RING-type 2.
 ZN_FING 963 996 RING-type 3.  
Keyword
 ANK repeat; Cell membrane; Coiled coil; Complete proteome; Cytoplasm; Disease mutation; Ligase; Membrane; Metal-binding; Notch signaling pathway; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1006 AA 
Protein Sequence
MSNSRNNRVM VEGVGARVVR GPDWKWGKQD GGEGHVGTVR SFESPEEVVV VWDNGTAANY 60
RCSGAYDLRI LDSAPTGIKH DGTMCDTCRQ QPIIGIRWKC AECTNYDLCT VCYHGDKHHL 120
RHRFYRITTP GSERVLLESR RKSKKITARG IFAGARVVRG VDWQWEDQDG GNGRRGKVTE 180
IQDWSASSPH SAAYVLWDNG AKNLYRVGFE GMSDLKCVQD AKGGSFYRDH CPVLGEQNGN 240
RNPGGLQIGD LVNIDLDLEI VQSLQHGHGG WTDGMFETLT TTGTVCGIDE DHDIVVQYPS 300
GNRWTFNPAV LTKANIVRSG DAAQGAEGGT SQFQVGDLVQ VCYDLERIKL LQRGHGEWAE 360
AMLPTLGKVG RVQQIYSDSD LKVEVCGTSW TYNPAAVSKV ASAGSAISNA SGERLSQLLK 420
KLFETQESGD LNEELVKAAA NGDVAKVEDL LKRPDVDVNG QCAGHTAMQA ASQNGHVDIL 480
KLLLKQNVDV EAEDKDGDRA VHHAAFGDEG AVIEVLHRGS ADLNARNKRR QTPLHIAVNK 540
GHLQVVKTLL DFGCHPSLQD SEGDTPLHDA ISKKRDDILA VLLEAGADVT ITNNNGFNAL 600
HHAALRGNPS AMRVLLSKLP RPWIVDEKKD DGYTALHLAA LNNHVEVAEL LVHQGNANLD 660
IQNVNQQTAL HLAVERQHTQ IVRLLVRAGA KLDIQDKDGD TPLHEALRHH TLSQLRQLQD 720
MQDVGKVDAA WEPSKNTLIM GLGTQGAEKK SAASIACFLA ANGADLSIRN KKGQSPLDLC 780
PDPNLCKALA KCHKEKVSGQ VGSRSPSMIS NDSETLEECM VCSDMKRDTL FGPCGHIATC 840
SLCSPRVKKC LICKEQVQSR TKIEECVVCS DKKAAVLFQP CGHMCACENC ANLMKKCVQC 900
RAVVERRVPF IMCCGGKSSE DATDDISSGN IPVLQKDKDN TNVNADVQKL QQQLQDIKEQ 960
TMCPVCLDRL KNMIFLCGHG TCQLCGDRMS ECPICRKAIE RRILLY 1006 
Gene Ontology
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0031410; C:cytoplasmic vesicle; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0031965; C:nuclear membrane; IDA:HPA.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0004842; F:ubiquitin-protein ligase activity; IEA:InterPro.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0001568; P:blood vessel development; IEA:Compara.
 GO:0001947; P:heart looping; IEA:Compara.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0045665; P:negative regulation of neuron differentiation; IEA:Compara.
 GO:0001841; P:neural tube formation; IEA:Compara.
 GO:0007219; P:Notch signaling pathway; TAS:Reactome.
 GO:0045807; P:positive regulation of endocytosis; IEA:Compara.
 GO:0001756; P:somitogenesis; IEA:Compara. 
Interpro
 IPR002110; Ankyrin_rpt.
 IPR020683; Ankyrin_rpt-contain_dom.
 IPR010606; Mib_Herc2.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR000433; Znf_ZZ. 
Pfam
 PF00023; Ank
 PF12796; Ank_2
 PF06701; MIB_HERC2
 PF00569; ZZ 
SMART
 SM00248; ANK
 SM00184; RING
 SM00291; ZnF_ZZ 
PROSITE
 PS50297; ANK_REP_REGION
 PS50088; ANK_REPEAT
 PS51416; MIB_HERC2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2
 PS01357; ZF_ZZ_1
 PS50135; ZF_ZZ_2 
PRINTS
 PR01415; ANKYRIN.