CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012170
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Cullin-3 
Protein Synonyms/Alias
 CUL-3 
Gene Name
 CUL3 
Gene Synonyms/Alias
 KIAA0617 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
6**MSNLSKGTGSRKDubiquitination[1, 2, 3]
47AIQEIQRKNNSGLSFubiquitination[2]
235NSASVYIKKVEARINacetylation[4]
235NSASVYIKKVEARINubiquitination[2]
236SASVYIKKVEARINEubiquitination[2]
254RVMHCLDKSTEEPIVubiquitination[3]
262STEEPIVKVVERELIubiquitination[2, 3, 5, 6, 7]
292VHMLKNGKTEDLGCMubiquitination[1, 2, 3]
301EDLGCMYKLFSRVPNubiquitination[2, 3]
336VSEEGEGKNPVDYIQubiquitination[6, 7]
349IQGLLDLKSRFDRFLubiquitination[2, 3, 5, 6, 7, 8]
398FIDDKLKKGVKGLTEubiquitination[2]
401DKLKKGVKGLTEQEVubiquitination[2, 3, 6]
425LFRFMQEKDVFERYYubiquitination[2]
433DVFERYYKQHLARRLubiquitination[2]
444ARRLLTNKSVSDDSEubiquitination[2, 3, 6]
457SEKNMISKLKTECGCubiquitination[2]
459KNMISKLKTECGCQFacetylation[3]
459KNMISKLKTECGCQFubiquitination[2, 3]
469CGCQFTSKLEGMFRDubiquitination[2]
569TFYGPVKKEDGSEVGubiquitination[6]
638LQSLACGKPTQRVLTubiquitination[2, 3]
651LTKEPKSKEIENGHIacetylation[3]
651LTKEPKSKEIENGHIubiquitination[2]
668VNDQFTSKLHRVKIQubiquitination[2, 5]
673TSKLHRVKIQTVAAKubiquitination[2]
680KIQTVAAKQGESDPEubiquitination[2, 3]
700QKVDDDRKHEIEAAIubiquitination[5, 7]
743PSPVVIKKRIEGLIEubiquitination[2]
Reference
 [1] 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]
 [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] 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]
 [4] 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]
 [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] 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]
 [8] 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] 
Functional Description
 Core component of multiple cullin-RING-based BCR (BTB- CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. 
Sequence Annotation
 MOD_RES 450 450 Phosphoserine (By similarity).
 CROSSLNK 712 712 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Disease mutation; ER-Golgi transport; Golgi apparatus; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transport; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 768 AA 
Protein Sequence
MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS GLSFEELYRN 60
AYTMVLHKHG EKLYTGLREV VTEHLINKVR EDVLNSLNNN FLQTLNQAWN DHQTAMVMIR 120
DILMYMDRVY VQQNNVENVY NLGLIIFRDQ VVRYGCIRDH LRQTLLDMIA RERKGEVVDR 180
GAIRNACQML MILGLEGRSV YEEDFEAPFL EMSAEFFQME SQKFLAENSA SVYIKKVEAR 240
INEEIERVMH CLDKSTEEPI VKVVERELIS KHMKTIVEME NSGLVHMLKN GKTEDLGCMY 300
KLFSRVPNGL KTMCECMSSY LREQGKALVS EEGEGKNPVD YIQGLLDLKS RFDRFLLESF 360
NNDRLFKQTI AGDFEYFLNL NSRSPEYLSL FIDDKLKKGV KGLTEQEVET ILDKAMVLFR 420
FMQEKDVFER YYKQHLARRL LTNKSVSDDS EKNMISKLKT ECGCQFTSKL EGMFRDMSIS 480
NTTMDEFRQH LQATGVSLGG VDLTVRVLTT GYWPTQSATP KCNIPPAPRH AFEIFRRFYL 540
AKHSGRQLTL QHHMGSADLN ATFYGPVKKE DGSEVGVGGA QVTGSNTRKH ILQVSTFQMT 600
ILMLFNNREK YTFEEIQQET DIPERELVRA LQSLACGKPT QRVLTKEPKS KEIENGHIFT 660
VNDQFTSKLH RVKIQTVAAK QGESDPERKE TRQKVDDDRK HEIEAAIVRI MKSRKKMQHN 720
VLVAEVTQQL KARFLPSPVV IKKRIEGLIE REYLARTPED RKVYTYVA 768 
Gene Ontology
 GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
 GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005827; C:polar microtubule; IDA:UniProtKB.
 GO:0031208; F:POZ domain binding; IDA:UniProtKB.
 GO:0007050; P:cell cycle arrest; TAS:ProtInc.
 GO:0016477; P:cell migration; IMP:UniProtKB.
 GO:0048208; P:COPII vesicle coating; IMP:UniProtKB.
 GO:0008054; P:cyclin catabolic process; IDA:MGI.
 GO:0000910; P:cytokinesis; IMP:UniProtKB.
 GO:0040016; P:embryonic cleavage; ISS:UniProtKB.
 GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
 GO:0007369; P:gastrulation; IEA:Compara.
 GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
 GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc.
 GO:0000090; P:mitotic anaphase; IMP:UniProtKB.
 GO:0035024; P:negative regulation of Rho protein signal transduction; IMP:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
 GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
 GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
 GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
 GO:0017145; P:stem cell division; ISS:UniProtKB.
 GO:0043149; P:stress fiber assembly; IMP:UniProtKB.
 GO:0001831; P:trophectodermal cellular morphogenesis; IEA:Compara.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:Compara. 
Interpro
 IPR016157; Cullin_CS.
 IPR016158; Cullin_homology.
 IPR001373; Cullin_N.
 IPR019559; Cullin_neddylation_domain.
 IPR016159; Cullin_repeat-like_dom.
 IPR011991; WHTH_DNA-bd_dom. 
Pfam
 PF00888; Cullin
 PF10557; Cullin_Nedd8 
SMART
 SM00182; CULLIN
 SM00884; Cullin_Nedd8 
PROSITE
 PS01256; CULLIN_1
 PS50069; CULLIN_2 
PRINTS