UniProt Accession

 CUL2_HUMAN; Q13617; B3KT95; B7Z6K8; D3DRY6; G3V1S2; O00200; Q5T2B6; Q9UNF9 

Genbank Protein ID

 U83410; AF126404; AK095217; AK300491; AL392046; CH471072; CH471072; CH471072; CH471072; CH471072; BC009591; BC110901; U58088 

Genbank Nucleotide ID

 AAC51190.1; AAD23581.1; BAG53007.1; BAH13294.1; CAI13163.1; EAW85924.1; EAW85925.1; EAW85926.1; EAW85927.1; EAW85928.1; AAH09591.1; AAI10902.1; AAC50545.1 

Protein Name

 Cullin-2 

Protein Synonyms/Alias

 CUL-2 

Gene Name

 CUL2 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
16	DFDETWNKLLTTIKA	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8]
149	LALDMWRKLMVEPLQ	ubiquitination	[7]
168	RMLLREIKNDRGGED	ubiquitination	[7]
382	VVNYREPKSVCKAPE	ubiquitination	[7, 8]
393	KAPELLAKYCDNLLK	acetylation	[8, 9, 10]
401	YCDNLLKKSAKGMTE	ubiquitination	[6, 7]
404	NLLKKSAKGMTENEV	ubiquitination	[4, 7]
423	TSFITVFKYIDDKDV	ubiquitination	[4, 7]
433	DDKDVFQKFYARMLA	ubiquitination	[3, 6]
462	EAMINKLKQACGYEF	ubiquitination	[7]
608	DSTQMNEKELTKTIK	acetylation	[10]
608	DSTQMNEKELTKTIK	ubiquitination	[3, 4, 8]
612	MNEKELTKTIKSLLD	acetylation	[10]
720	PSISMIKKCIEVLID	ubiquitination	[7]

Reference

 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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]
 [10] 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] 

Functional Description

 Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. May serve as a rigid scaffold in the complex and 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 ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF). 

Sequence Annotation

 MOD_RES 393 393 N6-acetyllysine.
 MOD_RES 394 394 Phosphotyrosine (By similarity).
 MOD_RES 661 661 Phosphothreonine.
 CROSSLNK 689 689 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 Acetylation; Alternative splicing; Complete proteome; Host-virus interaction; Isopeptide bond; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 745 AA 

Protein Sequence

Gene Ontology

 GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
 GO:0007050; P:cell cycle arrest; TAS:ProtInc.
 GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
 GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc.
 GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
 GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
 GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

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