UniProt Accession

 CUL4A_HUMAN; Q13619; A2A2W2; O75834; Q589T6; Q5TC62; Q6UP08; Q9UP17 

Genbank Protein ID

 AF077188; AY365124; AB178950; AL136221; AL136221; BC008308; AB012193; U58090 

Genbank Nucleotide ID

 AAD45191.1; AAR13072.1; BAD93235.1; CAM18410.1; CAI13795.1; AAH08308.2; BAA33146.1; AAC50547.1 

Protein Name

 Cullin-4A 

Protein Synonyms/Alias

 CUL-4A 

Gene Name

 CUL4A 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
8	MADEAPRKGSFSALV	ubiquitination	[1]
33	ALAAAPAKPGGAGGS	ubiquitination	[2]
104	KVSPMLYKQLRQACE	ubiquitination	[1, 3]
186	RTHIISDKMVQSKTI	ubiquitination	[4]
234	YKDSFELKFLEETNC	ubiquitination	[4]
265	EYLNHVSKRLEEEGD	ubiquitination	[1]
391	ERFVNLMKESFETFI	ubiquitination	[4, 5]
422	SKLRAGNKEATDEEL	ubiquitination	[4, 6, 7]
496	SKLEGMFKDMELSKD	ubiquitination	[5]
641	GKARVLIKSPKGKEV	acetylation	[8]
646	LIKSPKGKEVEDGDK	ubiquitination	[1]
708	VRIMKMRKTLGHNLL	ubiquitination	[5]
749	RDYMERDKDNPNQYH	ubiquitination	[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] Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry.
 Meierhofer D, Wang X, Huang L, Kaiser P.
 J Proteome Res. 2008 Oct;7(10):4566-76. [PMID: 18781797]
 [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] 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]
 [5] 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]
 [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] 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]
 [8] 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] 

Functional Description

 Core component of multiple cullin-RING-based 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. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. In association with RBX1, DDB1 and DDB2 is required for histone H3 and histone H4 ubiquitination in response to ultraviolet and may be important for subsequent DNA repair. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. 

Sequence Annotation

 MOD_RES 10 10 Phosphoserine.
 CROSSLNK 33 33 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 705 705 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Alternative splicing; Complete proteome; DNA damage; DNA repair; Host-virus interaction; Isopeptide bond; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 759 AA 

Protein Sequence

Gene Ontology

 GO:0031464; C:Cul4A-RING ubiquitin ligase complex; IDA:UniProtKB.
 GO:0007050; P:cell cycle arrest; TAS:ProtInc.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 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:0007346; P:regulation of mitotic cell cycle; IEA:Compara.
 GO:0051246; P:regulation of protein metabolic process; IEA:Compara.
 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