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CUL4A

Protein FULL name:

Cullin-4A,


Protein SHORT name:

CUL-4A.


CUL4A (Homo sapiens) is product of expression of CUL4A gene.


CUL4A is involved in:

NER in Homo sapiens

Keywords:



FUNCTION: 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 ubiquitiantion 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.

SUBUNIT: Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin- protein ligase complexes that seem to be formed of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the DCX(DET1-COP1) complex with the substrate recognition component DET1 and COP1. Component of the DCX(DDB2) complex with the substrate recognition component DDB2. Component of the DCX(ERCC8) complex with the putative substrate recognition component ERCC8. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Interacts with DDB1, RBX1, RNF7, CTD1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9. Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually exclusive. Interacts with VPRBP, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, RFWD2, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5 and DCAF8. May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5. Can self-associate.

INTERACTION: Q86VP6:CAND1; NbExp=2; IntAct=EBI-456106, EBI-456077; Q92466:DDB2; NbExp=1; IntAct=EBI-456106, EBI-1176171; Q15291:RBBP5; NbExp=1; IntAct=EBI-456106, EBI-592823;

PTM: Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity).

SIMILARITY: Belongs to the cullin family.


NCBI GenPept GI number(s): 108936013
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q13619 Q13619
PFAM: PF00888
PF10557
PF00888
PF10557
InterPro: IPR016157
IPR016158
IPR001373
IPR019559
IPR016159
IPR011991
IPR016157
IPR016158
IPR001373
IPR019559
IPR016159
IPR011991
CATH: None  
SCOP: None  
PDB: - -


Protein sequence:
MADEAPRKGSFSALVGRTNGLTKPAALAAAPAKPGGAGGSKKLVIKNFRD
RPRLPDNYTQDTWRKLHEAVRAVQSSTSIRYNLEELYQAVENLCSHKVSP
MLYKQLRQACEDHVQAQILPFREDSLDSVLFLKKINTCWQDHCRQMIMIR
SIFLFLDRTYVLQNSTLPSIWDMGLELFRTHIISDKMVQSKTIDGILLLI
ERERSGEAVDRSLLRSLLGMLSDLQVYKDSFELKFLEETNCLYAAEGQRL
MQEREVPEYLNHVSKRLEEEGDRVITYLDHSTQKPLIACVEKQLLGEHLT
AILQKGLDHLLDENRVPDLAQMYQLFSRVRGGQQALLQHWSEYIKTFGTA
IVINPEKDKDMVQDLLDFKDKVDHVIEVCFQKNERFVNLMKESFETFINK
RPNKPAELIAKHVDSKLRAGNKEATDEELERTLDKIMILFRFIHGKDVFE
AFYKKDLAKRLLVGKSASVDAEKSMLSKLKHECGAAFTSKLEGMFKDMEL
SKDIMVHFKQHMQNQSDSGPIDLTVNILTMGYWPTYTPMEVHLTPEMIKL
QEVFKAFYLGKHSGRKLQWQTTLGHAVLKAEFKEGKKEFQVSLFQTLVLL
MFNEGDGFSFEEIKMATGIEDSELRRTLQSLACGKARVLIKSPKGKEVED
GDKFIFNGEFKHKLFRIKINQIQMKETVEEQVSTTERVFQDRQYQIDAAI
VRIMKMRKTLGHNLLVSELYNQLKFPVKPGDLKKRIESLIDRDYMERDKD
NPNQYHYVA

CUL4A (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM Cell June 14, 1996
A new NEDD8-ligating system for cullin-4A. Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, Tanaka K, Kato S Genes Dev Aug. 1, 1998
The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers. Chen LC, Manjeshwar S, Lu Y, Moore D, Ljung BM, Kuo WL, Dairkee SH, Wernick M, Collins C, Smith HS Cancer Res Aug. 15, 1998
ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Ohta T, Michel JJ, Schottelius AJ, Xiong Y Mol Cell April 1, 1999
Covalent modification of all members of human cullin family proteins by NEDD8. Hori T, Osaka F, Chiba T, Miyamoto C, Okabayashi K, Shimbara N, Kato S, Tanaka K Oncogene Nov. 18, 1999
The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y Cell May 2, 2003
TIP120A associates with cullins and modulates ubiquitin ligase activity. Min KW, Hwang JW, Lee JS, Park Y, Tamura TA, Yoon JB J Biol Chem May 2, 2003
Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Higa LA, Mihaylov IS, Banks DP, Zheng J, Zhang H Nat Cell Biol Nov. 1, 2003
CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein. Zhang Y, Morrone G, Zhang J, Chen X, Lu X, Ma L, Moore M, Zhou P EMBO J Nov. 17, 2003
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Wertz IE, O'Rourke KM, Zhang Z, Dornan D, Arnott D, Deshaies RJ, Dixit VM Science Jan. 27, 2004
The DNA sequence and analysis of human chromosome 13. Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT Nature April 1, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Hu J, McCall CM, Ohta T, Xiong Y Nat Cell Biol Oct. 1, 2004
Cul4A physically associates with MDM2 and participates in the proteolysis of p53. Nag A, Bagchi S, Raychaudhuri P Cancer Res Nov. 15, 2004
DDB2, the xeroderma pigmentosum group E gene product, is directly ubiquitylated by Cullin 4A-based ubiquitin ligase complex. Matsuda N, Azuma K, Saijo M, Iemura S, Hioki Y, Natsume T, Chiba T, Tanaka K, Tanaka K DNA Repair (Amst) May 2, 2005
Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, Tsurimoto T, Nakayama KI, Nakayama K, Fujita M, Lygerou Z, Nishimoto T EMBO J March 8, 2006
Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome. Bondar T, Kalinina A, Khair L, Kopanja D, Nag A, Bagchi S, Raychaudhuri P Mol Cell Biol April 1, 2006
Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y Mol Cell May 5, 2006
A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Jin J, Arias EE, Chen J, Harper JW, Walter JC Mol Cell Sept. 1, 2006
Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N Nature Oct. 5, 2006
DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. He YJ, McCall CM, Hu J, Zeng Y, Xiong Y Genes Dev Nov. 1, 2006
CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H Nat Cell Biol Nov. 1, 2006
Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells--evidence for cullin dimerization. Chew EH, Poobalasingam T, Hawkey CJ, Hagen T Cell Signal May 1, 2007
Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y Anal Sci Feb. 1, 2008
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A Aug. 5, 2008
Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M Mol Cell Aug. 8, 2008
Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. Meierhofer D, Wang X, Huang L, Kaiser P J Proteome Res Oct. 1, 2008
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem June 1, 2009
A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases. Gastaldello S, Hildebrand S, Faridani O, Callegari S, Palmkvist M, Di Guglielmo C, Masucci MG Nat Cell Biol April 1, 2010


Last modification of this entry: Oct. 19, 2010.

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