CUL4A

Cullin 4A

PDB rendering based on 2do7.

Available structures
PDB	2do7, 2hye

Identifiers

Symbols

CUL4A;

External IDs

OMIM: 603137 MGI: 1914487 HomoloGene: 81724 GeneCards: CUL4A Gene

Gene Ontology
Molecular function	• protein binding • ubiquitin protein ligase binding
Cellular component	• cullin-RING ubiquitin ligase complex • Cul4A-RING ubiquitin ligase complex
Biological process	• G1/S transition of mitotic cell cycle • DNA repair • ubiquitin-dependent protein catabolic process • cell cycle arrest • regulation of mitotic cell cycle • negative regulation of cell proliferation • induction of apoptosis by intracellular signals • interspecies interaction between organisms • positive regulation of S phase of mitotic cell cycle • regulation of protein metabolic process • cellular response to protein stimulus
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 13:
113.86 – 113.92 Mb

Chr 8:
13.11 – 13.15 Mb

PubMed search

[1]

[2]

Cullin-4A is a protein that in humans is encoded by the CUL4A gene.^[1]^[2]

Interactions

CUL4A has been shown to interact with Merlin,^[3] DDB2,^[4] CAND1,^[5] RBX1,^[4]^[6]^[7] DDB1^[4] and P21.^[8]

References

^ Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM (Aug 1996). "cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family". Cell 85 (6): 829–39. doi:10.1016/S0092-8674(00)81267-2. PMID 8681378.
^ "Entrez Gene: CUL4A Cullin 4A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8451.
^ Huang, J; Chen J (Jul. 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene (England) 27 (29): 4056–64. doi:10.1038/onc.2008.44. PMID 18332868.
^ ^a ^b ^c Guerrero-Santoro, Jennifer; Kapetanaki Maria G, Hsieh Ching L, Gorbachinsky Ilya, Levine Arthur S, Rapić-Otrin Vesna (Jul. 2008). "The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A". Cancer Res. (United States) 68 (13): 5014–22. doi:10.1158/0008-5472.CAN-07-6162. PMID 18593899.
^ Min, Kyoeng-Woo; Hwang Ji-Won, Lee Jong-Sik, Park Yoon, Tamura Taka-aki, Yoon Jong-Bok (May. 2003). "TIP120A associates with cullins and modulates ubiquitin ligase activity". J. Biol. Chem. (United States) 278 (18): 15905–10. doi:10.1074/jbc.M213070200. ISSN 0021-9258. PMID 12609982.
^ Dias, Dora C; Dolios Georgia, Wang Rong, Pan Zhen-Qiang (Dec. 2002). "CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (26): 16601–6. doi:10.1073/pnas.252646399. ISSN 0027-8424. PMC 139190. PMID 12481031. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139190.
^ Ohta, T; Michel J J, Schottelius A J, Xiong Y (Apr. 1999). "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity". Mol. Cell (UNITED STATES) 3 (4): 535–41. doi:10.1016/S1097-2765(00)80482-7. ISSN 1097-2765. PMID 10230407.
^ Abbas, Tarek; Sivaprasad Uma, Terai Kenta, Amador Virginia, Pagano Michele, Dutta Anindya (Sep. 2008). "PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex". Genes Dev. (United States) 22 (18): 2496–506. doi:10.1101/gad.1676108. ISSN 0890-9369. PMC 2546691. PMID 18794347. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2546691.

Osaka F, Kawasaki H, Aida N, et al. (1998). "A new NEDD8-ligating system for cullin-4A.". Genes Dev. 12 (15): 2263–8. doi:10.1101/gad.12.15.2263. PMC 317039. PMID 9694792. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317039.
Chen LC, Manjeshwar S, Lu Y, et al. (1998). "The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers.". Cancer Res. 58 (16): 3677–83. PMID 9721878.
Ohta T, Michel JJ, Schottelius AJ, Xiong Y (1999). "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity.". Mol. Cell 3 (4): 535–41. doi:10.1016/S1097-2765(00)80482-7. PMID 10230407.
Hori T, Osaka F, Chiba T, et al. (2000). "Covalent modification of all members of human cullin family proteins by NEDD8.". Oncogene 18 (48): 6829–34. doi:10.1038/sj.onc.1203093. PMID 10597293.
Lyapina S, Cope G, Shevchenko A, et al. (2001). "Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.". Science 292 (5520): 1382–5. doi:10.1126/science.1059780. PMID 11337588.
Chen X, Zhang Y, Douglas L, Zhou P (2002). "UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation.". J. Biol. Chem. 276 (51): 48175–82. doi:10.1074/jbc.M106808200. PMID 11673459.
Yasui K, Arii S, Zhao C, et al. (2002). "TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas.". Hepatology 35 (6): 1476–84. doi:10.1053/jhep.2002.33683. PMID 12029633.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Liu J, Furukawa M, Matsumoto T, Xiong Y (2003). "NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases.". Mol. Cell 10 (6): 1511–8. doi:10.1016/S1097-2765(02)00783-9. PMID 12504025.
Min KW, Hwang JW, Lee JS, et al. (2003). "TIP120A associates with cullins and modulates ubiquitin ligase activity.". J. Biol. Chem. 278 (18): 15905–10. doi:10.1074/jbc.M213070200. PMID 12609982.
Groisman R, Polanowska J, Kuraoka I, et al. (2003). "The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.". Cell 113 (3): 357–67. doi:10.1016/S0092-8674(03)00316-7. PMID 12732143.
Higa LA, Mihaylov IS, Banks DP, et al. (2004). "Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint.". Nat. Cell Biol. 5 (11): 1008–15. doi:10.1038/ncb1061. PMID 14578910.
Wertz IE, O'Rourke KM, Zhang Z, et al. (2004). "Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.". Science 303 (5662): 1371–4. doi:10.1126/science.1093549. PMID 14739464.
Obuse C, Yang H, Nozaki N, et al. (2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase.". Genes Cells 9 (2): 105–20. doi:10.1111/j.1365-2443.2004.00705.x. PMID 15009096.
Dunham A, Matthews LH, Burton J, et al. (2004). "The DNA sequence and analysis of human chromosome 13.". Nature 428 (6982): 522–8. doi:10.1038/nature02379. PMC 2665288. PMID 15057823. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2665288.
Hu J, McCall CM, Ohta T, Xiong Y (2004). "Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage.". Nat. Cell Biol. 6 (10): 1003–9. doi:10.1038/ncb1172. PMID 15448697.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
Nag A, Bagchi S, Raychaudhuri P (2005). "Cul4A physically associates with MDM2 and participates in the proteolysis of p53.". Cancer Res. 64 (22): 8152–5. doi:10.1158/0008-5472.CAN-04-2598. PMID 15548678.
Matsuda N, Azuma K, Saijo M, et al. (2005). "DDB2, the xeroderma pigmentosum group E gene product, is directly ubiquitylated by Cullin 4A-based ubiquitin ligase complex.". DNA Repair (Amst.) 4 (5): 537–45. doi:10.1016/j.dnarep.2004.12.012. PMID 15811626.

PDB gallery

2do7: Solution structure of the winged helix-turn-helix motif of human CUL-4B

2hye: Crystal Structure of the DDB1-Cul4A-Rbx1-SV5V Complex

CUL4A

Interactions

References

Further reading