CUL3
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| Location (UCSC) | Chr 2: 224.47 – 224.59 Mb | Chr 1: 80.24 – 80.32 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Cullin 3 is a protein that in humans is encoded by the CUL3 gene.[5][6][7]
Cullin 3 protein belongs to the family of cullins which in mammals contains eight proteins (Cullin 1, Cullin 2, Cullin 3, Cullin 4A, Cullin 4B, Cullin 5, Cullin 7 and Cullin 9).[8] Cullin proteins are an evolutionarily conserved family of proteins throughout yeast, plants and mammals.[9]
Protein function
Cullin 3 is a component of Cullin-
Deletion of CUL3 gene in mice causes embryonic lethality.[13]
Cullin 3-RING E3 ubiquitin ligases
Cullin 3-RING complex consists of Cullin 3 protein, RING-box protein 1 (
Activation of the complex is regulated by the attachment of the ubiquitin-like protein NEDD8 to a conserved Lys residue in the cullin-homology domain, the process called neddylation.[16] Deneddylation is conducted by an eight-subunit CSN complex which mediates the cleavage of the isopeptidic bond between NEDD8 and cullin protein.[17] Another protein that interacts with cullin is CAND1 which binds to deneddylated form of cullin protein and disrupts the interaction between cullin and other subunits of the complex leading to inhibition of the E3 ubiquitin ligase activity.[18] Therefore, dynamic neddylation and deneddylation of cullin is important for regulation of CRL complex activity.[19]
Clinical significance
Familial hyperkalemic hypertension
Mutations in CUL3 gene are associated with Familial hyperkalemic hypertension disease. CRL complex containing Cullin 3 controls the activity of
Neurodevelopmental Disorders
Cullin 3 is heavily involved in the regulation of the central nervous system. Cullin 3 expression levels in the central nervous system change during fetal development, infancy, childhood and adulthood suggesting that the protein's expression plays a crucial role in brain development. The CUL3 gene has been identified as a risk gene for neurodevelopmental disorders particularly
Cancer
Deregulation of Cullin 3 expression level was observed in human cancers. It was shown that Cullin 3 is overexpressed in invasive cancers, and the protein expression level positively correlates with tumour stage. In breast cancer, the overexpression of Cullin 3 protein results in a decrease of
Interactions
CUL3 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000036257 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004364 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 15805562.
- PMID 17192413.
- ^ "Entrez Gene: CUL3 cullin 3".
- PMID 29128526.
- PMID 21554755.
- PMID 28499918.
- PMID 27200299.
- S2CID 24159190.
- PMID 29128526.
- PMID 29128526.
- PMID 25886174.
- S2CID 24159190.
- PMID 25886174.
- PMID 17439941.
- S2CID 17834925.
- PMID 27076645.
- PMID 29361671.
- PMID 37575562.
- PMID 22825334.
- PMID 12609982.
- PMID 10500095.
- PMID 18826954.
- PMID 18417180.
- PMID 18251510.
- PMID 18303015.
Further reading
- Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. PMID 8619474.
- Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. PMID 9110174.
- Michel JJ, Xiong Y (June 1998). "Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A". Cell Growth & Differentiation. 9 (6): 435–49. PMID 9663463.
- Du M, Sansores-Garcia L, Zu Z, Wu KK (September 1998). "Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family". The Journal of Biological Chemistry. 273 (38): 24289–92. PMID 9733711.
- Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (June 1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 5 (3): 169–76. PMID 9734811.
- Ohta T, Michel JJ, Schottelius AJ, Xiong Y (April 1999). "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity". Molecular Cell. 3 (4): 535–41. S2CID 19371828.
- Singer JD, Gurian-West M, Clurman B, Roberts JM (September 1999). "Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells". Genes & Development. 13 (18): 2375–87. PMID 10500095.
- Hori T, Osaka F, Chiba T, Miyamoto C, Okabayashi K, Shimbara N, Kato S, Tanaka K (November 1999). "Covalent modification of all members of human cullin family proteins by NEDD8". Oncogene. 18 (48): 6829–34. PMID 10597293.
- Maeda I, Ohta T, Koizumi H, Fukuda M (April 2001). "In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3". FEBS Letters. 494 (3): 181–5. S2CID 40693441.
- Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ (May 2001). "Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome". Science. 292 (5520): 1382–5. S2CID 14224920.
- Min KW, Hwang JW, Lee JS, Park Y, Tamura TA, Yoon JB (May 2003). "TIP120A associates with cullins and modulates ubiquitin ligase activity". The Journal of Biological Chemistry. 278 (18): 15905–10. PMID 12609982.
- Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, Chiba T, Igarashi K, Yamamoto M (August 2004). "Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2". Molecular and Cellular Biology. 24 (16): 7130–9. PMID 15282312.
- Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. PMID 15302935.
- Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (January 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology. 23 (1): 94–101. S2CID 7200157.
- Furukawa M, Xiong Y (January 2005). "BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase". Molecular and Cellular Biology. 25 (1): 162–71. PMID 15601839.
- Hernández-Muñoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M (May 2005). "Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase". Proceedings of the National Academy of Sciences of the United States of America. 102 (21): 7635–40. PMID 15897469.
- Lu L, Zhou ZM, Huang XY, Xu M, Yin LL, Wang H, Xu ZY, Sha JH (June 2005). "Identification and characterization of cul-3b, a novel hominine CUL-3 transcript variant". Asian Journal of Andrology. 7 (2): 205–11. PMID 15897978.
External links
- Human CUL3 genome location and CUL3 gene details page in the UCSC Genome Browser.
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