cullin 3
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The CUL3 gene provides instructions for making a protein called cullin-3. This protein plays a role in the ubiquitin-proteasome system, which breaks down (degrades) unwanted proteins inside cells.
Normal function
The CUL3 gene provides instructions for making a protein called cullin-3. This protein plays a role in the ubiquitin-proteasome system, which breaks down (degrades) unwanted proteins inside cells.
The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. Cullin-3 is a core piece of a complex known as an E3 ubiquitin ligase. E3 ubiquitin ligases tag proteins with molecules called ubiquitin. Ubiquitin signals specialized cell structures known as proteasomes to attach (bind) to the tagged proteins and degrade them. The ubiquitin-proteasome system also regulates several critical cell activities by controlling the amounts of proteins involved in them.
E3 ubiquitin ligases that contain cullin-3 tag many proteins that perform a variety of functions, such as cell growth and division. These ligases also tag blood pressure-related proteins called WNK1 and WNK4, which are produced from the WNK1 and WNK4 genes. By regulating the amount of WNK1 and WNK4 available, cullin-3 plays a role in blood pressure control.
Conditions referring to this gene or chromosome
Other names
CUL-3
cullin-3 isoform 1
cullin-3 isoform 2
cullin-3 isoform 3
PHA2E
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Vidare läsning och referenser
- cullin 3; MedlinePlus, National Library of Medicine.
- Blackburn PR, Ebstein F, Hsieh TC, Motta M, Radio FC, Herkert JC, Rinne T, Thiffault I, Rapp M, Alders M, Maas S, Gerard B, Smol T, Vincent-Delorme C, Cogne B, Isidor B, Vincent M, Bachmann-Gagescu R, Rauch A, Joset P, Ferrero GB, Ciolfi A, Husson T, Guerrot AM, Bacino C, Macmurdo C, Thompson SS, Rosenfeld JA, Faivre L, Mau-Them FT, Deb W, Vignard V, Agrawal PB, Madden JA, Goldenberg A, Lecoquierre F, Zech M, Prokisch H, Necpal J, Jech R, Winkelmann J, Koprusakova MT, Konstantopoulou V, Younce JR, Shinawi M, Mighton C, Fung C, Morel C, Ellis JL, DiTroia S, Barth M, Bonneau D, Krapels I, Stegmann S, van der Schoot V, Brunet T, Bussmann C, Mignot C, Courtin T, Ravelli C, Keren B, Ziegler A, Hasadsri L, Pichurin PN, Klee EW, Grand K, Sanchez-Lara PA, Kruger E, Bezieau S, Klinkhammer H, Krawitz PM, Eichler EE, Tartaglia M, Kury S, Wang T. Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder. medRxiv [Preprint]. 2023 Jun 16:2023.06.13.23290941. doi: 10.1101/2023.06.13.23290941.
- Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, Tikhonova IR, Bjornson R, Mane SM, Colussi G, Lebel M, Gordon RD, Semmekrot BA, Poujol A, Valimaki MJ, De Ferrari ME, Sanjad SA, Gutkin M, Karet FE, Tucci JR, Stockigt JR, Keppler-Noreuil KM, Porter CC, Anand SK, Whiteford ML, Davis ID, Dewar SB, Bettinelli A, Fadrowski JJ, Belsha CW, Hunley TE, Nelson RD, Trachtman H, Cole TR, Pinsk M, Bockenhauer D, Shenoy M, Vaidyanathan P, Foreman JW, Rasoulpour M, Thameem F, Al-Shahrouri HZ, Radhakrishnan J, Gharavi AG, Goilav B, Lifton RP. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature. 2012 Jan 22;482(7383):98-102. doi: 10.1038/nature10814.
- Kato K, Miya F, Oka Y, Mizuno S, Saitoh S. A novel missense variant in CUL3 shows altered binding ability to BTB-adaptor proteins leading to diverse phenotypes of CUL3-related disorders. J Hum Genet. 2021 May;66(5):491-498. doi: 10.1038/s10038-020-00868-9. Epub 2020 Oct 31.
- McCormick JA, Yang CL, Zhang C, Davidge B, Blankenstein KI, Terker AS, Yarbrough B, Meermeier NP, Park HJ, McCully B, West M, Borschewski A, Himmerkus N, Bleich M, Bachmann S, Mutig K, Argaiz ER, Gamba G, Singer JD, Ellison DH. Hyperkalemic hypertension-associated cullin 3 promotes WNK signaling by degrading KLHL3. J Clin Invest. 2014 Nov;124(11):4723-36. doi: 10.1172/JCI76126. Epub 2014 Sep 24.
- Ohta A, Schumacher FR, Mehellou Y, Johnson C, Knebel A, Macartney TJ, Wood NT, Alessi DR, Kurz T. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. Biochem J. 2013 Apr 1;451(1):111-22. doi: 10.1042/BJ20121903.
- Shibata S, Zhang J, Puthumana J, Stone KL, Lifton RP. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7838-43. doi: 10.1073/pnas.1304592110. Epub 2013 Apr 1.
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12 Sept 2023 | Senaste versionen
1 sept 2023 | Ursprungligen publicerad
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