CARD14
| CARD14 | |||||||||||||||||
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| Identifiers | |||||||||||||||||
| Aliases | CARD14, BIMP2, CARMA2, PRP, PSORS2, PSS1, caspase recruitment domain family member 14 | ||||||||||||||||
| External IDs | MGI: 2386258 HomoloGene: 11469 GeneCards: CARD14 | ||||||||||||||||
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| Orthologs | |||||||||||||||||
| Species | Human | Mouse | |||||||||||||||
| Entrez | |||||||||||||||||
| Ensembl | |||||||||||||||||
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| Location (UCSC) | Chr 17: 80.17 – 80.21 Mb | Chr 11: 119.31 – 119.35 Mb | |||||||||||||||
| PubMed search | [1] | [2] | |||||||||||||||
| Wikidata | |||||||||||||||||
| View/Edit Human | View/Edit Mouse |
Caspase recruitment domain-containing protein 14, also known as CARD-containing MAGUK protein 2 (Carma 2), is a protein that in humans is encoded by the CARD14 gene.[3][4][5]
Function
The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein shares a similar domain structure with CARD11 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-κB activation. The homotypic interaction with BCL10 is believed to be prevented by the linker region of CARD14, when in an inactive state.[6] CARD14 overexpression leads to an activation of the transcription factor NF-κB and phosphorylation of BCL10. CARD14 has been shown to form a CBM signalosome, similar to the signalling of CARD11, with BCL10 and MALT1.[3][6]
Link to Psoriasis
The CARD14 gene was recently identified as the first gene directly linked to the most common form of Psoriasis. It has been suggested that a mutation in the gene plus an environmental trigger were enough to elicit plaque psoriasis.[7][8] These rare, but highly penetrant, mutations were found to disrupt an auto-inhibited state of CARD14, which leads to the binding of BCL10 and the activation of NF-κB.[6]
References
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- 1 2 "Entrez Gene: caspase recruitment domain family".
- ↑ Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES (April 2001). "CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B". J. Biol. Chem. 276 (15): 11877–82. doi:10.1074/jbc.M010512200. PMID 11278692.
- ↑ Gaide O, Martinon F, Micheau O, Bonnet D, Thome M, Tschopp J (May 2001). "Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation". FEBS Lett. 496 (2-3): 121–7. doi:10.1016/S0014-5793(01)02414-0. PMID 11356195.
- 1 2 3 Howes, A; O'Sullivan, PA; Breyer, F; Ghose, A; Cao, L; Krappmann, D; Bowcock, AM; Ley, SC (12 April 2016). "Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation.". The Biochemical Journal. 473: 1759–68. doi:10.1042/BCJ20160270. PMID 27071417.
- ↑ Jordan CT, Cao L, Roberson EDO et al.. Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. The American Journal of Human Genetics. April 19, 2012. doi:10.1016/j.ajhg.2012.03.013.
- ↑ Jordan CT, Cao L, Roberson EDO et al.. PSORS2 is due to mutations in CARD14. The American Journal of Human Genetics. April 19, 2012. doi:10.1016/j.ajhg.2012.03.012.
Further reading
- Wang L, Guo Y, Huang WJ, et al. (2001). "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B.". J. Biol. Chem. 276 (24): 21405–9. doi:10.1074/jbc.M102488200. PMID 11259443.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.