CCDC22
Description
The CCDC22 (coiled-coil domain containing 22) is a protein-coding gene located on chromosome X.
Coiled-coil domain containing 22 is a protein that in humans is encoded by the CCDC22 gene. This gene encodes a protein containing a coiled-coil domain. The encoded protein functions in the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) by interacting with COMMD (copper metabolism Murr1 domain-containing) proteins. The mouse orthologous protein has been shown to bind copines, which are calcium-dependent, membrane-binding proteins that may function in calcium signaling. In humans, this gene has been identified as a novel candidate gene for syndromic X-linked intellectual disability. Mutations in CCDC22 are associated with Ritscher-Schinzel syndrome.
CCDC22 plays a key role in regulating the NF-kappa-B signaling pathway. It promotes the ubiquitination and subsequent degradation of I-kappa-B-kinase subunit IKBKB, ultimately leading to NF-kappa-B activation. This process may involve its interaction with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. Conversely, CCDC22 can also downregulate NF-kappa-B activity by associating with COMMD1 and a CUL2-dependent E3 ubiquitin ligase complex. Furthermore, CCDC22 regulates the cellular localization of COMM domain-containing proteins, such as COMMD1 and COMMD10. CCDC22 is a component of the CCC complex, which is crucial for regulating endosomal recycling of surface proteins, including integrins, signaling receptors, and channels. This complex interacts with SNX17, retriever, and WASH complexes to prevent lysosomal degradation and facilitate cell surface recycling of numerous cargos, such as integrins ITGA5:ITGB1. CCDC22 also plays a role in copper ion homeostasis by facilitating copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery. This function is likely dependent on its association within the CCC complex and cooperation with the WASH complex on early endosomes.
CCDC22 is also known as CXorf37, JM1, RTSC2.
