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CCDC22

Function

Involved in regulation of NF-kappa-B signaling. Promotes ubiquitination of I-kappa-B-kinase subunit IKBKB and its subsequent proteasomal degradation leading to NF-kappa-B activation; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. May down-regulate NF-kappa-B activity via association with COMMD1 and involving a CUL2-dependent E3 ubiquitin ligase complex. Regulates the cellular localization of COMM domain-containing proteins, such as COMMD1 and COMMD10 (PubMed:23563313). Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels. The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1 (PubMed:25355947, PubMed:28892079). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947).

(Microbial infection) The CCC complex, in collaboration with the heterotrimeric retriever complex, mediates the exit of human papillomavirus to the cell surface.

Involvement in disease

Ritscher-Schinzel syndrome 2

RTSC2

A form of Ritscher-Schinzel syndrome, a developmental malformation syndrome characterized by cerebellar brain malformations, congenital heart defects, and craniofacial abnormalities. RTSC2 is an X-linked recessive form characterized by intellectual disability associated with posterior fossa defects, cardiac malformations, and minor abnormalities of the face and distal extremities.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence Similarities

Belongs to the CCDC22 family.

Tissue Specificity

Widely expressed in adult tissues and in fetal liver and brain, with highest levels in prostate and lowest in skeletal muscle.

Cellular localization

Alternative names

CXorf37, JM1, CCDC22, Coiled-coil domain-containing protein 22

swissprot:O60826 entrezGene:28952 omim:300859