InterPro domain: IPR012879

This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes [ 1 ]. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins [ 2 ]. WDR83OS/Asterix is the substrate-interacting subunit of the PAT complex, whereas CCDC47 ( Q96A33 ) is required to maintain the stability of WDR83OS/Asterix [ 2 , 2 ]. The PAT complex favors the binding to TMDs with exposed hydrophilic amino acids within the lipid bilayer and provides a membrane-embedded partially hydrophilic environment in which TMD1 binds [ 3 ].

CCDC47 is associated with various membrane-associated processes and is component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis [ 3 ]. It is also involved in the regulation of calcium ion homeostasis in the ER [ 4 ], being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway [ 5 ].

This entry also includes the uncharacterised proteins YNR021W from S. cerevisiae, C2G5.01 from S. pombe and At5g49945 from Arabidopsis.

1. An intramembrane chaperone complex facilitates membrane protein biogenesis. Nature 584, 630-634
2. Different transmembrane domains associate with distinct endoplasmic reticulum components during membrane integration of a polytopic protein. Mol Biol Cell 13, 4114-29
3. An ER translocon for multi-pass membrane protein biogenesis. Elife 9, 794-807
4. Bi-allelic CCDC47 Variants Cause a Disorder Characterized by Woolly Hair, Liver Dysfunction, Dysmorphic Features, and Global Developmental Delay. Am J Hum Genet 103, 33-43
5. Contribution of calumin to embryogenesis through participation in the endoplasmic reticulum-associated degradation activity. Dev Biol 393