PDCD6
Description
The PDCD6 (programmed cell death 6) is a protein-coding gene located on chromosome 5.
Programmed cell death protein 6 is a protein that in humans is encoded by the PDCD6 gene. This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant.
== Interactions == PDCD6 has been shown to interact with ASK1, PDCD6IP, Fas receptor, ANXA11 and PEF1.
== References ==
== Further reading ==
== External links == PDCD6 human gene location in the UCSC Genome Browser. PDCD6 human gene details in the UCSC Genome Browser.
PDCD6 is a calcium sensor that plays a critical role in various cellular processes including endoplasmic reticulum (ER)-Golgi vesicular transport, endosomal biogenesis, and membrane repair. It functions as an adapter protein, bridging unrelated proteins or stabilizing weak protein-protein interactions in response to calcium influx. Calcium binding exposes hydrophobic surfaces on PDCD6, enabling it to interact with different sets of proteins through three distinct hydrophobic pockets, ultimately leading to its translocation to cellular membranes. PDCD6 contributes to ER-Golgi transport by facilitating the association between PDCD6IP and TSG101, effectively linking the ESCRT-III and ESCRT-I complexes. In collaboration with PEF1, PDCD6 acts as a calcium-dependent adapter for the BCR(KLHL12) complex, which regulates ER-Golgi transport by controlling the size of COPII coats. Upon a rise in cytosolic calcium levels, the PDCD6-PEF1 heterodimer interacts with and bridges the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, a crucial process in neural crest specification. PDCD6 is involved in regulating the distribution and function of MCOLN1 within the endosomal pathway. It promotes the localization and polymerization of TFG at the ER exit site. PDCD6 is essential for T-cell receptor-, Fas-, and glucocorticoid-induced apoptosis. It may mediate Ca(2+)-regulated signals within the apoptotic pathway, where its interaction with DAPK1 can accelerate apoptotic cell death by enhancing caspase-3 activity. However, knockout experiments suggest that its role in apoptosis might be indirect. PDCD6 may inhibit KDR/VEGFR2-dependent angiogenesis by suppressing VEGF-induced phosphorylation of the Akt signaling pathway. In cases of HIV-1 infection, PDCD6 indirectly inhibits HIV-1 production by influencing viral Gag expression and distribution.
PDCD6 is also known as ALG-2, ALG2, PEF1B.
