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used whole exome sequencing in a discovery cohort of 102 unrelated patients who were excluded for mutations in the 2 most common polycystic liver disease genes, PRKCSH (zeige PRKCSH Proteine) and SEC63 (zeige SEC63 Proteine), to identify heterozygous loss-of-function mutations in 3 additional genes, ALG8 (zeige ALG8 Proteine), GANAB (zeige GANAB Proteine), and SEC61B. Similarly to PRKCSH (zeige PRKCSH Proteine) and SEC63 (zeige SEC63 Proteine), these genes encode proteins that are integral to the protein biogenesis pathway in the endoplasmic reticulum.
Sec61beta overexpression increased tight junction modulation rates, in conjunction with enhanced delivery of claudin-4 (zeige CLDN4 Proteine) from and to plasma membranes.
Sec61beta-KD cells also exhibited altered ATP7A (zeige ATP7A Proteine) cellular distribution.
Sec61beta function provides an alternative pathway for nuclear transport that can be utilized by membrane-embedded proteins such as full-length EGFR (zeige EGFR Proteine).
This indicates that EGF (zeige EGF Proteine) receptors are trafficked from the endoplasmic reticulum to the nucleus by a novel pathway that involves the Sec61 (zeige SEC61A1 Proteine) translocon.
The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. Oligomers of the Sec61 complex form a transmembrane channel where proteins are translocated across and integrated into the ER membrane. This complex consists of three membrane proteins- alpha, beta, and gamma. This gene encodes the beta-subunit protein. The Sec61 subunits are also observed in the post-ER compartment, suggesting that these proteins can escape the ER and recycle back. There is evidence for multiple polyadenylated sites for this transcript.
Sec61 complex, beta subunit
, protein translocation complex beta
, protein transport protein SEC61 beta subunit
, protein transport protein Sec61 subunit beta
, protein translocation complex beta subunit