SEC63 (SEC63 homolog, protein translocation regulator)
SEC63 encodes an endoplasmic reticulum (ER) transmembrane protein that serves as a critical component of the protein translocation machinery and the ER-associated degradation (ERAD) pathway. As a member of the SEC63 gene family, characterized by conserved J-domains and transmembrane regions, the SEC63 protein interacts directly with the SEC61 translocon channel to facilitate the co-translational translocation of nascent polypeptide chains into the ER lumen, where they undergo proper folding and post-translational modifications. Its J-domain enables binding to the ER chaperone BiP (HSPA5), thereby regulating ATP hydrolysis to drive the folding process and maintain protein homeostasis. Dysregulation of SEC63 function has significant pathological implications; mutations in this gene are strongly associated with autosomal dominant polycystic kidney disease (ADPKD), where defective protein folding triggers ER stress and subsequent cyst formation. Additionally, SEC63 variants have been linked to hepatic conditions such as liver fibrosis and congenital hepatic fibrosis. While moderate overexpression of SEC63 may enhance ER folding capacity and alleviate stress, excessive activity can paradoxically lead to the accumulation of misfolded proteins. Conversely, reduced SEC63 expression impairs protein translocation and folding, activating the unfolded protein response (UPR) and potentially leading to apoptosis if chronic. Collectively, SEC63 plays a pivotal role in ER protein quality control, and its functional integrity is essential for maintaining cellular homeostasis and organ function.
Gene Ontology
Subcellular localization of SEC63 (and its protein):
- plasma membrane
- cytoplasm
- extracellular
- golgi
- vesicle
- cytoskeleton
- endoplasmic reticulum
- nucleus
- endosome
- lysosome
- mitochondrion
Gene Ontology (GO) terms for SEC63:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| 3060 Protein export [PATH:hsa03060] |
| 4141 Protein processing in endoplasmic reticulum [PATH:hsa04141] |
| Name |
|---|
| IRE1alpha activates chaperones |
| Metabolism of proteins |
| Unfolded Protein Response (UPR) |
| XBP1(S) activates chaperone genes |
| Disease | Score | NofPmids | NofSnps | Source |
| Polycystic liver disease | 0.442985861 | 12 | 3 | BeFree_CLINVAR_CTD_human_MGD_ORPHANET |
| Polycystic Kidney Diseases | 0.120271442 | 2 | 0 | BeFree_CTD_human |
| Liver diseases | 0.005091382 | 2 | 0 | GAD_LHGDN |
| Cyst | 0.003181358 | 4 | 0 | BeFree_GAD |
| Liver cyst | 0.000542884 | 2 | 0 | BeFree |
| Polycystic Kidney, Autosomal Dominant | 0.000271442 | 1 | 0 | BeFree |
| Cardiomyopathy, Familial Idiopathic | 0.000271442 | 1 | 0 | BeFree |
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