SEC61A1

The protein encoded by this gene belongs to the SECY/SEC61- alpha family. It appears to play a crucial role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. This protein found to be tightly associated with membrane-bound ribosomes, either directly or through adaptor proteins. This gene encodes an alpha subunit of the heteromeric SEC61 complex, which also contains beta and gamma subunits.

Full Name

Sec61 translocon alpha 1 subunit

Function

Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER) (PubMed:12475939, PubMed:22375059, PubMed:29719251, PubMed:32814900, PubMed:28782633).
Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides (PubMed:22375059, PubMed:29719251, PubMed:28782633).
May cooperate with auxiliary protein SEC62, SEC63 and HSPA5/BiP to enable post-translational transport of small presecretory proteins (PubMed:22375059, PubMed:29719251).
Component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis (PubMed:32820719).
The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER (PubMed:8616892).
Controls the passive efflux of calcium ions from the ER lumen to the cytosol through SEC61 channel, contributing to the maintenance of cellular calcium homeostasis (PubMed:28782633).
Plays a critical role in nephrogenesis, specifically at pronephros stage (By similarity).

Biological Process

Biological Process cotranslational protein targeting to membraneManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process endoplasmic reticulum organizationManual Assertion Based On ExperimentIMP:MGI
Biological Process post-translational protein targeting to endoplasmic reticulum membraneManual Assertion Based On ExperimentIMP:MGI
Biological Process post-translational protein targeting to membrane, translocationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process pronephric nephron developmentISS:UniProtKB
Biological Process protein insertion into ER membraneManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein targeting to ERISS:UniProtKB
Biological Process SRP-dependent cotranslational protein targeting to membraneManual Assertion Based On ExperimentIMP:MGI
Biological Process SRP-dependent cotranslational protein targeting to membrane, translocationManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Endoplasmic reticulum membrane
Localizes exclusively in granular structures in the endoplasmic reticulum (ER).

Involvement in disease

Tubulointerstitial kidney disease, autosomal dominant, 5 (ADTKD5):
A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance.

Topology

Cytoplasmic: 1-33
Helical: 34-53
Lumenal: 54-76
Helical: 77-96
Cytoplasmic: 97-117
Helical: 118-138
Lumenal: 139-144
Helical: 145-165
Cytoplasmic: 166-172
Helical: 173-193
Lumenal: 194-240
Helical: 241-261
Cytoplasmic: 262-288
Helical: 289-309
Lumenal: 310-354
Helical: 355-375
Cytoplasmic: 376-420
Helical: 421-441
Lumenal: 442-445
Helical: 446-462
Cytoplasmic: 463-476