Protein transport protein Sec61 subunit alpha isoform 1 (SEC61A1)
The protein contains 476 amino acids for an estimated molecular weight of 52265 Da.
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). (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| HNFJ4 | |
| Probable disease-associated variant found in a family with hypogammag | |
| HNFJ4 |
Biological Process
Cotranslational protein targeting to membrane
Endoplasmic reticulum organization
Posttranslational protein targeting to endoplasmic reticulum membrane
Posttranslational protein targeting to membrane, translocation
Pronephric nephron development
Protein targeting to ER
Response to interferon-gamma
SRP-dependent cotranslational protein targeting to membrane
SRP-dependent cotranslational protein targeting to membrane, translocation
The reference OMIM entry for this protein is 609213
Sec61 complex, alpha-1 subunit; sec61a1
Sec61a
Sec61, s. cerevisiae, homolog of; sec61
DESCRIPTION
SEC61A1 is a subunit of the heteromeric SEC61 complex, which also contains beta (SEC61B; 609214) and gamma (SEC61G; 609215) subunits. The SEC61 complex forms the core of the mammalian endoplasmic reticulum (ER) translocon, a transmembrane channel for the translocation of proteins across the ER membrane (Greenfield and High, 1999).GENE FUNCTION
The SEC61 complex is an essential translocation component that can associate with either ribosomes or the SEC62 (602173)/SEC63 (608648) complex to perform cotranslational or posttranslational transport, respectively (Wiertz et al., 1996). It was originally thought to have a role only in translocation of proteins from the cytosol into the ER. However, Wiertz et al. (1996), Bebok et al. (1998), Chen et al. (1998), and Petaja-Repo et al. (2001) presented evidence suggesting that the human SEC61 complex can also function in retrograde transport of multidomain integral membrane proteins from the ER to the cytosol for proteasomal degradation. By immunolocalization of fluorescence-tagged canine Sec61a transfected into COS-1 cells, Greenfield and High (1999) determined that the Sec61 complex distributed to both the ER and the ER-Golgi intermediate compartment, but not to the trans-Golgi network. Endogenous Sec61b and Sec61g showed the same distribution. Another translocon component, the glycoprotein Tram (see 605190) was also present in post-ER compartments, suggesting that the core components of the mammalian ER translocon are not permanently resident in the ER, but rather they are maintained in the ER by a specific retrieval mechanism. Hessa et al. (2005) challenged the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments and determined the basic features of the code for recognition of transmembrane helices, including a 'biological' hydrophobicity scale. They found that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Hessa et al. (2005) concluded that direct protein-lipid interactions are critical during translocon-mediated membrane insertion. Transmembrane alpha-helices in integral membrane proteins are recognized cotranslationally and inserted into the membrane of the endoplasmic reticulum by the Sec61 translocon. Using in vitro translation of a model protein in the presence of dog pancreas rough microsomes to analyze a large number of systematically designed hydrophobic segments, Hessa et al. (2007) presented a quantitative analysis of the position-dependent contribution of all 20 amino acids to membrane insertion efficiency, as well as of the effects of transmembrane segment length and flanking amino acids. The resulting picture of translocon-mediated transmembrane helix assembly is simple, with the critical sequence characteristics mirroring the physical properties of the lipid bilayer.BIOCHEMICAL FEATURES
- Crystal Structure Becker et al. (2009) determined subnanometer-resolution cryoelectron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination with biochemical data, they found that in both idle and active states, the Sec complex is not oligomeric and interacts mainly via 2 cytoplasmic loops with the universal ribosomal adaptor site. In the active state, the ribosomal tunnel and a central pore of the monomeric protein-conducting channel ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 609213 was added.
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).