Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A (STT3A)
The protein contains 705 amino acids for an estimated molecular weight of 80530 Da.
Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. This subunit contains the active site and the acceptor peptide and donor lipid-linked oligosaccharide (LLO) binding pockets (By similarity). STT3A is present in the majority of OST complexes and mediates cotranslational N-glycosylation of most sites on target proteins, while STT3B-containing complexes are required for efficient post-translational glycosylation and mediate glycosylation of sites that have been skipped by STT3A (PubMed:19167329). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
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 |
|---|---|
| CDG1W |
No binding partner found
Biological Process
Co-translational protein modification
Post-translational protein modification
Protein N-linked glycosylation
Protein N-linked glycosylation via asparagine
Viral protein processing
The reference OMIM entry for this protein is 601134
Oligosaccharyltransferase complex, catalytic subunit stt3a; stt3a
Stt3, s. cerevisiae, homolog of, a
Integral membrane protein 1; itm1
Transmembrane conserved gene; tmc
DESCRIPTION
The STT3A gene encodes a catalytic subunit of the oligosaccharide (OST) protein complex that carries out glycan chain transfer to proteins in the endoplasmic reticulum. The STT3 proteins (see also STT3B; 608605) specifically transfer oligosaccharides onto asparagine residues. STT3A and STT3B exist in different OST complexes with different kinetic properties and substrate preferences, but they have overlapping roles (summary by Shrimal et al., 2013).CLONING
From a fetal mouse mandibular condyle cDNA library, Hong et al. (1996) isolated a novel cDNA coding for a highly hydrophobic protein that the authors called B5. The full-length mouse B5 cDNA was 3,095 nucleotides long and contained a potential open reading frame coding for a protein of 705 amino acids with a calculated molecular mass of 80.5 kD. The B5 mRNA was differentially polyadenylated, with the most abundant transcript having a length of 2.7 kb. Hong et al. (1996) isolated the human homolog of B5 from a cDNA testis library. The amino acid sequence of the human B5 was 98.5% identical to that of the mouse protein. A striking feature of the B5 protein was the presence of numerous (10 to 14) potential transmembrane domains, characteristic of an integral membrane protein. Similarity searches in public databases revealed that B5 is 58% similar to the T12A2.2 gene of C. elegans and 60% similar to the STT3 gene of S. cerevisiae. A human EST related to human B5 and identical to the STT3 gene indicated to Hong et al. (1996) that B5 belongs to a larger gene family coding for novel putative transmembrane proteins. They observed that this family exhibits a remarkable degree of conservation across species. Lissy et al. (1996) used differential display PCR to identify genes expressed at higher levels in malignant mesotheliomas than in normal mesothelial cells. They isolated and cloned from a human fetal brain library a full-length ITM1 cDNA, which they termed TMC. The predicted 705-amino acid protein has 13 putative transmembrane domains. Northern blot analysis revealed that the gene is expressed in a variety of human tissues, with highest expression in ovary and testis. Northern blot and RT-PCR analysis showed no differences in the level of expression among normal and malignant mesothelial cell lines tested.MAPPING
By linkage analysis, Hong et al. (1996) mapped the mouse B5 gene, which they symbolized Itm1 (for integral membrane protein-1) to chromosome 9. Based on human/mouse homology and preliminary findings in a panel of rodent/human somatic cell hybrids, the human ITM1 gene is likely to map to 11q23-q24. Van Hul et al. (1996) mapped the ITM1 gene to 11q23.3 by fluorescence in situ hybridization (FISH) and by PCR screening of a chromosome 11-specific YAC library. By FISH, Lissy et al. (1996) mapped the ITM1 gene to human chromosome 11q24-q25.MOLECULAR GENETICS
In 2 sibs, born of consanguineous Pakistani parents, with congenital disorder of glycosylation type Iw (CDG1W; 615596), Shrimal et al. (2013) identified a homozygous missense mutation in the STT3A gene (V626A; 601134.0001). The mutation was found by homozygosity mapping and candidate gene sequencing. At age 13 years, both patients showed developmental delay, failure to thrive, seizures, and hypotonia. One was more severely affected, with an inability to sit, weak visual tracking, and intractable seizures. Serum transferrin analysis showed an abnormal type I pattern of glycosy ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 601134 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).