6s7t

Structural highlights

Disease

[MAGT1_HUMAN] X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia. The disease is caused by mutations affecting the gene represented in this entry. [STT3B_HUMAN] STT3B-CDG. The disease is caused by mutations affecting the gene represented in this entry. [RPN1_HUMAN] Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2).

Function

[RPN2_HUMAN] 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.[UniProtKB:F1PCT7] [TM258_HUMAN] 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 (PubMed:26472760, PubMed:27974209). Involved in ER homeostasis in the colonic epithelium (By similarity).[UniProtKB:P61166]^{[1] [2]} [A0A024RAD5_HUMAN] 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).[RuleBase:RU361142] [MLEC_HUMAN] Carbohydrate-binding protein with a strong ligand preference for Glc2-N-glycan. May play a role in the early steps of protein N-glycosylation (By similarity). [OST4_HUMAN] May be involved in N-glycosylation through its association with N-oligosaccharyl transferase (By similarity). [MAGT1_HUMAN] Acts as accessory component of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with TUSC3. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Has also oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition.^{[3] [4]} May be involved in Mg(2+) transport in epithelial cells.^{[5] [6]} [STT3B_HUMAN] 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). STT3B is present in a small subset of OST complexes and mediates both cotranslational and post-translational N-glycosylation of target proteins: STT3B-containing complexes are required for efficient post-translational glycosylation and while they are less competent than STT3A-containing complexes for cotranslational glycosylation, they have the ability to mediate glycosylation of some nascent sites that are not accessible for STT3A. STT3B-containing complexes also act post-translationally and mediate modification of skipped glycosylation sites in unfolded proteins. Plays a role in ER-associated degradation (ERAD) pathway that mediates ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins by mediating N-glycosylation of unfolded proteins, which are then recognized by the ERAD pathway and targeted for degradation. Mediates glycosylation of the disease variant AMYL-TTR 'Asp-38' of TTR at 'Asn-118', leading to its degradation (PubMed:19167329, PubMed:22607976).[UniProtKB:P39007]^{[7] [8]} [DAD1_HUMAN] 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 (PubMed:22467853). 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 (By similarity). Required for the assembly of both SST3A- and SS3B-containing OST complexes. Loss of the DAD1 protein triggers apoptosis (PubMed:22467853).[UniProtKB:E2R4X3]^[9] [RPN1_HUMAN] 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.[UniProtKB:E2RQ08]

References

1. ↑ Blomen VA, Majek P, Jae LT, Bigenzahn JW, Nieuwenhuis J, Staring J, Sacco R, van Diemen FR, Olk N, Stukalov A, Marceau C, Janssen H, Carette JE, Bennett KL, Colinge J, Superti-Furga G, Brummelkamp TR. Gene essentiality and synthetic lethality in haploid human cells. Science. 2015 Nov 27;350(6264):1092-6. doi: 10.1126/science.aac7557. Epub 2015, Oct 15. PMID:26472760 doi:http://dx.doi.org/10.1126/science.aac7557
2. ↑ Graham DB, Lefkovith A, Deelen P, de Klein N, Varma M, Boroughs A, Desch AN, Ng ACY, Guzman G, Schenone M, Petersen CP, Bhan AK, Rivas MA, Daly MJ, Carr SA, Wijmenga C, Xavier RJ. TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation. Cell Rep. 2016 Dec 13;17(11):2955-2965. doi: 10.1016/j.celrep.2016.11.042. PMID:27974209 doi:http://dx.doi.org/10.1016/j.celrep.2016.11.042
3. ↑ Cherepanova NA, Shrimal S, Gilmore R. Oxidoreductase activity is necessary for N-glycosylation of cysteine-proximal acceptor sites in glycoproteins. J Cell Biol. 2014 Aug 18;206(4):525-39. doi: 10.1083/jcb.201404083. PMID:25135935 doi:http://dx.doi.org/10.1083/jcb.201404083
4. ↑ Cherepanova NA, Gilmore R. Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. Sci Rep. 2016 Feb 11;6:20946. doi: 10.1038/srep20946. PMID:26864433 doi:http://dx.doi.org/10.1038/srep20946
5. ↑ Goytain A, Quamme GA. Identification and characterization of a novel mammalian Mg2+ transporter with channel-like properties. BMC Genomics. 2005 Apr 1;6:48. doi: 10.1186/1471-2164-6-48. PMID:15804357 doi:http://dx.doi.org/10.1186/1471-2164-6-48
6. ↑ Zhou H, Clapham DE. Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15750-5. Epub 2009 Aug 26. PMID:19717468 doi:http://dx.doi.org/0908332106
7. ↑ Ruiz-Canada C, Kelleher DJ, Gilmore R. Cotranslational and posttranslational N-glycosylation of polypeptides by distinct mammalian OST isoforms. Cell. 2009 Jan 23;136(2):272-83. doi: 10.1016/j.cell.2008.11.047. PMID:19167329 doi:10.1016/j.cell.2008.11.047
8. ↑ Sato T, Sako Y, Sho M, Momohara M, Suico MA, Shuto T, Nishitoh H, Okiyoneda T, Kokame K, Kaneko M, Taura M, Miyata M, Chosa K, Koga T, Morino-Koga S, Wada I, Kai H. STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein. Mol Cell. 2012 Jul 13;47(1):99-110. doi: 10.1016/j.molcel.2012.04.015. Epub 2012 , May 17. PMID:22607976 doi:10.1016/j.molcel.2012.04.015
9. ↑ Roboti P, High S. The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 function as ubiquitous and selective modulators of mammalian N-glycosylation. J Cell Sci. 2012 Jul 15;125(Pt 14):3474-84. doi: 10.1242/jcs.103952. Epub 2012, Mar 30. PMID:22467853 doi:http://dx.doi.org/10.1242/jcs.103952