Pre-NOTCH Processing in the Endoplasmic Reticulum

Stable Identifier
R-HSA-1912399
Type
Pathway
Species
Homo sapiens
Compartment
endoplasmic reticulum membrane, endoplasmic reticulum lumen
ReviewStatus
5/5
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Pre-NOTCH Processing in the Endoplasmic Reticulum
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In the endoplasmic reticulum, glycosyl transferases modify NOTCH precursors by glycosylating conserved serine and threonine residues in EGF repeats of NOTCH.

O-fucosyl transferase POFUT1 fucosylates NOTCH serine and threonine residues that conform to the consensus sequence C2-X(4-5)-S/T-C3, where C2 and C3 are the second and third cysteine residue within the EGF repeat, and X(4-5) is four to five amino acid residues of any type (Yao et al. 2011, Stahl et al. 2008, Wang et al. 2001, Shao et al. 2003).

O-glucosyl transferase POGLUT1, mammalian homolog of the Drosophila enzyme Rumi, adds a glucosyl group to conserved serine residues within the EGF repeats of NOTCH. The consensus sequence for POGLUT1-mediated glucosylation is C1-X-S-X-P-C2, where C1 and C2 are the first and second cysteine residue in the EGF repeat, respectively, while X represents any amino acid (Acar et al. 2008, Fernandez-Valdivia et al. 2011). Both fucosylation and glucosylation of NOTCH receptor precursors are essential for functionality.
Literature References
PubMed ID Title Journal Year
21490058 Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi

Lopez, M, Fernandez-Valdivia, R, Takeuchi, H, Leonardi, J, Haltiwanger, RS, Jafar-Nejad, H, Samarghandi, A

Development 2011
11524432 Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase

Shao, L, Harris, RJ, Stanley, P, Spellman, MW, Haltiwanger, RS, Shi, S, Wang, Y

J Biol Chem 2001
18347015 Roles of Pofut1 and O-fucose in mammalian Notch signaling

Tashima, Y, Stanley, P, Stahl, M, Shi, S, Ge, C, Uemura, K

J Biol Chem 2008
18243100 Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling

Rajan, A, Pan, H, Takeuchi, H, Acar, M, Rana, NA, Haltiwanger, RS, Bellen, HJ, Jafar-Nejad, H, Ibrani, D

Cell 2008
12486116 Fringe modifies O-fucose on mouse Notch1 at epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region

Shao, L, Haltiwanger, RS, Moloney, DJ

J Biol Chem 2003
21464368 Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions

Wei, L, Lowe, JB, Gerson, S, Xin, W, Zhou, L, Yao, D, Stanley, P, Yan, Q, Huang, X, Wang, W, Huang, Y

Blood 2011
Participants
Events
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Authored
Orlic-Milacic, M  (2011-11-14)
Egan, SE  (2011-11-14)
Reviewed
Haw, R  (2012-02-06)
Created
Orlic-Milacic, M  (2011-11-02)
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