Fucosylation of Pre-NOTCH by POFUT1

Stable Identifier
R-HSA-1912349
Type
Reaction [transition]
Species
Homo sapiens
Compartment
endoplasmic reticulum lumen, endoplasmic reticulum membrane
ReviewStatus
5/5
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Fucosylation of Pre-NOTCH by POFUT1
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In the endoplasmic reticulum, NOTCH receptor precursors are fucosylated on conserved serine and threonine residues in their EGF repeats. The consensus fucosylation site sequence is 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. Only those fucosylation sites that are conserved between human, mouse and rat NOTCH isoforms are annotated. Two additional potential fucosylation sites exist in human NOTCH1, on threonine 194 and threonine 1321, but since they are not conserved between all three species, they are not shown. Fucosylation is performed by the endoplasmic reticulum resident O-fucosyl transferase (POFUT1). Fucosylation by POFUT1 is considered to be essential for NOTCH folding/processing and production of a fully functional receptor. In addition to Notch fucosylation, Drosophila Pofut1 (o-fut1) acts as a Notch chaperone, playing an important role in Notch trafficking (Okajima et al. 2005). The chaperone role of POFUT1 may not be conserved in mammals (Stahl et al. 2008).
Literature References
PubMed ID Title Journal Year
15692013 Chaperone activity of protein O-fucosyltransferase 1 promotes notch receptor folding

Lei, L, Xu, A, Irvine, KD, Okajima, T

Science 2005
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
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
Input
Output
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as an event of
Catalyst Activity

peptide-O-fucosyltransferase activity of POFUT1 [endoplasmic reticulum membrane]

Physical Entity
POFUT1 [endoplasmic reticulum membrane] (Homo sapiens)
Activity
peptide-O-fucosyltransferase activity (GO:0046922)
Inferred From
Fucosylation of Pre-Notch by POFUT1 (Cricetulus griseus)
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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