Hh processing variants bind lectins

Stable Identifier
Reaction [binding]
Homo sapiens
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Like the WT C-terminal fragment of Hh, processing-defective variant precursors of full-length Hh are also targetted for degradation by the endoplasmic reticulum-associated degradtion (ERAD) pathway (Chen et al, 2011; Huang et al, 2013). This pathway delivers N-glycosylated ER-resident substrates to a retrotranslocation channel, where they are ubiquitinated and translocated to the cytosol for proteasome-mediated degradation in an ATP-ase dependent fashion (reviewed in Vembar and Brodsky, 2008). Recognition and targetting of ER proteins for the ERAD pathway depends at least in part by modification and binding of the glycosyl groups, and as is the case for the WT C-terminal fragment, lectins OS9 and ERLEC1 are required for the degradation of processing-defective variants of Hh (Chen et al, 2011). OS9 and ERLEC1 may target substrates to the retrotranslocation channel by virtue of their interaction SEL1, an ER membrane protein with established roles in the ERAD pathway (Christianson et al, 2008; Mueller et al, 2008; Hosokawa et al, 2008; Hosokawa et al, 2009).
Literature References
PubMed ID Title Journal Year
19346256 Human OS-9, a lectin required for glycoprotein endoplasmic reticulum-associated degradation, recognizes mannose-trimmed N-glycans

Hosokawa, N, Kamiya, Y, Nagata, K, Kamiya, D, Kato, K

J. Biol. Chem. 2009
21357747 Processing and turnover of the Hedgehog protein in the endoplasmic reticulum

Jao, C, Rapoport, TA, Tang, HY, Chu, YR, Schulman, S, Huang, CH, Chen, X, Salic, A, Mueller, B, Tukachinsky, H

J. Cell Biol. 2011
23867461 Derlin2 protein facilitates HRD1-mediated retro-translocation of sonic hedgehog at the endoplasmic reticulum

Ye, Y, Chu, YR, Hsiao, HT, Huang, CH, Chen, X

J. Biol. Chem. 2013
18711132 SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins

Ploegh, HL, Spooner, E, Klemm, EJ, Claessen, JH, Mueller, B

Proc. Natl. Acad. Sci. U.S.A. 2008
18502753 Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP

Hosokawa, N, Nagata, K, Wada, I, Okawa, K, Nagasawa, K, Moriyama, T

J. Biol. Chem. 2008
19002207 One step at a time: endoplasmic reticulum-associated degradation

Vembar, SS, Brodsky, JL

Nat. Rev. Mol. Cell Biol. 2008
18264092 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD

Tyler, RE, Christianson, JC, Kopito, RR, Shaler, TA

Nat. Cell Biol. 2008
Functional status

Gain of function of SHH variants [endoplasmic reticulum lumen]

Disease Entity
Name Identifier Synonyms
holoprosencephaly DOID:4621 Holoprosencephaly sequence (disorder)
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