Reactome | HHAT palmitoylates Hh N-terminal fragment

HHAT palmitoylates Hh N-terminal fragment

Stable Identifier

R-HSA-5358343

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum lumen

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HHAT palmitoylates Hh N-terminal fragment

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In addition to being modified by cholesterol at its C-terminal end, the N-terminal fragment of Hh (Hh-Np) is also palmitoylated by the O-acyltransferase HHAT (Pepinsky et al, 1998; Charmoun et al 2001; Chen et al, 2004; Hardy and Resh, 2007). HHAT-mediated palmitoylation of Hh can be recapitulated in vitro and in vivo, and the cholesterol- and palmitoyl-modified N-terminal fragment represents the predominant secreted form of Hh in vivo (Buglino and Resh, 2008; Buglino and Resh, 2010; Taipale et al, 2000). Mutation or depletion of the HHAT enzyme and mutation of the palmitoyl acceptor cysteine in Hh itself abrogates palmitoylation of the ligand and reduces Hh signaling (Chen et al, 2004; Chamoun et al, 2001; Pepinsky et al, 1998; Callier et al, 2014).

Literature References

PubMed ID	Title	Journal	Year
15075292	Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates Chen, MH, Li, YJ, Kawakami, T, Xu, SM, Chuang, PT	Genes Dev.	2004
24784881	Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling Callier, P, Calvel, P, Matevossian, A, Makrythanasis, P, Bernard, P, Kurosaka, H, Vannier, A, Thauvin-Robinet, C, Borel, C, Mazaud-Guittot, S, Rolland, A, Desdoits-Lethimonier, C, Guipponi, M, Zimmermann, C, Stévant, I, Kuhne, F, Conne, B, Santoni, F, Lambert, S, Huet, F, Mugneret, F, Jaruzelska, J, Faivre, L, Wilhelm, D, Jégou, B, Trainor, PA, Resh, MD, Antonarakis, SE, Nef, S	PLoS Genet.	2014
20585641	Identification of conserved regions and residues within Hedgehog acyltransferase critical for palmitoylation of Sonic Hedgehog Buglino, JA, Resh, MD	PLoS ONE	2010
10984056	Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine Taipale, J, Chen, JK, Cooper, MK, Wang, B, Mann, RK, Milenkovic, L, Scott, MP, Beachy, PA	Nature	2000
9593755	Identification of a palmitic acid-modified form of human Sonic hedgehog Pepinsky, RB, Zeng, C, Wen, D, Rayhorn, P, Baker, DP, Williams, KP, Bixler, SA, Ambrose, CM, Garber, EA, Miatkowski, K, Taylor, FR, Wang, EA, Galdes, A	J. Biol. Chem.	1998
23112049	Identification of N-terminal residues of Sonic Hedgehog important for palmitoylation by Hedgehog acyltransferase Hardy, RY, Resh, MD	J. Biol. Chem.	2012
18534984	Hhat is a palmitoylacyltransferase with specificity for N-palmitoylation of Sonic Hedgehog Buglino, JA, Resh, MD	J. Biol. Chem.	2008
11486055	Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal Chamoun, Z, Mann, RK, Nellen, D, von Kessler, DP, Bellotto, M, Beachy, PA, Basler, K	Science	2001