6jl7

Structural highlights

Disease

[TBC23_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.

Function

[TBC23_HUMAN] Putative Rab GTPase-activating protein which plays a role in vesicular trafficking (PubMed:28823707). Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (PubMed:29084197, PubMed:29426865). Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). Plays a role in brain development, including in cortical neuron positioning (By similarity). May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth (By similarity). May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge (By similarity).[UniProtKB:Q8K0F1]^{[1] [2] [3]}

References

1. ↑ Ivanova EL, Mau-Them FT, Riazuddin S, Kahrizi K, Laugel V, Schaefer E, de Saint Martin A, Runge K, Iqbal Z, Spitz MA, Laura M, Drouot N, Gerard B, Deleuze JF, de Brouwer APM, Razzaq A, Dollfus H, Assir MZ, Nitchke P, Hinckelmann MV, Ropers H, Riazuddin S, Najmabadi H, van Bokhoven H, Chelly J. Homozygous Truncating Variants in TBC1D23 Cause Pontocerebellar Hypoplasia and Alter Cortical Development. Am J Hum Genet. 2017 Sep 7;101(3):428-440. doi: 10.1016/j.ajhg.2017.07.010. Epub , 2017 Aug 17. PMID:28823707 doi:http://dx.doi.org/10.1016/j.ajhg.2017.07.010
2. ↑ Shin JJH, Gillingham AK, Begum F, Chadwick J, Munro S. TBC1D23 is a bridging factor for endosomal vesicle capture by golgins at the trans-Golgi. Nat Cell Biol. 2017 Dec;19(12):1424-1432. doi: 10.1038/ncb3627. Epub 2017 Oct 30. PMID:29084197 doi:http://dx.doi.org/10.1038/ncb3627
3. ↑ Navarro Negredo P, Edgar JR, Manna PT, Antrobus R, Robinson MS. The WDR11 complex facilitates the tethering of AP-1-derived vesicles. Nat Commun. 2018 Feb 9;9(1):596. doi: 10.1038/s41467-018-02919-4. PMID:29426865 doi:http://dx.doi.org/10.1038/s41467-018-02919-4