Structural highlights
Function
[RUSC1_HUMAN] Putative signaling adapter which may play a role in neuronal differentiation. May be involved in regulation of NGF-dependent neurite outgrowth. Proposed to play a role in neuronal vesicular trafficking, specifically involving pre-synaptic membrane proteins. Seems to be involved in signaling pathways that are regulated by the prolonged activation of MAPK. Can regulate the polyubiquitination of IKBKG and thus may be involved in regulation of the NF-kappa-B pathway.[1]
Publication Abstract from PubMed
NESCA, a newly discovered signaling adapter protein in the NGF-pathway, contains a RUN domain at its N-terminus. Here we report the crystal structure of the NESCA RUN domain determined at 2.0-A resolution. The overall fold of the NESCA RUN domain comprises nine helices, resembling the RUN domain of RPIPx and the RUN1 domain of Rab6IP1. However, compared to the other RUN domains, the RUN domain of NESCA has significantly different surface electrostatic distributions at the putative GTPase-interacting interface. We demonstrate that the RUN domain of NESCA can bind H-Ras, a downstream signaling molecule of TrkA, with high affinity. Moreover, NESCA RUN can directly interact with TrkA. These results provide new insights into how NESCA participates in the NGF-TrkA signaling pathway.
Crystal structure and functional implication of the RUN domain of human NESCA.,Sun Q, Han C, Liu L, Wang Y, Deng H, Bai L, Jiang T Protein Cell. 2012 Aug;3(8):609-17. Epub 2012 Jul 22. PMID:22821014[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Napolitano G, Mirra S, Monfregola J, Lavorgna A, Leonardi A, Ursini MV. NESCA: a new NEMO/IKKgamma and TRAF6 interacting protein. J Cell Physiol. 2009 Aug;220(2):410-7. doi: 10.1002/jcp.21782. PMID:19365808 doi:http://dx.doi.org/10.1002/jcp.21782
- ↑ Sun Q, Han C, Liu L, Wang Y, Deng H, Bai L, Jiang T. Crystal structure and functional implication of the RUN domain of human NESCA. Protein Cell. 2012 Aug;3(8):609-17. Epub 2012 Jul 22. PMID:22821014 doi:10.1007/s13238-012-2052-3
