2knb

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Template:STRUCTURE 2knb

Contents 1 Solution NMR structure of the parkin Ubl domain in complex with the endophilin-A1 SH3 domain 2 Function 3 About this Structure 4 Reference

Solution NMR structure of the parkin Ubl domain in complex with the endophilin-A1 SH3 domain

Template:ABSTRACT PUBMED 20064468

Function

[PRKN2_RAT] Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in role in regulation of neuron death. Limits the production of reactive oxygen species (ROS). Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. Regulates cyclin-E during neuronal apoptosis. May represent a tumor suppressor gene (By similarity). [SH3G2_RAT] Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature.^{[1] [2]}

About this Structure

2knb is a 2 chain structure with sequence from Rattus norvegicus. Full experimental information is available from OCA.

Reference

• Trempe JF, Chen CX, Grenier K, Camacho EM, Kozlov G, McPherson PS, Gehring K, Fon EA. SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination. Mol Cell. 2009 Dec 25;36(6):1034-47. PMID:20064468 doi:10.1016/j.molcel.2009.11.021

1. ↑ Farsad K, Ringstad N, Takei K, Floyd SR, Rose K, De Camilli P. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J Cell Biol. 2001 Oct 15;155(2):193-200. Epub 2001 Oct 15. PMID:11604418 doi:10.1083/jcb.200107075
2. ↑ Gallop JL, Jao CC, Kent HM, Butler PJ, Evans PR, Langen R, McMahon HT. Mechanism of endophilin N-BAR domain-mediated membrane curvature. EMBO J. 2006 Jun 21;25(12):2898-910. Epub 2006 Jun 8. PMID:16763559