Highly homologous HERC proteins localize to endosomes and exhibit specific interactions with hPLIC and Nm23B.
Small HERC proteins are defined by the presence of one RCC1-like domain and a HECT domain. Having evolved out of one common ancestor, the four members of the family exhibit a high degree of homology in genomic organization and amino acid sequence, thus it seems possible that they might accomplish similar functions. Here we show that small HERC proteins interact with each other and localize to the same cellular structures, which we identify as late endosomes and lysosomes. We demonstrate interaction of HERC3 with the ubiquitin-like proteins hPLIC-1 and hPLIC-2 and we establish interaction of HERC5 with the metastasis suppressor Nm23B. While hPLIC proteins are not ubiquitinated by HERC3, HERC5 plays an important role in ubiquitination of Nm23B. In summary, although small HERC proteins are highly homologous showing the same subcellular distribution, they undergo different molecular interactions.
Department of Vascular Biology and Thrombosis Research, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna, and Biomolecular Therapeutics, Vienna, Austria. kah2015@med.cornell.edu
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Hochrainer
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Kroismayr
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Baranyi
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Binder
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Lipp
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C402395:HERC5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D011994:Recombinant Proteins; C107792:UBQLN1 protein, human; C405662:UBQLN2 protein, human; D014452:Ubiquitins; C406215:HERC3 protein, human; D044767:Ubiquitin-Protein Ligases; C517940:NME2 protein, human