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PA-TM-RING proteins have an N-terminal protease-associated domain, a structure found in numerous proteases and implicated in protein binding, and C-terminal RING finger and PEST domains. Homologous proteins include GRAIL (gene related to anergy in leukocytes), which controls T-cell anergy, and AtRMR1 (receptor homology region-transmembrane domain-RING-H2 motif protein), a plant protein storage vacuole sorting receptor. | The PA-TM-RING protein RING finger protein 13 is an endosomal integral membrane E3 ubiquitin ligase whose RING finger domain is released to the cytoplasm by proteolysis Jeffrey P. Bocock1 Stephanie Carmicle1 Saba Chhotani1 Michael R. Ruffolo1 Haitao Chu2 and Ann H. Erickson1 1 Department of Biochemistry and Biophysics University of North Carolina Chapel Hill NC USA 2 Department of Biostatistics University of North Carolina Chapel Hill NC USA Keywords E3 ubiquitin ligase neurite outgrowth protease-associated domain proteolysis RNF13 Correspondence A. Erickson Department of Biochemistry and Biophysics CB 7260 GM University of North Carolina Chapel Hill NC 27599 USA Fax 1 929 966 2852 Tel 1 919 966 4694 E-mail ann_erickson@med.unc.edu Received 1 November 2008 revised 23 December 2008 accepted 20 January 2009 doi 10.1111 j.1742-4658.2009.06913.x PA-TM-RING proteins have an N-terminal protease-associated domain a structure found in numerous proteases and implicated in protein binding and C-terminal RING finger and PEST domains. Homologous proteins include GRAIL gene related to anergy in leukocytes which controls T-cell anergy and AtRMR1 receptor homology region-transmembrane domain-RING-H2 motif protein a plant protein storage vacuole sorting receptor. Another family member chicken RING zinc finger C-RZF was identified as being upregulated in embryonic chicken brain cells grown in the presence of tenascin-C. Despite algorithm predictions that the cDNA encodes a signal peptide and transmembrane domain the protein was found in the nucleus. We showed that RING finger protein 13 RNF13 the murine homolog of C-RZF is a type I integral membrane protein localized in the endosomal lysosomal system. By quantitative real-time RT-PCR analysis we demonstrated that expression of RNF13 is increased in adult relative to embryonic mouse tissues and is upregulated in B35 neuroblastoma cells stimulated to undergo neurite outgrowth. We found that RNF13 is very labile being subject to .