Calpain 5 is highly expressed in the central nervous system (CNS), carries dual nuclear localization signals, and is associated with nuclear promyelocytic leukemia protein bodies.
Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF hand motif characteristic of classical calpains but retains catalytic and Ca(2+) binding domains, and it contains a unique C-terminal domain. TRA-3, an ortholog of CAPN5, has been shown to be involved in necrotic cell death in Caenorhabditis elegans. CAPN5 is expressed throughout the CNS, but its expression relative to other calpains and subcellular distribution has not been investigated previously. Based on relative mRNA levels, Capn5 is the second most highly expressed calpain in the rat CNS, with Capn2 mRNA being the most abundant. Unlike classical calpains, CAPN5 is a non-cytosolic protein localized to the nucleus and extra-nuclear locations. CAPN5 possesses two nuclear localization signals (NLS): an N-terminal monopartite NLS and a unique bipartite NLS closer to the C terminus. The C-terminal NLS contains a SUMO-interacting motif that contributes to nuclear localization, and mutation or deletion of both NLS renders CAPN5 exclusively cytosolic. Dual NLS motifs are common among transcription factors. Interestingly, CAPN5 is found in punctate domains associated with promyelocytic leukemia (PML) protein within the nucleus. PML nuclear bodies are implicated in transcriptional regulation, cell differentiation, cellular response to stress, viral defense, apoptosis, and cell senescence as well as protein sequestration, modification, and degradation. The roles of nuclear CAPN5 remain to be determined.
From the Spinal Cord and Brain Injury Research Center and the Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536.
Ranjana
R
Singh
From the Spinal Cord and Brain Injury Research Center and.
M Kathryn
MK
Brewer
From the Spinal Cord and Brain Injury Research Center and.
Charles B
CB
Mashburn
From the Spinal Cord and Brain Injury Research Center and.
Dingyuan
D
Lou
From the Spinal Cord and Brain Injury Research Center and.
Vimala
V
Bondada
From the Spinal Cord and Brain Injury Research Center and.
Brantley
B
Graham
From the Spinal Cord and Brain Injury Research Center and the Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536 jgeddes@uky.edu.
James W
JW
Geddes
D020816:Amino Acid Motifs; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics; D002154:Calpain / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D045586:Intranuclear Inclusion Bodies / Q000201:enzymology* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D002154:Calpain; C403235:Capn5 protein, mouse; C494425:calpain 5, rat
Calpain; Nuclear Transport; Protease; SUMO-interacting Motif (SIM); SUMOylation