Activator of apoptosis harakiri (IPR017249)

Short name: Apoptosis_activator_harakiri

Overlapping homologous superfamilies


Family relationships



Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans [PMID: 11341280]. In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.

The protein harakiri (Hrk, also called death protein 5, DP5) is a pro-apoptotic Bcl-2 homology domain 3-only (BH3-only) member protein, which belongs to the Bcl-2 family. Hrk is associated to the mitochondrial outer membrane via a putative trans-membrane domain at the C-terminal, which adopts a predominantly alpha-helical structure. This domain is able to insert itself into membranes where it perturbs the physical properties of the membrane considerably [PMID: 17434443].

It can be activated by a diverse array of developmental cues or experimentally applied stress stimuli. Hrk contributes to apoptosis signalling elicited by trophic factor withdrawal in certain neuronal cells but is not critical for apoptosis of haematopoietic cells [PMID: 17535852]. DP5 is important in neuronal cell death that can be induced by axotomy and neuronal growth factor (NGF) deprivation. It acts by regulating the mitochondrial function and caspase-3 activation [PMID: 15084651].

Apoptosis regulation is a main cause of epithelial dysfunction in patients with ulcerative colitis. Six genes were found to be highly expressed in epithelial cells from people with and without ulcerative colitis, one of which is Hrk [PMID: 16907856]. Hrk is also up-regulated in a JNK-dependent manner during apoptosis induced by potassium deprivation in cerebellar granule neurons [PMID: 17428807].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.