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Description

Programmed cell death protein 10 (UniProt Q9BUL8, also known as Cerebral cavernous malformations 3 protein, TF-1 cell apoptosis-related protein 15) is encoded by the PDCD10 (also known as CCM3, TFAR15) gene (Gene ID 11235) in human. PDCD10/CCM3 is an ubiquitously expressed adaptor protein that plays a role in vascularization and vessel permeability, as well as in regulating cell survival and death. Both the N-terminal dimerization domain and the C-terminal focal adhesion targeting-homology (FAT-H) domain mediate its interaction with a diverse array of signaling partners. The FAT-H domain mediates PDCD10 interaction with CCM2 to form the KRIT1 CCM2 PDCD10 complex, as well as with striatin to form the striatin interacting phosphatase and kinase (STRIPAK) complex, while the dimerization domain mediates interactions with GCKIII serine/threonine kinases (MST4/MASK, STK24/MST3 and STK25). PDCD10 overexpression leads to increased cell migration, an essential process for blood vessel formation. Loss of either PDCD10 or STK24 increases neutrophil exocytosis as a result of disrupted interaction with UNC13D, a regulator of vesicle fusion. Loss-of-function mutations in CCM1/KRIT1, CCM2/OSM, or CCM3/PDCD10 gene cause cerebral cavernous malformations (CCMs).