CCM-3 Human Recombinant Protein

This gene encodes an evolutionarily conserved protein associated with cell apoptosis. The protein interacts with the serine/threonine protein kinase MST4 to modulate the extracellular signal-regulated kinase (ERK) pathway. It also interacts with and is phosphoryated by serine/threonine kinase 25, and is thought to function in a signaling pathway essential for vascular developent. Mutations in this gene are one cause of cerebral cavernous malformations, which are vascular malformations that cause seizures and cerebral hemorrhages. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

Function: Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and MST4 activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development

By similarity. Ref.8 Ref.9 Ref.12

Subunit structure: Homodimer. Interacts (via C-terminus) with CCM2 and PXN. Interacts (via N-terminus) with MST4, STK24 and STK25. Interacts with GOLGA2. Identified in a complex with CCM1 and CCM2. Interacts with KDR/VEGFR2. Interaction with KDR/VEGFR2 is enhanced by stimulation with VEGFA

By similarity. Ref.9 Ref.10 Ref.12 Ref.15

Subcellular location: Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Partially co-localizes with endogenous PXN at the leading edges of migrating cells. Ref.9 Ref.12 Ref.15

Tissue specificity: Ubiquitous. Ref.8

Involvement in disease: Cerebral cavernous malformations 3 (CCM3) [MIM:603285]: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities: Belongs to the PDCD10 family.