PEDF Human Active Protein

The protein encoded by this gene is a member of the serpin family, although it does not display the serine protease inhibitory activity shown by many of the other serpin family members. The encoded protein is secreted and strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells.[provided by RefSeq, Mar 2011]

Function: Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells. Potent inhibitor of angiogenesis. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. Ref.13 Ref.14

Subcellular location: Secreted. Melanosome. Note: Enriched in stage I melanosomes. Ref.17

Tissue specificity: Retinal pigment epithelial cells and blood plasma. Ref.11

Developmental stage: Expressed in quiescent cells.

Domain: The N-terminal (AA 44-121) exhibits neurite outgrowth-inducing activity. The C-terminal exposed loop (AA 382-418) is essential for serpin activity.

Post-translational modification: The N-terminus is blocked. Extracellular phosphorylation enhances antiangiogenic activity.N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan. Ref.19 Ref.23

Involvement in disease: Osteogenesis imperfecta 6 (OI6) [MIM:613982]: A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI6 is a severe, autosomal recessive form compatible with OI type III in the Sillence classification.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21

Sequence similarities: Belongs to the serpin family.

Sequence caution: The sequence AAA84914.1 differs from that shown. Reason: Frameshift at position 356. The sequence AAA93524.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.