Grn
Function
Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12524533, PubMed:20026663, PubMed:23041626, PubMed:27789271, PubMed:28073925, PubMed:28453791, PubMed:28541286, PubMed:8496151). Regulates protein trafficking to lysosomes and, also the activity of lysosomal enzymes (PubMed:27789271, PubMed:28453791, PubMed:28541286). Facilitates also the acidification of lysosomes, causing degradation of mature CTSD by CTSB (PubMed:28073925). In addition, functions as a wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures (PubMed:12524533). Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases (PubMed:8496151). Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity (PubMed:20026663, PubMed:23041626).
Granulin-3
Inhibits epithelial cell proliferation and induces epithelial cells to secrete IL-8.
Granulin-7
Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity.
Post-translational modifications
N-glycosylated.
Cleaved by ELANE; proteolysis is blocked by SLPI and is concentration- and time-dependent and induces CXCL8/IL-8 production; granulin-3 and granulin-4 are resistant to ELANE (By similarity). Cleaved by CTSL in lysosome thus regulating the maturation and turnover of progranulin within the lysosome (PubMed:28835281).
Sequence Similarities
Belongs to the granulin family.
Tissue Specificity
Highly expressed at the wound site and diminishes away from the wound. Not expressed in fibroblasts and endothelial cells in intact skin (PubMed:12524533). In adult brain, expressed primarily in neurons and in resting and reactive microglia (PubMed:23041626). Expressed in both neurons and microglia. Highly expressed in activated microglia in response to injury (PubMed:28541286). Expressed in macrophage (PubMed:27789271).
Cellular localization
- Secreted
- Lysosome
- Endocytosed by SORT1 and delivred to lysosomes. Targeted to lysosome by PSAP via M6PR and LRP1, in both biosynthetic and endocytic pathways (By similarity). Co-localized with GBA1 in the intracellular trafficking compartments until to lysosome (PubMed:27789271).
Alternative names
Progranulin, PGRN, Acrogranin, Epithelin/granulin precursor, Glycoprotein of 88 Kda, PC cell-derived growth factor, Proepithelin, GP88, Glycoprotein 88, PCDGF, PEPI, Grn