FEATURES

FAMILY

DESCRIPTION

Also known as GRN_HUMAN, GRN. 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:28541286, PubMed:28073925, PubMed:18378771, PubMed:28453791, PubMed:12526812). Regulates protein trafficking to lysosomes and, also the activity of lysosomal enzymes (PubMed:28453791, PubMed:28541286). Facilitates also the acidification of lysosomes, causing degradation of mature CTSD by CTSB (PubMed:28073925). In addition, functions as 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 (By similarity). Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases (PubMed:12526812). Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity (PubMed:18378771)., Promotes proliferation of the epithelial cell line A431 in culture., Inhibits epithelial cell proliferation and induces epithelial cells to secrete IL-8., Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity. Progranulin is secreted as a homodimer (PubMed:23364791). Interacts with SLPI; interaction protects progranulin from proteolysis (PubMed:12526812). Interacts (via region corresponding to granulin-7 peptide) with CTSD; stabilizes CTSD and increases its proteolytic activity (PubMed:28453791). Interacts (via region corresponding to granulin-7 peptide) with SORT1; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system (PubMed:21092856). Interacts with PSAP; facilitates lysosomal delivery of progranulin from the extracellular space and the biosynthetic pathway (PubMed:26370502). Forms a complex with PSAP and M6PR; PSAP bridges the binding between progranulin and M6PR (PubMed:26370502). Forms a complex with PSAP and SORT1; progranulin bridges the interaction between PSAP and SORT1; facilitates lysosomal targeting of PSAP via SORT1; interaction enhances PSAP uptake in primary cortical neurons (PubMed:28541286). Interacts (via regions corresponding to granulin-2 and granulin-7 peptides) with GBA; this interaction prevents aggregation of GBA-SCARB2 complex via interaction with HSPA1A upon stress (PubMed:27789271). Interacts (via region corresponding to granulin-7 peptide) with HSPA1A; mediates recruitment of HSPA1A to GBA and prevents GBA aggregation in response to stress (PubMed:27789271).

EXTERNAL LINKS

GRN

Progranulin

GRN

Molecular Synopsis