Mouse anti-Human sapiens (Human) GRN Monoclonal Antibody

Function

Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity

Subcellular Location

Secreted; Lysosome

Disease Association

Frontotemporal dementia 2 (FTD2) : A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. Gestural apraxia, parkinsonism, visual loss, and visual hallucinations are present in 25 to 40% of patients. [The disease is caused by variants affecting the gene represented in this entry] | Ceroid lipofuscinosis, neuronal, 11 (CLN11) : A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

In myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts, and very strongly in epithelial cell lines. Present in inflammatory cells and bone marrow. Highest levels in kidney

Subunit

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 GBA1; this interaction prevents aggregation of GBA1-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 GBA1 and prevents GBA1 aggregation in response to stress (PubMed:27789271)

• Bhandari V. et al. Structure and chromosomal location of the human granulin gene. — Biochem. Biophys. Res. Commun. (1992)
• Plowman G.D. et al. The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. — J. Biol. Chem. (1992)
• Bhandari V. et al. Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. — Proc. Natl. Acad. Sci. U.S.A. (1992)
• Lu R. et al. PCDGF sequence from lambda phage human Jurkat T cell cDNA library (Clontech). (JUN-)
• Yu W. et al. PubMed: CI-60FCUVGGQO9DA (MAR-)
• Kalnine N. et al. Cloning of human full-length CDSs in BD Creator(TM) system donor vector. (MAY-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Suzuki Y. et al. PubMed: CI-5AVBODINQ93DF (APR-)