Granulin

Granulin
the solution structure of a well-folded peptide based on the 31-residue amino-terminal subdomain of human granulin a
Identifiers
Symbol	Granulin
Pfam	PF00396
InterPro	IPR000118
PROSITE	PDOC00634
SCOP	1pcn
SUPERFAMILY	1pcn
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Granulin is a protein that in humans is encoded by the GRN gene.

Structure

Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and prostate cancer (PC) cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively.

Function

Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis.

Clinical significance

The human liver fluke (Opisthorchis viverrini) contributes to the development of bile duct (liver) cancer by secreting a granulin-like growth hormone.

Mutations in the GRN gene have been implicated in up to 25% of frontotemporal lobar degeneration, inherited in an autosomal dominant fashion with high penetrance. Several loss-of-function mutations disease-causing mutations in GRN have been identified.

Granulin release by macrophages has been associated with fibrotic hepatic metastasis in pancreatic cancer.

Interactions

Granulin has been shown to interact with Cyclin T1 and TRIB3.

External links

• GeneReviews/NCBI/NIH/UW entry on GRN-Related Frontotemporal Dementia