Granulin
Encyclopedia
Granulin is a protein
that in humans is encoded by the GRN gene
.
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 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.
. Granulin family members are important in normal development, wound healing
, and tumorigenesis
.
) 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.
with Cyclin T1 and TRIB3
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the GRN gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Structure
Granulins are a family of secreted, glycosylatedGlycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and 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 growthCell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
. Granulin family members are important in normal development, wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
, and tumorigenesis
Carcinogenesis
Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...
.
Clinical significance
The human liver fluke (Opisthorchis viverriniOpisthorchis viverrini
Opisthorchis viverrini, common name Southeast Asian liver fluke, is a trematode parasite from the family Opisthorchiidae that attacks the area of the bile duct. Infection is acquired when people ingest raw or undercooked fish. It causes the disease opisthorchiasis...
) contributes to the development of bile duct
Cholangiocarcinoma
Cholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
(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
Frontotemporal lobar degeneration
-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
, inherited in an autosomal dominant fashion with high penetrance. Several loss-of-function mutations disease-causing mutations in GRN have been identified.
Interactions
Granulin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Cyclin T1 and TRIB3
TRIB3
Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.-Interactions:TRIB3 has been shown to interact with CSNK2B, TIAF1, RELA, MCM3AP, ATF5, Granulin, ATF4, AKT1, Fibronectin and SIAH1.-Further reading:...
.