CILP

Major alterations in the composition of the cartilage extracellular matrix occur in joint disease, such as osteoarthrosis. This gene encodes the cartilage intermediate layer protein (CILP), which increases in early osteoarthrosis cartilage. The encoded protein was thought to encode a protein precursor for 2 different proteins, namely CILP and a homolog of NTPPHase, however later studies identified no nucleotide pyrophosphatase phosphodiesterase (NPP) activity. One isoform of the protein, CILP-1, functions as an IGF-1 antagonist. [provided by RefSeq]

Full Name

cartilage intermediate layer protein, nucleotide pyrophosphohydrolase

Function

Probably plays a role in cartilage scaffolding. May act by antagonizing TGF-beta1 (TGFB1) and IGF1 functions. Has the ability to suppress IGF1-induced proliferation and sulfated proteoglycan synthesis, and inhibits ligand-induced IGF1R autophosphorylation. May inhibit TGFB1-mediated induction of cartilage matrix genes via its interaction with TGFB1. Overexpression may lead to impair chondrocyte growth and matrix repair and indirectly promote inorganic pyrophosphate (PPi) supersaturation in aging and osteoarthritis cartilage.

Biological Process

Cellular response to transforming growth factor beta stimulus Source: BHF-UCL
Dephosphorylation Source: GOC
Negative regulation of gene expression Source: BHF-UCL
Negative regulation of insulin-like growth factor receptor signaling pathway Source: BHF-UCL
Negative regulation of SMAD protein signal transduction Source: BHF-UCL

Cellular Location

Extracellular matrix

Involvement in disease

Intervertebral disc disease (IDD):
A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain.

PTM

Cleaved into 2 chains possibly by a furin-like protease upon or preceding secretion.