background:
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 two different proteins; an N-terminal CILP and a SLCterminal homolog of NTPPHase, however, later studies identified no nucleotide pyrophosphatase phosphodiesterase (NPP) activity. The full-length and the N-terminal domain of this protein was shown to function as an IGF-1 antagonist. An allelic variant of this gene has been associated with lumbar disc disease. [provided by RefSeq, Sep 2010]
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.
Subcellular Location:
Secreted > extracellular space > extracellular matrix.
Tissue Specificity:
Specifically expressed in cartilage. Localizes in the intermediates layer of articular cartilage but neither in the superficial nor in the deepest regions. Specifically and highly expressed in intervertebral disk tissue. Expression increases with aging in hip articular cartilage. Overexpressed in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease (CPPD). Expression in intervertebral disk tissue from individuals with lumbar disk disease increases as disk degeneration progresses.
Post-translational modifications:
Cleaved into 2 chains possibly by a furin-like protease upon or preceding secretion.
DISEASE:
Defects in CILP are a cause of susceptibility to intervertebral disk disease (IDD) [MIM:603932]. 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. Note=Susceptibility to intervertebral disk disease, is conferred by variant p.Ile395Thr (PubMed:15864306).
Similarity:
Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
Contains 1 TSP type-1 domain.
Database links:
Entrez Gene: 8483 Human
Entrez Gene: 214425 Mouse
Entrez Gene: 397672 Pig
omim: 603489 Human
SwissProt: O75339 Human
SwissProt: Q66K08 Mouse
Unigene: 44236 Human
Unigene: 138455 Mouse
Unigene: 14477 Pig
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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