ADAMTS5
Domain
The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Function
Metalloproteinase that plays an important role in connective tissue organization, development, inflammation and cell migration. Extracellular matrix (ECM) degrading enzyme that show proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) including ACAN, VCAN, BCAN and NCAN (PubMed:16133547, PubMed:18992360). Cleavage within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a role in embryonic development, including limb and cardiac morphogenesis, and skeletal muscle development through its VCAN remodeling properties. Cleaves VCAN in the pericellular matrix surrounding myoblasts, facilitating myoblast contact and fusion which is required for skeletal muscle development and regeneration (By similarity). Participates in development of brown adipose tissue and browning of white adipose tissue (By similarity). Plays an important role for T-lymphocyte migration from draining lymph nodes following viral infection.
Post-translational modifications
The precursor is cleaved by furin and PCSK7 outside of the cell.
Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).
Tissue Specificity
Expressed at low level in placenta primarily but also detected in heart and brain, cervix, uterus, bladder, esophagus, rib cartilage, chondroblastoma, fibrous tissue and a joint capsule from an arthritic patient.
Cellular localization
- Secreted
- Extracellular space
- Extracellular matrix
Alternative names
ADAMTS11, ADMP2, ADAMTS5, A disintegrin and metalloproteinase with thrombospondin motifs 5, ADAM-TS 5, ADAM-TS5, ADAMTS-5, A disintegrin and metalloproteinase with thrombospondin motifs 11, ADMP-2, Aggrecanase-2, ADAM-TS 11, ADAMTS-11