A disintegrin and metalloproteinase with thrombospondin motifs 5

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. 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.

Classification

Family (Pfam)

PF17771 ADAMTS_CR_2, PF19236 ADAMTS_CR_3, PF05986 ADAMTS_spacer1, PF01421 Reprolysin, PF19030 TSP1_ADAMTS, PF00090 TSP_1

InterPro

ADAM_Cys-rich, ADAMTS/ADAMTS-like, ADAMTS_ADAMTS-like, ADAMTS_CR_2, ADAMTS_CR_3, ADAMTS_spacer1, MetalloPept_cat_dom_sf, Pept_M12B_ADAM-TS5, Peptidase_M12B, TSP1_rpt, TSP1_rpt_sf

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 7

• 2RJQ X-ray 2.60A
• 3B8Z X-ray 1.40A
• 3HY7 X-ray 1.69A
• 3HY9 X-ray 2.02A
• 3HYG X-ray 1.40A
• 3LJT X-ray 1.60A
• 6YJM X-ray 2.25A

A predicted model is available from AlphaFold.

Gene Ontology · 21

• GO:0005788 endoplasmic reticulum lumen
• GO:0031012 extracellular matrix
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0004175 endopeptidase activity
• GO:0050840 extracellular matrix binding
• GO:0008201 heparin binding
• GO:0042802 identical protein binding
• GO:0005178 integrin binding
• GO:0004222 metalloendopeptidase activity
• GO:0008237 metallopeptidase activity
• GO:0008233 peptidase activity
• GO:0008270 zinc ion binding
• GO:0003180 aortic valve morphogenesis
• GO:0003203 endocardial cushion morphogenesis
• GO:0022617 extracellular matrix disassembly
• GO:0030198 extracellular matrix organization
• GO:0007520 myoblast fusion
• GO:0120163 negative regulation of cold-induced thermogenesis
• GO:0006508 proteolysis
• GO:0003184 pulmonary valve morphogenesis

Drugs targeting this protein · 1

• ALDUMASTAT inhibitor

Related proteins · sequence + function similarity

• A disintegrin and metalloproteinase with thrombospondin motifs 5 0.97
• A disintegrin and metalloproteinase with thrombospondin motifs 15 0.94
• A disintegrin and metalloproteinase with thrombospondin motifs 15 0.93
• A disintegrin and metalloproteinase with thrombospondin motifs 1 0.92
• A disintegrin and metalloproteinase with thrombospondin motifs 1 0.91
• A disintegrin and metalloproteinase with thrombospondin motifs 1 0.91
• A disintegrin and metalloproteinase with thrombospondin motifs 16 0.91
• A disintegrin and metalloproteinase with thrombospondin motifs 16 0.90
• A disintegrin and metalloproteinase with thrombospondin motifs 18 0.90
• A disintegrin and metalloproteinase with thrombospondin motifs 14 0.90
• A disintegrin and metalloproteinase with thrombospondin motifs 2 0.89
• A disintegrin and metalloproteinase with thrombospondin motifs 2 0.89

Co-cited proteins · studied together in the literature

• ADAMTS-like protein 1 1 shared papers
• A disintegrin and metalloproteinase with thrombospondin motifs 4 1 shared papers
• A disintegrin and metalloproteinase with thrombospondin motifs 6 1 shared papers
• A disintegrin and metalloproteinase with thrombospondin motifs 5 1 shared papers
• A disintegrin and metalloproteinase with thrombospondin motifs 7 1 shared papers

Literature · 8 cited papers

• Post-translational modification of thrombospondin type-1 repeats in ADAMTS-like 1/punctin-1 by C-mannosylation of tryptophan. J. Biol. Chem. · 2009
• Characterization of proADAMTS5 processing by proprotein convertases. Int. J. Biochem. Cell Biol. · 2009
• Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5. Protein Sci. · 2008
• Human glioblastomas overexpress ADAMTS-5 that degrades brevican. Acta Neuropathol. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The DNA sequence of human chromosome 21. Nature · 2000
• ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. J. Biol. Chem. · 1999
• Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family. J. Biol. Chem. · 1999