ADAMTS3
Identifiers
Aliases	ADAMTS3, ADAMTS-4, ADAM metallopeptidase with thrombospondin type 1 motif 3, HKLLS3
External IDs	OMIM: 605011 MGI: 3045353 HomoloGene: 8596 GeneCards: ADAMTS3
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q13.3 Start 72,280,969 bp[1] End 72,569,221 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 E1 Start 89,824,946 bp[2] End 90,031,193 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell periodontal fiber parietal pleura germinal epithelium tibia caput epididymis secondary oocyte left uterine tube middle temporal gyrus Achilles tendon Top expressed in superior frontal gyrus secondary oocyte cerebellar cortex yolk sac neural tube footplate ganglionic eminence esophagus lip lens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function heparin binding zinc ion binding endopeptidase activity metal ion binding peptidase activity protein binding hydrolase activity metallopeptidase activity metalloendopeptidase activity Cellular component extracellular region extracellular exosome extracellular space extracellular matrix collagen-containing extracellular matrix Biological process vascular endothelial growth factor production collagen fibril organization protein processing proteolysis collagen biosynthetic process positive regulation of vascular endothelial growth factor signaling pathway collagen catabolic process supramolecular fiber organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9508 330119 Ensembl ENSG00000156140 ENSMUSG00000043635 UniProt O15072 n/a RefSeq (mRNA) NM_014243 NM_001081401 NM_177872 RefSeq (protein) NP_055058 n/a Location (UCSC) Chr 4: 72.28 – 72.57 Mb Chr 5: 89.82 – 90.03 Mb PubMed search [3] [4]
Wikidata
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A disintegrin and metalloproteinase with thrombospondin motifs 3 is an enzyme that in humans is encoded by the ADAMTS3 gene.^[5][6] The protein encoded by this gene is the major procollagen II N-propeptidase.^[6]

Structure

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene is the major procollagen II N-propeptidase.^[6]

Function

Because of the high similarity to ADAMTS2, the major substrate of ADAMTS3 had been erroneously assumed to be procollagen II.^[7] However, ADAMTS3 appears largely irrelevant for collagen maturation but instead is required for the activation of the lymphangiogenic growth factor VEGF-C.^[8] Hence, ADAMTS3 is essential for the development and growth of lymphatic vessels. The proteolytic processing of VEGF-C by ADAMTS3 is regulated by the CCBE1 protein.

ADAMTS3 has been shown to cleave reelin, a protein that regulates the proper lamination of the brain cortex and whose signal activity is found to be disrupted in a number of neuropsychiatric conditions.^[9]

Clinical significance

A deficiency of this protein may be responsible for dermatosparaxis, a genetic defect of connective tissues.^[6]

Some hereditary forms of lymphedema are caused by mutations in ADAMTS3.^[10][11]