ADAMTS3

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; OMA:ADAMTS3 - orthologs
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 cartilage tissue periodontal fiber parietal pleura germinal epithelium tibia testicle caput epididymis secondary oocyte left uterine tube Top expressed in neural layer of retina superior frontal gyrus zygote genital tubercle dentate gyrus of hippocampal formation granule cell primary visual cortex ventricular zone embryo tail of embryo secondary oocyte 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
View/Edit Human View/Edit Mouse

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]

References

1. GRCh38: Ensembl release 89: ENSG00000156140 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000043635 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Tang BL, Hong W (February 1999). "ADAMTS: a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats". FEBS Letters. 445 (2–3): 223–5. doi:10.1016/S0014-5793(99)00119-2. PMID 10094461. S2CID 37955930.
6. "Entrez Gene: ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3".
7. Fernandes RJ, Hirohata S, Engle JM, Colige A, Cohn DH, Eyre DR, Apte SS (August 2001). "Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis". The Journal of Biological Chemistry. 276 (34): 31502–9. doi:10.1074/jbc.M103466200. PMID 11408482.
8. Jeltsch M, Jha SK, Tvorogov D, Anisimov A, Leppänen VM, Holopainen T, Kivelä R, Ortega S, Kärpanen T, Alitalo K (May 2014). "CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation". Circulation. 129 (19): 1962–71. doi:10.1161/CIRCULATIONAHA.113.002779. PMID 24552833.
9. Hattori M, Kohno T (February 2021). "Regulation of Reelin functions by specific proteolytic processing in the brain". Journal of Biochemistry. 169 (5): 511–516. doi:10.1093/jb/mvab015. PMID 33566063.
10. Jha SK, Rauniyar K, Karpanen T, Leppänen VM, Brouillard P, Vikkula M, Alitalo K, Jeltsch M (July 2017). "Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C-terminal domain of VEGF-C and the N-terminal domain of CCBE1". Scientific Reports. 7 (1): 4916. Bibcode:2017NatSR...7.4916J. doi:10.1038/s41598-017-04982-1. PMC 5501841. PMID 28687807.
11. Brouillard P, Dupont L, Helaers R, Coulie R, Tiller GE, Peeden J, Colige A, Vikkula M (November 2017). "Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3". Human Molecular Genetics. 26 (21): 4095–4104. doi:10.1093/hmg/ddx297. PMID 28985353.

Further reading

• Tang BL (January 2001). "ADAMTS: a novel family of extracellular matrix proteases". The International Journal of Biochemistry & Cell Biology. 33 (1): 33–44. doi:10.1016/S1357-2725(00)00061-3. PMID 11167130.
• Martel-Pelletier J, Welsch DJ, Pelletier JP (December 2001). "Metalloproteases and inhibitors in arthritic diseases". Best Practice & Research. Clinical Rheumatology. 15 (5): 805–29. doi:10.1053/berh.2001.0195. PMID 11812023.
• Hirohata S (November 2001). "[ADAMTS family--new extracellular matrix degrading enzyme]". Seikagaku. The Journal of Japanese Biochemical Society. 73 (11): 1333–7. PMID 11831030.
• Hurskainen TL, Hirohata S, Seldin MF, Apte SS (September 1999). "ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family". The Journal of Biological Chemistry. 274 (36): 25555–63. doi:10.1074/jbc.274.36.25555. PMID 10464288.
• Colige A, Vandenberghe I, Thiry M, Lambert CA, Van Beeumen J, Li SW, Prockop DJ, Lapiere CM, Nusgens BV (February 2002). "Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3". The Journal of Biological Chemistry. 277 (8): 5756–66. doi:10.1074/jbc.M105601200. PMID 11741898.

External links

• The MEROPS online database for peptidases and their inhibitors: M12.220
• Human ADAMTS3 genome location and ADAMTS3 gene details page in the UCSC Genome Browser.