ADAMTS3

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]

ADAMTS3
Identifiers
AliasesADAMTS3, ADAMTS-4, ADAM metallopeptidase with thrombospondin type 1 motif 3, HKLLS3
External IDsOMIM: 605011 MGI: 3045353 HomoloGene: 8596 GeneCards: ADAMTS3
Orthologs
SpeciesHumanMouse
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 MbChr 5: 89.82 – 90.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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
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