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ADAMTS3

In this article, we will explore the fascinating world of ADAMTS3 and all the implications it has on our current society. From its impact on everyday life to its relevance in the professional field, ADAMTS3 has proven to be a topic of growing interest for people of all ages and occupations. Throughout these pages, we will delve into the origins, evolution and future perspectives of ADAMTS3, to better understand its importance in the current context. In addition, we will analyze the various approaches and opinions that exist around ADAMTS3, with the aim of providing a comprehensive and enriching vision of this topic that is so relevant today. Join us on this journey of discovery and reflection about ADAMTS3!

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ADAMTS3
Identifiers
AliasesADAMTS3, ADAMTS-4, ADAM metallopeptidase with thrombospondin type 1 motif 3, HKLLS3
External IDsOMIM: 605011; MGI: 3045353; HomoloGene: 8596; GeneCards: ADAMTS3; OMA:ADAMTS3 - orthologs
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

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000156140 – Ensembl, May 2017
  2. ^ a b c 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. Bibcode:1999FEBSL.445..223T. doi:10.1016/S0014-5793(99)00119-2. PMID 10094461. S2CID 37955930.
  6. ^ a b c d "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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