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)
End	72,569,221 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	90,031,193 bp
RNA expression pattern
	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
	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
	9508
	330119
	ENSG00000156140
	ENSMUSG00000043635
	O15072
	n/a
	NM_014243
	NM_001081401; NM_177872
	NP_055058
	n/a
	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 2 3 GRCh38: Ensembl release 89: ENSG00000156140 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000043635 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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.
1 2 3 4 "Entrez Gene: ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3".
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

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.

This article on a gene on human chromosome 4 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000156140 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[pmid10094461-5] 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.

[entrez-6] 1 2 3 4 "Entrez Gene: ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3".

[pmid11408482-7] 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.

[pmid24552833-8] 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.

[pmid33566063-9] 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.

[pmid28687807-10] 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.

[pmid28985353-11] 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.

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v t e Proteases: metalloendopeptidases (EC 3.4.24)
ADAM proteins	Alpha secretases ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
Matrix metalloproteinases	Collagenases MMP1 MMP8 Gelatinases MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23A MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
Other	Neprilysin Procollagen peptidase Thermolysin Pappalysin-1 Bone morphogenetic protein 1 Lysostaphin Insulin-degrading enzyme ZMPSTE24

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