Testican

Testican is a type of proteoglycan. Testican-1 is a highly conserved, multidomain proteoglycan that is most prominently expressed in the thalamus, and is upregulated in activated astroglial cells of the cerebrum. Several functions of this gene product have now been demonstrated in vitro including membrane-type matrix metalloproteinase inhibition, cathepsin L inhibition, and low-affinity calcium binding. The purified gene product has been shown to inhibit cell attachment and neurite extensions in culture. Functions of testican in vivo have yet to be demonstrated in knockout mice or other models. Testican has been shown to carry substantial amounts of chondroitin sulfate as well as other oligosaccharides, but the biological significance of these embellishments is not yet known.

In humans there are three testicans:

• SPOCK1 (Testican 1)
  • Testican-1 is a protein that in humans is encoded by the SPOCK1 gene. This gene encodes the protein core of a seminal plasma proteoglycan containing chondroitin- and heparan-sulfate chains. The protein’s function is under research, though it is from the same family of glycoproteins as SPARC. It is thought its similarity to thyropin-type cysteine protease inhibitors suggests its function may be related to protease inhibition.
    • GRCh38: Ensembl release 89: ENSG00000152377 – Ensembl, May 2017
    • GRCm38: Ensembl release 89: ENSMUSG00000056222 – 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.
    • Charbonnier F, Perin JP, Mattei MG, Camuzat A, Bonnet F, Gressin L, Alliel PM (Jun 1998). “Genomic organization of the human SPOCK gene and its chromosomal localization to 5q31”. Genomics. 48 (3): 377–80. doi:10.1006/geno.1997.5199. PMID 9545645.
    • “Entrez Gene: SPOCK1 sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 1”.
• SPOCK2 (Testican 2)
  • Testican-2 is a protein that in humans is encoded by the SPOCK2 gene. Proteoglycans, which consist of a core protein and covalently linked glycosaminoglycans, are components of the extracellular matrix. SPOCK2 encodes a member of a novel Ca(2+)-binding proteoglycan family.[supplied by OMIM]
    • GRCh38: Ensembl release 89: ENSG00000107742 – Ensembl, May 2017
    • GRCm38: Ensembl release 89: ENSMUSG00000058297 – 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.
    • Vannahme C, Schübel S, Herud M, Gösling S, Hülsmann H, Paulsson M, Hartmann U, Maurer P (July 1999). “Molecular cloning of testican-2: defining a novel calcium-binding proteoglycan family expressed in brain”. Journal of Neurochemistry. 73 (1): 12–20. doi:10.1046/j.1471-4159.1999.0730012.x. PMID 10386950. S2CID 21955542.
    • “Entrez Gene: SPOCK2 sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2”.
• SPOCK3 (Testican 3)
  • No Wikipedia page but shows up on:
    • Thyroglobulin domain
      • Thyroglobulin type-1 repeat is an evolutionary conserved protein domain. Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation. The domain usually contains six conserved cysteines. These form three disulphide bridges. Cysteines 1 pairs with 2, 3 with 4 and 5 with 6. Human proteins containing this domain
        • CD74; IGFBP-4; IGFBP1; IGFBP2; IGFBP3; IGFBP4; IGFBP5; IGFBP6; NID1; NID2; SMOC1; SMOC2; SPOCK1; SPOCK2; SPOCK3; TACSTD1; TACSTD2; TG;
    • List of human protein-coding genes 4
    • Kazal domain
      • The Kazal domain is an evolutionary conserved protein domain usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. In animals, serine protease inhibitors that act via their Kazal domain are grouped under the MEROPS inhibitor family I1, clan IA. Kazal inhibitors, which inhibit a number of serine proteases (such as trypsin and elastase), belong to family of proteins that includes pancreatic secretory trypsin inhibitor; avian ovomucoid; acrosin inhibitor; and elastase inhibitor. These proteins contain between 1 and 7 Kazal-type inhibitor repeats. Kazal 2 domain is usually indicative of serine protease inhibitors that belong to Merops inhibitor families: I1, I2, I17 and I31. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays and have a central alpha-helix, a short two-stranded antiparallel beta-sheet and several disulphide bonds. The amino terminal segment of this domain binds to the active site of its target proteases, thus inhibiting their function.
      • Human proteins with Kazal 1 domains:
        • AGRIN, CPAMD8
        • FST, FSTL3, FSTL4, FSTL5
        • IGFBPL1
        • SMOC1, SPARC, SPARCL1, SPINK1, SPINK2, SPINK4, SPINK5, SPINK5L2, SPINK5L3, SPINK6, SPINK7, SPINK9
        • TMEFF1, TMEFF2
      • Human proteins with Kazal 2 domains:
        • C6, CFI
        • FSTL1, FSTL3
        • HTRA1, HTRA3, HTRA4
        • IGFBP7, KAZALD1, LST3, RECK
        • SLC21A8, SLCO1A2, SLCO1B1, SLCO1B3, SLCO1C1, SLCO2A1, SLCO3A1, SLCO4A1, SLCO4C1, SLCO5A1, SLCO6A1, SMOC2, SPINK5, SPOCK1, SPOCK2, SPOCK3
        • WFIKKN1, WFIKKN2
    • Testican

Testican-1 plays a role in lapatinib resistance, which is a drug used to treat HER2-positive gastric cancer. When testican-1 levels are artificially reduced, sensitivity towards lapatinib was once again increased. This shows the potential for future use in combating drug resistance.

• Kim, H.-P.; Han, S.-W.; Song, S.-H.; Jeong, E.-G.; Lee, M.-Y.; Hwang, D.; Im, S.-A.; Bang, Y.-J.; Kim, T.-Y. (2014). “Testican-1-mediated epithelial–mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer”. Oncogene. 33 (25): 3334–3341. doi:10.1038/onc.2013.285. ISSN 1476-5594. PMID 23873022.

1. Kim, H.-P.; Han, S.-W.; Song, S.-H.; Jeong, E.-G.; Lee, M.-Y.; Hwang, D.; Im, S.-A.; Bang, Y.-J.; Kim, T.-Y. (2014). “Testican-1-mediated epithelial–mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer”. Oncogene. 33 (25): 3334–3341. doi:10.1038/onc.2013.285. ISSN 1476-5594. PMID 23873022.

Categories: 

• Testicans
• Biochemistry stubs

This page was last edited on 17 November 2023, at 07:09 (UTC).