Cathepsin Z

CTSZ
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DEU, 1EF7
Identifiers
Aliases	CTSZ, CTSX, cathepsin Z
External IDs	OMIM: 603169; MGI: 1891190; HomoloGene: 1022; GeneCards: CTSZ; OMA:CTSZ - orthologs
Gene location (Human) Chr. Chromosome 20 (human) Band 20q13.32 Start 58,985,686 bp End 59,008,238 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 H4|2 97.94 cM Start 174,269,286 bp End 174,280,832 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte granulocyte mucosa of transverse colon right coronary artery ascending aorta Descending thoracic aorta rectum upper lobe of left lung right lobe of liver right lung Top expressed in stroma of bone marrow yolk sac dermis left lung lobe migratory enteric neural crest cell calvaria decidua supraoptic nucleus parotid gland efferent ductule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding peptidase activity hydrolase activity cysteine-type endopeptidase activity cysteine-type peptidase activity carboxypeptidase activity Cellular component endoplasmic reticulum lumen COPII-coated ER to Golgi transport vesicle intracellular membrane-bounded organelle endoplasmic reticulum plasma membrane endoplasmic reticulum-Golgi intermediate compartment membrane extracellular exosome Golgi membrane extracellular region specific granule lumen ficolin-1-rich granule lumen extracellular space lysosome cell surface growth cone cytoplasmic vesicle cell cortex region collagen-containing extracellular matrix Biological process proteolysis involved in cellular protein catabolic process COPII vesicle coating endoplasmic reticulum to Golgi vesicle-mediated transport epithelial tube branching involved in lung morphogenesis angiotensin maturation neutrophil degranulation proteolysis negative regulation of plasminogen activation negative regulation of neuron projection development negative regulation of protein binding positive regulation of neuron apoptotic process regulation of neuron death positive regulation of neural precursor cell proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1522 64138 Ensembl ENSG00000101160 ENSMUSG00000016256 UniProt Q9UBR2 Q9WUU7 RefSeq (mRNA) NM_001336 NM_022325 RefSeq (protein) NP_001327 NP_071720 Location (UCSC) Chr 20: 58.99 – 59.01 Mb Chr 2: 174.27 – 174.28 Mb PubMed search
Wikidata
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Cathepsin Z, also called cathepsin X or cathepsin P, is a protein that in humans is encoded by the CTSZ gene. It is a member of the cysteine cathepsin family of cysteine proteases, which has 11 members. As one of the 11 cathepsins, cathepsin Z contains distinctive features from others. Cathepsin Z has been reported involved in cancer malignancy and inflammation.

Structure

Gene

The CTSZ gene is located at 20q13.32 on chromosome 20, consisting of 6 exons. At least two transcript variants of this gene have been found, but the full-length nature of only one of them has been determined.

Protein

Cathepsin Z is characterized by an unusual and unique 3-amino acid insertion in the highly conserved region between the glutamine of the putative oxynion hole and the active site cysteine. The pro-region of cathepsin Z shares no significant similarity with other cathepsin family sequences. It contains only 41 amino acid residues without the conserved motif of ERFNIN or GNFD found in other cysteine proteinases. Besides, the proregion sequence contains no lysine residue.

Function

The protein encoded by this gene is a lysosomal cysteine proteinase and member of the peptidase C1 family. It exhibits both carboxy-monopeptidase and carboxy-dipeptidase activities. Up to date, eleven human cysteine proteinases have been identified, including cathepsin B, cathepsin C, cathepsin F, cathepsin H, cathepsin K, cathepsin L, cathepsin L2 or V, cathepsin O, cathepsin S, cathepsin Z, and cathepsin W. These cysteine proteinases belong to the papain family and represent a major component of the lysosomal proteolytic system. In addition to playing a critical role in protein degradation and turnover, these proteinases appear to play an extracellular role in a number of normal and pathological conditions. The human cathepsin Z contains distinctive features from other human cysteine proteases. It is an exopeptidase with strict carboxypeptidase activity, while most other cathepsins are endopeptidases. Cathepsin Z has an exposed integrin-binding Arg-Gly-Asp motif within the propeptide of the enzyme, through which cathepsin Z has been shown to interact with several integrins during normal homeostasis, immune processes and cancer. It is also shown to bind cell surface heparin sulphate proteoglycans, indicating possible functions in cellular adhesion and phagocytosis.

Clinical significance

This gene is expressed ubiquitously in cancer cell lines and primary tumors and, like other members of this family, may be involved in tumorigenesis. For instance, cathepsin Z promotes invasion and migration via a noncatalytic mechanism, suggesting multiple modes of cell invasion may be involved in cancer malignancy. Cathepsin Z is also reported to have a protective, but not proteolytic, function in inflammatory gastric disease. It is reported in another study that cathepsin Z may be responsible for dopamine neuron death and thus involved in the pathogenic cascade event. Single-nucleotide polymorphism in CTSZ is found associated with tuberculosis susceptibility, indicating that the pathways involving this protein could yield novel therapies for tuberculosis.

Interactions

Cathepsin Z has been shown to interact with the following proteins: CEP55, FBXO6, KIFC1, KRT40, KRTAP5-9, KRTAP5-9, LYPLAL1, MID2, MSN, MTUS2, NOTCH2NL, PLK2, PLSCR1, SGOL2, and SPRED2.

Cathepsin Z has also been found to interact with:

• Integrin,
• PRLP0, and
• γ-Enolase.

Further reading

• Nägler DK, Ménard R (August 1998). "Human cathepsin X: a novel cysteine protease of the papain family with a very short proregion and unique insertions". FEBS Letters. 434 (1–2): 135–9. doi:10.1016/S0014-5793(98)00964-8. PMID 9738465. S2CID 22899822.
• Pungercar J, Ivanovski G (2000). "Identification and molecular cloning of cathepsin P, a novel human putative cysteine protease of the papain family". Pflügers Archiv. 439 (3 Suppl): R116–8. doi:10.1007/s004240000112. PMID 10653162. S2CID 22775842.
• Pungercar J, Viyjak A, Ivanovski G, Krizaj I (2000). "Tissue expression and immunolocalization of a novel human cathepsin P". Pflügers Archiv. 439 (3 Suppl): R119–21. doi:10.1007/s004240000113. PMID 10653163. S2CID 22728027.
• Sivaraman J, Nägler DK, Zhang R, Ménard R, Cygler M (January 2000). "Crystal structure of human procathepsin X: a cysteine protease with the proregion covalently linked to the active site cysteine". Journal of Molecular Biology. 295 (4): 939–51. doi:10.1006/jmbi.1999.3410. PMID 10656802.
• Guncar G, Klemencic I, Turk B, Turk V, Karaoglanovic-Carmona A, Juliano L, Turk D (March 2000). "Crystal structure of cathepsin X: a flip-flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease". Structure. 8 (3): 305–13. doi:10.1016/S0969-2126(00)00108-8. PMID 10745011.
• Deussing J, von Olshausen I, Peters C (April 2000). "Murine and human cathepsin Z: cDNA-cloning, characterization of the genes and chromosomal localization". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1491 (1–3): 93–106. doi:10.1016/s0167-4781(00)00021-x. PMID 10760573.
• Bonthron DT, Hayward BE, Moran V, Strain L (August 2000). "Characterization of TH1 and CTSZ, two non-imprinted genes downstream of GNAS1 in chromosome 20q13". Human Genetics. 107 (2): 165–75. doi:10.1007/s004395000344. PMID 11030415. S2CID 25570066.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Puzer L, Barros NM, Oliveira V, Juliano MA, Lu G, Hassanein M, Juliano L, Mason RW, Carmona AK (March 2005). "Defining the substrate specificity of mouse cathepsin P". Archives of Biochemistry and Biophysics. 435 (1): 190–6. doi:10.1016/j.abb.2004.12.007. PMID 15680921.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Lechner AM, Assfalg-Machleidt I, Zahler S, Stoeckelhuber M, Machleidt W, Jochum M, Nägler DK (December 2006). "RGD-dependent binding of procathepsin X to integrin alphavbeta3 mediates cell-adhesive properties". The Journal of Biological Chemistry. 281 (51): 39588–97. doi:10.1074/jbc.M513439200. PMID 17065156.

External links

• The MEROPS online database for peptidases and their inhibitors: C01.013
• Overview of all the structural information available in the PDB for UniProt: Q9UBR2 (Cathepsin Z) at the PDBe-KB.