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FLASH GENE
Symbol CTSZ contributors: mct - updated : 11-05-2016
HGNC name cathepsin Z
HGNC id 2547
Location 20q13.32      Physical location : 57.570.241 - 57.582.309
Synonym name
  • lysosomal cysteine carboxypeptidase cathepsin X
  • preprocathepsin P
  • Synonym symbol(s) CTSX, CATX
    EC.number 3.4.22.-/ 3.4.18.1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE opposite orientation, tail to tail
    text tail to tail with TH1l
    STRUCTURE 12.08 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    text structure absence of a TATA box, a high G+C content, a CpG island and the presence of several Sp1-binding sites, housekeeping gene
    MAPPING cloned Y linked   status confirmed
    regionally located tail to tail with TH1l
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1517 - 303 - 2012 22451661
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     stomach   highly
    Nervousbrain     Homo sapiens
    Reproductivefemale systembreastmammary gland highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a very short proregion
  • a three residue insertion between Gly22 and Cys31
  • a highly conserved region of the catalytic triad,
  • a second insertion homologous to the occluding loop in CTSB
  • an RGD motif located in a highly exposed region of the propeptide, which may allow binding of the proenzyme to RGD-recognizing integrins
  • isoforms Precursor
    HOMOLOGY
    Homologene
    FAMILY papain family of thiol proteases
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • placental cysteine proteinase, with putative exopeptidase activity
  • may be involved in tumorigenesis
  • has a restricted catalytic specificity
  • extracellular function of cathepsin Z may include binding to integrins thereby modulating the attachment of migrating cells to extracellular matrix components
  • with BLMH, are both cysteine proteases of a papain-like structure, and mediate N-terminal proteolysis and toxicity of mutant huntingtin
  • cysteine carboxypeptidase, that is involved in the regulation of T cell migration by interaction with ITGAL, ITGB2
  • potential role of cathepsin Z in bypassing cellular senescence
  • CTSL, CTSZ, account for the lysosome's capacity to digest polyQ sequences, and are important in defending against the accumulation and toxicity of polyQ proteins
  • several of the tumor-promoting functions of CTSZ were not dependent on its described catalytic activity but instead were mediated via the Arg-Gly-Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins and the extracellular matrix
  • role for CTSZ in the anti-tumor immune response
  • predominantly supplied by tumor-associated macrophages, and is the compensatory protease that regulates the acquired tumor-promoting functions of lesions deficient in both CTSB and CTSS
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with ITGAL
  • it is likely that CTSL carries out initial cleavages yielding shorter peptides that are hydrolyzed to amino acids by CTSZ
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in high grade intraepithelial colorectal neoplasia and in early tumor stages
    Susceptibility
  • to tuberculosis
  • Variant & Polymorphism SNP
  • rs34069356 in the 3 prime UTR of CTSZ showed significant association with tuberculosis susceptibility
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativehuntington chorea
    with BLMH, are potential novel targets for Huntington disease therapeutics
    ANIMAL & CELL MODELS