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FLASH GENE

Symbol

CTSZ

contributors: mct - updated : 11-05-2016

HGNC name	cathepsin Z
HGNC id	2547

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001336 6 - 1517 NP_001327 - 303 - 2012 22451661

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly   stomach       highly Nervous brain         Homo sapiens Reproductive female system breast mammary gland   highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Lymphoid/Immune macrophage 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed neurology neurodegenerative huntington chorea with BLMH, are potential novel targets for Huntington disease therapeutics

ANIMAL & CELL MODELS