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FLASH GENE

Symbol

CTSB

contributors: mct/npt/pgu - updated : 04-06-2018

HGNC name	cathepsin B
HGNC id	2527

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	KWE keratolytic winter erythema
Location	8p23.1      Physical location : 11.700.035 - 11.725.646
Synonym name	APP secretase
	cysteine protease
	preprocathepsin B
	amyloid precursor protein secretase
Synonym symbol(s)	CPSB, STFB, D6F4, APPS, CATB
EC.number	3.4.22.1

DNA

TYPE	functioning gene
STRUCTURE	25.61 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	All transcripts encode the same protein.

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001908 10 - 3783 NP_001899 - 339 - 1992 1577456 also called CTSB variant 1 NM_147780 12 - 3945 NP_680090 - 339 - 1992 1577456 also called CTSB variant 2 NM_147781 11 - 3902 NP_680091 - 339 - 1992 1577456 also called CTSB variant 3 NM_147782 11 - 3871 NP_680092 - 339 - 1992 1577456 also called CTSB variant 4 NM_147783 11 - 3857 NP_680093 - 339 - 1992 1577456 also called CTSB variant 5

EXPRESSION

Type	ubiquitous

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 esophagus       highly Endocrine thyroid       highly Lymphoid/Immune spleen       highly Reproductive female system placenta     highly Skin/Tegument skin palmoplantar     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Epithelial barrier lining epidermis stratum spinosum highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol not specific mast cell Homo sapiens Skin/Tegument keratinocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal peptide
	a catalytic triad, cysteine, histidine and asparagine

mono polymer

monomer

isoforms

Precursor

HOMOLOGY

Homologene

FAMILY	papain superfamily
	peptidase C1 family

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytosolic,granule
	intracellular,nucleus,nucleolus
text	association of active cathepsin B with plasma membrane caveolae
	CTSL1 and CTSB colocalize to the secretory granule compartment of skin mast cells

basic FUNCTION	lysosomal cysteine and aspartyl proteinase, involved in matrix degradation during endochondral ossification
	APP secretase, may be prorenin-processing enzyme
	involved in skeletal myoblast differentiation and fusion
	contributing to both local invasion at the early stage and remote metastasis in colorectal cancer
	contributing to cartilage destruction in osteoarthritis and pathological proteolysis in rheumatoid arthritis and cancer
	involved in the motor neuron degeneration in ALS
	active form is secreted from fusing myoblasts at physiological pH
	playing a role in the physiological functions of placental and decidual macrophages in mediating villous angiogenesis and decidual apoptosis
	may play important roles during normal placentation and in the etiology of pre-eclampsia
	lysosomal protease that is localized throughout the epidermal layers and secreted into pericellular spaces
	essential during initial stages of wound healing, while its contribution to the subsequent processes of proliferation and differentiation of keratinocytes was of less significance
	might directly cleave ECM constituents or it may initiate proteolytic cascades that involve other proteases with the ability to degrade ECM components
	target of Hedgehog signaling in pancreatic cancer
	molecular link between autophagy and apoptosis
	pivotal role in cell death induced by SPARC in primitive neuroectodermal tumors cells (PNET)
	induces apoptosis through BID cleavage in SPARC overexpressed PNET cells
	importance of CTSB, CTSS and Cystatins in immunomodulation
	CTSL1 and CTSB are central to the processing of protryptase(s) in human mast cells
	CTSB, CTSK, CTSL, CTSS may be putative leptin activity regulators in white adipose tissue (WAT)
	prometastatic role for cathepsin B in distant metastasis
	is an essential enzyme for the induction of chronic inflammatory pain through its activation of proCASP1, which subsequently induces the maturation and secretion of IL1B and IL18 by spinal microglia
	is a novel gender-dependent determinant of cholesterol absorption from the intestine
	may act as an oncogene inendometrial cancer
	lysosomal cysteine protease primarily involved in the degradation or processing of lysosomal proteins
	CTSB and CTSL are essential in SNCA lysosomal degradation, establishing groundwork to explore mechanisms to enhance their cellular activity and levels as a potential strategy for clearance of SNCA
	cysteine protease involved in keratinocyte homeostasis
	crucial cysteine protease for keratinocyte differentiation and desquamation
	co-release of CBLN1 and CTSB from lysosomes serves as a new mechanism of activity-dependent coordinated synapse modification

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

dimer of heavy and light chains linked by disulfide bonds

INTERACTION

DNA

RNA

small molecule

protein	interacting with TNC for progression of gliomas
	ADAMTSL4 binding protein, with bikunin (involved in the apoptotic pathway of ovarian cancer cells)
	BID is putative cathepsin B target in SPARC-induced apoptosis
	MCOLN1 loss specifically causes, an increase in the lysosomal protease CTSB and the lysosomal membrane protein LAMP1
	ATG7-induced CTSB overexpression contributes to an NLRP3-dependent proinflammatory response and subsequently impairs glucose-stimulated insulin secretion (GSIS) independently of apoptosis
	critical regulatory role for that endogenous CTSD activity in dopaminergic cells in SNCA homeostasis which cannot be compensated for by increased CTSB
	APP is able to affect the downstream effects of protease inhibition in neural cells including enhancement of CTSB activity, with these changes in CTSB significantly and inversely related to the levels of ubiquitinated protein
	CTSZ is the compensatory protease that regulates the acquired tumor-promoting functions of lesions deficient in both CTSB and CTSS

cell & other

REGULATION

inhibited by

gene silencing and antisense DNA in human chondrocytes

ASSOCIATED DISORDERS

corresponding disease(s)

KWE

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in amyotrophic lateral sclerosis tumoral     --over   in malignant anaplastic astrocytomas and glioblastomas constitutional       gain of function in Dementia with Lewy bodies (DLB)

Susceptibility

to osteoarthritis

Variant & Polymorphism other	overexpression of truncated form (lacking exons 2 and 3) in osteoarthritic cartilage

Candidate gene
Marker	might serve as a prognostic and therapeutic marker for lung squamous cell carcinoma
Therapy target
	System Type Disorder Pubmed cancer reproductive breast with its substrate BID were shown to be molecular links between apoptosis and autophagy in breast cancer MCF-7 cells exposed to the cytostatic drug, camptothecin metabolism lysosome   targeting CTSB may be of relevance in the treatment of liver fibrosis in patients with Niemann-Pick disease cancer reproductive uterus potential to provide a new therapeutic target for treating endometrial malignancy miscelleaneous pain   CTSB-specific inhibitors may represent a useful new strategy for treating inflammation-associated pain cancer metastases   therapeutic benefits of its selective inhibition in bone metastasis in breast cancer

ANIMAL & CELL MODELS