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FLASH GENE

Symbol

USP5

contributors: mct - updated : 15-04-2021

HGNC name	ubiquitin specific protease 5 (isopeptidase T)
HGNC id	12628

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	one zinc biding site
	a catalytic site resembling that of other cysteine proteases, containing one Cys, one Asp and one His
	a cryptic ZnF-UBP domain (residues 1-156), which was tightly bound to the catalytic core and was indispensable for catalytic activity

HOMOLOGY

intraspecies

paralog to ubiquitin C terminal hydrolases ucl+

Homologene

FAMILY

deubiquitin family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	zinc-binding deubiquitinating enzyme, clearing bonds between UB and unfolded polypeptide or UB and small substituents, also disassembling branched polyubiquitin chains
	recycles ubiquitin by hydrolyzing isopeptide bonds in a variety of unanchored polyubiquitin substrates
	deubiquitinating enzyme, involved in the elimination of the ubiquitin signal from damaged sites and required for efficient DNA double-strand break (DSB) repair
	disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair
	USP5 contributed to hepatocarcinogenesis by acting as an oncogene
	USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains

CELLULAR PROCESS

protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	zinc required for its catalytic activity

protein	USP5 uses multiple ZnF-UBP domains for substrate targeting and core catalytic function
	USP5 and UBE1, are interacting partners of UBTD2
	critical for the production of Tumor Necrosis Factor-alpha (TNF), a pivotal mediator for inflammatory responses
	E3 ligase SMURF1 regulates USP5 protein stability and USP5-mediated TNF production through the ubiquitin proteasome pathway
	expression of USP5 and OTUD6A may be affected by TP53

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function in hepatocellular carcinoma (HCC) cells constitutional     --other   dysregulation of USP5 SUMOylation after peripheral nerve injury may contribute to the well described alteration in CACNA1H activity during neuropathic pain states

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	may serve as a novel prognostic biomarker in non-small cell lung cancer (NSCLC)
Therapy target
	System Type Disorder Pubmed miscelleaneous pain   enhancement of CACNA1H currents in afferent neurons is mediated by deubiquitination of the channels by the deubiquitinase USP5, and disrupting USP5/CACNA1H interactions protected from inflammatory and neuropathic pain cancer lung   potential target for the treatment of metastasis in NSCLC

ANIMAL & CELL MODELS