USP53

Chr 4q26

ubiquitin specific peptidase 53

Aliases:: KIAA1350
MANE:: ENST00000692078.1

OMIM: 617431 ↗NCBI: 54532 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

USP53 · Q70EK8

v62025-08-01

Predicted Aligned Error matrix for USP53 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

55.1/ 100

Low

1,073 residues

Confidence breakdown

Very high(≥ 90)28%
Confident(70–90)3%
Low(50–70)3%
Very low(< 50)65%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Cholestasis
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

cholestasis, progressive familial intrahepatic, 7, with or without hearing loss
0.72
cholestasis
0.62
deafness
0.39
arthropathy
0.33
Varicose veins
0.31
vein disorder
0.20
lymphatic system disorder
0.20
hereditary disease
0.19
Premature ovarian insufficiency
0.16
coronary artery disorder
0.15

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Ubiquitin carboxyl-terminal hydrolase 53

Deubiquitinase that mediates 'Lys-63'-linked deubiquitination of tight junction proteins, such as MARVELD2 and LSR, and which is involved in the survival of auditory hair cells and hearing (PubMed:32124521, PubMed:39587316). Specifically cleaves 'Lys-63'-linked polyubiquitin chains composed of at least 3 ubiquitin molecules, while it is not able to deubiquitinate substrates with shorter ubiquitin chains: recognizes ubiquitin chain in position S2 and catalyzes en bloc cleavage of polyubiquitin chains from substrate proteins (PubMed:39587316). Probably acts by modulating the barrier properties and mechanical stability of tight junctions via deubiquitination of MARVELD2 and LSR (PubMed:32124521, PubMed:39587316)