USP14

Chr 18p11.32

ubiquitin specific peptidase 14

Aliases:: TGT, Ubp6
MANE:: ENST00000261601.8

OMIM: 607274 ↗NCBI: 9097 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

USP14 · P54578

v62025-08-01

Predicted Aligned Error matrix for USP14 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

81.9/ 100

Confident

494 residues

Confidence breakdown

Very high(≥ 90)42%
Confident(70–90)41%
Low(50–70)10%
Very low(< 50)8%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

distal arthrogryposis
0.38
Abnormality of the skeletal system
0.37
diabetes mellitus
0.27
complex neurodevelopmental disorder
0.18
neoplasm
0.11
hepatocellular carcinoma
0.11
gastric cancer
0.11
glioblastoma
0.10
breast cancer
0.10
breast carcinoma
0.10

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

Protein function (UniProt)

Ubiquitin carboxyl-terminal hydrolase 14

Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins (PubMed:35145029). Ensures the regeneration of ubiquitin at the proteasome (PubMed:18162577, PubMed:28396413). Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell (PubMed:18162577). Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (PubMed:19106094). Also serves as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1 (PubMed:19135427). Indispensable for synaptic development and function at neuromuscular junctions (NMJs) (By similarity). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation (PubMed:27666593). Inhibits OPTN-mediated selective autophagic degradation of KDM4D and thereby negatively regulates H3K9me2 and H3K9me3 (PubMed:35145029)