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Overview

Uniprot ID	O00487
Protein Name	Ubiquitin C-terminal hydrolase PSMD14
Gene Name	PSMD14
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
152	VDPIQSVKGKVVIDA
154	PIQSVKGKVVIDAFR
277	LAIKNVGKQDPKRHL

Function

Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair (PubMed:9374539, PubMed:1317798). The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex (PubMed:22909820). Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation (PubMed:22909820). Also involved in homologous recombination repair by promoting RAD51 loading (PubMed:22909820). Regulates macroautophagy by ensuring Golgi-to-ER retrograde transport through its deubiquitinating activity on K63-linked ubiquitin chains. This activity prevents the retention of essential autophagy proteins at the Golgi, enabling their trafficking to autophagosome formation sites and supporting Golgi-ER membrane recycling critical for effective autophagy (PubMed:32210007)

Protein Sequence

10 MDRLLRLGGG 20 MPGLGQGPPT 30 DAPAVDTAEQ 40 VYISSLALLK 50 MLKHGRAGVP 60 MEVMGLMLGE 70 FVDDYTVRVI 80 DVFAMPQSGT 90 GVSVEAVDPV 100 FQAKMLDMLK 110 QTGRPEMVVG 120 WYHSHPGFGC 130 WLSGVDINTQ 140 QSFEALSERA 150 VAVVVDPIQS 160 VKGKVVIDAF 170 RLINANMMVL 180 GHEPRQTTSN 190 LGHLNKPSIQ 200 ALIHGLNRHY 210 YSITINYRKN 220 ELEQKMLLNL 230 HKKSWMEGLT 240 LQDYSEHCKH 250 NESVVKEMLE 260 LAKNYNKAVE 270 EEDKMTPEQL 280 AIKNVGKQDP 290 KRHLEEHVDV 300 LMTSNIVQCL 310 AAMLDTVVFK

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005829	cytosol
Biological Process	GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process	GO:0016579	protein deubiquitination
Biological Process	GO:0070536	protein K63-linked deubiquitination
Biological Process	GO:0016241	regulation of macroautophagy
Biological Process	GO:0061136	regulation of proteasomal protein catabolic process
Biological Process	GO:0045471	response to ethanol
Biological Process	GO:0006979	response to oxidative stress
Biological Process	GO:0006890	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
Biological Process	GO:0006511	ubiquitin-dependent protein catabolic process
Cellular Component	GO:0031597	cytosolic proteasome complex
Cellular Component	GO:0005576	extracellular region
Cellular Component	GO:1904813	ficolin-1-rich granule lumen
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0022624	proteasome accessory complex
Cellular Component	GO:0000502	proteasome complex
Cellular Component	GO:0008541	proteasome regulatory particle, lid subcomplex
Cellular Component	GO:0034774	secretory granule lumen
Cellular Component	GO:0008021	synaptic vesicle
Molecular Function	GO:0004843	cysteine-type deubiquitinase activity
Molecular Function	GO:0061133	endopeptidase activator activity
Molecular Function	GO:0061578	K63-linked deubiquitinase activity
Molecular Function	GO:0046872	metal ion binding
Molecular Function	GO:0140492	metal-dependent deubiquitinase activity
Molecular Function	GO:0008237	metallopeptidase activity
Molecular Function	GO:0070628	proteasome binding
Biological Process	GO:0006914	autophagy
Biological Process	GO:0071357	cellular response to type I interferon
Biological Process	GO:0000724	double-strand break repair via homologous recombination
Biological Process	GO:0006303	double-strand break repair via nonhomologous end joining
Biological Process	GO:0010498	proteasomal protein catabolic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.