UBA52

Summary

UBA52 (ubiquitin A-52 residue ribosomal protein fusion product 1, HGNC:12458) is a protein-coding gene on chromosome 19p13.1-p12, encoding Ubiquitin-ribosomal protein eL40 fusion protein (P62987). Exists either covalently attached to another protein, or free (unanchored). It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

Ubiquitin is a highly conserved nuclear and cytoplasmic protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein L40 at the C terminus, a C-terminal extension protein (CEP). Multiple processed pseudogenes derived from this gene are present in the genome.

Source: NCBI Gene 7311 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001033930

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12458
Approved symbol	UBA52
Name	ubiquitin A-52 residue ribosomal protein fusion product 1
Location	19p13.1-p12
Locus type	gene with protein product
Status	Approved
Aliases	RPL40, CEP52, HUBCEP52, MGC57125, MGC126879, MGC126881, L40
Ensembl gene	ENSG00000221983
Ensembl biotype	protein_coding
OMIM	191321
Entrez	7311

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 43 protein_coding, 1 retained_intron

ENST00000430157, ENST00000442744, ENST00000594527, ENST00000595158, ENST00000595683, ENST00000596272, ENST00000596273, ENST00000596304, ENST00000597451, ENST00000598780, ENST00000598814, ENST00000599256, ENST00000599551, ENST00000599595, ENST00000896905, ENST00000896906, ENST00000896907, ENST00000896908, ENST00000896909, ENST00000896910, ENST00000896911, ENST00000921806, ENST00000921807, ENST00000921808, ENST00000921809, ENST00000921810, ENST00000921811, ENST00000921812, ENST00000921813, ENST00000921814, ENST00000921815, ENST00000921816, ENST00000921817, ENST00000921818, ENST00000921819, ENST00000921820, ENST00000921821, ENST00000921822, ENST00000921823, ENST00000921824, ENST00000921825, ENST00000946389, ENST00000946390, ENST00000946391

RefSeq mRNA: 8 — MANE Select: NM_001033930 NM_001033930, NM_001321017, NM_001321018, NM_001321019, NM_001321020, NM_001321021, NM_001321022, NM_003333

CCDS: CCDS12382

Canonical transcript exons

ENST00000442744 — 5 exons

Exon	Start	End
ENSE00001565875	18573293	18573403
ENSE00001584696	18574870	18574972
ENSE00001640007	18575057	18577550
ENSE00003002064	18571857	18571909
ENSE00003784201	18573662	18573748

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 322.8612 / max 3950.0157, expressed in 1828 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174690	318.3378	1828
174691	1.8543	1001
174695	1.1894	649
174692	1.0579	633
174689	0.4218	197

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.88	gold quality
right testis	UBERON:0004534	99.88	gold quality
left testis	UBERON:0004533	99.87	gold quality
granulocyte	CL:0000094	99.82	gold quality
sperm	CL:0000019	99.80	gold quality
male germ cell	CL:0000015	99.78	gold quality
stromal cell of endometrium	CL:0002255	99.77	gold quality
lymph node	UBERON:0000029	99.77	gold quality
leukocyte	CL:0000738	99.75	gold quality
left ovary	UBERON:0002119	99.75	gold quality
monocyte	CL:0000576	99.74	gold quality
mononuclear cell	CL:0000842	99.74	gold quality
endocervix	UBERON:0000458	99.74	gold quality
superficial temporal artery	UBERON:0001614	99.74	gold quality
trabecular bone tissue	UBERON:0002483	99.74	gold quality
skin of abdomen	UBERON:0001416	99.73	gold quality
skin of leg	UBERON:0001511	99.73	gold quality
apex of heart	UBERON:0002098	99.73	gold quality
right ovary	UBERON:0002118	99.73	gold quality
cartilage tissue	UBERON:0002418	99.73	gold quality
adult organism	UBERON:0007023	99.73	gold quality
periodontal ligament	UBERON:0008266	99.73	gold quality
islet of Langerhans	UBERON:0000006	99.72	gold quality
pituitary gland	UBERON:0000007	99.72	gold quality
zone of skin	UBERON:0000014	99.72	gold quality
right adrenal gland	UBERON:0001233	99.72	gold quality
nipple	UBERON:0002030	99.72	gold quality
ganglionic eminence	UBERON:0004023	99.72	gold quality
body of uterus	UBERON:0009853	99.72	gold quality
vagina	UBERON:0000996	99.71	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	73.31
E-CURD-88	yes	61.98
E-MTAB-7316	yes	15.95
E-MTAB-10042	yes	12.28
E-GEOD-137537	yes	6.85
E-MTAB-10596	no	2975.76
E-GEOD-89232	no	2026.05
E-CURD-85	no	2015.95
E-GEOD-100618	no	1753.84
E-MTAB-6819	no	588.71
E-HCAD-1	no	109.64
E-MTAB-8142	no	93.83
E-MTAB-6701	no	87.55
E-CURD-46	no	49.22
E-MTAB-8410	no	36.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SIX4

miRNA regulators (miRDB)

74 targeting UBA52, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6512-3P	99.65	66.07	1468

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• Select activation-degradation regions like the ones found in EKLF and SREBP1a function in part through their ability to form noncovalent interactions with ubiquitin. (PMID:24139988)
• UBA52 supplies RPL40 and ubiquitin simultaneously to the ribosome. (PMID:27829658)
• our findings indicate that suppression of LUCAT1 induces CRC cell cycle arrest and apoptosis by binding UBA52 and activating the RPL40-MDM2-p53 pathway. These results implicate LUCAT1 as a potential prognostic biomarker and therapeutic target for CRC. (PMID:30690837)
• RPS27a and RPL40, Which Are Produced as Ubiquitin Fusion Proteins, Are Not Essential for p53 Signalling. (PMID:37371478)
• UBA80 and UBA52 fine-tune RNF168-dependent histone ubiquitination and DNA repair. (PMID:37451480)
• Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression. (PMID:38445807)
• SMYD5 methylation of rpL40 links ribosomal output to gastric cancer. (PMID:39048817)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	uba52	ENSDARG00000041435
mus_musculus	Uba52	ENSMUSG00000090137
rattus_norvegicus		ENSRNOG00000090524
drosophila_melanogaster	RpL40	FBGN0003941
caenorhabditis_elegans		WBGENE00006728

Paralogs (10): UBL4A (ENSG00000102178), NEDD8 (ENSG00000129559), RPS27A (ENSG00000143947), UBC (ENSG00000150991), UBB (ENSG00000170315), ZFAND4 (ENSG00000172671), UBL4B (ENSG00000186150), ISG15 (ENSG00000187608), ANKUB1 (ENSG00000206199), UBD (ENSG00000213886)

Protein

Protein identifiers

Ubiquitin-ribosomal protein eL40 fusion protein — P62987 (reviewed: P62987)

Alternative names: CEP52, Ubiquitin A-52 residue ribosomal protein fusion product 1

All UniProt accessions (5): P62987, M0R1M6, M0R1V7, M0R2S1, Q3MIH3

UniProt curated annotations — full annotation on UniProt →

Function. Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. Component of the 60S subunit of the ribosome. Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, and especially for cap-dependent translation of vesicular stomatitis virus mRNAs.

Subunit / interactions. Ribosomal protein L40 is part of the 60S ribosomal subunit. Interacts with UBQLN1 (via UBA domain).

Subcellular location. Cytoplasm. Nucleus Cytoplasm.

Post-translational modifications. Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy. Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30. Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones. (Microbial infection) Mono-ADP-ribosylated at Thr-66 by the C.violaceum CteC virulence factor. ADP-ribosylation causes the shutdown of polyubiquitin synthesis and disrupts the recognition and reversal of polyubiquitin. Trimethylation of Lys-98 (‘Lys-22’ of the mature chain) by SMYD5 promotes translation elongation and protein synthesis.

Miscellaneous. Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40 and eS31, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.

Similarity. In the N-terminal section; belongs to the ubiquitin family. In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.

RefSeq proteins (8): NP_001029102, NP_001307946, NP_001307947, NP_001307948, NP_001307949, NP_001307950, NP_001307951, NP_003324 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR001975	Ribosomal_eL40_dom	Domain
IPR019954	Ubiquitin_CS	Conserved_site
IPR019956	Ubiquitin_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR038587	Ribosomal_eL40_sf	Homologous_superfamily
IPR050158	Ubiquitin_ubiquitin-like	Family

Pfam: PF00240, PF01020

UniProt features (41 total): mutagenesis site 12, cross-link 8, strand 8, modified residue 4, site 3, helix 3, chain 2, domain 1

Structure

Experimental structures (PDB)

203 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5GOD	X-RAY DIFFRACTION	1.15
5GOB	X-RAY DIFFRACTION	1.15
4PIH	X-RAY DIFFRACTION	1.5
4PIJ	X-RAY DIFFRACTION	1.5
5GOJ	X-RAY DIFFRACTION	1.55
5J8P	X-RAY DIFFRACTION	1.55
5GOI	X-RAY DIFFRACTION	1.59
8A3D	ELECTRON MICROSCOPY	1.67
5GOC	X-RAY DIFFRACTION	1.73
8QYX	ELECTRON MICROSCOPY	1.78
4HJK	X-RAY DIFFRACTION	1.78
5GO7	X-RAY DIFFRACTION	1.8
5GOK	X-RAY DIFFRACTION	1.84
7OWC	X-RAY DIFFRACTION	1.85
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8IKM	X-RAY DIFFRACTION	1.92
5GOH	X-RAY DIFFRACTION	1.95
4PIG	X-RAY DIFFRACTION	1.95
5GOG	X-RAY DIFFRACTION	1.98
5JBY	X-RAY DIFFRACTION	1.99
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
8IPJ	X-RAY DIFFRACTION	2
5HPS	X-RAY DIFFRACTION	2.05
4XKL	X-RAY DIFFRACTION	2.1
5JBV	X-RAY DIFFRACTION	2.1
4RF1	X-RAY DIFFRACTION	2.15
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62987-F1	93.61	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 54 (interacts with activating enzyme); 68 (essential for function); 72 (interacts with activating enzyme)

Post-translational modifications (12): 6, 11, 27, 29, 33, 48, 63, 76, 65, 66, 76, 98

Mutagenesis-validated functional residues (12):

Position	Phenotype
48	no effect on hltf-mediated polyubiquitination of pcna.
63	abolishes hltf-mediated polyubiquitination of pcna.
65	prevents phosphorylation in case of mitophagy. impaired translocation of prkn to mitochondria.
65	phosphomimetic mutant that binds and activates prkn.
65	phosphomimetic mutant that can recruit prkn to mitochondria.
68	loss of dtx3l-mediated polyubiquitination of histone h3 and h4.
72	no effect on adp-ribosylation.
72	no effect on adp-ribosylation, when associated with k-74.
74	no effect on adp-ribosylation.
74	no effect on adp-ribosylation, when associated with k-72.
76	loss of adp-ribosylation.
98	abolished methylation by smyd5, leading to decreased translation initiation and protein synthesis.

Function

Pathways and Gene Ontology

Reactome pathways

214 pathways

ID	Pathway
R-HSA-110312	Translesion synthesis by REV1
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-110320	Translesion Synthesis by POLH
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1253288	Downregulation of ERBB4 signaling
R-HSA-1295596	Spry regulation of FGF signaling
R-HSA-1358803	Downregulation of ERBB2:ERBB3 signaling
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-162588	Budding and maturation of HIV virion
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-174490	Membrane binding and targetting of GAG proteins
R-HSA-175474	Assembly Of The HIV Virion
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-180534	Vpu mediated degradation of CD4
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-182971	EGFR downregulation

MSigDB gene sets: 0 (showing top):

GO Biological Process (6): cytoplasmic translation (GO:0002181), protein ubiquitination (GO:0016567), response to insecticide (GO:0017085), modification-dependent protein catabolic process (GO:0019941), protein modification process (GO:0036211), translation (GO:0006412)

GO Molecular Function (4): structural constituent of ribosome (GO:0003735), protein tag activity (GO:0031386), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (18): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), endocytic vesicle membrane (GO:0030666), vesicle (GO:0031982), extracellular exosome (GO:0070062), ribosome (GO:0005840), large ribosomal subunit (GO:0015934), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-22 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	2
DNA Damage Bypass	1
Downstream signaling events of B Cell Receptor (BCR)	1
Antimicrobial mechanism of IFN-stimulated genes	1
Cellular response to hypoxia	1
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Antigen processing-Cross presentation	1
Signaling by ERBB4	1
Negative regulation of FGFR1 signaling	1
Negative regulation of FGFR2 signaling	1
Negative regulation of FGFR3 signaling	1
Negative regulation of FGFR4 signaling	1
Downregulation of ERBB2 signaling	1
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein metabolic process	2
ribosome	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
translation	1
protein modification by small protein conjugation	1
response to toxic substance	1
protein catabolic process	1
protein modification process	1
modification-dependent macromolecule catabolic process	1
macromolecule modification	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein biosynthetic process	1
structural molecule activity	1
molecular tag activity	1
ubiquitin-like protein ligase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
lysosome	1
lytic vacuole membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
membrane	1
cell periphery	1
endosome	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
endocytic vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

217 interactions, top by confidence:

A	B	Type	Score
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
UBA52	DAZAP2	psi-mi:“MI:0915”(physical association)	0.670
RNF11	UBA52	psi-mi:“MI:0915”(physical association)	0.670
UBA52	UBE2O	psi-mi:“MI:0915”(physical association)	0.660
EIF2B2	SLC27A2	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
UBA52	DESI1	psi-mi:“MI:0915”(physical association)	0.600
UBA52	TAX1BP1	psi-mi:“MI:0915”(physical association)	0.560
UBA52	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
UBA52	RABGEF1	psi-mi:“MI:0915”(physical association)	0.560
UBA52	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
UBA52	LITAF	psi-mi:“MI:0915”(physical association)	0.560
UBA52	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
UBA52	MTURN	psi-mi:“MI:0915”(physical association)	0.560
EPN2	UBA52	psi-mi:“MI:0915”(physical association)	0.560
UBA52	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
RAD23A	UBA52	psi-mi:“MI:0915”(physical association)	0.560
UBA52	ARRDC3	psi-mi:“MI:0915”(physical association)	0.560
UBA52	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
DCTN1	UBA52	psi-mi:“MI:0915”(physical association)	0.560
SNCA	UBA52	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (581): UBA52 (Biochemical Activity), UBA52 (Biochemical Activity), UBA52 (Affinity Capture-MS), RAB2A (Co-fractionation), RPL13 (Co-fractionation), RPL35 (Co-fractionation), RPL35A (Co-fractionation), RPL4 (Co-fractionation), RPLP2 (Co-fractionation), RPS4X (Co-fractionation), UBA52 (Co-fractionation), UBA52 (Co-fractionation), UBA52 (Co-fractionation), UBA52 (Co-fractionation), UBA52 (Co-fractionation)

ESM2 similar proteins: B9DHA6, P05759, P0C016, P0C224, P0C273, P0C275, P0C276, P0C8R3, P0CH06, P0CH07, P0CH08, P0CH09, P0CH10, P0CH11, P0CH34, P0CH35, P0DJ25, P0DXC2, P14794, P14795, P14797, P15357, P18101, P21899, P29504, P33190, P40909, P46575, P49632, P49633, P49636, P51423, P62982, P62983, P62984, P62986, P62987, P63048, P63050, P63052

Diamond homologs: A0A1D8PL68, A1RRS5, B1YA13, B9DHA6, P0C224, P0C273, P0C275, P0C276, P0CH06, P0CH07, P0CH08, P0CH09, P0CH10, P0CH11, P0CH27, P0CH34, P0CH35, P0DJ25, P0DXC2, P14794, P14795, P18101, P19379, P21899, P33190, P40909, P46575, P49632, P49633, P49636, P51423, P62984, P62985, P62986, P62987, P63048, P63050, P63052, P63053, P68205

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
USP7	“up-regulates quantity”	UBA52	cleavage
USP9X	“up-regulates quantity”	UBA52	cleavage
UCHL3	“up-regulates quantity”	UBA52	cleavage
SIX4	“up-regulates quantity by expression”	UBA52	“transcriptional regulation”
PINK1	up-regulates	UBA52	phosphorylation
UBA52	“up-regulates activity”	PRKN	binding
UBA52	“form complex”	“60S cytosolic large ribosomal subunit”	binding
SEC23B	unknown	UBA52	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 181 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Packaging Of Telomere Ends	6	10.4×	1e-02
Recognition and association of DNA glycosylase with site containing an affected purine	6	9.6×	1e-02
Cleavage of the damaged purine	6	9.6×	1e-02
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	6	8.7×	1e-02
Cleavage of the damaged pyrimidine	6	8.7×	1e-02
FXIIa activates plasma kallikrein-kinin system	6	8.2×	1e-02
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	6	7.9×	1e-02
Inhibition of DNA recombination at telomere	6	7.9×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

21 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

803 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18571829:GCGAT:G	donor_gain	1.0000
19:18573288:T:A	acceptor_gain	1.0000
19:18573291:A:AG	acceptor_gain	1.0000
19:18573291:AGAC:A	acceptor_gain	1.0000
19:18573292:G:GG	acceptor_gain	1.0000
19:18573292:GAC:G	acceptor_gain	1.0000
19:18573292:GACG:G	acceptor_gain	1.0000
19:18573292:GACGC:G	acceptor_gain	1.0000
19:18573399:GGAGG:G	donor_gain	1.0000
19:18573400:GAGG:G	donor_gain	1.0000
19:18573400:GAGGG:G	donor_gain	1.0000
19:18573401:A:T	donor_gain	1.0000
19:18573401:AGG:A	donor_gain	1.0000
19:18573402:GG:G	donor_gain	1.0000
19:18573402:GGG:G	donor_gain	1.0000
19:18573403:GG:G	donor_gain	1.0000
19:18573404:G:GG	donor_gain	1.0000
19:18573404:GTGA:G	donor_loss	1.0000
19:18573405:T:A	donor_loss	1.0000
19:18573657:CTCA:C	acceptor_loss	1.0000
19:18573658:TCAG:T	acceptor_loss	1.0000
19:18573659:CAG:C	acceptor_loss	1.0000
19:18573660:A:AG	acceptor_gain	1.0000
19:18573660:AG:A	acceptor_gain	1.0000
19:18573661:G:GA	acceptor_gain	1.0000
19:18573661:GG:G	acceptor_gain	1.0000
19:18573661:GGT:G	acceptor_gain	1.0000
19:18573661:GGTA:G	acceptor_gain	1.0000
19:18573661:GGTAT:G	acceptor_gain	1.0000
19:18573744:GAAAG:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000106213 (19:18573550 C>G), RS1000129444 (19:18577183 T>C), RS1000322249 (19:18575766 A>G), RS1000428428 (19:18563628 C>G), RS1000520443 (19:18567483 T>C), RS1000624330 (19:18572015 G>A), RS1000656914 (19:18572225 C>T), RS1000954637 (19:18567669 C>T), RS1001025787 (19:18562648 G>A), RS1001472505 (19:18566687 G>A), RS1001754503 (19:18568296 A>C,G), RS1001761508 (19:18571729 C>T), RS1001996685 (19:18571771 C>G,T), RS1002054519 (19:18577061 C>T), RS1002107854 (19:18571527 A>C,G)

Disease associations

OMIM: gene MIM:191321 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523259 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects reaction, increases expression, increases reaction, decreases reaction, increases methylation	2
Arsenic	affects methylation, decreases expression, increases abundance	2
moringin	increases expression	1
AKT activator SC79	increases expression, increases reaction	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression	1
decamethrin	increases expression	1
cobaltous chloride	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
dinophysistoxin 1	increases expression	1
CD 437	decreases expression	1
chloropicrin	affects expression	1
fenpyroximate	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
pyrimidifen	increases expression	1
abrine	decreases expression	1
enzalutamide	affects expression	1
picoxystrobin	increases expression	1
capivasertib	decreases reaction, increases expression	1
Aluminum	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cannabidiol	decreases expression	1
Copper	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Diuron	decreases expression	1
Gallic Acid	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4341430	Binding	Binding affinity to UBA52 in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis relative to untreated control	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.