UBE2K

Summary

UBE2K (ubiquitin conjugating enzyme E2 K, HGNC:4914) is a protein-coding gene on chromosome 4p14, encoding Ubiquitin-conjugating enzyme E2 K (P61086). Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.

The protein encoded by this gene belongs to the ubiquitin-conjugating enzyme family. This protein interacts with RING finger proteins, and it can ubiquitinate huntingtin, the gene product for Huntington’s disease. Known functions for this protein include a role in aggregate formation of expanded polyglutamine proteins and the suppression of apoptosis in polyglutamine diseases, a role in the dislocation of newly synthesized MHC class I heavy chains from the endoplasmic reticulum, and involvement in foam cell formation. Multiple transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 3093 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 12 total
• Druggable target: yes
• MANE Select transcript: NM_005339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4914
Approved symbol	UBE2K
Name	ubiquitin conjugating enzyme E2 K
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	HYPG, UBC1
Ensembl gene	ENSG00000078140
Ensembl biotype	protein_coding
OMIM	602846
Entrez	3093

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261427, ENST00000438068, ENST00000445950, ENST00000503368, ENST00000510719, ENST00000510934, ENST00000513231, ENST00000853975, ENST00000853976, ENST00000932516, ENST00000932517, ENST00000932518

RefSeq mRNA: 6 — MANE Select: NM_005339 NM_001111112, NM_001111113, NM_001312646, NM_001312647, NM_001312648, NM_005339

CCDS: CCDS33976, CCDS47043, CCDS47044

Canonical transcript exons

ENST00000261427 — 7 exons

Exon	Start	End
ENSE00001077328	39778360	39782792
ENSE00001368901	39698136	39698390
ENSE00003459917	39777682	39777810
ENSE00003492171	39755657	39755739
ENSE00003495184	39737420	39737513
ENSE00003643780	39745752	39745810
ENSE00003659372	39774834	39774933

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.4995 / max 1418.2269, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47385	48.9819	1820
47386	23.5176	1810

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.60	gold quality
secondary oocyte	CL:0000655	97.55	gold quality
esophagus squamous epithelium	UBERON:0006920	97.18	gold quality
islet of Langerhans	UBERON:0000006	96.83	gold quality
epithelium of esophagus	UBERON:0001976	96.78	gold quality
postcentral gyrus	UBERON:0002581	96.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.55	gold quality
cortical plate	UBERON:0005343	96.54	gold quality
parietal lobe	UBERON:0001872	96.53	gold quality
male germ cell	CL:0000015	96.44	gold quality
middle temporal gyrus	UBERON:0002771	96.34	gold quality
amniotic fluid	UBERON:0000173	96.26	gold quality
buccal mucosa cell	CL:0002336	96.25	gold quality
lower esophagus mucosa	UBERON:0035834	95.93	gold quality
superior frontal gyrus	UBERON:0002661	95.92	gold quality
tongue squamous epithelium	UBERON:0006919	95.78	gold quality
stromal cell of endometrium	CL:0002255	95.58	gold quality
entorhinal cortex	UBERON:0002728	95.54	gold quality
esophagus mucosa	UBERON:0002469	95.51	gold quality
monocyte	CL:0000576	95.42	gold quality
oral cavity	UBERON:0000167	95.41	gold quality
ventricular zone	UBERON:0003053	95.35	gold quality
pons	UBERON:0000988	95.32	gold quality
mucosa of transverse colon	UBERON:0004991	95.22	gold quality
rectum	UBERON:0001052	95.21	gold quality
mononuclear cell	CL:0000842	95.04	gold quality
endothelial cell	CL:0000115	94.96	gold quality
squamous epithelium	UBERON:0006914	94.96	gold quality
leukocyte	CL:0000738	94.95	gold quality
mammalian vulva	UBERON:0000997	94.90	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

277 targeting UBE2K, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 17)

• Results suggest that in permeabilized, US11-expressing cells polyubiquitination of the MHC class I heavy chain substrate can be catalyzed by E2-25K. (PMID:16868077)
• E2-25K is involved in aggregate formation of expanded polyglutamine proteins and polyglutamine-induced cell death. (PMID:17092742)
• This study suggests that Hip2 might be involved in the regulation of Smac-mediated apoptosis. (PMID:20537984)
• Results suggest that the interaction between E2-25K and UBB(+1) is critical for the synthesis and accumulation of UBB(+1)-anchored polyubiquitin, which results in proteasomal inhibition and neuronal cell death. (PMID:20826778)
• one of the roles of the C-terminal UBA domain, in the context of E2-25K, is to increase processivity in Lys48-linked polyubiquitin chain synthesis, possibly through increased binding to the ubiquitinated substrate. (PMID:21281599)
• An extract of bark from the tropical rainforest plant Byrsonima crassifolia was screened for inhibition of diubiquitin formation by the human ubiquitin-conjugating enzyme E2-25K. (PMID:22164771)
• Hip2, a ubiquitin-conjugating enzyme, can overcome radiation-induced G2/M cell cycle arrest and trigger the entry into mitosis. (PMID:23933584)
• The crystal structure of a Ube2K~ubiquitin conjugate has been described, and it was shown that even though it is monomeric, Ube2K can synthesize Lys48-linked ubiquitin chains. (PMID:26592444)
• The data indicate that active site gate opening and closing rates for E2-25K are precisely balanced. (PMID:29725124)
• Hip2 works as a regulator in UV-induced cell cycle arrest and re-entry. (PMID:30264212)
• Crystal structure of the Ube2K/E2-25K and K48-linked diubiquitin complex provides structural insight into the mechanism of K48-specific ubiquitin chain synthesis. (PMID:30336976)
• Expression of UBE2K’s transcript has been shown to be dysregulated in the brain of individuals with a psychiatric illness and in the blood transcript expression was associated with positive symptom severity in schizophrenia. (PMID:30901725)
• The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells. (PMID:32451438)
• UBE2K promotes the malignant progression of hepatocellular carcinoma by regulating c-Myc. (PMID:36481361)
• Hypoxia-induced UBE2K promotes the malignant progression of HCC. (PMID:37003132)
• Simulation and Computational Study of RING Domain Mutants of BRCA1 and Ube2k in AD/PD Pathophysiology. (PMID:38172369)
• Silencing UBE2K inhibits the growth of glioma cells by inducing the autophagy-related apoptosis. (PMID:38963134)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2kb	ENSDARG00000013505
danio_rerio	ube2ka	ENSDARG00000089055
mus_musculus	Ube2k	ENSMUSG00000029203
rattus_norvegicus	Ube2k	ENSRNOG00000027088
drosophila_melanogaster	Ubc4	FBGN0015321

Paralogs (24): UBE2T (ENSG00000077152), UBE2A (ENSG00000077721), CDC34 (ENSG00000099804), UBE2I (ENSG00000103275), UBE2W (ENSG00000104343), UBE2R2 (ENSG00000107341), UBE2S (ENSG00000108106), UBE2B (ENSG00000119048), UBE2G1 (ENSG00000132388), UBE2Z (ENSG00000159202), UBE2J2 (ENSG00000160087), AKTIP (ENSG00000166971), UBE2V2 (ENSG00000169139), UBE2C (ENSG00000175063), UBE2O (ENSG00000175931), UBE2U (ENSG00000177414), UBE2N (ENSG00000177889), UBE2F (ENSG00000184182), UBE2G2 (ENSG00000184787), UBE2H (ENSG00000186591), UBE2J1 (ENSG00000198833), PEDS1 (ENSG00000240849), UBE2V1 (ENSG00000244687), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 K — P61086 (reviewed: P61086)

Alternative names: E2 ubiquitin-conjugating enzyme K, Huntingtin-interacting protein 2, Ubiquitin carrier protein, Ubiquitin-conjugating enzyme E2-25 kDa, Ubiquitin-protein ligase

All UniProt accessions (3): P61086, D6RDM7, D6RFX1

UniProt curated annotations — full annotation on UniProt →

Function. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of ‘Lys-48’-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.

Subunit / interactions. Interacts with RNF138/NARF. Interacts with BRCA1.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in all tissues tested, including spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes, T-lymphocytes, monocytes, granulocytes and bone marrow mononuclear cells. Highly expressed in brain, with highest levels found in cortex and striatum and at lower levels in cerebellum and brainstem.

Post-translational modifications. Sumoylation at Lys-14 impairs catalytic activity.

Induction. By aggregated low-density lipoprotein.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. May be inactive.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

Isoforms (3)

UniProt ID	Names	Canonical?
P61086-1	1	yes
P61086-2	2
P61086-3	3

RefSeq proteins (6): NP_001104582, NP_001104583, NP_001299575, NP_001299576, NP_001299577, NP_005330* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR015940	UBA	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site
IPR042599	UBE2K_UBA	Domain

Pfam: PF00179, PF00627

Enzyme classification (BRENDA):

• EC 2.3.2.23 — E2 ubiquitin-conjugating enzyme (BRENDA: 20 organisms, 93 substrates, 28 inhibitors, 12 Km, 8 kcat entries)
• EC 2.3.2.24 — (E3-independent) E2 ubiquitin-conjugating enzyme (BRENDA: 5 organisms, 56 substrates, 7 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBIQUITIN-CARRIER-PROTEIN UBC2B]-L-CYSTEINE	0.0001	5
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.2203–0.3014	2
[HISTONE H2A]-L-LYSINE	0.0008–0.0028	2
[HISTONE H2B]-L-LYSINE	0.0015–0.012	2
S-UBIQUITINYL-[E1 UBIQUITIN-ACTIVATING ENZYME]-L	1	1
[UBIQUITIN CARRIER PROTEIN UBC4]-L-CYSTEINE	0.0019	1
[CYTOCHROME C]-L-LYSINE	0.125	1
[HISTONE H3]-L-LYSINE	0.0013	1

UniProt features (33 total): helix 9, strand 6, turn 6, modified residue 3, splice variant 2, domain 2, initiator methionine 1, chain 1, mutagenesis site 1, active site 1, cross-link 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3K9O	X-RAY DIFFRACTION	1.8
3E46	X-RAY DIFFRACTION	1.86
5DFL	X-RAY DIFFRACTION	2.1
6JB7	X-RAY DIFFRACTION	2.1
3F92	X-RAY DIFFRACTION	2.23
7MYH	X-RAY DIFFRACTION	2.39
1YLA	X-RAY DIFFRACTION	2.4
7OJX	X-RAY DIFFRACTION	2.4
6IF1	X-RAY DIFFRACTION	2.47
2O25	X-RAY DIFFRACTION	2.6
6JB6	X-RAY DIFFRACTION	2.7
3K9P	X-RAY DIFFRACTION	2.8
7MYF	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61086-F1	96.71	0.95

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 (1): 92 (glycyl thioester intermediate)

Post-translational modifications (4): 2, 14, 159, 14

Mutagenesis-validated functional residues (1):

Position	Phenotype
94	decreased lysine reactivity and impaired formation of free polyubiquitin chains.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 337 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, GCM_MAP4K4, MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GAANYNYGACNY_UNKNOWN, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GCANCTGNY_MYOD_Q6, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (11): protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), positive regulation of peptidyl-threonine phosphorylation (GO:0010800), free ubiquitin chain polymerization (GO:0010994), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), cellular response to interferon-beta (GO:0035458), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), protein K48-linked ubiquitination (GO:0070936), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), protein ubiquitination (GO:0016567), type I interferon-mediated signaling pathway (GO:0060337)

GO Molecular Function (8): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ubiquitin protein ligase binding (GO:0031625), ubiquitin-ubiquitin ligase activity (GO:0034450), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), filopodium tip (GO:0032433)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Protein ubiquitination	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein ubiquitination	2
positive regulation of cytokine-mediated signaling pathway	2
modification-dependent protein catabolic process	1
positive regulation of protein phosphorylation	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
ubiquitin recycling	1
protein polymerization	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
response to interferon-beta	1
cellular response to cytokine stimulus	1
positive regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
protein polyubiquitination	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
protein modification by small protein conjugation	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ubiquitin-like protein ligase binding	1
ubiquitin protein ligase activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein conjugating enzyme activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
filopodium	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

374 interactions, top by confidence:

A	B	Type	Score
UBE2K	RNF138	psi-mi:“MI:0915”(physical association)	0.940
RNF138	UBE2K	psi-mi:“MI:0915”(physical association)	0.940
RNF5	UBE2K	psi-mi:“MI:0915”(physical association)	0.810
UBE2K	RNF5	psi-mi:“MI:0915”(physical association)	0.810
UBE2K	TRIM27	psi-mi:“MI:0915”(physical association)	0.810
TRIM27	UBE2K	psi-mi:“MI:0915”(physical association)	0.810
UBE2K	DTX3	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	UBE2K	psi-mi:“MI:0915”(physical association)	0.720
UBE2K	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
DTX3	UBE2K	psi-mi:“MI:0915”(physical association)	0.720
UBE2K	TRIM39	psi-mi:“MI:0915”(physical association)	0.720
UBE2K	RING1	psi-mi:“MI:0915”(physical association)	0.720
UBE2K	BFAR	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (266): UBE2K (Reconstituted Complex), UBE2K (Reconstituted Complex), UBE2K (Affinity Capture-MS), UBE2K (Affinity Capture-Western), REL (Two-hybrid), RNF5 (Two-hybrid), SIAH1 (Two-hybrid), RNF138 (Two-hybrid), TRIM39 (Two-hybrid), MIPOL1 (Two-hybrid), DTX3 (Two-hybrid), DDI1 (Two-hybrid), UBE2K (Two-hybrid), MDM2 (Reconstituted Complex), UBE2K (Biochemical Activity)

ESM2 similar proteins: A2Z5S8, A7SM54, A8Q8J2, A8XAF4, A9UR29, B0WVC4, B3MC02, B3NPZ0, B3RTL9, B4H538, B4HSI1, B4J9W6, B4KQQ4, B4LL39, B4MIX7, B4P6S9, B4QHD6, C3ZDX5, P34477, P42747, P52486, P52487, P60604, P60605, P61085, P61086, P61087, P62253, P62254, P62255, Q03598, Q178A5, Q17QG5, Q1ZXC9, Q28X71, Q32L27, Q42540, Q42541, Q4R5Y8, Q5RF84

Diamond homologs: A5PKP9, C4R826, D3ZDK2, I1RRW0, O60015, O74196, O74201, O74810, P06104, P0CS16, P0CS17, P15731, P15732, P16577, P23566, P25153, P25865, P25866, P25867, P29340, P35129, P35130, P35131, P35132, P35133, P35134, P35135, P42745, P42746, P43102, P46595, P49428, P49459, P51668, P52478, P52483, P52486, P52491, P52493, P60604

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2K	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2K	ubiquitination
UBE2K	“up-regulates activity”	RNF138	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Interferon gamma signaling	7	17.2×	2e-05
Class I MHC mediated antigen processing & presentation	8	11.0×	5e-05
Antigen processing: Ubiquitination & Proteasome degradation	13	9.5×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein K63-linked ubiquitination	6	24.7×	2e-05
protein polyubiquitination	11	19.5×	1e-09
protein autoubiquitination	5	18.0×	6e-04
ubiquitin-dependent protein catabolic process	14	16.0×	4e-11
protein ubiquitination	18	11.5×	5e-12
autophagy	6	10.2×	2e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	7	5.6×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1701 predictions. Top by Δscore:

Variant	Effect	Δscore
4:39698370:G:GT	donor_gain	1.0000
4:39698388:G:GT	donor_gain	1.0000
4:39737417:A:AG	acceptor_gain	1.0000
4:39737417:AAGAC:A	acceptor_gain	1.0000
4:39737418:A:G	acceptor_gain	1.0000
4:39737419:G:GG	acceptor_gain	1.0000
4:39737419:GAC:G	acceptor_gain	1.0000
4:39737419:GACGA:G	acceptor_gain	1.0000
4:39774824:T:TA	acceptor_gain	1.0000
4:39774827:A:AG	acceptor_gain	1.0000
4:39774828:T:G	acceptor_gain	1.0000
4:39774830:TTA:T	acceptor_loss	1.0000
4:39774831:TA:T	acceptor_loss	1.0000
4:39774832:A:AC	acceptor_loss	1.0000
4:39774832:A:AG	acceptor_gain	1.0000
4:39774832:AG:A	acceptor_gain	1.0000
4:39774832:AGG:A	acceptor_gain	1.0000
4:39774833:G:A	acceptor_gain	1.0000
4:39774833:G:GA	acceptor_gain	1.0000
4:39774833:GGG:G	acceptor_gain	1.0000
4:39774833:GGGC:G	acceptor_gain	1.0000
4:39774833:GGGCA:G	acceptor_gain	1.0000
4:39774929:ATCAG:A	donor_gain	1.0000
4:39774930:TCAG:T	donor_gain	1.0000
4:39774934:G:GC	donor_loss	1.0000
4:39774934:G:GG	donor_gain	1.0000
4:39777679:T:G	acceptor_gain	1.0000
4:39777680:A:AG	acceptor_gain	1.0000
4:39777681:G:GA	acceptor_gain	1.0000
4:39777681:GT:G	acceptor_gain	1.0000

AlphaMissense

1303 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:39698350:G:C	R8P	1.000
4:39698359:G:C	R11P	1.000
4:39698361:G:A	E12K	1.000
4:39737477:G:A	G41R	1.000
4:39737477:G:C	G41R	1.000
4:39737478:G:A	G41E	1.000
4:39737489:G:A	G45R	1.000
4:39737489:G:C	G45R	1.000
4:39737490:G:A	G45E	1.000
4:39745767:T:C	L58P	1.000
4:39745773:T:A	I60K	1.000
4:39745779:T:A	I62K	1.000
4:39745790:T:C	Y66H	1.000
4:39745793:C:A	P67T	1.000
4:39745793:C:T	P67S	1.000
4:39745794:C:A	P67Q	1.000
4:39745796:T:C	F68L	1.000
4:39745797:T:C	F68S	1.000
4:39745797:T:G	F68C	1.000
4:39745798:T:A	F68L	1.000
4:39745798:T:G	F68L	1.000
4:39745805:C:T	P71S	1.000
4:39745806:C:A	P71H	1.000
4:39755663:T:C	F75L	1.000
4:39755664:T:C	F75S	1.000
4:39755665:T:A	F75L	1.000
4:39755665:T:G	F75L	1.000
4:39755678:T:A	W80R	1.000
4:39755678:T:C	W80R	1.000
4:39755680:G:C	W80C	1.000

dbSNP variants (sampled 300 via entrez): RS1000034657 (4:39740050 A>G), RS1000046882 (4:39700531 A>G), RS1000069707 (4:39753117 A>G), RS1000123194 (4:39752892 T>C), RS10001359 (4:39725560 G>A,T), RS1000149110 (4:39719363 C>T), RS1000149686 (4:39746332 C>T), RS1000176469 (4:39768097 C>T), RS1000176841 (4:39745993 A>C,G), RS1000180385 (4:39719685 A>G), RS1000200055 (4:39751816 A>G), RS1000203339 (4:39719120 C>G,T), RS1000213341 (4:39713479 G>A), RS1000213912 (4:39716004 C>T), RS1000312469 (4:39763840 A>G)

Disease associations

OMIM: gene MIM:602846 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002360_6	Plasma amyloid beta peptide concentrations (ABx-40)	7.000000e-06
GCST010241_44	Apolipoprotein A1 levels	3.000000e-15
GCST010242_332	HDL cholesterol levels	3.000000e-13
GCST90002402_731	Platelet count	5.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005659	plasma beta-amyloid 1-40 measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105835 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression	3
sodium arsenite	affects reaction, increases expression	3
Valproic Acid	decreases expression, affects expression	3
Tobacco Smoke Pollution	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
methylmercuric chloride	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
methylparaben	decreases expression	1
cobaltous chloride	increases expression	1
ochratoxin A	increases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Aminoglutethimide	decreases expression	1
Arsenic	affects methylation	1
Aspirin	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Deoxycholic Acid	affects cotreatment, increases expression	1
Dieldrin	increases response to substance	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4030868	Binding	Inhibition of E2-25K (unknown origin) at 2.5 to 10 uM preincubated for 15 mins followed by E1, Ub and ATP addition measured after 40 mins by Western blot analysis	Discovery of Potent Small-Molecule Inhibitors of Ubiquitin-Conjugating Enzyme UbcH5c from α-Santonin Derivatives. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1EE	Abcam HCT 116 UBE2K KO	Cancer cell line	Male
CVCL_B2K7	Abcam HeLa UBE2K KO	Cancer cell line	Female
CVCL_TV78	HAP1 UBE2K (-) 1	Cancer cell line	Male
CVCL_TV79	HAP1 UBE2K (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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