UBE2D2

Summary

UBE2D2 (ubiquitin conjugating enzyme E2 D2, HGNC:12475) is a protein-coding gene on chromosome 5q31.2, encoding Ubiquitin-conjugating enzyme E2 D2 (P62837). Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.

Regulated degradation of misfolded, damaged or short-lived proteins in eukaryotes occurs via the ubiquitin (Ub)-proteasome system (UPS). An integral part of the UPS system is the ubiquitination of target proteins and covalent linkage of Ub-containing proteins to form polymeric chains, marking them as targets for 26S proteasome-mediated degradation. Ubiquitination of proteins is mediated by a cascade of enzymes which includes E1 (ubiquitin activating), E2 (ubiquitin conjugating), and E3 (ubiquitin ligases) enzymes. This gene encodes a member of the E2 enzyme family. Substrates of this enzyme include the tumor suppressor protein p53 and peroxisomal biogenesis factor 5 (PEX5). Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 7322 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 16 total
• Druggable target: yes
• MANE Select transcript: NM_003339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12475
Approved symbol	UBE2D2
Name	ubiquitin conjugating enzyme E2 D2
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	UbcH5B, UBC4
Ensembl gene	ENSG00000131508
Ensembl biotype	protein_coding
OMIM	602962
Entrez	7322

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000398733, ENST00000398734, ENST00000505007, ENST00000505548, ENST00000510470, ENST00000511691, ENST00000511725, ENST00000698321, ENST00000698322, ENST00000698323, ENST00000867071, ENST00000867072, ENST00000867073, ENST00000867074, ENST00000867075, ENST00000867076, ENST00000867077, ENST00000932351, ENST00000965736

RefSeq mRNA: 2 — MANE Select: NM_003339 NM_003339, NM_181838

CCDS: CCDS43369, CCDS47275

Canonical transcript exons

ENST00000398733 — 7 exons

Exon	Start	End
ENSE00001549340	139626756	139628434
ENSE00001694979	139623368	139623461
ENSE00003504948	139614697	139614774
ENSE00003547850	139600372	139600435
ENSE00003551948	139614861	139614966
ENSE00003632262	139561339	139561815
ENSE00003690818	139614586	139614617

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 156.6462 / max 678.5559, expressed in 1827 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58841	82.0626	1825
58843	55.2352	1823
58842	5.6139	1655
58845	3.3683	1550
58844	3.2790	1583
58850	2.0467	1325
58849	1.2545	942
58840	1.1620	789
58848	0.8388	453
58838	0.5677	277

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.90	gold quality
ganglionic eminence	UBERON:0004023	98.80	gold quality
right testis	UBERON:0004534	98.66	gold quality
left testis	UBERON:0004533	98.62	gold quality
cortical plate	UBERON:0005343	98.59	gold quality
right uterine tube	UBERON:0001302	98.37	gold quality
gastrocnemius	UBERON:0001388	98.06	gold quality
granulocyte	CL:0000094	98.05	gold quality
sperm	CL:0000019	98.00	gold quality
muscle of leg	UBERON:0001383	97.99	gold quality
rectum	UBERON:0001052	97.93	gold quality
popliteal artery	UBERON:0002250	97.91	gold quality
tibial artery	UBERON:0007610	97.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.72	gold quality
right lung	UBERON:0002167	97.70	gold quality
right coronary artery	UBERON:0001625	97.67	gold quality
aorta	UBERON:0000947	97.66	gold quality
left uterine tube	UBERON:0001303	97.62	gold quality
ectocervix	UBERON:0012249	97.62	gold quality
lower esophagus	UBERON:0013473	97.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.60	gold quality
male germ cell	CL:0000015	97.57	gold quality
endocervix	UBERON:0000458	97.57	gold quality
islet of Langerhans	UBERON:0000006	97.52	gold quality
descending thoracic aorta	UBERON:0002345	97.52	gold quality
mucosa of transverse colon	UBERON:0004991	97.52	gold quality
testis	UBERON:0000473	97.50	gold quality
left coronary artery	UBERON:0001626	97.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.47	gold quality
esophagus	UBERON:0001043	97.43	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	9.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

118 targeting UBE2D2, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4671-3P	99.88	72.46	1045

Literature-anchored findings (GeneRIF, showing 20)

• Data show that binding of the CNOT4 RING finger to the ubiquitin-conjugating enzyme (E2) UbcH5B is highly selective. (PMID:15001359)
• UbcH5B/C are E2s for Mdm2, which contribute to the maintenance of low levels of p53 and Mdm2 in unstressed cells; inhibition of p53 ubiquitination and degradation by targeting UbcH5B/C is not sufficient to up-regulate p53 transcriptional activity. (PMID:15280377)
• Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation (PMID:18508924)
• UBE2D2 is required for GCMa ubiquitination and for association with the SCF(FBXW2) complex. (PMID:18703417)
• The results imply that the interaction specificity between c-Cbl, UbcH7 and UbcH5b is required but not sufficient for transfer of ubiquitin to potential targets. (PMID:18996392)
• role of WW3 and WW4 domains of Nedd4-2 in dopamine transporter ubiquitination was demonstrated; siRNA analysis demonstrated that this polyubiquitination is mediated by Nedd4-2 cooperation with UBE2D and UBE2L3 E2 ubiquitin-conjugating enzymes (PMID:20051513)
• Results describe the crystal structure of a complex between the HECT domain of NEDD4L and the E2 UbcH5B bearing a covalently linked Ub at its active site (UbcH5B approximately Ub). (PMID:20064473)
• determined the 2.2 A crystal structure of an intermediate of UbcH5b approximately ubiquitin (Ub) conjugate, which is assembled into an infinite spiral through the backside interaction. (PMID:20152160)
• Whereas UbcH5(A, B and C) is highly efficient in converting IkBa into monoubiquitinated forms, Cdc34 drives ubiquitin (Ub)-Ub conjugation (PMID:20347421)
• Presented is the structure of the human dimeric RING domain from BIRC7 in complex with the E2 UbcH5B covalently linked to Ub. (PMID:22902369)
• together with UBE2L3 and UBE2N, synergistically contribute to Parkin-mediated mitophagy (PMID:24906799)
• mutations having marked effects on function only minimally affect the intermolecular interactions between the AO7 RING and UbcH5B, establishing a high degree of complexity in activation through the RING-E2 interface. (PMID:26475854)
• Data show that ubiquitin E2 enzymes UBE2D1/2/3 and E3 ligase RNF138 accumulate at DNA-damage sites and act at early resection stages by promoting CtIP protein ubiquitylation and accrual. (PMID:26502057)
• Knockdown of UBE2D2 caused an increase in p53 protein levels, and knockdown of p53 attenuated not only cadmium-induced apoptosis, but also cadmium-induced apoptosis-related gene expression. (PMID:26912277)
• These results point to an important role of the affinity between RNF4 and its cognate RAD6B or UBCH5B in governing the multiplicity of substrate ubiquitination. (PMID:27678051)
• results disclose the mechanism by which cIAP1 RING dimer activates UbcH5B approximately Ub and indicate that noncovalent Ubiquitin (Ub) binding further stabilizes the cIAP1-UbcH5B approximately Ubiquitin (Ub) complex in the active conformation to stimulate Ub transfer (PMID:30523153)
• Ube2D2 was validated as a functional E2 enzyme for the ubiquitylation of the p53 transactivation domain (p53-TAD) by MUL1-RING, and purification and crystallization processes for MUL1-RING and the MUL1-RING-Ube2D2 complex are reported. (PMID:31929179)
• Exosomes Mediated Transfer of Circ_UBE2D2 Enhances the Resistance of Breast Cancer to Tamoxifen by Binding to MiR-200a-3p. (PMID:32756532)
• The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function. (PMID:37226882)
• CircUBE2D2 regulates HMGB1 through miR-885-5p to promote ovarian cancer malignancy. (PMID:38848634)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ube2d2a	ENSMUSG00000091896
rattus_norvegicus	Ube2d2	ENSRNOG00000069286

Paralogs (12): UBE2D1 (ENSG00000072401), UBE2D4 (ENSG00000078967), UBE2D3 (ENSG00000109332), UBE2Q2 (ENSG00000140367), UBE2L6 (ENSG00000156587), UBE2Q1 (ENSG00000160714), UBE2E3 (ENSG00000170035), UBE2E1 (ENSG00000170142), UBE2E2 (ENSG00000182247), UBE2L3 (ENSG00000185651), UBE2QL1 (ENSG00000215218), UBE2L5 (ENSG00000236444)

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 D2 — P62837 (reviewed: P62837)

Alternative names: (E3-independent) E2 ubiquitin-conjugating enzyme D2, E2 ubiquitin-conjugating enzyme D2, Ubiquitin carrier protein D2, Ubiquitin-conjugating enzyme E2(17)KB 2, Ubiquitin-conjugating enzyme E2-17 kDa 2, Ubiquitin-protein ligase D2, p53-regulated ubiquitin-conjugating enzyme 1

All UniProt accessions (2): D6RFM0, P62837

UniProt curated annotations — full annotation on UniProt →

Function. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes ‘Lys-48’-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and SQSTM1 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by RIGI in response to viral infection. Essential for viral activation of IRF3.

Subunit / interactions. Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Interacts with CNOT4 (via RING domain). Interacts with E3 ubiquitin-protein ligases CBLC, PJA1 and PJA2. Interacts with PDZRN3. Interacts with PPP1R11. Interacts with E3 ubiquitin-protein ligase PHF7; the interaction inhibits cleavage of PHF7 and promotes association of the complex with the nucleosome core particle.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
P62837-1	1	yes
P62837-2	2

RefSeq proteins (2): NP_003330, NP_862821 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site

Pfam: PF00179

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)
• EC 2.3.2.B8 — (BRENDA: organisms, substrates, inhibitors, Km, 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 (28 total): strand 8, mutagenesis site 7, helix 5, turn 3, chain 1, domain 1, sequence conflict 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

61 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9GLS	X-RAY DIFFRACTION	1.25
2ESK	X-RAY DIFFRACTION	1.36
6SQO	X-RAY DIFFRACTION	1.41
2ESQ	X-RAY DIFFRACTION	1.44
2ESO	X-RAY DIFFRACTION	1.5
2ESP	X-RAY DIFFRACTION	1.52
4V3L	X-RAY DIFFRACTION	1.53
7AI0	X-RAY DIFFRACTION	1.56
5D1M	X-RAY DIFFRACTION	1.58
3L1Y	X-RAY DIFFRACTION	1.6
5D1L	X-RAY DIFFRACTION	1.62
6HPR	X-RAY DIFFRACTION	1.7
8GBQ	X-RAY DIFFRACTION	1.74
5D1K	X-RAY DIFFRACTION	1.78
7BOL	X-RAY DIFFRACTION	1.8
3TGD	X-RAY DIFFRACTION	1.8
5ULF	X-RAY DIFFRACTION	1.8
6W7Z	X-RAY DIFFRACTION	1.8
6SQS	X-RAY DIFFRACTION	1.83
9YEA	X-RAY DIFFRACTION	1.83
4LDT	X-RAY DIFFRACTION	1.9
5D0M	X-RAY DIFFRACTION	1.91
2CLW	X-RAY DIFFRACTION	1.95
5ULH	X-RAY DIFFRACTION	1.95
8VK9	X-RAY DIFFRACTION	2
9YE9	X-RAY DIFFRACTION	2.01
4V3K	X-RAY DIFFRACTION	2.04
7AI1	X-RAY DIFFRACTION	2.07
5MNJ	X-RAY DIFFRACTION	2.16
4AUQ	X-RAY DIFFRACTION	2.18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62837-F1	96.61	0.97

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): 85 (glycyl thioester intermediate)

Mutagenesis-validated functional residues (7):

Position	Phenotype
144	abolishes histone h3 ubiquitination.
63	strongly reduced interaction with cnto4.
64	abolishes histone h3 ubiquitination and decreases interaction with phf7.
85	catalytically inactive. loss of ability to promote fbxw2-mediated gcm1 ubiquitination. inhibition of tnf-induced degrada
90	abolishes histone h3 ubiquitination and decreases interaction with phf7.
93	abolishes histone h3 ubiquitination and decreases interaction with phf7.
122	abolishes histone h3 ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-202424	Downstream TCR signaling
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-8951664	Neddylation
R-HSA-9033241	Peroxisomal protein import
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA
R-HSA-9956593	Enterobacterial factors antagonize host defense

MSigDB gene sets: 286 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, MORF_HDAC1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, WONG_PROTEASOME_GENE_MODULE, KAUFFMANN_DNA_REPAIR_GENES, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP

GO Biological Process (6): protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), protein modification process (GO:0036211), protein autoubiquitination (GO:0051865), protein K48-linked ubiquitination (GO:0070936)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ubiquitin protein ligase activity (GO:0061630), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Protein ubiquitination	2
Ribosome-associated quality control	2
Cellular response to hypoxia	1
Toll Like Receptor 3 (TLR3) Cascade	1
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
Mitophagy	1
TNF signaling	1
C-type lectin receptors (CLRs)	1
Post-translational protein modification	1
Protein localization	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
TRIF (TICAM1)-mediated TLR4 signaling	1
Signaling by CSF3 (G-CSF)	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	3
ubiquitin-protein transferase activity	2
cellular anatomical structure	2
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
protein metabolic process	1
macromolecule modification	1
protein polyubiquitination	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ubiquitin-like protein ligase 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
nuclear lumen	1
cytoplasm	1
cellular_component	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

298 interactions, top by confidence:

A	B	Type	Score
OTUB1	UBE2D2	psi-mi:“MI:0915”(physical association)	0.920
RNF11	UBE2D2	psi-mi:“MI:0915”(physical association)	0.840
UBE2D2	RNF11	psi-mi:“MI:0220”(ubiquitination reaction)	0.840
UBE2D2		psi-mi:“MI:0407”(direct interaction)	0.830
UBE2D2	RNF5	psi-mi:“MI:0407”(direct interaction)	0.820
UBE2D2	RNF5	psi-mi:“MI:0915”(physical association)	0.820
RNF25	UBE2D2	psi-mi:“MI:0915”(physical association)	0.800
UBE2D2	RNF25	psi-mi:“MI:0915”(physical association)	0.800
ZNRF1	UBE2D2	psi-mi:“MI:0915”(physical association)	0.790
UBE2D2	ZNRF1	psi-mi:“MI:0915”(physical association)	0.790
ZNRF1	UBE2D2	psi-mi:“MI:0220”(ubiquitination reaction)	0.790
STUB1	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.730
UBE2D2	TRAF6	psi-mi:“MI:0915”(physical association)	0.710
TRAF6	UBE2D2	psi-mi:“MI:0220”(ubiquitination reaction)	0.710
RNF115	UBE2D2	psi-mi:“MI:0915”(physical association)	0.670
RNF8	UBE2D2	psi-mi:“MI:0915”(physical association)	0.670
MID1	UBE2D2	psi-mi:“MI:0915”(physical association)	0.670
UBE2D2	RING1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (991): UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Biochemical Activity), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Biochemical Activity), RNF26 (Two-hybrid), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GUS4, A5PJC4, A5PKP9, D3ZDK2, O13685, O14933, O74196, O74549, P15731, P15732, P25867, P35129, P35131, P35132, P35133, P35134, P35135, P43102, P51668, P52487, P60604, P60605, P61080, P62837, P62838, P62839, P62840, P68036, P68037, P70711, Q17QG5, Q1RMX2, Q21633, Q2TA10, Q3MHP1, Q3ZCF7, Q4V8J2, Q5R5I4, Q5RF84, Q6C9W0

Diamond homologs: A0A1B0GUS4, A5PJC4, A5PKP9, D3ZDK2, O13685, O14933, O74196, O74810, P0C8G3, P0C8G4, P0C8G5, P15731, P15732, P21734, P25867, P25869, P27949, P35128, P35129, P35131, P35132, P35133, P35134, P35135, P43102, P46595, P49427, P51668, P51965, P52482, P52483, P52485, P52487, P52490, P52492, P61077, P61078, P61079, P61080, P61088

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2D2	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2D2	ubiquitination
UBE2D2	“up-regulates activity”	TRIM9	binding
UBE2D2	“up-regulates activity”	VPS18	binding
UBE2D2	“up-regulates activity”	TRIM5	binding
UBE2D2	“up-regulates activity”	TRIM22	binding
UBE2D2	“up-regulates activity”	KPC	binding
UBE2D2	“down-regulates quantity by destabilization”	PEX5	ubiquitination
PEX2	“up-regulates activity”	UBE2D2	binding
UBE2D2	“up-regulates activity”	PDZRN3	binding
UBE2D2	“up-regulates activity”	UBR5	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
ER Quality Control Compartment (ERQC)	5	30.2×	5e-05
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	5	23.5×	2e-04
Class I MHC mediated antigen processing & presentation	18	14.0×	1e-13
Antigen processing: Ubiquitination & Proteasome degradation	32	13.2×	4e-25
Interferon gamma signaling	9	12.6×	4e-06
Regulation of TNFR1 signaling	5	12.4×	3e-03
Adaptive Immune System	19	6.3×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
suppression of viral release by host	7	56.0×	2e-09
protein autoubiquitination	25	47.2×	1e-33
protein K63-linked ubiquitination	19	41.0×	6e-24
protein K6-linked ubiquitination	5	40.0×	7e-06
host-mediated suppression of symbiont invasion	7	39.6×	2e-08
negative regulation of epidermal growth factor receptor signaling pathway	5	30.9×	2e-05
ubiquitin-dependent protein catabolic process	39	23.4×	3e-40
protein polyubiquitination	24	22.3×	9e-24

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1587 predictions. Top by Δscore:

Variant	Effect	Δscore
5:139600367:T:A	acceptor_gain	1.0000
5:139600368:GTAG:G	acceptor_loss	1.0000
5:139600369:TAGG:T	acceptor_loss	1.0000
5:139600370:A:AG	acceptor_gain	1.0000
5:139600370:A:G	acceptor_loss	1.0000
5:139600370:AG:A	acceptor_gain	1.0000
5:139600371:G:GT	acceptor_gain	1.0000
5:139600371:GG:G	acceptor_gain	1.0000
5:139600371:GGA:G	acceptor_gain	1.0000
5:139600371:GGAA:G	acceptor_gain	1.0000
5:139600371:GGAAT:G	acceptor_gain	1.0000
5:139600431:TGATA:T	donor_gain	1.0000
5:139600432:GATA:G	donor_gain	1.0000
5:139600432:GATAG:G	donor_gain	1.0000
5:139600433:ATA:A	donor_gain	1.0000
5:139600434:TA:T	donor_gain	1.0000
5:139600434:TAGTA:T	donor_loss	1.0000
5:139600435:AGTA:A	donor_loss	1.0000
5:139600436:G:GG	donor_gain	1.0000
5:139600436:GT:G	donor_loss	1.0000
5:139600437:TAAG:T	donor_loss	1.0000
5:139614584:A:AG	acceptor_gain	1.0000
5:139614585:G:GG	acceptor_gain	1.0000
5:139614585:GT:G	acceptor_gain	1.0000
5:139614618:G:GG	donor_gain	1.0000
5:139614855:CTGTA:C	acceptor_loss	1.0000
5:139614856:TGTAG:T	acceptor_loss	1.0000
5:139614857:GTAG:G	acceptor_loss	1.0000
5:139614858:TAGG:T	acceptor_loss	1.0000
5:139623365:TA:T	acceptor_loss	1.0000

AlphaMissense

964 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:139614907:G:A	G82D	1.000
5:139614939:T:A	W93R	1.000
5:139614939:T:C	W93R	1.000
5:139614941:G:C	W93C	1.000
5:139614941:G:T	W93C	1.000
5:139614594:T:A	W33R	0.999
5:139614594:T:C	W33R	0.999
5:139614607:T:A	I37K	0.999
5:139614612:G:A	G39R	0.999
5:139614612:G:C	G39R	0.999
5:139614754:T:C	Y60H	0.999
5:139614758:C:A	P61H	0.999
5:139614760:T:C	F62L	0.999
5:139614762:C:A	F62L	0.999
5:139614762:C:G	F62L	0.999
5:139614770:C:A	P65H	0.999
5:139614893:T:A	N77K	0.999
5:139614893:T:G	N77K	0.999
5:139614906:G:C	G82R	0.999
5:139614907:G:T	G82V	0.999
5:139614919:T:A	L86H	0.999
5:139614919:T:C	L86P	0.999
5:139614922:A:T	D87V	0.999
5:139614952:T:C	L97P	0.999
5:139623389:T:C	L109P	0.999
5:139561806:A:C	R5S	0.998
5:139561806:A:T	R5S	0.998
5:139600372:G:A	E9K	0.998
5:139614600:G:C	A35P	0.998
5:139614601:C:A	A35D	0.998

dbSNP variants (sampled 300 via entrez): RS1000002977 (5:139612990 A>C,G), RS1000014842 (5:139532457 T>C), RS1000020851 (5:139534960 A>G), RS1000030439 (5:139619949 G>A), RS1000048009 (5:139593329 A>G), RS1000119430 (5:139605429 A>G), RS1000119438 (5:139526012 C>G), RS1000146935 (5:139587795 A>C,G), RS1000150948 (5:139619758 G>A), RS1000156178 (5:139576486 ATT>A,AT,ATTT), RS1000156807 (5:139579113 G>A), RS1000198508 (5:139570356 C>G,T), RS1000211359 (5:139526556 C>G), RS1000250858 (5:139570534 T>C), RS1000287 (5:139525148 C>T)

Disease associations

OMIM: gene MIM:602962 | 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
GCST001538_25	Immune reponse to smallpox (secreted IFN-alpha)	3.000000e-07
GCST005951_151	Body mass index	6.000000e-07
GCST007511_20	Alzheimer’s disease (late onset)	4.000000e-06
GCST009856_47	Leukocyte telomere length	7.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004340	body mass index
EFO:1001870	late-onset Alzheimers disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105990 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — E2 ubiquitin-conjugating enzymes

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
biochanin A	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	increases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
dinophysistoxin 1	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Amiodarone	increases expression	1
Cadmium	decreases expression	1
Cannabidiol	increases expression	1
Coumestrol	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Manganese	decreases expression, increases abundance	1
Methapyrilene	decreases methylation	1
Smoke	decreases expression	1
Uranium	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4030880	Binding	Inhibition of UbcH5b (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

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8A9	Abcam Raji UBE2D2 KO	Cancer cell line	Male
CVCL_C0B3	Abcam THP-1 UBE2D2 KO	Cancer cell line	Male
CVCL_C7CR	Abcam PC-3 UBE2D2 KO	Cancer cell line	Male
CVCL_TV55	HAP1 UBE2D2 (-) 1	Cancer cell line	Male
CVCL_TV56	HAP1 UBE2D2 (-) 2	Cancer cell line	Male
CVCL_TV57	HAP1 UBE2D2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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