UBE2B

Summary

UBE2B (ubiquitin conjugating enzyme E2 B, HGNC:12473) is a protein-coding gene on chromosome 5q31.1, encoding Ubiquitin-conjugating enzyme E2 B (P63146). E2 ubiquitin-conjugating enzyme that accepts ubiquitin from the ubiquitin-activating enzyme E1 and transfers it to a E3 ubiquitin-protein ligase.

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is required for post-replicative DNA damage repair. Its protein sequence is 100% identical to the mouse, rat, and rabbit homologs, which indicates that this enzyme is highly conserved in eukaryotic evolution.

Source: NCBI Gene 7320 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• Druggable target: yes
• MANE Select transcript: NM_003337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12473
Approved symbol	UBE2B
Name	ubiquitin conjugating enzyme E2 B
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	UBC2, HHR6B, RAD6B
Ensembl gene	ENSG00000119048
Ensembl biotype	protein_coding
OMIM	179095
Entrez	7320

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000265339, ENST00000499038, ENST00000503080, ENST00000504431, ENST00000506787, ENST00000507277, ENST00000510021, ENST00000511807, ENST00000903232, ENST00000903233, ENST00000903234, ENST00000924154

RefSeq mRNA: 1 — MANE Select: NM_003337 NM_003337

CCDS: CCDS4174

Canonical transcript exons

ENST00000265339 — 6 exons

Exon	Start	End
ENSE00000803566	134380719	134380808
ENSE00000803567	134390225	134392108
ENSE00000953701	134374383	134374463
ENSE00001042373	134376669	134376694
ENSE00001042376	134371569	134371639
ENSE00003552509	134388325	134388413

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.5405 / max 705.5640, expressed in 1821 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58572	23.4267	1796
58570	19.2422	1805
58571	5.9117	1679
58569	2.3694	1352
58568	0.5905	369

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.15	gold quality
gastrocnemius	UBERON:0001388	99.12	gold quality
muscle of leg	UBERON:0001383	99.04	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.88	gold quality
lower esophagus mucosa	UBERON:0035834	98.79	gold quality
right lung	UBERON:0002167	98.76	gold quality
right atrium auricular region	UBERON:0006631	98.74	gold quality
biceps brachii	UBERON:0001507	98.73	gold quality
body of pancreas	UBERON:0001150	98.65	gold quality
cardiac atrium	UBERON:0002081	98.61	gold quality
adenohypophysis	UBERON:0002196	98.59	gold quality
descending thoracic aorta	UBERON:0002345	98.59	gold quality
cortical plate	UBERON:0005343	98.58	gold quality
ganglionic eminence	UBERON:0004023	98.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.53	gold quality
heart left ventricle	UBERON:0002084	98.50	gold quality
cardiac ventricle	UBERON:0002082	98.49	gold quality
right adrenal gland cortex	UBERON:0035827	98.48	gold quality
mucosa of stomach	UBERON:0001199	98.46	gold quality
tibial artery	UBERON:0007610	98.46	gold quality
popliteal artery	UBERON:0002250	98.45	gold quality
blood	UBERON:0000178	98.42	gold quality
aorta	UBERON:0000947	98.41	gold quality
heart	UBERON:0000948	98.41	gold quality
left coronary artery	UBERON:0001626	98.41	gold quality
artery	UBERON:0001637	98.41	gold quality
peritoneum	UBERON:0002358	98.41	gold quality
omental fat pad	UBERON:0010414	98.41	gold quality
ascending aorta	UBERON:0001496	98.39	gold quality
thoracic aorta	UBERON:0001515	98.39	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	2390.18
E-MTAB-6701	yes	40.68
E-HCAD-4	yes	20.95
E-GEOD-124858	no	440.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CTNNB1, FOS, HNF4A, JUN, NFKB1, NR1I2, PARP1, SP1, TAF1, TCF3, TCF7L2, TP53

miRNA regulators (miRDB)

192 targeting UBE2B, 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-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 31)

• MCF10A cells stably transfected with antisense RAD6B display hypersensitivity to damage-inducing drugs. (PMID:14981545)
• These data reveal a potentially important role for transcriptionally active beta-catenin in the regulation of Rad6B gene expression, and link aberrant beta-catenin signaling with transcriptional deregulation of Rad6B and breast cancer development. (PMID:17050667)
• Findings reveal a positive regulatory feedback loop between Rad6B and beta-catenin and a novel mechanism of beta-catenin stabilization/activation in breast cancer cells. (PMID:18339854)
• The SAP domain of RAD18 (residues 248-282) is crucial for binding of RAD18 complexed with RAD6B to DNA substrates. (PMID:18363965)
• deletions in this suspected promoter region are associated with increased binding affinity for SP1, and might represent one of several factors required for alteration of UBE2B gene expression (PMID:18385908)
• study suggests that the UBE2B gene is associated with male infertility in Indian men (PMID:18497339)
• Rad6B is a fundamental component of postreplication DNA repair and can be used as an independent marker for determining response to neoadjuvant chemotherapy. (PMID:19466589)
• Hydroquinone could upregulate the expression of Rad6B in L-02 hepatic cells. (PMID:19548583)
• Ubc2/Rad6 ser(120) regulates ubiquitin-dependent N-end rule targeting by E3{alpha}/Ubr1 (PMID:21041297)
• Data show that the homodimeric Rad18 RING domain can recruit two Rad6b E2 enzymes, whereas the full-length Rad18 homodimer binds only to a single Rad6b molecule. (PMID:21549715)
• RAD6 can form a ternary complex with MDM2 and p53 that contributes to the degradation of p53. (PMID:22083959)
• The Rad6-Rad18 enzyme plays an essential role in promoting replication through DNA lesions by translesion synthesis in mammalian cells. (PMID:22547805)
• beta-catenin and Rad6B interacting regions, were identified. (PMID:22705350)
• UBE2B polymorphisms g.-293T>G, g.20016A>G and g.9157A>G are not associated with male infertility, and the GA haplotype is likely a protective factor for male fertility in Northeast Chinese men. (PMID:23079972)
• UBE2B mRNA alterations are associated with severe oligozoospermia in infertile men. (PMID:23378580)
• RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade. (PMID:23525009)
• RAD6 physically interacts with heterochromatin protein 1alpha and ubiquitinates HP1alpha at residue K154, thereby promoting heterochromatin protein 1alpha degradation through the autophagy pathway (PMID:25384975)
• A novel variant (Chr5.133706925 A > G) residing in the UBE2B gene promoter region confers a high risk for idiopathic azoospermia in a Chinese population. (PMID:26223869)
• Data show that the ubiquitin-conjugating enzyme E2 RAD6A/B-MDM2 ubiquitin ligase machinery regulates anti-silencing function 1A protein (ASF1A) degradation. (PMID:26336826)
• These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer. (PMID:26679603)
• In conclusion, we reveal that miR-455-5p expression is regulated by the TGF-beta-dependent pathway, which subsequently leads to UBE2B down-regulation and contributes to oral cancer tumourigenesis. (PMID:27235675)
• 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)
• RAD6 promotes proteasome activity and nuclear translocation by enhancing the degradation of PSMF1 and the lamin B receptor. (PMID:28031328)
• These data deepen insights into the vital role of RAD6/translesion synthesis in platinum drug tolerance and reveal clinical benefits of targeting RAD6 with SMI#9 for managing chemoresistant cancers. (PMID:28490629)
• RAD6 is upregulated in response to chemotherapy and significantly correlated with expression of ovarian cancer (OC) stem cell signaling genes ALDH1A1 and SOX2 and poor prognosis of OC patients. (PMID:28806395)
• These RAD6B activities are unaffected by BRCA1 status. (PMID:31639439)
• Authors confirmed that RAD6BDeltaexon4 and RAD6Bintron5ins variants are expressed as 14 and 15 kDa proteins, respectively, with functional in vivo ubiquitin conjugating activity. (PMID:31683936)
• High Expression of UBE2B as a Poor Prognosis Factor in Patients With Rectal Cancer Following Chemoradiotherapy. (PMID:33109568)
• RAD6B Loss Disrupts Expression of Melanoma Phenotype in Part by Inhibiting WNT/beta-Catenin Signaling. (PMID:33181138)
• UBE2B promotes ovarian cancer growth via promoting RAD18 mediated ZMYM2 monoubiquitination and stabilization. (PMID:35313791)
• Mutations of Rad6 E2 ubiquitin-conjugating enzymes at alanine-126 in helix-3 affect ubiquitination activity and decrease enzyme stability. (PMID:36162503)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2b	ENSDARG00000026035
mus_musculus	Ube2b	ENSMUSG00000020390
rattus_norvegicus	Ube2b	ENSRNOG00000059348
drosophila_melanogaster	Ubc6	FBGN0004436

Paralogs (24): UBE2T (ENSG00000077152), UBE2A (ENSG00000077721), UBE2K (ENSG00000078140), CDC34 (ENSG00000099804), UBE2I (ENSG00000103275), UBE2W (ENSG00000104343), UBE2R2 (ENSG00000107341), UBE2S (ENSG00000108106), 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 B — P63146 (reviewed: P63146)

Alternative names: E2 ubiquitin-conjugating enzyme B, RAD6 homolog B, Ubiquitin carrier protein B, Ubiquitin-conjugating enzyme E2-17 kDa, Ubiquitin-protein ligase B

All UniProt accessions (4): P63146, D6RDW8, H0Y9V2, H0YA80

UniProt curated annotations — full annotation on UniProt →

Function. E2 ubiquitin-conjugating enzyme that accepts ubiquitin from the ubiquitin-activating enzyme E1 and transfers it to a E3 ubiquitin-protein ligase. In vitro catalyzes ‘Lys-11’-, as well as ‘Lys-48’- and ‘Lys-63’-linked polyubiquitination. Together with the E3 enzyme BRE1 (RNF20 and/or RNF40), plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at ‘Lys-120’ to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. May play a role in DNA repair. Associates to the E3 ligase RAD18 to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on ‘Lys-164’. In association with the E3 enzyme UBR4, is involved in N-end rule-dependent protein degradation. May be involved in neurite outgrowth.

Subunit / interactions. Interacts with RAD18, UBR2 and WAC.

Subcellular location. Cell membrane. Nucleus.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (1): NP_003328* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site
IPR050113	Ub_conjugating_enzyme-E2-like	Family

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)

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 (19 total): strand 5, helix 5, turn 3, sequence conflict 3, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2YB6	X-RAY DIFFRACTION	1.5
2YBF	X-RAY DIFFRACTION	2
1JAS	SOLUTION NMR
2Y4W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63146-F1	95.83	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): 88 (glycyl thioester intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 429 (showing top): ATF_B, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GGGNRMNNYCAT_UNKNOWN, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_DNA_DAMAGE_TOLERANCE

GO Biological Process (30): protein polyubiquitination (GO:0000209), in utero embryonic development (GO:0001701), DNA repair (GO:0006281), DNA damage tolerance (GO:0006301), chromatin organization (GO:0006325), ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), DNA damage response (GO:0006974), spermatogenesis (GO:0007283), sperm axoneme assembly (GO:0007288), response to xenobiotic stimulus (GO:0009410), response to UV (GO:0009411), positive regulation of reciprocal meiotic recombination (GO:0010845), protein ubiquitination (GO:0016567), ectopic germ cell programmed cell death (GO:0035234), negative regulation of apoptotic process (GO:0043066), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), meiotic telomere clustering (GO:0045141), protein stabilization (GO:0050821), chiasma assembly (GO:0051026), negative regulation of developmental process (GO:0051093), protein autoubiquitination (GO:0051865), synaptonemal complex organization (GO:0070193), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), protein K11-linked ubiquitination (GO:0070979), positive regulation of canonical Wnt signaling pathway (GO:0090263), negative regulation of post-translational protein modification (GO:1901874), negative regulation of reproductive process (GO:2000242), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (8): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ubiquitin protein ligase binding (GO:0031625), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), ubiquitin-like protein transferase activity (GO:0019787)

GO Cellular Component (9): chromatin (GO:0000785), XY body (GO:0001741), nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), cytoplasm (GO:0005737), plasma membrane (GO:0005886), HULC complex (GO:0033503), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Protein ubiquitination	2
DNA Damage Bypass	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	5
developmental process involved in reproduction	3
protein ubiquitination	2
DNA metabolic process	2
DNA damage response	2
reciprocal meiotic recombination	2
chromosome	2
chordate embryonic development	1
DNA replication	1
cellular component organization	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
male gamete generation	1
axoneme assembly	1
sperm flagellum assembly	1
response to chemical	1
response to light stimulus	1
regulation of reciprocal meiotic recombination	1
positive regulation of meiotic nuclear division	1
positive regulation of DNA recombination	1
protein modification by small protein conjugation	1
programmed cell death involved in cell development	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
telomere localization	1
chromosome organization involved in meiotic cell cycle	1
chromosome localization to nuclear envelope involved in homologous chromosome segregation	1
regulation of protein stability	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
meiotic cell cycle process	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

39 interactions, top by confidence:

A	B	Type	Score
UBE2B	RAD18	psi-mi:“MI:0407”(direct interaction)	0.840
RAD18	UBE2B	psi-mi:“MI:0915”(physical association)	0.840
RNF20	RNF40	psi-mi:“MI:0220”(ubiquitination reaction)	0.820
HLTF	UBE2N	psi-mi:“MI:0914”(association)	0.680
UBE2B	UBR1	psi-mi:“MI:0407”(direct interaction)	0.590
UBE2B		psi-mi:“MI:0195”(covalent binding)	0.560
UBE2B		psi-mi:“MI:0407”(direct interaction)	0.560
UBE2B	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
UBE2B	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
UBR4	UBE2B	psi-mi:“MI:0915”(physical association)	0.550
UBE2B	UBE2A	psi-mi:“MI:0914”(association)	0.530
UBE2B	H2AC25	psi-mi:“MI:0407”(direct interaction)	0.520
SHPRH	UBE2N	psi-mi:“MI:0914”(association)	0.500
UBE2B	UBC	psi-mi:“MI:0195”(covalent binding)	0.440
UBE2B	COL20A1	psi-mi:“MI:0915”(physical association)	0.400
UBE2B		psi-mi:“MI:0915”(physical association)	0.370
IRF7	UBE2B	psi-mi:“MI:0915”(physical association)	0.370
UBE2B	UBR3	psi-mi:“MI:0915”(physical association)	0.370
UBE2B	Ubr2	psi-mi:“MI:0914”(association)	0.350
UBE2B	RNF40	psi-mi:“MI:0914”(association)	0.350
UBR4	METTL15	psi-mi:“MI:0914”(association)	0.350

BioGRID (184): UBE2B (Reconstituted Complex), UBE2B (Reconstituted Complex), UBE2B (Affinity Capture-Western), UBE2B (Biochemical Activity), CBX5 (Affinity Capture-Western), UBE2B (Affinity Capture-Western), UBE2B (Co-localization), HIST2H2AC (Biochemical Activity), UBE2B (Biochemical Activity), UBE2B (Reconstituted Complex), CBX5 (Reconstituted Complex), UBE2B (Biochemical Activity), UBE2B (Affinity Capture-MS), UBE2A (Affinity Capture-MS), UBC (Affinity Capture-MS)

ESM2 similar proteins: O09181, P0CS16, P0CS17, P23566, P25153, P34477, P40984, P42746, P49459, P50623, P52484, P52493, P56616, P63146, P63147, P63148, P63149, P63279, P63280, P63281, P63282, P63283, P78717, Q28CQ4, Q2EF73, Q32P99, Q32PA5, Q42551, Q4WLA7, Q54XS6, Q553F3, Q58FS2, Q6BU36, Q6CUD9, Q6FR76, Q6Y1Z4, Q7ZY08, Q8LGF7, Q94A97, Q95017

Diamond homologs: A1L3K1, A5PKP9, A7SE05, B3MQV3, B3NWW9, B4H9W2, B4IF39, B4JKB7, B4L7V4, B4MA02, B4N208, B4Q2J2, B4R6G1, B5DFI8, B5DKM4, C1C3R6, C3Z724, D3ZDK2, O13685, O74196, O74810, P0CS16, P0CS17, P15731, P15732, P25153, P25865, P25866, P25867, P35128, P35129, P35130, P35131, P35132, P35133, P35134, P35135, P42745, P42746, P43102

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2B	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2B	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
E3 ubiquitin ligases ubiquitinate target proteins	8	81.5×	6e-12
Antigen processing: Ubiquitination & Proteasome degradation	5	9.8×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein polyubiquitination	5	25.1×	7e-05
ubiquitin-dependent protein catabolic process	5	16.1×	5e-04
protein ubiquitination	8	14.4×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1030 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134371637:GCG:G	donor_gain	1.0000
5:134388320:TGCA:T	acceptor_loss	1.0000
5:134388321:GCA:G	acceptor_loss	1.0000
5:134388322:CAG:C	acceptor_loss	1.0000
5:134388323:A:AG	acceptor_gain	1.0000
5:134388323:AGT:A	acceptor_gain	1.0000
5:134388323:AGTG:A	acceptor_loss	1.0000
5:134388324:G:GA	acceptor_gain	1.0000
5:134388324:GT:G	acceptor_gain	1.0000
5:134388324:GTG:G	acceptor_gain	1.0000
5:134388324:GTGT:G	acceptor_gain	1.0000
5:134388324:GTGTA:G	acceptor_gain	1.0000
5:134388414:G:GA	donor_loss	1.0000
5:134388414:G:GG	donor_gain	1.0000
5:134388415:T:A	donor_loss	1.0000
5:134390223:A:AC	acceptor_loss	1.0000
5:134390223:A:AG	acceptor_gain	1.0000
5:134390224:G:GT	acceptor_gain	1.0000
5:134390224:GT:G	acceptor_gain	1.0000
5:134390224:GTC:G	acceptor_gain	1.0000
5:134390224:GTCT:G	acceptor_gain	1.0000
5:134390224:GTCTC:G	acceptor_gain	1.0000
5:134371638:CGG:C	donor_loss	0.9900
5:134371639:GGT:G	donor_loss	0.9900
5:134371640:G:GG	donor_gain	0.9900
5:134371641:T:TC	donor_loss	0.9900
5:134374372:T:A	acceptor_gain	0.9900
5:134376667:A:AG	acceptor_gain	0.9900
5:134376668:G:GG	acceptor_gain	0.9900
5:134380713:CTCTA:C	acceptor_loss	0.9900

AlphaMissense

1001 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:134374444:T:A	W36R	1.000
5:134374444:T:C	W36R	1.000
5:134388337:G:T	G85V	1.000
5:134388343:T:A	I87K	1.000
5:134388369:T:A	W96R	1.000
5:134388369:T:C	W96R	1.000
5:134388371:G:C	W96C	1.000
5:134388371:G:T	W96C	1.000
5:134390259:C:A	A122D	1.000
5:134371618:G:T	R8M	0.999
5:134371621:T:A	L9H	0.999
5:134374415:G:A	G26D	0.999
5:134374451:C:A	A38E	0.999
5:134374457:T:A	I40K	0.999
5:134374457:T:G	I40R	0.999
5:134374463:G:A	G42E	0.999
5:134380719:G:A	G51D	0.999
5:134380725:T:C	F53S	0.999
5:134380731:T:C	L55P	0.999
5:134380754:T:C	Y63H	0.999
5:134380755:A:G	Y63C	0.999
5:134380770:C:A	P68Q	0.999
5:134380776:T:A	V70D	0.999
5:134380781:T:C	F72L	0.999
5:134380782:T:C	F72S	0.999
5:134380783:T:A	F72L	0.999
5:134380783:T:G	F72L	0.999
5:134380799:C:G	H78D	0.999
5:134380800:A:G	H78R	0.999
5:134380801:T:A	H78Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000090740 (5:134370530 C>A,T), RS1000179830 (5:134385972 C>T), RS1000191349 (5:134371377 C>G,T), RS1000199793 (5:134371197 C>T), RS1000242295 (5:134376624 G>A), RS1000318037 (5:134377015 C>G), RS1000349605 (5:134377725 G>A,T), RS1000538951 (5:134370002 G>A), RS1000570182 (5:134389769 A>G), RS1000597380 (5:134376445 T>C), RS1000704474 (5:134383255 T>C), RS1000756946 (5:134382980 C>T), RS1000847550 (5:134383073 G>A,C), RS1000961535 (5:134389708 G>A), RS1001022324 (5:134371242 T>C)

Disease associations

OMIM: gene MIM:179095 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006397_7	Relative amplitude of rest-activity cycles	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3784907 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.60	IC50	25	nM	CHEMBL3787660

PubChem BioAssay actives

1 with measured affinity, of 17 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4-amino-6-anilino-1,3,5-triazin-2-yl)methyl 4-nitrobenzoate	1424615: Inhibition of human recombinant Rad6B using ubiquitin and histone H2A and ubiquitin-activating enzyme E1 preincubated for 1 hr before ubiquitin and histone H2A addition by SDS-PAGE and immunoblotting analysis	ic50	0.0250	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	2
sodium arsenite	affects localization, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	increases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
celastrol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
gedunin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	affects expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Berberine	decreases expression	1
Cannabidiol	increases expression	1
Carbamazepine	affects expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3790331	Binding	Inhibition of human recombinant Rad6B assessed as suppression of Rad6B conjugation to ubiquitin at 25 nM pre-incubated for 1 hr by Western blot analysis	Synthesis and in vitro anticancer evaluation of some 4,6-diamino-1,3,5-triazine-2-carbohydrazides as Rad6 ubiquitin conjugating enzyme inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TV48	HAP1 UBE2B (-) 1	Cancer cell line	Male
CVCL_TV49	HAP1 UBE2B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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