UBE2D1

Summary

UBE2D1 (ubiquitin conjugating enzyme E2 D1, HGNC:12474) is a protein-coding gene on chromosome 10q21.1, encoding Ubiquitin-conjugating enzyme E2 D1 (P51668). Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.

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 closely related to a stimulator of iron transport (SFT), and is up-regulated in hereditary hemochromatosis. It also functions in the ubiquitination of the tumor-suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7321 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 10 total
• Druggable target: yes
• MANE Select transcript: NM_003338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12474
Approved symbol	UBE2D1
Name	ubiquitin conjugating enzyme E2 D1
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Aliases	UbcH5A, UBCH5, UBC4/5, E2(17)KB1
Ensembl gene	ENSG00000072401
Ensembl biotype	protein_coding
OMIM	602961
Entrez	7321

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000373910, ENST00000473824, ENST00000606483, ENST00000615793, ENST00000909472, ENST00000909473

RefSeq mRNA: 2 — MANE Select: NM_003338 NM_001204880, NM_003338

CCDS: CCDS7252, CCDS73139

Canonical transcript exons

ENST00000373910 — 7 exons

Exon	Start	End
ENSE00000705064	58361495	58361526
ENSE00000705068	58363609	58363686
ENSE00000705083	58364771	58364876
ENSE00000833888	58361338	58361401
ENSE00001334393	58335006	58335225
ENSE00003553025	58367923	58368016
ENSE00003695252	58368720	58370748

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.1788 / max 1938.8140, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104990	62.5297	1816
104989	8.6491	1762

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	99.00	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.55	gold quality
vastus lateralis	UBERON:0001379	98.34	gold quality
quadriceps femoris	UBERON:0001377	97.65	gold quality
heart right ventricle	UBERON:0002080	97.53	gold quality
skeletal muscle tissue	UBERON:0001134	97.13	gold quality
monocyte	CL:0000576	97.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.02	gold quality
mononuclear cell	CL:0000842	96.51	gold quality
leukocyte	CL:0000738	96.35	gold quality
muscle organ	UBERON:0001630	96.29	gold quality
gastrocnemius	UBERON:0001388	96.03	gold quality
muscle of leg	UBERON:0001383	95.80	gold quality
body of tongue	UBERON:0011876	95.72	gold quality
diaphragm	UBERON:0001103	95.67	gold quality
triceps brachii	UBERON:0001509	95.48	gold quality
amniotic fluid	UBERON:0000173	95.22	gold quality
muscle tissue	UBERON:0002385	95.13	gold quality
deltoid	UBERON:0001476	94.73	gold quality
blood	UBERON:0000178	94.50	gold quality
germinal epithelium of ovary	UBERON:0001304	94.49	gold quality
cortical plate	UBERON:0005343	94.35	gold quality
ganglionic eminence	UBERON:0004023	93.96	gold quality
tongue	UBERON:0001723	93.49	gold quality
gluteal muscle	UBERON:0002000	93.48	gold quality
superior surface of tongue	UBERON:0007371	93.29	gold quality
oral cavity	UBERON:0000167	92.92	gold quality
visceral pleura	UBERON:0002401	92.81	gold quality
cardiac ventricle	UBERON:0002082	92.66	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	192.50
E-ANND-3	yes	8.26
E-HCAD-5	no	2.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

181 targeting UBE2D1, 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-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
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-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593

Literature-anchored findings (GeneRIF, showing 24)

• UbcH5A is up-regulated in the liver of iron-overloaded patients with hereditary hemochromatosis, but in vitro studies failed to show regulation in response to iron loading or chelation. Earlier in vivo mRNA expression data for SFT might be UbcH5A. (PMID:12480712)
• comparison of the regional distribution of SFT/UbcH5A and DMT1 mRNA in the adult brain (PMID:15139022)
• Ro52 has both cytoplasmic and nuclear substrates, and mediates ubiquitination through UBE2D1 in the cytoplasm and through UBE2E1 in the nucleus. (PMID:18845142)
• Catalytically active Ubc5 is required for IRF3 activation by viral infection. (PMID:19854139)
• conformational changes in CHIP upon binding of Hsp70, Hsp90, and their respective C-terminal EEVD peptides, and in complex with the different E2 ubiquitin-conjugating enzymes UbcH5a and Ubc13 (PMID:20146531)
• Whereas UbcH5(A, B and C) is highly efficient in converting IkBa into monoubiquitinated forms, Cdc34 drives ubiquitin (Ub)-Ub conjugation (PMID:20347421)
• The authors demonstrate that c-IAP1 and UbcH5 family promote K11-linked polyubiquitination of receptor-interacting protein 1 (RIP1) in vitro and in vivo. (PMID:21113135)
• This structure reveals an interaction between the ubiquitin surface flanking K11 and residues adjacent to the E2 catalytic cysteine and suggests a possible role for this surface in formation of K11 linkages. (PMID:21396940)
• identify the IDOL-UBE2D complex as an important determinant of LDLR activity, and provide insight into molecular mechanisms underlying the regulation of cholesterol uptake (PMID:21685362)
• These data demonstrate that the ability of ICP0 to interact with cellular E2 ubiquitin-conjugating enzyme UBE2D1 is fundamentally important for its biological functions during HSV-1 infection. (PMID:22438555)
• crystal structure of the dimeric RING domain of rat RNF4 in complex with E2 (UbcH5A) linked by an isopeptide bond to ubiquitin (PMID:22842904)
• Biochemical characterization of recombinant UBTD1 and UBE2D demonstrated that the two proteins form a stable, stoichiometric complex that can be purified to near homogeneity. (PMID:24211586)
• The SMURF2:UBCH5 complex is critical in maintaining KRAS protein stability. (PMID:24709419)
• The Asp17 mutation in MDM2 stimulated its discharge of the UBCH5a-ubiquitin thioester adduct. (PMID:25543083)
• 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)
• The anaphase-promoting complex/cyclosome C activity in human cells is tuned by the combinatorial use of three E2 ubiquitin-conjugating enzymes, namely UBE2C, UBE2S, and UBE2D. (PMID:26904940)
• March-I undergoes lysine-independent ubiquitination by an as yet unidentified E3 ubiquitin ligase that, together with Ube2D1, regulates March-I expression (PMID:29414787)
• Results showed that although UBE2D1 RNA was significantly upregulated in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues; its expression was even higher in LUAD tissues than in LUSC. UBE2D1 RNA upregulation was associated with poor survival in LUAD patients, but not in LUSC suggesting it as an independent indicator of unfavorable prognosis in LUAD, but not in LUSC. (PMID:30420903)
• Upregulation of UBE2D1 promoted HCC growth in vitro and in vivo by decreasing the p53 in ubiquitination-dependent pathway. High expression of UBE2D1 was attributed to the recurrent genomic copy number gain, which was associated with high serum IL-6 level of HCC patients. (PMID:30482241)
• S-Nitrosylation at the active site decreases the ubiquitin-conjugating activity of ubiquitin-conjugating enzyme E2 D1 (UBE2D1), an ERAD-associated protein. (PMID:32051088)
• Functional interaction of ubiquitin ligase RNF167 with UBE2D1 and UBE2N promotes ubiquitination of AMPA receptor. (PMID:33650289)
• UBCH5 Family Members Differentially Impact Stabilization of Mutant p53 via RNF128 Iso1 During Barrett’s Progression to Esophageal Adenocarcinoma. (PMID:34416429)
• B-box1 Domain of MID1 Interacts with the Ube2D1 E2 Enzyme Differently Than RING E3 Ligases. (PMID:36820504)
• The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function. (PMID:37226882)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2d1a	ENSDARG00000029107
danio_rerio	ube2d1b	ENSDARG00000038576
mus_musculus	Ube2d1	ENSMUSG00000019927
rattus_norvegicus	Ube2d1	ENSRNOG00000000611
drosophila_melanogaster	eff	FBGN0011217
caenorhabditis_elegans		WBGENE00002344

Paralogs (12): UBE2D4 (ENSG00000078967), UBE2D3 (ENSG00000109332), UBE2D2 (ENSG00000131508), 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 D1 — P51668 (reviewed: P51668)

Alternative names: (E3-independent) E2 ubiquitin-conjugating enzyme D1, E2 ubiquitin-conjugating enzyme D1, Stimulator of Fe transport, UBC4/5 homolog, UbcH5, Ubiquitin carrier protein D1, Ubiquitin-conjugating enzyme E2(17)KB 1, Ubiquitin-conjugating enzyme E2-17 kDa 1, Ubiquitin-protein ligase D1

All UniProt accessions (2): P51668, A0A087WW00

UniProt curated annotations — full annotation on UniProt →

Function. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro 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 auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1. Ubiquitinates STUB1-associated HSP90AB1 in vitro. Lacks inherent specificity for any particular lysine residue of ubiquitin. Essential for viral activation of IRF3. Mediates polyubiquitination of CYP3A4.

Subunit / interactions. Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with RNF11.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous. Up-regulated in livers of iron-overloaded patients with hereditary hemochromatosis.

Post-translational modifications. Autoubiquitinated in vitro.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (2): NP_001191809, NP_003329* (*=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 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)
• EC 2.3.2.B8 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. 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
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (26 total): mutagenesis site 9, strand 6, helix 5, turn 3, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
4QPL	X-RAY DIFFRACTION	1.9
2YHO	X-RAY DIFFRACTION	2.1
6D4P	X-RAY DIFFRACTION	2.11
4AP4	X-RAY DIFFRACTION	2.21
5FER	X-RAY DIFFRACTION	2.34
2C4P	X-RAY DIFFRACTION	2.35
7ZJ3	X-RAY DIFFRACTION	2.53
5TUT	X-RAY DIFFRACTION	2.6
3PTF	X-RAY DIFFRACTION	2.7
3OJ4	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51668-F1	96.49	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 (9):

Position	Phenotype
116	decrease in autoubiquitination.
117	decrease in autoubiquitination.
4	decrease in autoubiquitination.
42	decrease in autoubiquitination.
62	decrease in autoubiquitination.
87	decrease in autoubiquitination.
94	decrease in autoubiquitination.
98	decrease in autoubiquitination.
112	decrease in autoubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

37 pathways

ID	Pathway
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-141430	Inactivation of APC/C via direct inhibition of the APC/C complex
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
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-176407	Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176409	APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-176412	Phosphorylation of the APC/C
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-201451	Signaling by BMP
R-HSA-202424	Downstream TCR signaling
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-68867	Assembly of the pre-replicative complex
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-8853884	Transcriptional Regulation by VENTX
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

MSigDB gene sets: 368 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, REACTOME_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, REACTOME_CONVERSION_FROM_APC_C_CDC20_TO_APC_C_CDH1_IN_LATE_ANAPHASE, REACTOME_PHOSPHORYLATION_OF_THE_APC_C, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), negative regulation of BMP signaling pathway (GO:0030514), positive regulation of protein ubiquitination (GO:0031398), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein K48-linked ubiquitination (GO:0070936), positive regulation of protein polyubiquitination (GO:1902916), negative regulation of TORC1 signaling (GO:1904262), protein ubiquitination (GO:0016567), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202)

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), cytoplasm (GO:0005737), cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
APC/C-mediated degradation of cell cycle proteins	4
APC/C:Cdc20 mediated degradation of mitotic proteins	2
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	2
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	2
Cellular response to hypoxia	1
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1
Toll Like Receptor 3 (TLR3) Cascade	1
Signaling by TGFB family members	1
TCR signaling	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Mitotic Anaphase	1
Cellular Senescence	1
Fc epsilon receptor (FCERI) signaling	1
TNF signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	3
cellular anatomical structure	3
protein polyubiquitination	2
ubiquitin-protein transferase activity	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
modification-dependent protein catabolic process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
positive regulation of protein ubiquitination	1
regulation of protein polyubiquitination	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
protein modification by small protein conjugation	1
response to nutrient levels	1
cellular response to stimulus	1
TOR signaling	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
intracellular anatomical structure	1
cytoplasm	1
cellular_component	1

Protein interactions and networks

STRING

3398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2D1	STUB1	Q9UNE7	992
UBE2D1	RNF4	P78317	979
UBE2D1	UBA1	P22314	957
UBE2D1	UBE3A	P78355	881
UBE2D1	G3V2F7	G3V2F7	856
UBE2D1	HSPBP1	Q9NZL4	837
UBE2D1	OTUB1	Q96FW1	821
UBE2D1	HSPA8	P11142	815
UBE2D1	RBX1	P62877	796
UBE2D1	HSPA4	P34932	796
UBE2D1	BRCA1	P38398	749
UBE2D1	UBE2V2	Q15819	745
UBE2D1	CUL1	Q13616	732
UBE2D1	NEDD8	Q15843	731
UBE2D1	BARD1	Q99728	729

IntAct

307 interactions, top by confidence:

A	B	Type	Score
UBE2D1	OTUB1	psi-mi:“MI:0915”(physical association)	0.850
RNF115	UBE2D1	psi-mi:“MI:0915”(physical association)	0.830
UBE2D1	RNF115	psi-mi:“MI:0915”(physical association)	0.830
UBE2D1	RNF126	psi-mi:“MI:0915”(physical association)	0.820
RNF126	UBE2D1	psi-mi:“MI:0915”(physical association)	0.820
TRIM39	UBE2D1	psi-mi:“MI:0915”(physical association)	0.800
UBE2D1	TRIM39	psi-mi:“MI:0915”(physical association)	0.800
UBE2D1	RNF25	psi-mi:“MI:0915”(physical association)	0.800
RNF25	UBE2D1	psi-mi:“MI:0915”(physical association)	0.800
UBE2D1	RNF5	psi-mi:“MI:0915”(physical association)	0.790
RNF5	UBE2D1	psi-mi:“MI:0915”(physical association)	0.790
RNF11	UBE2D1	psi-mi:“MI:0915”(physical association)	0.790
UBE2D1	ZNRF1	psi-mi:“MI:0915”(physical association)	0.790
UBE2D1	RNF11	psi-mi:“MI:0915”(physical association)	0.790
ZNRF1	UBE2D1	psi-mi:“MI:0915”(physical association)	0.790
ZNRF1	UBE2D1	psi-mi:“MI:0220”(ubiquitination reaction)	0.790

BioGRID (943): UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D1 (Biochemical Activity), UBE2D1 (Co-crystal Structure), UBE2D1 (Reconstituted Complex), RNF26 (Two-hybrid)

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

12 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2D1	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2D1	ubiquitination
UBE2D1	“up-regulates activity”	ZSWIM2	binding
UBE2D1	“up-regulates activity”	MGRN1	binding
UBE2D1	“up-regulates activity”	TRIM2	binding
UBE2D1	“up-regulates activity”	TRIM65	ubiquitination
SMURF2	“up-regulates activity”	UBE2D1	ubiquitination
UBE2D1	“up-regulates activity”	KPC	binding
UBE2D1	“up-regulates activity”	PEX5	ubiquitination
PEX12	“up-regulates activity”	UBE2D1	binding
UBE2D1	“up-regulates activity”	“Elongin E3-Cul-5”	binding
UBE2D1	“up-regulates activity”	MPG	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
Calnexin/calreticulin cycle	5	54.1×	2e-06
ER Quality Control Compartment (ERQC)	6	49.4×	1e-07
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	6	38.5×	7e-07
Activated NOTCH1 Transmits Signal to the Nucleus	5	27.0×	4e-05
DDX58/IFIH1-mediated induction of interferon-alpha/beta	6	23.1×	1e-05
Ovarian tumor domain proteases	5	21.1×	1e-04
Interferon gamma signaling	11	20.9×	5e-10
Class I MHC mediated antigen processing & presentation	16	17.0×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
suppression of viral release by host	7	73.8×	1e-10
negative regulation of viral transcription	5	56.0×	8e-07
host-mediated suppression of symbiont invasion	6	44.8×	1e-07
protein K63-linked ubiquitination	15	42.7×	5e-19
protein autoubiquitination	14	34.9×	2e-16
protein polyubiquitination	24	29.5×	6e-27
protein K48-linked ubiquitination	15	26.9×	6e-16
ubiquitin-dependent protein catabolic process	33	26.1×	9e-36

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	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1166 predictions. Top by Δscore:

Variant	Effect	Δscore
10:58335222:GAAA:G	donor_gain	1.0000
10:58335223:AAA:A	donor_gain	1.0000
10:58335223:AAAGT:A	donor_loss	1.0000
10:58335224:AA:A	donor_gain	1.0000
10:58335225:AGT:A	donor_loss	1.0000
10:58335226:G:GG	donor_gain	1.0000
10:58335226:GTGA:G	donor_loss	1.0000
10:58361332:CTTCA:C	acceptor_loss	1.0000
10:58361333:TTCAG:T	acceptor_loss	1.0000
10:58361334:TCAGG:T	acceptor_loss	1.0000
10:58361335:CA:C	acceptor_loss	1.0000
10:58361337:GGA:G	acceptor_gain	1.0000
10:58361398:GACT:G	donor_gain	1.0000
10:58361402:G:GG	donor_gain	1.0000
10:58364764:T:G	acceptor_gain	1.0000
10:58364765:GTTTA:G	acceptor_loss	1.0000
10:58364766:TTTAG:T	acceptor_loss	1.0000
10:58364767:TTA:T	acceptor_loss	1.0000
10:58364768:TAGAT:T	acceptor_loss	1.0000
10:58364769:A:C	acceptor_loss	1.0000
10:58364770:G:A	acceptor_loss	1.0000
10:58367921:A:AG	acceptor_gain	1.0000
10:58367922:G:GG	acceptor_gain	1.0000
10:58367922:GTTTT:G	acceptor_gain	1.0000
10:58367937:T:G	acceptor_gain	1.0000
10:58368017:G:GG	donor_gain	1.0000
10:58335221:AGAAA:A	donor_gain	0.9900
10:58335222:GAAAG:G	donor_gain	0.9900
10:58335223:A:T	donor_gain	0.9900
10:58335228:GAGT:G	donor_loss	0.9900

AlphaMissense

964 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:58364803:C:A	N77K	1.000
10:58364803:C:G	N77K	1.000
10:58364849:T:A	W93R	1.000
10:58364849:T:C	W93R	1.000
10:58364851:G:C	W93C	1.000
10:58364851:G:T	W93C	1.000
10:58335215:G:T	R5M	0.999
10:58361503:T:A	W33R	0.999
10:58361503:T:C	W33R	0.999
10:58361521:G:A	G39R	0.999
10:58361521:G:C	G39R	0.999
10:58363672:T:C	F62L	0.999
10:58363674:T:A	F62L	0.999
10:58363674:T:G	F62L	0.999
10:58364796:A:G	H75R	0.999
10:58364805:T:A	I78K	0.999
10:58364817:G:A	G82E	0.999
10:58364817:G:T	G82V	0.999
10:58364823:T:A	I84N	0.999
10:58364829:T:A	L86H	0.999
10:58364832:A:T	D87V	0.999
10:58364859:C:A	A96D	0.999
10:58364862:T:C	L97P	0.999
10:58367935:T:A	I106K	0.999
10:58367944:T:C	L109P	0.999
10:58335216:G:C	R5S	0.998
10:58335216:G:T	R5S	0.998
10:58361338:G:A	E9K	0.998
10:58361381:C:A	A23D	0.998
10:58361516:T:A	I37N	0.998

dbSNP variants (sampled 300 via entrez): RS1000118514 (10:58354695 C>T), RS1000154180 (10:58336384 G>A), RS1000238981 (10:58362050 C>T), RS1000437565 (10:58369975 G>A), RS1000501956 (10:58349078 A>C,G), RS1000748442 (10:58342617 T>G), RS1000832215 (10:58369069 T>G), RS1001020253 (10:58335714 C>T), RS1001045270 (10:58342364 A>C), RS1001059394 (10:58341781 GC>G), RS1001109045 (10:58335406 G>A,T), RS1001130941 (10:58353788 G>A,T), RS1001135668 (10:58355383 ATTTT>A,ATTT,ATTTTT), RS1001241503 (10:58360429 A>AG), RS1001247189 (10:58354107 C>G,T)

Disease associations

OMIM: gene MIM:602961 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000573_7	Brain imaging	1.000000e-06
GCST000879_6	Crohn’s disease	9.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105766 (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

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

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression	2
Cannabidiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Okadaic Acid	increases expression	2
moringin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
cinnamaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
sulindac sulfide	increases expression	1
pinosylvin	decreases expression	1
dinophysistoxin 1	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Coumestrol	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	decreases expression	1
Plant Oils	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
CHEMBL4030879	Binding	Inhibition of UbcH5a (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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TV53	HAP1 UBE2D1 (-) 1	Cancer cell line	Male
CVCL_TV54	HAP1 UBE2D1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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