CDC34

Summary

CDC34 (cell division cycle 34, ubiquitin conjugating enzyme, HGNC:1734) is a protein-coding gene on chromosome 19p13.3, encoding Ubiquitin-conjugating enzyme E2 R1 (P49427). E2 ubiquitin-conjugating enzyme that accepts ubiquitin from an E1 ubiquitin-activating protein, and catalyzes its covalent attachment to other proteins by an E3 ubiquitin-protein ligase complex.

The protein encoded by this gene is a member of the ubiquitin-conjugating enzyme family. Ubiquitin-conjugating enzyme catalyzes the covalent attachment of ubiquitin to other proteins. This protein is a part of the large multiprotein complex, which is required for ubiquitin-mediated degradation of cell cycle G1 regulators, and for the initiation of DNA replication.

Source: NCBI Gene 997 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• GTEx eGene: eQTL in 23 tissues, sQTL in 34 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.14 (unconstrained)
• MANE Select transcript: NM_004359
• Interaction hub: 2,265 STRING partners (top 5% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1734
Approved symbol	CDC34
Name	cell division cycle 34, ubiquitin conjugating enzyme
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	E2-CDC34, UBE2R1, UBC3
Ensembl gene	ENSG00000099804
Ensembl biotype	protein_coding
OMIM	116948
Entrez	997

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000215574

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 2, TSL 5: 2

ENST00000215574, ENST00000586283, ENST00000586788, ENST00000593036, ENST00000606065, ENST00000606400, ENST00000607527, ENST00000874791, ENST00000874792, ENST00000874793, ENST00000991994, ENST00001054058, ENST00001054059, ENST00001121682, ENST00001121683, ENST00001123227, ENST00001138889

RefSeq mRNA: 1 — MANE Select: NM_004359 NM_004359

CCDS: CCDS12030

Canonical transcript exons

ENST00000215574 — 5 exons

Exon	Start	End
ENSE00000655676	531760	532108
ENSE00000655678	536243	536340
ENSE00000655679	537013	537147
ENSE00000655680	541339	542087
ENSE00003643788	535837	535923

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 97.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.0587 / max 767.7012, expressed in 1820 samples.

Highest expression (Bgee): testis, lower esophagus mucosa, apex of heart, ventricular zone, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDC34 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 34 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 57 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	1.5e-48	+0.59	19:535004:T:C
Nerve Tibial	sqtl	1.9e-46	+0.54	19:535004:T:C
Lung	sqtl	9.0e-35	+0.48	19:535004:T:C
Skin Sun Exposed Lower leg	sqtl	2.0e-34	+0.49	19:535004:T:C
Skin Not Sun Exposed Suprapubic	sqtl	3.8e-31	+0.60	19:539279:C:T
Breast Mammary Tissue	sqtl	4.1e-29	+0.58	19:535004:T:C
Thyroid	sqtl	8.8e-29	+0.46	19:541095:C:T
Whole Blood	eqtl	1.0e-28	-0.28	19:563639:T:C
Nerve Tibial	eqtl	7.1e-18	+0.21	19:535004:T:C
Colon Transverse	sqtl	4.6e-17	+0.45	19:535004:T:C
Esophagus Mucosa	sqtl	7.2e-17	+0.44	19:541095:C:T
Brain Cerebellum	sqtl	1.8e-16	+0.69	19:541095:C:T
Brain Cerebellum	eqtl	1.9e-16	+0.31	19:535004:T:C
Colon Sigmoid	eqtl	1.7e-15	-0.28	19:563639:T:C
Adipose Visceral Omentum	sqtl	2.9e-15	+0.41	19:535004:T:C
Brain Cerebellar Hemisphere	eqtl	9.6e-15	+0.23	19:535621:C:G
Brain Cerebellar Hemisphere	sqtl	2.7e-14	+0.65	19:541095:C:T
Muscle Skeletal	sqtl	1.6e-13	+0.29	19:541095:C:T
Esophagus Muscularis	sqtl	4.3e-13	+0.36	19:535004:T:C
Esophagus Gastroesophageal Junction	sqtl	5.3e-13	+0.48	19:535004:T:C

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
172687	19.5079	1804
172686	18.2800	1804
172688	0.5141	290
172683	0.3361	92
172689	0.2128	86
172685	0.1802	64
172684	0.0275	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.47	gold quality
right testis	UBERON:0004534	97.33	gold quality
lower esophagus mucosa	UBERON:0035834	97.05	gold quality
apex of heart	UBERON:0002098	97.04	gold quality
ventricular zone	UBERON:0003053	96.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.74	gold quality
cerebellar hemisphere	UBERON:0002245	96.48	gold quality
cerebellar cortex	UBERON:0002129	96.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.18	gold quality
ganglionic eminence	UBERON:0004023	96.15	gold quality
right lobe of liver	UBERON:0001114	96.09	gold quality
gastrocnemius	UBERON:0001388	96.01	gold quality
blood	UBERON:0000178	95.96	gold quality
mucosa of transverse colon	UBERON:0004991	95.85	gold quality
right frontal lobe	UBERON:0002810	95.74	gold quality
adenohypophysis	UBERON:0002196	95.67	gold quality
muscle of leg	UBERON:0001383	95.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.49	gold quality
lower esophagus	UBERON:0013473	95.48	gold quality
testis	UBERON:0000473	95.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.26	gold quality
skin of leg	UBERON:0001511	95.19	gold quality
right atrium auricular region	UBERON:0006631	95.16	gold quality
granulocyte	CL:0000094	94.76	gold quality
heart left ventricle	UBERON:0002084	94.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.76	gold quality
cerebellum	UBERON:0002037	94.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.63	gold quality
mucosa of stomach	UBERON:0001199	94.48	gold quality
body of pancreas	UBERON:0001150	94.47	gold quality
cardiac ventricle	UBERON:0002082	94.46	gold quality
stromal cell of endometrium	CL:0002255	94.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.29	gold quality
skin of abdomen	UBERON:0001416	94.27	gold quality
body of stomach	UBERON:0001161	94.18	gold quality
pituitary gland	UBERON:0000007	94.15	gold quality
prefrontal cortex	UBERON:0000451	94.14	gold quality
endocervix	UBERON:0000458	94.08	gold quality
body of uterus	UBERON:0009853	93.96	gold quality
left ovary	UBERON:0002119	93.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.91	gold quality
amygdala	UBERON:0001876	93.89	gold quality
left coronary artery	UBERON:0001626	93.85	gold quality
cardiac atrium	UBERON:0002081	93.82	gold quality
tibial artery	UBERON:0007610	93.79	gold quality
popliteal artery	UBERON:0002250	93.78	gold quality
transverse colon	UBERON:0001157	93.76	gold quality
left uterine tube	UBERON:0001303	93.68	gold quality
right ovary	UBERON:0002118	93.60	gold quality
esophagus	UBERON:0001043	93.54	gold quality
right coronary artery	UBERON:0001625	93.53	gold quality
monocyte	CL:0000576	93.49	gold quality
cortical plate	UBERON:0005343	93.47	gold quality
heart	UBERON:0000948	93.43	gold quality
aorta	UBERON:0000947	93.41	gold quality
coronary artery	UBERON:0001621	93.34	gold quality
ectocervix	UBERON:0012249	93.33	gold quality
metanephros cortex	UBERON:0010533	93.31	gold quality
muscle organ	UBERON:0001630	93.27	gold quality
ascending aorta	UBERON:0001496	93.24	gold quality
mononuclear cell	CL:0000842	93.22	gold quality
leukocyte	CL:0000738	93.09	gold quality
thoracic aorta	UBERON:0001515	93.09	gold quality
sigmoid colon	UBERON:0001159	93.08	gold quality
minor salivary gland	UBERON:0001830	93.07	gold quality
left adrenal gland cortex	UBERON:0035825	92.90	gold quality
right lung	UBERON:0002167	92.87	gold quality
omental fat pad	UBERON:0010414	92.80	gold quality
embryo	UBERON:0000922	92.73	gold quality
left adrenal gland	UBERON:0001234	92.73	gold quality
peritoneum	UBERON:0002358	92.73	gold quality
saliva-secreting gland	UBERON:0001044	92.67	gold quality
cingulate cortex	UBERON:0003027	92.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.60	gold quality
nucleus accumbens	UBERON:0001882	92.56	gold quality
right uterine tube	UBERON:0001302	92.52	gold quality
upper lobe of left lung	UBERON:0008952	92.52	gold quality
zone of skin	UBERON:0000014	92.50	gold quality
tibial nerve	UBERON:0001323	92.48	gold quality
caudate nucleus	UBERON:0001873	92.46	gold quality
left lobe of thyroid gland	UBERON:0001120	92.44	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.41	gold quality
putamen	UBERON:0001874	92.39	gold quality
right adrenal gland cortex	UBERON:0035827	92.37	gold quality
esophagus mucosa	UBERON:0002469	92.36	gold quality
anterior cingulate cortex	UBERON:0009835	92.36	gold quality
right adrenal gland	UBERON:0001233	92.35	gold quality
stomach	UBERON:0000945	92.12	gold quality
frontal cortex	UBERON:0001870	91.97	gold quality
neocortex	UBERON:0001950	91.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.90	gold quality
spinal cord	UBERON:0002240	91.86	gold quality
spleen	UBERON:0002106	91.85	gold quality
adrenal cortex	UBERON:0001235	91.79	gold quality
mouth mucosa	UBERON:0003729	91.78	gold quality
colon	UBERON:0001155	91.77	gold quality
right lobe of thyroid gland	UBERON:0001119	91.71	gold quality
descending thoracic aorta	UBERON:0002345	91.69	gold quality
parotid gland	UBERON:0001831	91.61	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	12.78
E-HCAD-13	yes	7.57
E-MTAB-6524	no	72.31
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	81.4
Skeletal muscle	tissue	81.3	low
Caudate putamen	tissue	70.2
Spinal cord	tissue	66.8
Thalamus	tissue	62.8
Superior colliculi	tissue	60.6
Tongue	tissue	58.9
Midbrain	tissue	57.3
Pons	tissue	57.2
Cerebral cortex	tissue	55.6	medium
Somatosensory cortex	tissue	55.6
Motor cortex	tissue	53.3
Prefrontal cortex	tissue	50.9
Medulla oblongata	tissue	49.6
Hippocampal formation	tissue	49.1
Entorhinal cortex	tissue	49.1
Temporal cortex	tissue	49.1
Hippocampus	tissue	48.2	medium
Occipital cortex	tissue	48.2
Putamen	tissue	47.2
Insular cortex	tissue	46.2
Substantia nigra	tissue	45.6
Basal ganglia	tissue	45.1	medium
Retrosplenial and cingulate cortex	tissue	44.3
Locus coeruleus	tissue	44.2
Pituitary gland	tissue	44.1
Postcentral gyrus	tissue	43.3
Retrosplenial cortex	tissue	41.6
Pancreas	tissue	41.5	medium
Choroid plexus	tissue	39.6
Periaqueductal gray	tissue	39.3
Septum	tissue	39.0
Hypothalamus	tissue	38.6
Ventral forebrain	tissue	38.6
Cerebellum	tissue	38.3	medium
Amygdala	tissue	37.0
Vagina	tissue	35.6	low
Nucleus accumbens	tissue	34.8
Liver	tissue	34.7	medium
Corpus callosum	tissue	33.7
Bone marrow	tissue	32.6	low
Heart muscle	tissue	32.5	low
Testis	tissue	32.2	medium
Salivary gland	tissue	30.1	medium
Placenta	tissue	27.4	medium
Retina	tissue	26.2
Olfactory bulb	tissue	25.9
Skin 1	tissue	21.3	low
Ovary	tissue	20.3	low
Adipose tissue	tissue	18.3	low
Seminal vesicle	tissue	18.2	medium
Colon	tissue	18.0	medium
Stomach 1	tissue	17.7	medium
Parathyroid gland	tissue	17.6	medium
Smooth muscle	tissue	17.3	low
Duodenum	tissue	16.8	high
Adrenal gland	tissue	16.2	medium
Urinary bladder	tissue	15.8	medium
Thymus	tissue	15.3
Small intestine	tissue	14.7	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (66.8), Temporo-occipital transitional zone (55.2), Olfactory area (54.1), Area parastriata, superior (51.3), Fusiform gyrus (50.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

Targeting CDC34 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 32 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-6878-5P	98.49	67.91	2142

Functional genomics

gnomAD constraint: pLI 1.4e-05, LOEUF 1.14, missense Z 0.576 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000215574 — one region, missense o/e 0.84.

Literature-anchored findings (GeneRIF, showing 26)

• degraded by HSV-1 ICP0 while stabilizing cyclins D1 and D3 (PMID:14645576)
• antisense oligonucleotides targeting the human ubiquitin-conjugating enzyme Cdc34 downregulate its expression, inhibit the degradation of p27Kip1, and prevent cellular proliferation (PMID:15652359)
• although a Cdc34 mutant bearing a deletion of the C-terminal 36 amino acids (Cdc34 1-200) was efficiently charged with ubiquitin by E1, it was severely reduced for the ability to ubiquitinate p27(Kip1) in vitro compared to wildtype Cdc34 (PMID:16123592)
• Data suggest that the Skp1.CUL1.F-box-mediated polyubiquitination reaction may require the conversion of Cdc34 from an inactive monomer to a highly active dimeric form. (PMID:16210246)
• in vivo phosphorylation sites on budding yeast Cdc34 (yCdc34; Ser207 and Ser216) and human Cdc34 (hCdc34 Ser203, Ser222 and Ser231) to serine residues in the acidic tail domain, a region that is critical for Cdc34’s cell cycle function (PMID:17461777)
• In tissue culture cells, Uba6 is required for charging a previously uncharacterized Uba6-specific E2 (Use1), whereas Ube1 is required for charging the cell-cycle E2s Cdc34A and Cdc34B (PMID:17597759)
• These findings support the hypothesis that human Cdc34 S95 and E108/E112 are required to position the donor ubiquitin optimally for catalysis, in a manner that might depend on E2 dimerization. (PMID:17698585)
• cisplatin increased ATF5 protein expression via preventing its ubiquitin-dependent degradation, which might be associated with its promoting the nucleus-to-cytoplasm translocation of E2 ubiquitin-conjugating enzyme Cdc34 (PMID:18458088)
• Cdc34 is a functional target of let-7 and that let-7 induces down-regulation of Cdc34, stabilization of the Wee1 kinase, and an increased fraction of cells in G(2)/M in primary fibroblasts. (PMID:19126550)
• The acidic tail of the Cdc34 ubiquitin-conjugating enzyme functions in both binding to and catalysis with ubiquitin ligase SCFCdc4. (PMID:19875449)
• Study shows that chain assembly by ubiquitin ligase SCF and ubiquitin-conjugating enzyme Cdc34 is facilitated by the unusual nature of Cdc34-SCF transactions: Cdc34 binds SCF with nanomolar affinity, nevertheless the complex is extremely dynamic. (PMID:19945379)
• determined that a ubiquitin (Ub) fused at I kappaB alpha K21 acts as a receptor, directing Cdc34 for rapid and efficient K48-linked Ub chain synthesis that depends on SCF(beta TrCP2) and the substrate’s N terminus. (PMID:20347421)
• the human Cdc34 carboxyl terminus contains a non-covalent ubiquitin binding activity that contributes to SCF-dependent ubiquitination (PMID:20353940)
• COP9 signalosome protects ubiquitin-conjugating enzyme 3 (UBC3/Cdc34) from beta-transducin repeat-containing protein (betaTrCP)-mediated degradation (PMID:20378537)
• work provides the first structural details that show how the C-terminus of CDC34 might direct a thiolester-bound Ub to control polyubiquitin chain formation (PMID:21296085)
• Tristetraprolin promotes an increase in expression of mature let-7, which leads to the inhibition of let-7 target gene CDC34 expression and suppresses cell growth. (PMID:22210895)
• Data show that anaphase-promoting complex or cyclosome (APC/C)-mediated multiple monoubiquitylation targeting cyclin B1 for degradation. (PMID:22286100)
• These data suggest that FBXO15 and Ube2r1 regulate P-gp expression through the ubiquitin-proteasome pathway. (PMID:23465077)
• Here we have investigated how the acidic loop in human Cdc34 promotes ubiquitination, identifying two key molecular events during which the acidic loop exerts its influence (PMID:24129577)
• We discuss how these results can explain the rapid association of Cdc34 and SCF. (PMID:25425648)
• ubiquitin binding by the acidic loops of Ube2g1 and Ube2r1 enzymes distinguishes their Lys-48-ubiquitylation activities (PMID:25471371)
• Study shows that Ube2R1/2 forms a salt bridge interaction between a conserved Asp residue on Ube2R1/2 and acceptor ubiquitin residue Arg 54 and that perturbation of this interaction leads to the severe loss of UbeR2 activity. Results also provide new insight into how the Ube2R1/2 acidic loop may participate in catalysis. (PMID:27044868)
• study finds that mutation of the catalytically active cysteine to serine (C93S) results in the reduced ubiquitination, increased stability, and attenuated degradation rate of CDC34; Through semi-quantitative proteomics, identified the CDC34-interacting proteins and discovered that the wild-type and mutant proteins have many differentially interacted proteins (PMID:29564676)
• UBE2R2 alone had negligible ubiquitylation activity at physiological concentrations and the ablation of UBE2R1/2 had no effect on the stability of SCF substrates in cells. A genome-wide CRISPR screen revealed that an additional E2 enzyme, UBE2G1, buffers against the loss of UBE2R1/2. (PMID:31868589)
• Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis. (PMID:32114396)
• Targeting CDC34 E2 ubiquitin conjugating enzyme for lung cancer therapy. (PMID:32268269)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdc34b	ENSMUSG00000020870
rattus_norvegicus	Cdc34	ENSRNOG00000060530

Paralogs (24): UBE2T (ENSG00000077152), UBE2A (ENSG00000077721), UBE2K (ENSG00000078140), 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:102657) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal nail morphology	1
male infertility	1
preweaning lethality, incomplete penetrance	1
increased fasting circulating glucose level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	P63282	100.0%	Diamond
Gallus gallus	P63283	100.0%	Diamond
Xenopus tropicalis	Q28CQ4	100.0%	Diamond
Oryctolagus cuniculus	Q29503	100.0%	Diamond
Ictidomys tridecemlineatus	Q2EF73	100.0%	Diamond
Bos taurus	Q3MHP1	100.0%	Diamond
Pongo abelii	Q5RF84	100.0%	Diamond
Macaca fascicularis	Q4R5Y8	99.4%	Diamond
Danio rerio	Q9DDJ0	99.4%	Diamond
Arabidopsis thaliana	Q42540	95.8%	Diamond
Mesocricetus auratus	O09181	95.6%	Diamond
Triticum aestivum	P25868	83.0%	Diamond
Caenorhabditis elegans	P34477	74.1%	Diamond
Schizosaccharomyces pombe 972h-	O00102	68.9%	Diamond
Saccharomyces cerevisiae S288C	Q02159	62.8%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SSK3	47.1%	Diamond
African swine fever virus warthog/Namibia/Wart80/1980	P0C8G5	94.6%	Diamond
African swine fever virus BA71V	P27949	94.6%	Diamond
African swine fever virus tick/South Africa/Pretoriuskop Pr4/1996	P0C8G4	90.1%	Diamond
African swine fever virus pig/Kenya/KEN-50/1950	P0C8G3	85.4%	Diamond
African swine fever virus Malawi LIL 20/1	P25869	85.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SHC2	protein-coding	25759
CIMAP1D	protein-coding	284451
GZMM	protein-coding	3004
MADCAM1	protein-coding	8174
TPGS1	protein-coding	91978
HCN2	protein-coding	610
BSG	protein-coding	682
BSG-AS1	ncRNA	105372233
MADCAM1-AS1	ncRNA	105372232

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 R1 — P49427 (reviewed: P49427)

Alternative names: (E3-independent) E2 ubiquitin-conjugating enzyme R1, E2 ubiquitin-conjugating enzyme R1, Ubiquitin-conjugating enzyme E2-32 kDa complementing, Ubiquitin-conjugating enzyme E2-CDC34, Ubiquitin-protein ligase R1

All UniProt accessions (4): P49427, U3KPV8, U3KQ77, U3KQP9

UniProt curated annotations — full annotation on UniProt →

Function. E2 ubiquitin-conjugating enzyme that accepts ubiquitin from an E1 ubiquitin-activating protein, and catalyzes its covalent attachment to other proteins by an E3 ubiquitin-protein ligase complex. In vitro catalyzes ‘Lys-48’-linked polyubiquitination. Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions ‘Lys-21’ and/or ‘Lys-22’ with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation. Also involved in the degradation of beta-catenin. Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes.

Subunit / interactions. Interacts with multiple Cul1-RING E3 ubiquitin-protein ligase complexes, also known as SCF (SKP1-CUL1-F-box protein) complexes. Identified in a SCF E3 ubiquitin ligase complex together with HINT1 and RBX1. When cullin is neddylated, the interaction between the E2 and the SCF complex is strengthened. Interacts with multiple Cul2-RING (CRL2) E3 ubiquitin-protein ligase complexes, also known as ECS (Elongin BC-CUL2/5-SOCS-box protein) complexes. When phosphorylated, interacts with beta-TrCP (BTRC). Interacts with human herpes virus 1 protein ICP0 and associates with the proteasome for degradation. Interacts with casein kinase subunit CSNK2B. Interacts with CNTD1; this interaction regulates the cell-cycle progression.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in testes during spermatogenesis to regulate repression of cAMP-induced transcription.

Post-translational modifications. Autoubiquitinated. Autoubiquitination is promoted by the human herpes virus 1 protein ICP0 and leads to degradation by the Ubiquitin-proteasomal pathway. Phosphorylated by CK2. Phosphorylation of the C-terminal tail by CK2 controls the nuclear localization.

Activity regulation. CDC34-catalyzed polyubiquitin chain assembly activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF E3 ligase complex subunit.

Domain organisation. The C-terminal acidic tail is required for nuclear localization and is involved in the binding to SCF E3 ligase complexes, and more specifically with the CUL1 subunit.

Induction. Negatively regulated by the let-7 microRNA.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (1): NP_004350* (*=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 (51 total): mutagenesis site 26, modified residue 5, helix 5, strand 5, region of interest 3, turn 3, chain 1, domain 1, sequence variant 1, active site 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
3RZ3	Human Cdc34 E2 in complex with CC0651 inhibitor	X-RAY DIFFRACTION	2.3
2OB4	Human Ubiquitin-Conjugating Enzyme CDC34	X-RAY DIFFRACTION	2.4
7M2K	CDC34A-Ubiquitin-2ab inhibitor complex	X-RAY DIFFRACTION	2.47
4MDK	Cdc34-ubiquitin-CC0651 complex	X-RAY DIFFRACTION	2.61
8RX0	(NEDD8)-CRL2VHL-MZ1-Brd4BD2-Ub(G76S, K48C)-UBE2R1(C93K, S138C, C191S, C223S)-Ub	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49427-F1	85.52	0.71

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles; nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
93	glycyl thioester intermediate

Post-translational modifications (5)

Type	Positions
Phosphoserine	236, 203, 222, 231
Phosphothreonine	233

Mutagenesis-validated functional residues (26)

Position	Phenotype
70	loss of rbx1-binding.
85	inhibits both mono and polyubiquitination of nfkbia.
87	decreases polyubiquitination of nfkbia.
93	loss of function.
95	inhibits both mono and polyubiquitination of nfkbia.
97	loss of function.
102	inhibits polyubiquitination of nfkbia; when associated with a-103.
103	inhibits polyubiquitination of nfkbia; when associated with a-102.
108	decrease in substrate affinity and ubiquitin transfer rate for neddylated crl2(fem1c)-ube2r1 complex. inhibits both mono and …
112	inhibits both mono and polyubiquitination of nfkbia; when associated with a-108.
113	decrease in substrate affinity and ubiquitin transfer rate for neddylated crl2(fem1c)-ube2r1 complex.
117	loss of rbx1-binding.
129	no effect on activity, when assayed in a sic1-scf-cdc4 ubiquitination assay.
129	complete loss of activity, when assayed in a sic1-scf-cdc4 ubiquitination assay.
133	no effect on activity, when assayed in a sic1-scf-cdc4 ubiquitination assay.
138	decreases monoubiquitination of nfkbia and inhibits polyubiquitination of nfkbia.
143	inhibits polyubiquitination of nfkbia; when associated with a-147; a-149; a-150 and a-153.
147	inhibits polyubiquitination of nfkbia; when associated with a-143; a-149; a-150 and a-153.
149	inhibits polyubiquitination of nfkbia; when associated with a-147; a-147; a-150 and a-153.
150	inhibits polyubiquitination of nfkbia; when associated with a-143; a-147; a-149 and a-153.
153	inhibits polyubiquitination of nfkbia; when associated with a-143; a-147; a-149 and a-150.
203	abolishes phosphorylation by ck2. impairs nuclear localization; when associated with a-222; a-231; a-233 and a-236.
222	abolishes phosphorylation by ck2. impairs nuclear localization; when associated with a-203; a-231; a-233 and a-236.
231	abolishes phosphorylation by ck2. impairs nuclear localization; when associated with a-203; a-222; a-233 and a-236.
233	abolishes phosphorylation by ck2. impairs nuclear localization; when associated with a-203; a-222; a-231 and a-236.

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 15; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

15 pathways:

ID	Pathway	Evidence
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	curated
R-HSA-5607764	CLEC7A (Dectin-1) signaling	curated
R-HSA-202424	Downstream TCR signaling	curated
R-HSA-2871837	FCERI mediated NF-kB activation	curated
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-5621481	C-type lectin receptors (CLRs)	—
R-HSA-983169	Class I MHC mediated antigen processing & presentation	—
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-8852135	Protein ubiquitination	—
R-HSA-202403	TCR signaling	—

MSigDB gene sets: 196 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, WONG_PROTEASOME_GENE_MODULE, GOBP_RESPONSE_TO_INTERFERON_BETA, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_DOWNSTREAM_TCR_SIGNALING, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (10): G1/S transition of mitotic cell cycle (GO:0000082), protein polyubiquitination (GO:0000209), DNA replication initiation (GO:0006270), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), cellular response to interferon-beta (GO:0035458), protein modification process (GO:0036211), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein K48-linked ubiquitination (GO:0070936), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), 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 (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), cytoplasm (GO:0005737)

Reactome top-level categories

10 top-level categories:

Category	Pathways
Immune System	2
Adaptive Immune System	2
Innate Immune System	2
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
C-type lectin receptors (CLRs)	1
Protein ubiquitination	1
Class I MHC mediated antigen processing & presentation	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

34 GO namespaces:

Category	Terms
cellular anatomical structure	3
protein ubiquitination	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
DNA metabolic process	1
DNA-templated DNA replication	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
response to interferon-beta	1
cellular response to cytokine stimulus	1
protein metabolic process	1
macromolecule modification	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein polyubiquitination	1
protein modification by small protein conjugation or removal	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	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
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to interferon-beta	BP	mutant phenotype
proteasome-mediated ubiquitin-dependent protein catabolic process	BP	direct assay
protein K48-linked ubiquitination	BP	direct assay
protein polyubiquitination	BP	direct assay
protein ubiquitination	BP	direct assay
cytosol	CC	direct assay
nuclear speck	CC	direct assay
nucleoplasm	CC	direct assay
ubiquitin conjugating enzyme activity	MF	direct assay
ubiquitin-protein transferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,265 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC34	FBXW7	Q969H0	901
CDC34	SKP1	P34991	854
CDC34	UBA1	P22314	842
CDC34	FLI1	Q01543	826
CDC34	CUL1	Q13616	823
CDC34	UBB	P02248	770
CDC34	BTRC	Q9Y297	739
CDC34	UBB	P02248	734
CDC34	RBX1	P62877	727
CDC34	MGRN1	O60291	716
CDC34	HEY1	Q9Y5J3	685
CDC34	DIAPH2	O60879	683
CDC34	DIAPH3	Q9NSV4	664
CDC34	NEDD8	Q15843	649
CDC34	MARCHF1	Q8TCQ1	642

IntAct

Human interaction partners of CDC34 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

23 partners by confidence:

Partner	Interaction type	MIscore	Records
BTRC	direct interaction	0.730	2
SDCBP	physical association	0.720	6
CSNK2B	physical association	0.590	4
MEOX1	physical association	0.560	3
MEOX2	physical association	0.560	3
SIAH1	physical association	0.560	3
CUL1	physical association	0.540	3
RBX1	direct interaction	0.440	1
ZNRF1	ubiquitination reaction	0.440	1
CORO7	physical association	0.400	1
STT3B	physical association	0.400	1
ATF5	physical association	0.370	1
CREM	physical association	0.370	1
ECE1	physical association	0.370	1
EIF3K	physical association	0.370	1
TIMM13	physical association	0.370	1
TMEM14C	physical association	0.370	1
CTC1	association	0.350	2
SPRYD4	association	0.350	1
UBE2R2	association	0.350	1
CSNK2A1	phosphorylation reaction	0.310	1
PPP1CB	physical association	0.000	1
PPP1CC	physical association	0.000	1

BioGRID (513 interactions; top human partners by supporting records): RBX1 (Reconstituted Complex; 90 records), UBC (Biochemical Activity; 16 records), BTRC (Reconstituted Complex; 10 records), UBA1 (Biochemical Activity; 9 records), CUL1 (Reconstituted Complex; 7 records), FBXW11 (Affinity Capture-MS; 7 records), EGFR (Affinity Capture-Western; 5 records), RNF7 (Reconstituted Complex; 5 records), CSNK2B (Affinity Capture-MS; 4 records), CDKN1B (Biochemical Activity; 3 records), HINT1 (Reconstituted Complex; 3 records), ITCH (Reconstituted Complex; 3 records), RAD21 (Affinity Capture-MS; 3 records), SKP2 (Reconstituted Complex; 3 records), ATF5 (Two-hybrid; 2 records)

SIGNOR signaling

showing 8 of 16 signaling interactions:

A	Effect	B	Mechanism
CSNK2A1	“down-regulates activity”	CDC34	phosphorylation
CSNK2B	unknown	CDC34	phosphorylation
RNF7	“down-regulates activity”	CDC34	polyubiquitination
CDC34	“up-regulates activity”	SCF-betaTRCP	binding
CDC34	“up-regulates activity”	SCF-FBW2	binding
CDC34	“up-regulates activity”	SCF-FBW7	binding
CDC34	“up-regulates activity”	SCF-SKP2	binding
RPS6KA1	“down-regulates quantity by destabilization”	CDC34	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Ubiquitin E3 ligase (CDC34, CUL1, RBX1)	3	CDC34, CUL1, RBX1
HINT1-UBC3-RBX1 complex	3	RBX1, CDC34, HINT1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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
Antigen processing: Ubiquitination & Proteasome degradation	6	12.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	5	38.3×	3e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	5	11.9×	2e-03
spermatogenesis	5	8.0×	5e-03

Disease & clinical

Genetic variants

Variant evidence for CDC34: 42 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 583):

Position(s)	Effect	Δscore	Sites
19:532109–532110	donor_loss	1.0000	4
19:535924–535925	donor_loss	1.0000	4
19:536236	acceptor_gain	1.0000
19:536241–536242	acceptor_loss	1.0000	2
19:536341–536342	donor_loss	1.0000	5
19:537104	donor_gain	1.0000
19:537118	donor_gain	1.0000
19:532109	donor_loss	0.9900
19:535835–535836	acceptor_loss	0.9900	6
19:535924	donor_loss	0.9900

AlphaMissense

886 missense substitutions predicted likely pathogenic (of 1,544 scored), across 171 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M147	9	0.892	0.994
H83	8	0.999	1.000
H98	8	0.999	1.000
F77	8	0.996	1.000
S126	8	0.996	1.000
F64	8	0.993	1.000
N85	8	0.993	1.000
D103	8	0.993	0.998
D143	8	0.984	0.997
N135	8	0.978	1.000
F28	8	0.976	0.999
F58	8	0.976	1.000
N115	8	0.973	0.999
N141	8	0.963	0.999
S106	8	0.955	0.999
F46	8	0.945	0.998
F75	8	0.912	0.997
D67	8	0.907	0.981
M81	8	0.891	0.999
D179	8	0.848	0.961

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000133

Disease associations

OMIM: gene MIM:116948 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Arsenic Trioxide	increases expression, decreases expression	2
Acrolein	affects cotreatment, increases oxidation, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Benzo(a)pyrene	decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
cryptolepine	decreases expression	1
ochratoxin A	decreases expression, affects cotreatment	1
cupric chloride	affects expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
U 0126	affects expression, affects reaction	1
2-palmitoylglycerol	increases expression	1
licochalcone B	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	increases expression	1
Sunitinib	increases expression	1
Citrinin	decreases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, decreases expression	1
Environmental Pollutants	affects expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SI03	HAP1 CDC34 (-) 1	Cancer cell line	Male
CVCL_SI04	HAP1 CDC34 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.