ELOB

Summary

ELOB (elongin B, HGNC:11619) is a protein-coding gene on chromosome 16p13.3, encoding Elongin-B (Q15370). SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. It is a common-essential gene (DepMap: required in 98.1% of cancer cell lines).

This gene encodes the protein elongin B, which is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. Pseudogenes have been identified on chromosomes 11 and 13.

Source: NCBI Gene 6923 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_007108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11619
Approved symbol	ELOB
Name	elongin B
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SIII
Ensembl gene	ENSG00000103363
Ensembl biotype	protein_coding
OMIM	600787
Entrez	6923

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000262306, ENST00000409477, ENST00000409906, ENST00000494946, ENST00000572954, ENST00000688784, ENST00000691758, ENST00000693239, ENST00000919674, ENST00000919675

RefSeq mRNA: 2 — MANE Select: NM_007108 NM_007108, NM_207013

CCDS: CCDS32374, CCDS45387

Canonical transcript exons

ENST00000409906 — 4 exons

Exon	Start	End
ENSE00001118908	2775451	2775556
ENSE00001214130	2776993	2777127
ENSE00001827105	2771414	2772102
ENSE00002635192	2777237	2777280

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.8874 / max 367.9660, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155948	80.0032	1824
207707	0.8842	394

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.70	gold quality
right testis	UBERON:0004534	99.68	gold quality
apex of heart	UBERON:0002098	99.48	gold quality
adult organism	UBERON:0007023	99.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.40	gold quality
stromal cell of endometrium	CL:0002255	99.39	gold quality
prefrontal cortex	UBERON:0000451	99.29	gold quality
nucleus accumbens	UBERON:0001882	99.29	gold quality
adenohypophysis	UBERON:0002196	99.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.29	gold quality
ganglionic eminence	UBERON:0004023	99.27	gold quality
pituitary gland	UBERON:0000007	99.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.24	gold quality
amygdala	UBERON:0001876	99.23	gold quality
cortical plate	UBERON:0005343	99.22	gold quality
caudate nucleus	UBERON:0001873	99.21	gold quality
mucosa of transverse colon	UBERON:0004991	99.18	gold quality
right atrium auricular region	UBERON:0006631	99.15	gold quality
trabecular bone tissue	UBERON:0002483	99.14	gold quality
gastrocnemius	UBERON:0001388	99.12	gold quality
right frontal lobe	UBERON:0002810	99.12	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.11	gold quality
left adrenal gland	UBERON:0001234	99.09	gold quality
left coronary artery	UBERON:0001626	99.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.09	gold quality
left adrenal gland cortex	UBERON:0035825	99.09	gold quality
spinal cord	UBERON:0002240	99.07	gold quality
granulocyte	CL:0000094	99.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.06	gold quality
testis	UBERON:0000473	99.05	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	9320.34
E-HCAD-4	yes	239.67
E-GEOD-84465	yes	21.92
E-ANND-3	yes	15.45
E-CURD-122	yes	9.33
E-MTAB-7316	yes	7.27
E-MTAB-8410	yes	4.80
E-MTAB-9388	no	1627.87
E-GEOD-125970	no	20.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting ELOB, 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-4753-3P	99.90	71.03	3786
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-1470	98.11	63.53	399
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-4323	93.93	63.89	656

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 15)

• findings report that HIV-1 Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)-like complex (PMID:14564014)
• show that ASB2, by interacting with the Elongin BC complex, can assemble with Cullin5.Rbx1 to form an E3 ubiquitin ligase complex that stimulates polyubiquitination by the E2 ubiquitin-conjugating enzyme Ubc5 (PMID:15590664)
• the E3 ubiquitin ligase activity of the Vif-BC-Cul5 complex is essential for Vif function against APOBEC3G (PMID:15781449)
• Results describe the 1.9-A crystal structure of the ternary complex of SOCS2 with elongin C and elongin B. (PMID:16675548)
• nuclear level of active P-TEFb is controlled by dynamic and reversible remodelling of 7SK snRNP (PMID:17611602)
• Elongin B/C recruitment regulates substrate binding by CIS (PMID:18508766)
• Recombinant full-length Vif interacted with the Elongin BC complex in vitro with a K(d) of 1.9 muM and resulted in observable changes in deuterium uptake in both Elongin C and B. (PMID:20728451)
• Elongin B also enhances gene expression from the double-stranded DNA genome of human cytomegalovirus. (PMID:21447700)
• ASB9 is unstable alone but forms a stable ternary complex with EloBC that binds with high affinity to the Cullin 5 N-terminal domain. (PMID:23837592)
• Vif interaction with EloB-EloC may contribute to recruitment of CBF-beta to Vif, demonstrating that the EloB C-teminus may play a role in improving Vif function and that the over-expression of EloB results in Vif stabilization. (PMID:23988114)
• The crystal structure of VHL bound to a Cul2 N-terminal domain, Elongin B, and Elongin C. (PMID:25661653)
• crystals of SOCS2 in complex with its adaptor proteins, Elongin C and Elongin B, underwent a change in crystallographic parameters when treated with dimethyl sulfoxide during soaking experiments. (PMID:26121586)
• Study shows that TCEB2 is involved in the development of acquired resistance to bevacizumab in ovarian cancer cells via the mechanisms of suppression of VEGF-A expression by promoting HIF-1alpha degradation and induction of interleukin-8 (IL-8) expression. (PMID:26531153)
• Enhancing radiosensitivity in triple-negative breast cancer through targeting ELOB. (PMID:38472737)
• Elongin B promotes breast cancer progression by ubiquitinating tumor suppressor p14/ARF. (PMID:38653919)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	elob	ENSDARG00000037980
mus_musculus	Elob	ENSMUSG00000055839
rattus_norvegicus	Elob	ENSRNOG00000004814
rattus_norvegicus	Elobl7	ENSRNOG00000062517
drosophila_melanogaster	EloB	FBGN0023212
caenorhabditis_elegans		WBGENE00001235

Protein

Protein identifiers

Elongin-B — Q15370 (reviewed: Q15370)

Alternative names: Elongin 18 kDa subunit, RNA polymerase II transcription factor SIII subunit B, SIII p18, Transcription elongation factor B polypeptide 2

All UniProt accessions (7): Q15370, A0A0B4J296, A0A384MDL3, A0A8I5KQX6, A0A8I5KUS5, B8ZZU8, I3L0M9

UniProt curated annotations — full annotation on UniProt →

Function. SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important feature of pluripotent stem cells. Core component of multiple cullin-2 and cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes), which mediate the ubiquitination of target proteins. By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. Component the von Hippel-Lindau ubiquitination complex CBC(VHL). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The ECS(ASB9) complex mediates ubiquitination and degradation of CKB. As part of a multisubunit ubiquitin ligase complex, polyubiquitinates monoubiquitinated POLR2A. ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase. As part of the ECS(RAB40C) complex, mediates ANKRD28 ubiquitination and degradation, thereby inhibiting protein phosphatase 6 (PP6) complex activity and focal adhesion assembly during cell migration. The ECS(ASB7) complex acts a negative regulator of H3K9me3 histone mark by mediating ubiquitination and degradation of SUV39H1. (Microbial infection) Following infection by HIV-1 virus, component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, which catalyzes ubiquitination and degradation of APOBEC3F and APOBEC3G. The complex can also ubiquitinate APOBEC3H to some extent.

Subunit / interactions. Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit. The elongin BC complex interacts with EPOP; leading to recruit the elongin BC complex to Polycomb group (PcG) target genes, thereby restricting excessive activity of the PRC2/EED-EZH2 complex. Component of multiple cullin-RING E3 ubiquitin-protein ligase complexes composed of Elongin BC (ELOB and ELOC), a cullin (either CUL2 or CUL5), a catalytic subunit (either RBX1 or RNF7/RBX2), as well as a substrate adapter protein that can be either ASB2, ASB7, ASB9, ASB11, KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B, FEM1C, LRR1, PCMTD1, SOCS1, SOCS2, SOCS5, SPSB1, SPSB3, ELOA, VHL, WSB1 or RAB40C. As part of the Elongin BC E3 ubiquitin ligase complex; interacts with NRBP1. May also interact with DCUN1D1, DCUN1D2, DCUN1D3 and DCUN1D5. May form oligomers as a KLHDC2/KLHDC3-ELOB-ELOC complex; this interaction is autoinhibitory for the E3 ligase complex as the substrate-binding site of KLHDC2/KLHDC3 is blocked in the oligomer. (Microbial infection) Following infection by HIV-1 virus, component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein. (Microbial infection) Substrate adapter protein can be a viral protein such as HIV Vif. (Microbial infection) Interacts with molluscum contagiosum virus MC132. (Microbial infection) Interacts with herpes virus 8 virus protein LANA1.

Subcellular location. Nucleus.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the Elongin B family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15370-1	1	yes
Q15370-2	2

RefSeq proteins (2): NP_009039, NP_996896 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039049	ELOB	Family

Pfam: PF00240

UniProt features (27 total): strand 11, helix 5, modified residue 4, turn 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

156 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7Z76	X-RAY DIFFRACTION	1.32
7JTO	X-RAY DIFFRACTION	1.7
8BDS	X-RAY DIFFRACTION	1.72
4AJY	X-RAY DIFFRACTION	1.73
6GMR	X-RAY DIFFRACTION	1.75
6HR2	X-RAY DIFFRACTION	1.76
7ZLM	X-RAY DIFFRACTION	1.79
6I7Q	X-RAY DIFFRACTION	1.8
8BB3	X-RAY DIFFRACTION	1.8
6GFX	X-RAY DIFFRACTION	1.83
1LM8	X-RAY DIFFRACTION	1.85
2C9W	X-RAY DIFFRACTION	1.9
6ZHC	X-RAY DIFFRACTION	1.92
7ZLS	X-RAY DIFFRACTION	1.92
6GMN	X-RAY DIFFRACTION	1.94
7ZLP	X-RAY DIFFRACTION	1.94
6I7R	X-RAY DIFFRACTION	1.95
7Z77	X-RAY DIFFRACTION	1.97
6I5N	X-RAY DIFFRACTION	1.98
8P0F	X-RAY DIFFRACTION	1.98
1LQB	X-RAY DIFFRACTION	2
4B9K	X-RAY DIFFRACTION	2
6BVB	X-RAY DIFFRACTION	2
7ZLR	X-RAY DIFFRACTION	2.01
8BDJ	X-RAY DIFFRACTION	2.02
8BDM	X-RAY DIFFRACTION	2.02
8BB2	X-RAY DIFFRACTION	2.05
4W9F	X-RAY DIFFRACTION	2.1
4W9H	X-RAY DIFFRACTION	2.1
4W9K	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15370-F1	93.01	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 1, 84, 108, 111

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-8951664	Neddylation
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9833109	Evasion by RSV of host interferon responses
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide

MSigDB gene sets: 216 (showing top): GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, MORF_RAB5A, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MODULE_150, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317

GO Biological Process (8): transcription initiation at RNA polymerase II promoter (GO:0006367), transcription elongation by RNA polymerase II (GO:0006368), protein ubiquitination (GO:0016567), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), protein-containing complex assembly (GO:0065003), ubiquitin-dependent protein catabolic process via the C-end degron rule pathway (GO:0140627), target-directed miRNA degradation (GO:0140958), translational elongation (GO:0006414)

GO Molecular Function (4): transcription corepressor binding (GO:0001222), ubiquitin protein ligase binding (GO:0031625), translation elongation factor activity (GO:0003746), protein binding (GO:0005515)

GO Cellular Component (9): nucleoplasm (GO:0005654), cytosol (GO:0005829), VCB complex (GO:0030891), Cul2-RING ubiquitin ligase complex (GO:0031462), Cul5-RING ubiquitin ligase complex (GO:0031466), elongin complex (GO:0070449), ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Transcription of the HIV genome	5
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1
Cellular response to hypoxia	1
Tat-mediated elongation of the HIV-1 transcript	1
HIV Transcription Elongation	1
Host Interactions of HIV factors	1
Transcriptional Regulation by TP53	1
Post-translational protein modification	1
Signaling by ROBO receptors	1
Signaling by CSF3 (G-CSF)	1
Class I MHC mediated antigen processing & presentation	1
RSV-host interactions	1
Ribosome-associated quality control	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transcription by RNA polymerase II	2
proteasome-mediated ubiquitin-dependent protein catabolic process	2
cullin-RING ubiquitin ligase complex	2
DNA-templated transcription initiation	1
DNA-templated transcription elongation	1
protein modification by small protein conjugation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
cellular component assembly	1
protein-containing complex organization	1
miRNA catabolic process	1
post-transcriptional gene silencing	1
negative regulation of miRNA-mediated gene silencing	1
translation	1
macromolecule biosynthetic process	1
transcription coregulator binding	1
ubiquitin-like protein ligase binding	1
translational elongation	1
translation factor activity	1
binding	1
nuclear lumen	1
cytoplasm	1
cytoplasmic ubiquitin ligase complex	1
transcription elongation factor complex	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELOB	RBX1	P62877	999
ELOB	CUL2	Q13617	999
ELOB	ELOC	Q15369	999
ELOB	CUL5	Q93034	998
ELOB	VHL	P40337	997
ELOB	RNF7	Q9UBF6	997
ELOB	CBFB	Q13951	994
ELOB	CISH	Q9NSE2	984
ELOB	NEDD8	Q15843	980
ELOB	SOCS1	O15524	973
ELOB	HIF1A	Q16665	972
ELOB	ELOA2	Q8IYF1	966
ELOB	ELOA	Q14241	958
ELOB	CUL1	Q13616	951
ELOB	SKP1	P34991	920

IntAct

265 interactions, top by confidence:

A	B	Type	Score
ELOB	VHL	psi-mi:“MI:0915”(physical association)	0.960
ELOC	ELOB	psi-mi:“MI:0915”(physical association)	0.950
ELOB	ELOC	psi-mi:“MI:0915”(physical association)	0.950
ELOB	ELOC	psi-mi:“MI:0914”(association)	0.950
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
VHL	ELOC	psi-mi:“MI:0914”(association)	0.920
VHL	ELOC	psi-mi:“MI:0915”(physical association)	0.920
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
PRAME	CUL2	psi-mi:“MI:0914”(association)	0.830
KLHDC3	CUL2	psi-mi:“MI:0914”(association)	0.770
PRAME	ELOC	psi-mi:“MI:0914”(association)	0.740
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
NRBP1	TSC22D2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710

BioGRID (715): TCEB2 (Co-purification), TCEB2 (Two-hybrid), TCEB2 (Reconstituted Complex), TCEB2 (Affinity Capture-Western), vif (Co-purification), TCEB2 (Co-purification), TCEB2 (Co-purification), TCEB2 (Co-purification), TCEB2 (Affinity Capture-Western), TCEB2 (Two-hybrid), TCEB2 (Affinity Capture-Western), TCEB2 (Affinity Capture-MS), TCEB2 (Affinity Capture-Western), TCEB2 (Affinity Capture-Western), AP1S1 (Co-fractionation)

ESM2 similar proteins: A0A0E0SC50, A1CTJ1, A1D4X8, A1DMW6, A2X052, A4D9P4, A4RN19, A6RA46, A7EAE5, A7EGK5, A7KAM3, B4FTR7, B8AK78, F7W503, O35954, O94817, P0CM28, P0CM29, P49842, P62869, P62870, Q01317, Q0JCC3, Q0UNW1, Q10CI8, Q13367, Q15370, Q1DY54, Q1E8C2, Q2GSG9, Q2TBJ5, Q2UMW6, Q2URI8, Q3T0W7, Q42713, Q43307, Q4WKD7, Q51P78, Q5BCH0, Q5R7W1

Diamond homologs: P62869, P62870, Q15370

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ELOB	“form complex”	VCB-Cul2	binding
ELOB	“form complex”	“Elongin E3-Cul-5”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 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
Inactivation of CSF3 (G-CSF) signaling	6	20.4×	5e-05
DNA Damage Recognition in GG-NER	9	19.9×	1e-07
Formation of TC-NER Pre-Incision Complex	11	18.0×	4e-09
Recognition of DNA damage by PCNA-containing replication complex	6	17.7×	9e-05
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	7	14.4×	6e-05
Neddylation	36	13.2×	6e-28
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	8	12.2×	4e-05
Vif-mediated degradation of APOBEC3G	6	11.8×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
ubiquitin-dependent protein catabolic process via the C-end degron rule pathway	8	58.7×	8e-11
protein neddylation	9	41.3×	1e-10
regulation of protein neddylation	6	36.7×	2e-06
intrinsic apoptotic signaling pathway	6	14.1×	5e-04
protein ubiquitination	37	10.0×	1e-23
cellular response to UV	5	9.7×	9e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	28	9.6×	5e-17
positive regulation of protein catabolic process	6	8.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

743 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2771992:A:AC	donor_gain	1.0000
16:2771993:C:CC	donor_gain	1.0000
16:2776988:CCCA:C	donor_loss	1.0000
16:2776989:CCA:C	donor_loss	1.0000
16:2776990:CACCT:C	donor_loss	1.0000
16:2776991:ACCTT:A	donor_loss	1.0000
16:2776992:C:A	donor_loss	1.0000
16:2777124:CGTC:C	acceptor_gain	1.0000
16:2775445:TCTCA:T	donor_loss	0.9900
16:2775446:CTCA:C	donor_loss	0.9900
16:2775447:T:TA	donor_loss	0.9900
16:2775448:C:CA	donor_loss	0.9900
16:2775449:A:AT	donor_loss	0.9900
16:2775450:CCT:C	donor_loss	0.9900
16:2775557:C:CC	acceptor_gain	0.9900
16:2776991:A:AC	donor_gain	0.9900
16:2776992:C:CC	donor_gain	0.9900
16:2771988:C:A	donor_gain	0.9800
16:2772101:ATCT:A	acceptor_loss	0.9800
16:2772102:TCTGT:T	acceptor_loss	0.9800
16:2772103:C:CA	acceptor_loss	0.9800
16:2772103:C:CC	acceptor_gain	0.9800
16:2772104:T:G	acceptor_loss	0.9800
16:2775443:CCTCT:C	donor_loss	0.9800
16:2775444:CTCTC:C	donor_loss	0.9800
16:2775453:G:A	donor_gain	0.9800
16:2775553:CATC:C	acceptor_gain	0.9800
16:2775554:ATCCT:A	acceptor_loss	0.9800
16:2775555:TC:T	acceptor_gain	0.9800
16:2775555:TCC:T	acceptor_loss	0.9800

AlphaMissense

775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2772039:A:G	M103T	1.000
16:2772051:A:T	L99Q	1.000
16:2775465:A:G	L77P	1.000
16:2775480:G:T	P72Q	1.000
16:2775495:G:T	A67E	1.000
16:2775510:A:G	F62S	1.000
16:2775525:A:T	L57Q	1.000
16:2777039:A:T	V31D	1.000
16:2777047:C:A	K28N	1.000
16:2777047:C:G	K28N	1.000
16:2777051:A:G	L27P	1.000
16:2777086:G:C	F15L	1.000
16:2777086:G:T	F15L	1.000
16:2777087:A:G	F15S	1.000
16:2777088:A:G	F15L	1.000
16:2777111:A:T	I7N	1.000
16:2777117:A:G	L5P	1.000
16:2777119:G:C	F4L	1.000
16:2777119:G:T	F4L	1.000
16:2777121:A:G	F4L	1.000
16:2772038:C:A	M103I	0.999
16:2772038:C:G	M103I	0.999
16:2772038:C:T	M103I	0.999
16:2772039:A:T	M103K	0.999
16:2772048:G:T	P100H	0.999
16:2772049:G:A	P100S	0.999
16:2772049:G:T	P100T	0.999
16:2775465:A:T	L77Q	0.999
16:2775468:C:T	G76E	0.999
16:2775471:A:T	V75E	0.999

dbSNP variants (sampled 300 via entrez): RS1000338801 (16:2772363 C>A,T), RS1000375926 (16:2777447 T>A,C), RS1000705525 (16:2771078 G>C,T), RS1000721371 (16:2774875 G>A), RS1001265857 (16:2773008 C>T), RS1001266048 (16:2777469 C>G,T), RS1001316834 (16:2777375 C>G,T), RS1001316889 (16:2772827 C>G), RS1001427395 (16:2777934 T>C,G), RS1001898321 (16:2777703 G>C), RS1002168890 (16:2774219 G>A), RS1002266819 (16:2778463 C>G), RS1002667824 (16:2772433 T>C), RS1002720552 (16:2776897 C>T), RS1002782728 (16:2772614 G>A)

Disease associations

OMIM: gene MIM:600787 | 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
GCST004624_163	Sum eosinophil basophil counts	5.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0005090	basophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL3259468 (SINGLE PROTEIN), CHEMBL3301400 (PROTEIN COMPLEX), CHEMBL4296117 (PROTEIN COMPLEX), CHEMBL4296148 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296149 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296150 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169077 (PROTEIN-PROTEIN INTERACTION)

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

Binding affinities (BindingDB)

3 measured of 4 human assays (4 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
8-(3,5-difluoro-2-pyridinyl)-N-[5-[[5-[(2S)-1-[(2R,4R)-4-hydroxy-2-[4-methyl-4-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-5-oxo-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-1,2-oxazol-3-yl]oxy]pentyl]-15-methyl-4-(methylsulfonylmethyl)-14-oxo-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaene-5-carboxamide	IC50	795 nM	US-11242344: (4-hydroxypyrrolidin-2-yl)-heterocyclic compounds and methods of use thereof
8-(3,5-difluoro-2-pyridinyl)-N-[5-[[5-[(2R)-1-[(4R)-4-hydroxy-2-[(4S)-4-methyl-4-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-5-oxo-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-1,2-oxazol-3-yl]oxy]pentyl]-15-methyl-4-(methylsulfonylmethyl)-14-oxo-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaene-5-carboxamide	IC50	16900 nM	US-11242344: (4-hydroxypyrrolidin-2-yl)-heterocyclic compounds and methods of use thereof
4-(3,5-difluoropyridin-2-yl)-N-(11-(((2S)-1-((4R)-4-hydroxy-2-((S)-5-methyl-5-(4-(4-methylthiazol-5-yl)phenyl)-4-oxo-4,5-dihydro-1H-imidazol-2-yl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-11-oxoundecyl)-10-methyl-7-((methylsulfonyl)methyl)-11-oxo-3,4,10,11-tetrahydro-1H-1,4,10-triazadibenzo[cd,f]azulene-6-carboxamide (2 Single Diastereomers)	IC50	255000 nM	US-11242344: (4-hydroxypyrrolidin-2-yl)-heterocyclic compounds and methods of use thereof

ChEMBL bioactivities

241 potent at pChembl≥5 of 320 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	Kd	5	nM	CHEMBL4244103
8.17	Kd	6.7	nM	CHEMBL4241500
8.17	IC50	6.8	nM	CHEMBL5184620
8.05	Kd	9	nM	CHEMBL4226570
7.82	Kd	15	nM	CHEMBL4227226
7.80	Kd	16	nM	CHEMBL4225470
7.62	Kd	24	nM	CHEMBL4225470
7.62	Kd	24	nM	CHEMBL5274606
7.60	Kd	25	nM	CHEMBL5421220
7.58	Kd	26	nM	CHEMBL4227158
7.58	Kd	26	nM	CHEMBL5182441
7.57	Kd	27	nM	CHEMBL5182441
7.53	Kd	29.3	nM	CHEMBL6035425
7.47	Kd	34	nM	CHEMBL5425050
7.47	Kd	34	nM	CHEMBL5592905
7.46	Kd	35	nM	CHEMBL5182441
7.43	Kd	37	nM	CHEMBL5421220
7.43	Kd	37	nM	CHEMBL5595966
7.41	Ki	39	nM	CHEMBL4740486
7.39	Kd	41	nM	CHEMBL5405990
7.39	Kd	41	nM	CHEMBL5403921
7.36	Kd	44	nM	CHEMBL4225470
7.36	Kd	44	nM	CHEMBL5425778
7.36	Kd	43.8	nM	CHEMBL6035425
7.35	Kd	45	nM	CHEMBL5398197
7.28	Kd	52	nM	CHEMBL4225537
7.28	Kd	53	nM	CHEMBL5403921
7.25	Kd	56	nM	CHEMBL5205396
7.22	Kd	60	nM	CHEMBL5274502
7.21	Kd	62	nM	CHEMBL5592812
7.20	Kd	63	nM	CHEMBL5425778
7.20	IC50	62.8	nM	CHEMBL6063790
7.18	Kd	66	nM	CHEMBL5412800
7.16	Kd	69	nM	CHEMBL4226570
7.16	Kd	70	nM	CHEMBL5274502
7.15	Ki	71	nM	CHEMBL5176799
7.14	Kd	73	nM	CHEMBL4227226
7.14	Kd	73	nM	CHEMBL5398197
7.14	Kd	72	nM	CHEMBL5422221
7.10	Kd	80	nM	CHEMBL4225537
7.10	Kd	80	nM	CHEMBL5422221
7.08	Kd	83	nM	CHEMBL5274502
7.07	Kd	86	nM	CHEMBL5416084
7.06	Kd	87	nM	CHEMBL5274502
7.05	Kd	90	nM	CHEMBL4225470
7.05	Kd	90	nM	CHEMBL4225537
7.04	Ki	91	nM	CHEMBL4226570
7.01	Kd	97	nM	CHEMBL4228950
7.01	Kd	98	nM	CHEMBL5274606
7.01	Kd	97	nM	CHEMBL5423283

PubChem BioAssay actives

184 with measured affinity, of 384 total; 50 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-pyrrol-1-ylphenyl)methanol	1398315: Binding affinity to N-terminal His6 tagged VHL (54 to 213 residues)/ELoC (17 to 112 residues)/EloB (1 to 120 residues) (unknown origin) complex expressed in Escherichia coli BL21(DE3) assessed as dissociation constant by ITC method	kd	0.0050	uM
6-chloro-2,3-dihydrothiochromen-4-one	1398315: Binding affinity to N-terminal His6 tagged VHL (54 to 213 residues)/ELoC (17 to 112 residues)/EloB (1 to 120 residues) (unknown origin) complex expressed in Escherichia coli BL21(DE3) assessed as dissociation constant by ITC method	kd	0.0067	uM
(2S,4R)-1-[(2S)-2-[[2-[4-[4-[3-[2,6-difluoro-3-(propylsulfonylamino)benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]phenyl]piperazin-1-yl]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2119304: Inhibition of 6xHis-tagged VHL (1 to 213 residues)/Elongin B/Elogin C (unknown origin) expressed in Escherichia coli BL21 cells by fluorescence polarization assay	ic50	0.0068	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387966: Induction of interaction of N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) co-expressed in Escherichia coli BL21 (DE3) with recombinant human Brd4 BD2 assessed as VCB/BRD4/compound ternary complex formation by isothermal titration calorimetry-based assay	kd	0.0090	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387966: Induction of interaction of N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) co-expressed in Escherichia coli BL21 (DE3) with recombinant human Brd4 BD2 assessed as VCB/BRD4/compound ternary complex formation by isothermal titration calorimetry-based assay	kd	0.0150	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.0160	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1960422: Binding affinity to 6His-tagged human VHL/ElonginC/ElonginB expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant using FAM-DEALAHypYIPMDDDFQLRSF peptide as substrate by fluorescence polarisation	kd	0.0240	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0250	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387966: Induction of interaction of N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) co-expressed in Escherichia coli BL21 (DE3) with recombinant human Brd4 BD2 assessed as VCB/BRD4/compound ternary complex formation by isothermal titration calorimetry-based assay	kd	0.0260	uM
(2S,4R)-N-[[2-[5-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]pentoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1960409: Binding affinity to 6His-tagged human VHL/ElonginC/ElonginB expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by ITC analysis	kd	0.0260	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[5-fluoro-2-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0340	uM
[4-[[1-[5-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]pentyl]triazol-4-yl]methoxy]phenyl]methyl N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.0340	uM
sodium (2S)-1-hydroxy-2-[[(2S)-2-[[4-[[1-[5-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]pentyl]triazol-4-yl]methoxy]phenyl]methoxycarbonylamino]-4-methylpentanoyl]amino]-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.0370	uM
(2S,4R)-4-hydroxy-1-[(2S)-2-[[2-[2-[2-[2-[2-[2-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1853529: Displacement of (2S,4R)-N-(4-bromobenzyl)-4-hydroxy-1-(3,3,3-trifluoropropanoyl)pyrrolidine-2-carboxamide from dual VBC E3 ligase (unknown origin) ternary complex assessed as inhibition constant by 19F NMR assay	ki	0.0390	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0410	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[5-fluoro-2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0410	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[5-fluoro-2-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0440	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0450	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.0520	uM
(2S,4R)-1-[(2S)-2-[9-[4-[6-chloro-2-(2,6-diazaspiro[3.3]heptan-2-yl)-1-[(4-fluoro-3,5-dimethylphenyl)methyl]benzimidazol-4-yl]piperazin-1-yl]nonanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	1903595: Binding affinity to VCB E3 ligase (unknown origin) assessed as binary equilibrium dissociation constant by surface plasmon resonance analysis	kd	0.0560	uM
(2S,4R)-N-[[2-[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1960424: Co-operative binding affinity to 6His-tagged human VHL/ElonginC/ElonginB expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant in the presence of BRD9-BD as complex with compound using FAM-DEALAHypYIPMDDDFQLRSF peptide as substrate by fluorescence polarization assay	kd	0.0600	uM
[4-[[1-[5-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]pentyl]triazol-4-yl]methoxy]phenyl]methyl N-[(2S)-1-[[(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.0620	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0660	uM
(2R,3S,4S)-1-[(2S)-2-[[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1853501: Displacement of (2S,4R)-N-(4-bromobenzyl)-4-hydroxy-1-(3,3,3-trifluoropropanoyl)pyrrolidine-2-carboxamide from BRD4 bromodomain 2/VBC E3 ligase (unknown origin) ternary complex assessed as inhibition constant by 19F NMR assay	ki	0.0710	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[5-fluoro-2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0720	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.0860	uM
(2S,4R)-1-[(2S)-2-[(1-acetylcyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.0970	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.0970	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[[4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387965: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay	kd	0.1050	uM
(2S,4R)-4-hydroxy-1-[(2S)-2-[(2-hydroxyacetyl)amino]-3,3-dimethylbutanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.1050	uM
(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.1070	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[2-[[4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387965: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay	kd	0.1090	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[[4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoyl]amino]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387965: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay	kd	0.1160	uM
2-cyclopentyl-4-[7-[10-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-10-oxodecoxy]quinazolin-4-yl]benzoic acid	2023220: Binding affinity to N-terminal 6 his tagged VHL (54 to 213 residues)/truncated ElonginC (17 to 122 residues) /full length ElonginB (unknown origin) expressed in Escherichia coli assessed as dissociation constant measured upto 300 secs by SPR analysis	kd	0.1300	uM
(2S,4R)-1-[(2S)-2-(cyclopropanecarbonylamino)-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.1320	uM
(2S,4R)-1-[(2S)-2-[(1-acetamidocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.1380	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[3-fluoro-2-hydroxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1410	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1490	uM
(2S,4R)-1-[(2R)-3-[[4-[[4-[4-[[5-chloro-4-(methylamino)pyrimidin-2-yl]amino]-3-methoxybenzoyl]piperazin-1-yl]methyl]cyclohexyl]methylsulfanyl]-2-[(1-fluorocyclopropanecarbonyl)amino]-3-methylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2120188: Binding affinity to VHL/Elongin C/Elogin B (unknown origin) using FAM-DEALA-Hyp-YIPMDDDFQLRSF as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1600	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[3-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1630	uM
(2S,4R)-1-[(2R)-2-[(1-fluorocyclopropanecarbonyl)amino]-3-methyl-3-[[4-(morpholin-4-ylmethyl)cyclohexyl]methylsulfanyl]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2120195: Binding affinity to VHL/Elongin C/Elogin B (unknown origin) assessed as dissociation constant at 20 uM by ITC analysis	kd	0.1650	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[2-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1830	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1860	uM
(2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.1890	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-[(2,2,2-trichloroacetyl)amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388318: Displacement of FAM-labeled HIF-1alpha peptide from VBC (unknown origin) by fluorescence polarization assay	kd	0.2000	uM
(2S,4R)-1-[(2S)-2-(cyclobutanecarbonylamino)-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.2100	uM
(2S,4R)-N-[[3-chloro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.2200	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-(oxetane-3-carbonylamino)butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.2300	uM
(2R,3R,4S)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014875: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B (1 to 104 residues)/Elongin C (17 to 112 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) cells assessed as dissociation constant by ITC analysis	kd	0.2440	uM
(2S,4R)-N-[[2-chloro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.2450	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	5
Benzo(a)pyrene	decreases expression, decreases methylation	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
versicolorin A	increases expression	1
arsenic trichloride	affects cotreatment, increases abundance, increases expression	1
dinophysistoxin 1	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	decreases expression	1
Copper	affects cotreatment, increases abundance, increases expression	1
Dactinomycin	increases secretion, affects cotreatment	1

ChEMBL screening assays

97 unique, capped per target: 97 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652604	Binding	Binding affinity to human TCEB2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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