CUL1

Summary

CUL1 (cullin 1, HGNC:2551) is a protein-coding gene on chromosome 7q36.1, encoding Cullin-1 (Q13616). Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. It is a selective cancer dependency (DepMap: 84.9% of cell lines).

Enables ubiquitin ligase complex scaffold activity and ubiquitin protein ligase binding activity. Involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; positive regulation of canonical NF-kappaB signal transduction; and protein K48-linked ubiquitination. Located in plasma membrane. Part of Parkin-FBXW7-Cul1 ubiquitin ligase complex and SCF ubiquitin ligase complex.

Source: NCBI Gene 8454 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 47 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 84.9% of screened cell lines
• MANE Select transcript: NM_003592

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2551
Approved symbol	CUL1
Name	cullin 1
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000055130
Ensembl biotype	protein_coding
OMIM	603134
Entrez	8454

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 41 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000325222, ENST00000409469, ENST00000602748, ENST00000655324, ENST00000656001, ENST00000660013, ENST00000660240, ENST00000662132, ENST00000662670, ENST00000662716, ENST00000662975, ENST00000663044, ENST00000663835, ENST00000665936, ENST00000666124, ENST00000671397, ENST00000671421, ENST00000869857, ENST00000869858, ENST00000869859, ENST00000869860, ENST00000869861, ENST00000869862, ENST00000869863, ENST00000869864, ENST00000869865, ENST00000869866, ENST00000934511, ENST00000934512, ENST00000934513, ENST00000934514, ENST00000934515, ENST00000934516, ENST00000934517, ENST00000934518, ENST00000934519, ENST00000934520, ENST00000934521, ENST00000971843, ENST00000971844, ENST00000971845, ENST00000971846, ENST00000971847, ENST00000971848, ENST00000971849, ENST00000971850

RefSeq mRNA: 6 — MANE Select: NM_003592 NM_001370660, NM_001370661, NM_001370662, NM_001370663, NM_001370664, NM_003592

CCDS: CCDS34772

Canonical transcript exons

ENST00000325222 — 22 exons

Exon	Start	End
ENSE00000466125	148759548	148759638
ENSE00000729482	148756983	148757150
ENSE00000729503	148760333	148760496
ENSE00000872301	148753976	148754150
ENSE00000909624	148729962	148730262
ENSE00000909625	148759304	148759354
ENSE00000909626	148766561	148766723
ENSE00000909627	148767619	148767749
ENSE00000909628	148783783	148783890
ENSE00000909629	148783971	148784077
ENSE00000909630	148786551	148786599
ENSE00000909631	148786989	148787120
ENSE00000909632	148788557	148788674
ENSE00000909633	148789750	148789826
ENSE00000909634	148790310	148790441
ENSE00000909635	148792726	148792818
ENSE00000909636	148797812	148797859
ENSE00000909637	148797937	148798019
ENSE00001513479	148698903	148699029
ENSE00002461187	148799275	148799388
ENSE00002526381	148798572	148798677
ENSE00003450823	148800502	148801110

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 97.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.0731 / max 399.7117, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81864	42.0471	1822
81865	1.6136	821
81862	0.2940	136
81867	0.0657	6
81869	0.0246	5
81868	0.0150	4
81866	0.0132	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.74	gold quality
oocyte	CL:0000023	97.13	gold quality
left testis	UBERON:0004533	97.01	gold quality
right testis	UBERON:0004534	96.93	gold quality
ganglionic eminence	UBERON:0004023	96.22	gold quality
sperm	CL:0000019	95.96	gold quality
gastrocnemius	UBERON:0001388	95.81	gold quality
testis	UBERON:0000473	95.80	gold quality
muscle of leg	UBERON:0001383	95.63	gold quality
calcaneal tendon	UBERON:0003701	95.55	gold quality
biceps brachii	UBERON:0001507	95.35	gold quality
ventricular zone	UBERON:0003053	95.15	gold quality
male germ cell	CL:0000015	95.08	gold quality
muscle organ	UBERON:0001630	94.90	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.26	gold quality
cortical plate	UBERON:0005343	94.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.18	gold quality
lower esophagus	UBERON:0013473	94.17	gold quality
adrenal tissue	UBERON:0018303	94.10	gold quality
deltoid	UBERON:0001476	94.04	gold quality
embryo	UBERON:0000922	93.98	gold quality
mucosa of stomach	UBERON:0001199	93.82	gold quality
popliteal artery	UBERON:0002250	93.77	gold quality
tibial artery	UBERON:0007610	93.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.60	gold quality
frontal pole	UBERON:0002795	93.58	gold quality
tendon	UBERON:0000043	93.41	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.25	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.36
E-GEOD-106540	no	421.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

58 targeting CUL1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5680	99.91	69.83	3421
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6762-3P	99.66	66.94	1188

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex (PMID:11961546)
• The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase progression via deneddylation of SCF Cul1. (PMID:11967155)
• Data show that interference with Skp1 function through expression of the Cul1-N252 mutant results in the formation of multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. (PMID:12417738)
• p120(CAND1) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation (PMID:12504025)
• unnedyylated protein binds to CAND1 and regulates the formation of SCF ubiquitin E3 ligase complex (PMID:12504026)
• TIP120A functions as a negative regulator of SCF E3 ubiquitin ligases and may modulate other cullin ligases in a similar fashion. (PMID:12609982)
• results suggest a unique role for NEDD8-specific protease 1(DEN1) in regulating the modification of cullin 1 by Nedd8 protein (PMID:12759363)
• regulation of CUL1 expression may affect the susceptibility of rheumatoid arthritis via altering lymphocyte signal transduction (PMID:15759013)
• CAND1 & COP9 signalosome (CSN), major deneddylase of cullins, bind to unneddylated CUL1 in mutually exclusive way. Binding of CSN to CUL1 required 4 helix bundle in CUL1 C-terminal domain, which was wrapped around by CAND1 in CAND1-CUL1-Rbx1 complex. (PMID:16036220)
• the SCF complex (Skp1/Cul1/F-box protein/Roc1) intervenes in the surveillance of Cdh1 cellular abundance in S-phase (PMID:16123585)
• Results describe the regulation of neddylation and deneddylation of cullin1 by Nedd8 in SCFSkp2 ubiquitin ligase by F-box protein and substrate. (PMID:16861300)
• Cul1 and Cul3, as well as their associated substrate recognition subunits Skp2 and Keap1, respectively, homooligomerize in intact cells, suggesting that cullin-based ligases are dimeric. (PMID:17254749)
• Thiazolidinediones modulate the expression of beta catenin and other cell cycle proteins by targeting CUL1 independently of PPARG. (PMID:17569795)
• CUL1 ECTD (extreme C-terminal domain; spanning the C-terminal 50 amino acids), did not contribute to CUL1’s stable association with ROC1. (PMID:18723677)
• p18-Cyclin E by the Skp1-Cul1-Fbw7 (SCF) complex and its interaction with the Fbw7 protein isoforms can take place independently of phosphorylation of p18-Cyclin E at a C-terminal phosphodegron. (PMID:18784078)
• SCCRO recruits Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin neddylation (PMID:18826954)
• The positive rates of ubiquitin and cul-1 were significantly higher in lung cancer than those in benign lesion tissues of the lung. (PMID:19349673)
• CUL1 may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles. (PMID:19679553)
• Cdc34 binds SCF with nanomolar affinity, the complex is extremely dynamic; these properties are enabled by rapid association driven by electrostatic interactions between the acidic tail of Cdc34 and a basic ‘canyon’ in the Cul1 subunit of SCF. (PMID:19945379)
• The Cul1 expression is significantly correlated with melanoma development at early stages, implying targeting Cul1 may serve as a potential therapy for melanoma. (PMID:20518860)
• Rictor forms a complex with Cullin-1 to promote SGK1 ubiquitination and destruction. (PMID:20832730)
• Cul1 regulates melanoma cell growth and cell cycle progression through degradation of p27 (PMID:20878082)
• Data show that CRN7 interacted with Cullin1 and Roc1 to form a novel SCF-like E3 complex. (PMID:21130766)
• Our data indicated that Cullin1 may be an important marker for human gastric cancer lymph node metastasis and prognosis. (PMID:21190721)
• Association with CUL1 haplotype indicates a possible role of CUL1 variation(s) in rheumatoid arthritis and its response to methotrexate. (PMID:21738080)
• binding of Cul1-Rbx1 to Cul7-Rbx1 is mediated via heterodimerization of Fbxw8 with other F-box proteins which function to recruit substrates into the E3 ligase complex (PMID:21946088)
• Glomulin binds Rbx1 and regulates cullin-1 RING ligase-mediated turnover of Fbw7. (PMID:22405651)
• The Epstein-Barr virus protein BPLF1, is targeted to cullin-RING ubiquitin ligases (CRLs) via the interaction of the conserved helix-2 with helix-23 of cullins, at a site involved in electrostatic interaction with CAND1. (PMID:22474075)
• RBX1-containing cullin-RING ligases can bind glomulin (GLMN), which binds RING-box1’s RING domain, regulating the RBX1-CUL1-containing SCF(FBW7) complex. (PMID:22748924)
• Deconjugation of Nedd8 from Cul1 is directly regulated by Skp1-F-box and substrate, and the COP9 signalosome inhibits deneddylated SCF by a noncatalytic mechanism. (PMID:22767593)
• Skp1-Cul1-F-box ubiquitin ligase (SCF(betaTrCP))-mediated destruction of the ubiquitin-specific protease USP37 during G2-phase promotes mitotic entry (PMID:23027877)
• CUL1 promotes human trophoblast cell invasion and dysregulation of CUL1 expression may be associated with pre-eclampsia. (PMID:23429288)
• Cul1 overexpression is significantly correlated with breast cancer progression and predicts worse survival. Cul1 regulates breast cancer cell proliferation, migration and invasion. (PMID:23592700)
• Studies indicate that in SCFs, Rbx1 serves as the RING-containing enzyme, Cul1 is the Cullin scaffold, and Skp1 is an adaptor, which serves to link the beta-TrCP F-box substrate-specific factor to the rest of the ligase. (PMID:23624913)
• Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein complex. (PMID:24085301)
• By integrating our WES and CN data we identified three mutated putative candidate genes targeted by 7q deletions (CUL1, EZH2 and FLNC), with FLNC positioned within the well-characterized 7q minimally deleted region. (PMID:24349473)
• data suggested that Cullin1 might promote the progression of non-small-cell lung cancer (PMID:24767980)
• In papillary thyroid carcinoma, cytoplasmic expression of Cul1 was correlated with tumor occurrence, N stage and Cyclin D1 expression. Nuclear Cul1 expression was negatively correlated with tumor occurence. (PMID:24819753)
• Our data indicated that Cul1 expression significantly increased in human glioma, and it may be involved in proliferation, migration and invasion of glioma cells. (PMID:25201578)
• We discuss how these results can explain the rapid association of Cdc34 and SCF. (PMID:25425648)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cul1b	ENSDARG00000007691
danio_rerio	cul1a	ENSDARG00000019239
mus_musculus	Cul1	ENSMUSG00000029686
rattus_norvegicus	Cul1	ENSRNOG00000005310
drosophila_melanogaster	Cul1	FBGN0015509
caenorhabditis_elegans		WBGENE00000836
caenorhabditis_elegans		WBGENE00000841

Paralogs (7): CUL3 (ENSG00000036257), CUL2 (ENSG00000108094), CUL4A (ENSG00000139842), CACUL1 (ENSG00000151893), CUL4B (ENSG00000158290), CUL5 (ENSG00000166266), ANAPC2 (ENSG00000176248)

Protein

Protein identifiers

Cullin-1 — Q13616 (reviewed: Q13616)

All UniProt accessions (12): A0A090N7U0, A0A590UJ21, A0A590UJ50, A0A590UJ56, A0A590UJ59, A0A590UJ97, A0A590UJA0, A0A590UJC4, A0A590UJM8, A0A590UJR3, A0A590UK34, Q13616

UniProt curated annotations — full annotation on UniProt →

Function. Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at ‘Lys-21’ and ‘Lys-22’; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. Neddylated CUL1-RBX1 ubiquitinates p53/TP53 recruited by Cul7-RING(FBXW8) complex. SCF(BTRC) directs ‘Lys-48’-linked ubiquitination of UBR2 in the T-cell receptor signaling pathway. The SCF(FBXO31) protein ligase complex specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress.

Subunit / interactions. Component of multiple Cul1-RING E3 ubiquitin-protein ligase complexes commonly known as SCF (SKP1-CUL1-F-box) complexes, consisting of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit. Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Interacts with CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7. Component of the SCF(FBXO31) complex composed of CUL1, SKP1, RBX1 and FBXO31. Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate. Interacts with FBXW8. Interacts with RNF7. Interacts with TRIM21. Interacts with COPS2. Interacts with UBE2M. Identified in a complex with RBX1 and GLMN. Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1. Interacts with COPS9 isoform 2. Interacts with UBXN1. Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination. Interacts with NOTCH2. Part of a complex that contains DCUN1D5, CUL1 and RBX1; this complex is bridged by CUL1. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation. Interacts (via the C-terminal domain) with CUL7; the interaction seems to be mediated by FBXW8; it is likely specific to FBXW8, but not other F-box proteins. Interacts with UBR2, as part of SCF(BTRC) complex; the interaction mediates ‘Lys-48’-linked ubiquitination of UBR2 and is regulated by DUSP22 in the T-cell receptor signaling pathway. (Microbial infection) Interacts with Epstein-Barr virus BPLF1. (Microbial infection) Interacts with Human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBXW7) complex. (Microbial infection) Interacts with vaccinia virus protein C9L. (Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction might facilitate CUL1 recruitment to STAT2, leading to ubiquitination and degradation of the latter.

Tissue specificity. Expressed in lung fibroblasts.

Post-translational modifications. Neddylated; which enhances the ubiquitination activity of SCF. Neddylation prevents binding of the inhibitor CAND1. Neddylation leads to structural rearrangment in the complex that allows interaction between the E2 ubiquitin-conjugating enzyme and the acceptor ubiquitin. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. (Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome.

Domain organisation. The Cullin neddylation domain restrains the RING domain of RBX1 in the E3 ubiquitin-protein ligase complex; this restraint is removed upon neddylation of the cullin.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the cullin family.

RefSeq proteins (6): NP_001357589, NP_001357590, NP_001357591, NP_001357592, NP_001357593, NP_003583* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001373	Cullin_N	Domain
IPR016157	Cullin_CS	Conserved_site
IPR016158	Cullin_homology	Domain
IPR016159	Cullin_repeat-like_dom_sf	Homologous_superfamily
IPR019559	Cullin_neddylation_domain	Domain
IPR036317	Cullin_homology_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045093	Cullin	Family
IPR059120	Cullin-like_AB	Domain

Pfam: PF00888, PF10557, PF26557

UniProt features (64 total): helix 37, strand 13, turn 7, sequence conflict 2, chain 1, domain 1, modified residue 1, cross-link 1, mutagenesis site 1

Structure

Experimental structures (PDB)

48 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3TDU	X-RAY DIFFRACTION	1.5
5V89	X-RAY DIFFRACTION	1.55
3TDZ	X-RAY DIFFRACTION	2
8CAF	X-RAY DIFFRACTION	2.66
7Z8R	ELECTRON MICROSCOPY	2.7
7Z8V	ELECTRON MICROSCOPY	2.7
8OR3	ELECTRON MICROSCOPY	2.9
9QO4	ELECTRON MICROSCOPY	2.95
1LDJ	X-RAY DIFFRACTION	3
4F52	X-RAY DIFFRACTION	3
7Z8T	ELECTRON MICROSCOPY	3
9XZL	ELECTRON MICROSCOPY	3
9EFV	ELECTRON MICROSCOPY	3.03
1LDK	X-RAY DIFFRACTION	3.1
1U6G	X-RAY DIFFRACTION	3.1
7ZBZ	ELECTRON MICROSCOPY	3.1
8OR0	ELECTRON MICROSCOPY	3.1
8UBT	ELECTRON MICROSCOPY	3.1
4P5O	X-RAY DIFFRACTION	3.11
9XZJ	ELECTRON MICROSCOPY	3.13
9EFM	ELECTRON MICROSCOPY	3.16
8OR2	ELECTRON MICROSCOPY	3.2
3RTR	X-RAY DIFFRACTION	3.21
9QO1	ELECTRON MICROSCOPY	3.23
9QO0	ELECTRON MICROSCOPY	3.26
8CDK	ELECTRON MICROSCOPY	3.32
8CDJ	ELECTRON MICROSCOPY	3.4
8VVY	ELECTRON MICROSCOPY	3.49
7ZBW	ELECTRON MICROSCOPY	3.5
7B5N	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13616-F1	89.23	0.72

Antibody-complex structures (SAbDab): 1 — 8CAF

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 (2): 63, 720

Mutagenesis-validated functional residues (1):

Position	Phenotype
1–331	abolishes interaction with cul7-ring(fbxw8) complex; does not disrupt interaction with rbx1.

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1170546	Prolactin receptor signaling
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-202424	Downstream TCR signaling
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2644607	Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5610780	Degradation of GLI1 by the proteasome
R-HSA-5610783	Degradation of GLI2 by the proteasome
R-HSA-5610785	GLI3 is processed to GLI3R by the proteasome
R-HSA-5676590	NIK–>noncanonical NF-kB signaling
R-HSA-5684264	MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-68949	Orc1 removal from chromatin
R-HSA-69231	Cyclin D associated events in G1
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A
R-HSA-8854050	FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-HSA-8939902	Regulation of RUNX2 expression and activity
R-HSA-8951664	Neddylation
R-HSA-9020702	Interleukin-1 signaling
R-HSA-917937	Iron uptake and transport
R-HSA-9604323	Negative regulation of NOTCH4 signaling
R-HSA-9708530	Regulation of BACH1 activity
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer

MSigDB gene sets: 385 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21

GO Biological Process (26): G1/S transition of mitotic cell cycle (GO:0000082), protein monoubiquitination (GO:0006513), cell population proliferation (GO:0008283), animal organ morphogenesis (GO:0009887), protein ubiquitination (GO:0016567), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), cellular response to oxidative stress (GO:0034599), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein K48-linked ubiquitination (GO:0070936), intrinsic apoptotic signaling pathway (GO:0097193), autophagosome assembly (GO:0000045), protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), lysosome organization (GO:0007040), proteasomal protein catabolic process (GO:0010498), negative regulation of autophagy (GO:0010507), positive regulation of autophagy (GO:0010508), protein catabolic process (GO:0030163), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), antiviral innate immune response (GO:0140374), positive regulation of epithelial cell apoptotic process (GO:1904037), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (4): protein-macromolecule adaptor activity (GO:0030674), ubiquitin protein ligase binding (GO:0031625), ubiquitin ligase complex scaffold activity (GO:0160072), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), SCF ubiquitin ligase complex (GO:0019005), cullin-RING ubiquitin ligase complex (GO:0031461), Parkin-FBXW7-Cul1 ubiquitin ligase complex (GO:1990452)

Reactome top-level categories

Rollup of top-20 pathways:

Category	Pathways
Hedgehog ‘off’ state	3
Downstream signaling events of B Cell Receptor (BCR)	1
Cytokine Signaling in Immune system	1
Regulation of APC/C activators between G1/S and early anaphase	1
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Signaling by WNT	1
TCR signaling	1
Signaling by NOTCH1	1
G2/M Transition	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
FBXW7 Mutants and NOTCH1 in Cancer	1
Fc epsilon receptor (FCERI) signaling	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
CLEC7A (Dectin-1) signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	3
cellular anatomical structure	3
apoptotic signaling pathway	2
autophagy	2
regulation of autophagy	2
ubiquitin ligase complex	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cellular process	1
anatomical structure morphogenesis	1
animal organ development	1
protein modification by small protein conjugation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
response to oxidative stress	1
cellular response to chemical stress	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein polyubiquitination	1
intracellular signal transduction	1
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
modification-dependent protein catabolic process	1
programmed cell death	1
execution phase of apoptosis	1
lytic vacuole organization	1
protein catabolic process	1
negative regulation of catabolic process	1
positive regulation of catabolic process	1
macromolecule catabolic process	1
protein metabolic process	1
protein binding	1

Protein interactions and networks

STRING

4928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUL1	RBX1	P62877	999
CUL1	SKP1	P34991	999
CUL1	BTRC	Q9Y297	999
CUL1	SKP2	Q13309	998
CUL1	NEDD8	Q15843	997
CUL1	FBXW7	Q969H0	997
CUL1	RNF7	Q9UBF6	995
CUL1	CAND1	Q86VP6	993
CUL1	HEY1	Q9Y5J3	988
CUL1	CUL4A	Q13619	987
CUL1	ELOC	Q15369	979
CUL1	FBXL5	Q9UKA1	973
CUL1	CDC34	P49427	968
CUL1	CUL3	Q13618	968
CUL1	ACVR1	Q04771	963

IntAct

448 interactions, top by confidence:

A	B	Type	Score
CUL1	RBX1	psi-mi:“MI:0915”(physical association)	0.980
CUL1	RBX1	psi-mi:“MI:0407”(direct interaction)	0.980
RBX1	CUL1	psi-mi:“MI:0407”(direct interaction)	0.980
CUL1	SKP1	psi-mi:“MI:0915”(physical association)	0.960
CUL1	CAND1	psi-mi:“MI:0915”(physical association)	0.960
NEDD8	CUL1	psi-mi:“MI:0407”(direct interaction)	0.960
CUL1	NEDD8	psi-mi:“MI:0195”(covalent binding)	0.960
CUL1	NEDD8	psi-mi:“MI:0915”(physical association)	0.960
CUL1	NEDD8	psi-mi:“MI:0407”(direct interaction)	0.960
CUL1	CAND1	psi-mi:“MI:0407”(direct interaction)	0.960
CAND1	CUL1	psi-mi:“MI:0914”(association)	0.960
CAND1	CUL1	psi-mi:“MI:0915”(physical association)	0.960
CUL1	CAND1	psi-mi:“MI:0914”(association)	0.960
CUL1	SKP1	psi-mi:“MI:0914”(association)	0.960
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
FBXW11	SKP1	psi-mi:“MI:0914”(association)	0.940
FBXW11	SKP1	psi-mi:“MI:0915”(physical association)	0.940
FBXO4	SKP1	psi-mi:“MI:0914”(association)	0.930
FBXW11	CUL1	psi-mi:“MI:0915”(physical association)	0.930

BioGRID (1966): CUL1 (Reconstituted Complex), CUL1 (Biochemical Activity), CUL1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL1 (Biochemical Activity), CUL1 (Biochemical Activity), RBX1 (Reconstituted Complex), CUL1 (Biochemical Activity), CUL1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN39, A1C4A5, A1DBH2, A2R5J1, B0Y9Q4, D2SW95, F1QGH9, O13396, O24617, P21271, P23514, P33121, P35249, P43246, P43247, P46735, P53041, P53042, P53618, P54275, P70569, Q00647, Q05096, Q06364, Q0CEX5, Q0DBU5, Q13616, Q1DLP2, Q2U919, Q2US45, Q3MHE4, Q4WC55, Q5R4A0, Q5R4G6, Q5R922, Q5XXB5, Q5ZIA5, Q60676, Q66HV4, Q7ZVX6

Diamond homologs: A2A432, A4IHP4, B5DF89, O13790, O14122, O60999, P0CH31, Q09760, Q13616, Q13618, Q13619, Q13620, Q17391, Q17392, Q24311, Q3TCH7, Q54CS2, Q54NZ5, Q54XF7, Q5R4G6, Q5ZC88, Q6DE95, Q6GPF3, Q8LGH4, Q94AH6, Q9C9L0, Q9JLV5, Q9SRZ0, Q9WTX6, Q9ZVH4, Q12018, Q13617, Q17389, Q17390, Q21346, Q5RCF3, Q9D4H8, Q9SZ75, Q9XZJ3, Q23639

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CUL1	“down-regulates quantity by destabilization”	CDKN1B	ubiquitination
MYC	“up-regulates quantity by expression”	CUL1	“transcriptional regulation”
NAE	“up-regulates activity”	CUL1	neddylation
CUL1	“form complex”	SCF-SKP2	binding
CUL1	“form complex”	SCF-FBW7	binding
CUL1	“up-regulates activity”	ARIH1	binding
CUL1	“up-regulates activity”	RNF7	binding
CUL1	“form complex”	SCF-FBW2	binding
CUL1	“form complex”	“Cullin 1-RBX1-Skp1”	binding
CUL1	“down-regulates quantity by destabilization”	CTNNB1	ubiquitination
CUL1	“form complex”	SCF-betaTRCP	binding
SKP1	up-regulates	CUL1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 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
Signaling by PTK6	5	26.4×	8e-05
Signaling by Non-Receptor Tyrosine Kinases	5	26.4×	8e-05
Aberrant regulation of mitotic cell cycle due to RB1 defects	5	19.8×	2e-04
Neddylation	43	19.8×	8e-43
G1 Phase	5	19.1×	2e-04
Diseases of mitotic cell cycle	5	19.1×	2e-04
Switching of origins to a post-replicative state	6	17.5×	8e-05
Iron uptake and transport	5	16.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	20	57.2×	4e-28
protein neddylation	10	53.6×	3e-13
regulation of protein neddylation	6	42.9×	5e-07
positive regulation of protein ubiquitination	10	16.3×	9e-08
post-translational protein modification	5	16.1×	9e-04
G1/S transition of mitotic cell cycle	10	15.3×	2e-07
protein destabilization	6	13.3×	4e-04
protein K48-linked ubiquitination	9	11.6×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3943 predictions. Top by Δscore:

Variant	Effect	Δscore
7:148729956:CCTCA:C	acceptor_loss	1.0000
7:148729957:CTCAG:C	acceptor_loss	1.0000
7:148729958:TCAGG:T	acceptor_loss	1.0000
7:148729959:CAGGT:C	acceptor_loss	1.0000
7:148729961:G:GT	acceptor_loss	1.0000
7:148730245:A:G	donor_gain	1.0000
7:148753974:A:G	acceptor_gain	1.0000
7:148753975:G:GG	acceptor_gain	1.0000
7:148753975:GTCAT:G	acceptor_gain	1.0000
7:148753998:A:AG	acceptor_gain	1.0000
7:148753999:G:GG	acceptor_gain	1.0000
7:148753999:GT:G	acceptor_gain	1.0000
7:148754147:TAAGG:T	donor_loss	1.0000
7:148754148:AAGG:A	donor_loss	1.0000
7:148754149:AGGTA:A	donor_loss	1.0000
7:148754150:GGT:G	donor_loss	1.0000
7:148754151:G:GC	donor_loss	1.0000
7:148754152:T:G	donor_loss	1.0000
7:148756978:TTTA:T	acceptor_loss	1.0000
7:148756981:A:AG	acceptor_gain	1.0000
7:148756981:AG:A	acceptor_gain	1.0000
7:148756982:G:A	acceptor_loss	1.0000
7:148756982:G:GA	acceptor_gain	1.0000
7:148756982:GG:G	acceptor_gain	1.0000
7:148756982:GGAT:G	acceptor_gain	1.0000
7:148757131:G:GT	donor_gain	1.0000
7:148757146:ATTCG:A	donor_gain	1.0000
7:148757147:TTCG:T	donor_gain	1.0000
7:148757148:TCG:T	donor_gain	1.0000
7:148757149:CG:C	donor_gain	1.0000

AlphaMissense

5137 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:148730183:T:A	W21R	1.000
7:148730183:T:C	W21R	1.000
7:148730184:G:C	W21S	1.000
7:148730185:G:C	W21C	1.000
7:148730185:G:T	W21C	1.000
7:148730193:T:A	L24H	1.000
7:148730193:T:C	L24P	1.000
7:148730201:G:C	G27R	1.000
7:148730202:G:A	G27D	1.000
7:148730246:T:C	Y42H	1.000
7:148730246:T:G	Y42D	1.000
7:148730256:T:C	L45P	1.000
7:148730262:C:T	T47I	1.000
7:148753981:T:A	V49D	1.000
7:148753983:T:G	Y50D	1.000
7:148753989:T:G	Y52D	1.000
7:148753992:T:C	C53R	1.000
7:148753993:G:A	C53Y	1.000
7:148753993:G:T	C53F	1.000
7:148753994:T:G	C53W	1.000
7:148754086:T:A	V84D	1.000
7:148754088:G:A	G85S	1.000
7:148754088:G:C	G85R	1.000
7:148754088:G:T	G85C	1.000
7:148754089:G:A	G85D	1.000
7:148754089:G:T	G85V	1.000
7:148754098:T:C	L88S	1.000
7:148754100:T:G	Y89D	1.000
7:148754110:T:C	L92P	1.000
7:148757014:T:C	L116P	1.000

dbSNP variants (sampled 300 via entrez): RS1000035239 (7:148702938 A>G), RS1000099201 (7:148742238 G>A), RS1000153860 (7:148736875 G>A), RS1000187366 (7:148698144 T>C), RS1000206601 (7:148737102 A>G), RS1000207489 (7:148727209 G>A), RS1000287913 (7:148771765 G>A), RS1000357843 (7:148800654 G>A), RS1000358700 (7:148758094 T>G), RS1000367814 (7:148765107 C>A,T), RS1000429740 (7:148751659 T>C), RS1000447978 (7:148742039 C>T), RS1000475822 (7:148699034 G>T), RS1000476279 (7:148777629 C>G), RS1000546740 (7:148753600 C>T)

Disease associations

OMIM: gene MIM:603134 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004131_11	Inflammatory bowel disease	3.000000e-10
GCST004132_80	Crohn’s disease	6.000000e-07
GCST006617_5	Uterine fibroid size (maximum volume)	4.000000e-07
GCST009391_1940	Metabolite levels	5.000000e-06
GCST90002390_230	Mean corpuscular hemoglobin	1.000000e-15
GCST90002392_340	Mean corpuscular volume	3.000000e-20

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009410	uterine fibroid measurement
EFO:0009766	asparagine measurement
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3758068 (SINGLE PROTEIN), CHEMBL3885547 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523655 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.35	Kd	0.443	nM	CHEMBL3752910
9.35	ED50	0.443	nM	CHEMBL3752910
8.29	Kd	5.097	nM	CHEMBL5653589
8.29	ED50	5.097	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 26 total; 2 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-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148180: Binding affinity to human CUL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0004	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148180: Binding affinity to human CUL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0051	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	5
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
methylselenic acid	increases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
isobutyl alcohol	increases abundance, increases expression, affects cotreatment	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
tetraarsenic tetrasulfide	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Imatinib Mesylate	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Glyphosate	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418844	Binding	Inhibition of CUL1 in human U20S cells assessed as reduction in TNF-alpha-induced IkappaB-alpha degradation at 50 uM incubated for 2 hrs followed by TNFalpha stimulation for 15 mins by Western blotting analysis	Inhibitors of crl4 ubiquitin ligase and uses thereof

Clinical trials (associated diseases)

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