SKP1

Summary

SKP1 (S-phase kinase associated protein 1, HGNC:10899) is a protein-coding gene on chromosome 5q31.1, encoding S-phase kinase-associated protein 1 (P63208). Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

This gene encodes a component of SCF complexes, which are composed of this protein, cullin 1, a ring-box protein, and one member of the F-box family of proteins. This protein binds directly to the F-box motif found in F-box proteins. SCF complexes are involved in the regulated ubiquitination of specific protein substrates, which targets them for degradation by the proteosome. Specific F-box proteins recognize different target protein(s), and many specific SCF substrates have been identified including regulators of cell cycle progression and development. Studies have also characterized the protein as an RNA polymerase II elongation factor. Alternative splicing of this gene results in two transcript variants. A related pseudogene has been identified on chromosome 7.

Source: NCBI Gene 6500 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 13 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_170679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10899
Approved symbol	SKP1
Name	S-phase kinase associated protein 1
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	EMC19, OCP2, TCEB1L, MGC34403, OCP-II, p19A
Ensembl gene	ENSG00000113558
Ensembl biotype	protein_coding
OMIM	601434
Entrez	6500

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000328392, ENST00000353411, ENST00000517625, ENST00000517691, ENST00000519054, ENST00000519321, ENST00000520417, ENST00000521216, ENST00000522552, ENST00000522855, ENST00000523359, ENST00000523966, ENST00000524288, ENST00000880996, ENST00000880997, ENST00000880998, ENST00000880999, ENST00000881000, ENST00000934648, ENST00000934649, ENST00000934650, ENST00000934651, ENST00000934652, ENST00000934653, ENST00000934654, ENST00000968700, ENST00000968701

RefSeq mRNA: 2 — MANE Select: NM_170679 NM_006930, NM_170679

CCDS: CCDS4171, CCDS4172

Canonical transcript exons

ENST00000353411 — 6 exons

Exon	Start	End
ENSE00001291683	134148935	134157768
ENSE00003480233	134158455	134158595
ENSE00003524683	134167170	134167243
ENSE00003597727	134173926	134174022
ENSE00003652195	134160987	134161130
ENSE00003899662	134176855	134176950

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 397.2885 / max 6891.6965, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63445	343.1766	1827
63446	41.2887	1815
63447	12.3488	1783
63448	0.2921	109
63444	0.1823	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	99.76	gold quality
cerebellar hemisphere	UBERON:0002245	99.71	gold quality
right frontal lobe	UBERON:0002810	99.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.71	gold quality
pons	UBERON:0000988	99.70	gold quality
right testis	UBERON:0004534	99.70	gold quality
cerebellar cortex	UBERON:0002129	99.69	gold quality
left testis	UBERON:0004533	99.67	gold quality
cortical plate	UBERON:0005343	99.66	gold quality
cerebellum	UBERON:0002037	99.63	gold quality
ganglionic eminence	UBERON:0004023	99.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.62	gold quality
right adrenal gland	UBERON:0001233	99.61	gold quality
descending thoracic aorta	UBERON:0002345	99.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.61	gold quality
right adrenal gland cortex	UBERON:0035827	99.61	gold quality
ventricular zone	UBERON:0003053	99.60	gold quality
frontal cortex	UBERON:0001870	99.59	gold quality
adenohypophysis	UBERON:0002196	99.59	gold quality
left adrenal gland	UBERON:0001234	99.58	gold quality
right coronary artery	UBERON:0001625	99.58	gold quality
popliteal artery	UBERON:0002250	99.58	gold quality
tibial artery	UBERON:0007610	99.58	gold quality
islet of Langerhans	UBERON:0000006	99.57	gold quality
aorta	UBERON:0000947	99.57	gold quality
ascending aorta	UBERON:0001496	99.57	gold quality
thoracic aorta	UBERON:0001515	99.57	gold quality
left coronary artery	UBERON:0001626	99.57	gold quality
neocortex	UBERON:0001950	99.57	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	23.24
E-MTAB-8410	yes	20.32
E-CURD-88	yes	19.29
E-CURD-46	yes	16.82
E-CURD-122	yes	9.19
E-HCAD-9	yes	9.14
E-MTAB-7316	yes	8.28
E-MTAB-7249	no	11190.11
E-MTAB-6819	no	1814.23
E-MTAB-10287	no	48.48
E-HCAD-10	no	44.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, RUNX1

miRNA regulators (miRDB)

79 targeting SKP1, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 37)

• OCP2 immunoreactivity is evident at a prenatal age of 11 weeks, peaks in expression at the onset of cochlear function at 20 weeks and achieves adult-like patterns of distribution just prior to histological maturation at 28 weeks. (PMID:12117534)
• 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)
• SKP1 complexes with beta-TrCP1 and beta catenin. The destruction motif binding and lysine specificity of the SCF (beta-TrCP1) ubiquitin ligase were studied. (PMID:12820959)
• specific Elongin C and Skp1 sequences determine Cullin selection (PMID:15280393)
• the SCF complex (Skp1/Cul1/F-box protein/Roc1) intervenes in the surveillance of Cdh1 cellular abundance in S-phase (PMID:16123585)
• Treatment of cells with okadaic acid, a potent inhibitor of PP2A, results in various hyperphosphorylated forms of hSecurin which are extremely unstable, due to the action of the Skp1/Cul1/F-box protein complex ubiquitin ligase. (PMID:16705156)
• Thiazolidinediones modulate the expression of beta catenin and other cell cycle proteins by targeting SKP1 independently of PPARG. (PMID:17569795)
• 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)
• The authors report that M-T5 can bind Akt and the host SCF complex (via Skp1) simultaneously in myxoma virus-infected cells. (PMID:19776120)
• Skp1 and Fbg3 were co-expressed in E. coli. The plate-shaped crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 34.1, b = 76.6, c = 193.9 A and one molecule per asymmetric unit. (PMID:20057081)
• These findings support a novel role for Hsp90-Sgt1 chaperones in ensuring the fidelity of Mis12 multiprotein complex assembly. (PMID:20404110)
• The siRNA-induced suppression of Skp2 increased p27 expression, decreased cellular proliferation, and increased apoptosis in human laryngeal carcinoma cells (PMID:20668394)
• Skp1 binding prevented Fbxo7 from contacting CRM1. (PMID:21378169)
• Data demonstrate that PFKFB3 is essential for cell division and that it is regulated by APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP. (PMID:21402913)
• These observations suggest that Skp1 plays an important role in stabilizing the conformation of these F-box proteins, which increases their expression levels and substrate-binding. (PMID:21640084)
• SKP1-Cul1-F-box and leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A) protein (PMID:21757720)
• This review suggested that SKP1 decreased in in sporadic Parkinson’s disease. (PMID:22205206)
• phosphorylated NIPA is degraded in late mitosis in an APC/C(Cdh1)-dependent manner (PMID:22205987)
• we determined that the phage-encoded GogB effector protein in Salmonella targets the host SCF E3 type ubiquitin ligase through an interaction with Skp1 and the human F-box only 22 (FBXO22) protein (PMID:22761574)
• 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)
• 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)
• SKP1 variation modifies association between Parkinson’s disease and ubiquitin-proteasome system-inhibiting pesticides (PMID:23988235)
• Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein complex. (PMID:24085301)
• We discuss how these results can explain the rapid association of Cdc34 and Skp1-cullin-F-box ligase (SCF). (PMID:25425648)
• Data show that epithelial-mesenchymal transition (EMT)-transcription factors can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45). (PMID:25460509)
• Skp1 is critical to lung cancer pathogenesis (PMID:26474281)
• Both the F-box domain of Skp2 and Skp1-Skp2 domain motions displaying preferential conformational control can together facilitate polyubiquitination of a wide variety of substrates. (PMID:26573739)
• Segregation analysis revealed that variants c.475T>G in SKP1, c.671G>A in PROB1, and c.527G>A in IL17B in the 5q31.1-q35.3 linkage region, and c.850G>A in HKDC1 in the 10q22 locus completely segregated with the phenotype in the studied Keratoconus family (PMID:27703147)
• a novel role for SKP1 as an auxiliary component of the target recognition module that enhances binding of FBXO45 to NMNAT2. (PMID:29997255)
• High SKP1 expression is associated with Lung Adenocarcinogenesis. (PMID:30728155)
• Skp1 Dimerization Conceals Its F-Box Protein Binding Site. (PMID:32227851)
• Long non-coding RNA CCDC183-AS1 acts AS a miR-589-5p sponge to promote the progression of hepatocellular carcinoma through regulating SKP1 expression. (PMID:33541391)
• Reduced SKP1 and CUL1 expression underlies increases in Cyclin E1 and chromosome instability in cellular precursors of high-grade serous ovarian cancer. (PMID:33731859)
• A Comprehensive Assessment of Genetic and Epigenetic Alterations Identifies Frequent Variations Impacting Six Prototypic SCF Complex Members. (PMID:35008511)
• The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei. (PMID:36898988)
• A noncanonical function of SKP1 regulates the switch between autophagy and unconventional secretion. (PMID:37831778)

Cross-species orthologs

27 orthologs

Organism	Symbol	Gene ID
danio_rerio	skp1	ENSDARG00000003151
mus_musculus	Skp1	ENSMUSG00000036309
rattus_norvegicus	Skp1	ENSRNOG00000005828
drosophila_melanogaster	SkpA	FBGN0025637
drosophila_melanogaster	SkpD	FBGN0026174
drosophila_melanogaster	SkpC	FBGN0026175
drosophila_melanogaster	SkpB	FBGN0026176
drosophila_melanogaster	SkpE	FBGN0031074
drosophila_melanogaster	SkpF	FBGN0034863
caenorhabditis_elegans	skr-1	WBGENE00004807
caenorhabditis_elegans	skr-2	WBGENE00004808
caenorhabditis_elegans		WBGENE00004809
caenorhabditis_elegans		WBGENE00004810
caenorhabditis_elegans		WBGENE00004811
caenorhabditis_elegans		WBGENE00004812
caenorhabditis_elegans		WBGENE00004813
caenorhabditis_elegans		WBGENE00004814
caenorhabditis_elegans		WBGENE00004815
caenorhabditis_elegans		WBGENE00004816
caenorhabditis_elegans		WBGENE00004818
caenorhabditis_elegans		WBGENE00004819
caenorhabditis_elegans		WBGENE00004820
caenorhabditis_elegans		WBGENE00004821
caenorhabditis_elegans		WBGENE00004822
caenorhabditis_elegans		WBGENE00004823
caenorhabditis_elegans		WBGENE00004826
caenorhabditis_elegans		WBGENE00018935

Protein

Protein identifiers

S-phase kinase-associated protein 1 — P63208 (reviewed: P63208)

Alternative names: Cyclin-A/CDK2-associated protein p19, Organ of Corti protein 2, Organ of Corti protein II, RNA polymerase II elongation factor-like protein, SIII, Transcription elongation factor B polypeptide 1-like, p19skp1

All UniProt accessions (8): P63208, E5RGM3, E5RGM4, E5RHM3, E5RJR5, E5RK33, E7ERH2, F8W8N3

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. 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, CEP68 and probably NFKB2. 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 cyclin E, 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(FBXO11) 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. Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Also acts as a core component of the Cul1-RING(FBXL4) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of BNIP3 and BNI3L.

Subunit / interactions. Interacts with KDM2B, forming heterodimers. The KDM2B-SKP1 heterodimeric complex interacts with the PCGF1-BCORL heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1). Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed 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. 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) complex composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) complex composed of CUL1, SKP1, RBX1 and FBXW7. Component of the SCF(FBXO31) complex composed of CUL1, SKP1, RBX1 and FBXO31. Component of the SCF(FBXW15) complex composed of CUL1, SKP1, RBX1 and FBXW15. Component of the SCF(FBXL2) complex composed of CUL1, SKP1, RBX1 and FBXL2. Interacts with CEP68. Interacts with NOTCH2. Interacts with FBXW15. The SKP1-KDM2A and SKP1-KDM2B complexes interact with UBB. Component of the Cul7-RING(FBXW8) complex consisting of CUL7, RBX1, SKP1 and FBXW8; within the complex interacts with FBXW8. Interacts with BCORL1. Interacts with FBXL4. (Microbial infection) Interacts with vaccinia virus protein C9L.

Post-translational modifications. Undergoes autophagy-mediated degradation in the liver in a time-dependent manner.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the SKP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P63208-1	1	yes
P63208-2	2

RefSeq proteins (2): NP_008861, NP_733779* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001232	SKP1-like	Family
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR016072	Skp1_comp_dimer	Domain
IPR016073	Skp1_comp_POZ	Domain
IPR016897	SKP1	Family
IPR036296	SKP1-like_dim_sf	Homologous_superfamily

Pfam: PF01466, PF03931

UniProt features (27 total): helix 10, strand 9, region of interest 2, initiator methionine 1, chain 1, turn 1, modified residue 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

72 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1FS1	X-RAY DIFFRACTION	1.8
6M90	X-RAY DIFFRACTION	2.05
2AST	X-RAY DIFFRACTION	2.3
6M92	X-RAY DIFFRACTION	2.35
2E31	X-RAY DIFFRACTION	2.4
6M91	X-RAY DIFFRACTION	2.4
2OVR	X-RAY DIFFRACTION	2.5
6M93	X-RAY DIFFRACTION	2.5
6WNX	X-RAY DIFFRACTION	2.5
5IBK	X-RAY DIFFRACTION	2.5
6O60	X-RAY DIFFRACTION	2.5
5JH5	X-RAY DIFFRACTION	2.55
7T1Y	X-RAY DIFFRACTION	2.55
2OVQ	X-RAY DIFFRACTION	2.6
3WSO	X-RAY DIFFRACTION	2.6
5V4B	X-RAY DIFFRACTION	2.6
6BYH	X-RAY DIFFRACTION	2.61
6BVA	X-RAY DIFFRACTION	2.66
4I6J	X-RAY DIFFRACTION	2.7
5VZT	X-RAY DIFFRACTION	2.7
5VZU	X-RAY DIFFRACTION	2.7
6M94	X-RAY DIFFRACTION	2.7
7Z8V	ELECTRON MICROSCOPY	2.7
7T1Z	X-RAY DIFFRACTION	2.77
1FQV	X-RAY DIFFRACTION	2.8
3L2O	X-RAY DIFFRACTION	2.8
7Z8B	ELECTRON MICROSCOPY	2.8
5K35	X-RAY DIFFRACTION	2.85
1FS2	X-RAY DIFFRACTION	2.9
2OVP	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63208-F1	90.11	0.72

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): 131, 142

Function

Pathways and Gene Ontology

Reactome pathways

114 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-180534	Vpu mediated degradation of CD4
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

MSigDB gene sets: 457 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MBD4, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, MORF_RAB5A, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (12): protein polyubiquitination (GO:0000209), chromatin remodeling (GO:0006338), protein monoubiquitination (GO:0006513), protein ubiquitination (GO:0016567), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), maintenance of protein location in nucleus (GO:0051457), protein K48-linked ubiquitination (GO:0070936), ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), axon development (GO:0061564), positive regulation of epithelial cell apoptotic process (GO:1904037)

GO Molecular Function (9): beta-catenin binding (GO:0008013), protein domain specific binding (GO:0019904), cullin family protein binding (GO:0097602), molecular function activator activity (GO:0140677), ubiquitin ligase complex scaffold activity (GO:0160072), F-box domain binding (GO:1990444), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), ubiquitin ligase activator activity (GO:1990757), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), SCF ubiquitin ligase complex (GO:0019005), Cul7-RING ubiquitin ligase complex (GO:0031467), PcG protein complex (GO:0031519)

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
Host Interactions of HIV factors	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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	3
protein binding	3
cellular anatomical structure	3
cullin-RING ubiquitin ligase complex	2
chromatin organization	1
protein modification by small protein conjugation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	1
protein polyubiquitination	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
neuron projection development	1
positive regulation of apoptotic process	1
epithelial cell apoptotic process	1
regulation of epithelial cell apoptotic process	1
molecular function regulator activity	1
protein complex scaffold activity	1
protein domain specific binding	1
enzyme-substrate adaptor activity	1
ubiquitin-protein transferase activator activity	1
positive regulation of ubiquitin protein ligase activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

592 interactions, top by confidence:

A	B	Type	Score
SKP1	BTRC	psi-mi:“MI:0915”(physical association)	0.960
CUL1	SKP1	psi-mi:“MI:0915”(physical association)	0.960
SKP1	SKP2	psi-mi:“MI:2364”(proximity)	0.960
SKP1	BTRC	psi-mi:“MI:2364”(proximity)	0.960
CUL1	SKP1	psi-mi:“MI:0914”(association)	0.960
SKP1	FBXO28	psi-mi:“MI:0915”(physical association)	0.940
FBXO28	SKP1	psi-mi:“MI:0915”(physical association)	0.940
CUL2	VHL	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
FBXO11	SKP1	psi-mi:“MI:0915”(physical association)	0.930
SKP1	FBXL8	psi-mi:“MI:0915”(physical association)	0.930
SKP1	FBXO11	psi-mi:“MI:0915”(physical association)	0.930
FBXL8	SKP1	psi-mi:“MI:0915”(physical association)	0.930
FBXO4	SKP1	psi-mi:“MI:0914”(association)	0.930

BioGRID (1439): SKP1 (Co-fractionation), FBXW2 (Reconstituted Complex), FBXL2 (Reconstituted Complex), FBXO8 (Reconstituted Complex), FBXO2 (Reconstituted Complex), Fbxw5 (Reconstituted Complex), Fbxl8 (Reconstituted Complex), Fbxw14 (Reconstituted Complex), Fbxo15 (Reconstituted Complex), FBXO7 (Reconstituted Complex), SKP1 (Affinity Capture-MS), SKP1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), SKP1 (Affinity Capture-MS)

ESM2 similar proteins: A0PGB3, A1C9U5, A1CZG3, B0Y3B5, B6QGB9, B8MDP8, B8NSJ0, C5FHU9, D4ARL8, G5ECU1, O49484, O65674, O81055, O81057, P52285, P52286, P63208, P63209, Q0CA59, Q15369, Q1PEL7, Q2KII4, Q39255, Q3ZCF3, Q4R5B9, Q4WTT8, Q557E4, Q5BAX8, Q5KU00, Q5R512, Q5ZKF5, Q651E8, Q6H4D6, Q6PEC4, Q6PL11, Q71U00, Q8NK13, Q8TGW7, Q9FHW7, Q9LNT9

Diamond homologs: A0PGB3, A1C9U5, A1CZG3, A8MQG7, B0Y3B5, B6QGB9, B8MDP8, B8NSJ0, C5FHU9, D4ARL8, G5ECU1, O49484, O65674, O81055, O81057, O81058, P52285, P52286, P63208, P63209, Q0CA59, Q1PEF6, Q1PEL7, Q39255, Q3ZCF3, Q4R5B9, Q4WTT8, Q557E4, Q5BAX8, Q5KU00, Q5R512, Q5ZKF5, Q651E8, Q6H4D6, Q6PEC4, Q6PL11, Q71U00, Q8LF97, Q8NK13, Q8TGW7

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
SKP1	“form complex”	SCF-SKP2	binding
SKP1	“form complex”	SCF-FBW7	binding
SKP1	“form complex”	SCF-FBW2	binding
SKP1	“up-regulates activity”	“Cullin 3-RBX1-Skp1”	binding
SKP1	“form complex”	“Cullin 3-RBX1-Skp1”	binding
SKP1	“form complex”	“Cullin 7-RBX1-Skp1”	binding
SKP1	“form complex”	“Cullin 1-RBX1-Skp1”	binding
SKP1	“form complex”	SCF(TBL1)	binding
SKP1	“form complex”	“Skp1-Pam E3”	binding
FBXW11	up-regulates	SKP1	binding
SKP1	up-regulates	CUL1	binding
SKP1	“form complex”	SCF-betaTRCP	binding
SKP1	“form complex”	“Noncanonical PRC1”	binding
miR-582-5p	“down-regulates quantity by destabilization”	SKP1	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 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
DNA Damage Recognition in GG-NER	7	22.5×	3e-06
Neddylation	40	21.3×	3e-41
Degradation of CRY and PER proteins	8	19.7×	1e-06
Iron uptake and transport	5	19.4×	2e-04
Formation of TC-NER Pre-Incision Complex	7	16.6×	2e-05
Association of TriC/CCT with target proteins during biosynthesis	5	16.4×	3e-04
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	7	16.0×	2e-05
NOTCH1 Intracellular Domain Regulates Transcription	6	16.0×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	21	70.2×	9e-32
glycoprotein catabolic process	5	47.0×	8e-06
protein neddylation	5	31.4×	6e-05
G1/S transition of mitotic cell cycle	12	21.5×	8e-11
intrinsic apoptotic signaling pathway	6	19.2×	7e-05
G2/M transition of mitotic cell cycle	6	16.7×	1e-04
protein destabilization	6	15.6×	2e-04
regulation of circadian rhythm	6	13.9×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1337 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134157705:A:AC	donor_gain	1.0000
5:134157706:C:CC	donor_gain	1.0000
5:134158452:TAC:T	donor_loss	1.0000
5:134158453:A:AC	donor_gain	1.0000
5:134158453:ACCTG:A	donor_loss	1.0000
5:134158454:C:A	donor_loss	1.0000
5:134158454:C:CC	donor_gain	1.0000
5:134158591:GCAGC:G	acceptor_gain	1.0000
5:134158592:CAGC:C	acceptor_gain	1.0000
5:134158592:CAGCC:C	acceptor_gain	1.0000
5:134158593:AGC:A	acceptor_gain	1.0000
5:134158594:GC:G	acceptor_gain	1.0000
5:134158595:CC:C	acceptor_gain	1.0000
5:134158595:CCTG:C	acceptor_loss	1.0000
5:134158596:C:CC	acceptor_gain	1.0000
5:134158596:CTGTA:C	acceptor_loss	1.0000
5:134158598:G:GC	acceptor_gain	1.0000
5:134160982:CTTA:C	donor_loss	1.0000
5:134160984:TACC:T	donor_loss	1.0000
5:134160985:A:AC	donor_gain	1.0000
5:134160985:AC:A	donor_gain	1.0000
5:134160985:ACCA:A	donor_loss	1.0000
5:134160986:C:CC	donor_gain	1.0000
5:134160986:CC:C	donor_gain	1.0000
5:134160986:CCA:C	donor_gain	1.0000
5:134160986:CCAG:C	donor_gain	1.0000
5:134160986:CCAGA:C	donor_gain	1.0000
5:134161126:ATGAC:A	acceptor_gain	1.0000
5:134161127:TGAC:T	acceptor_gain	1.0000
5:134161128:GACC:G	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000175431 (5:134161607 T>C), RS1000329743 (5:134154910 C>T), RS1000416790 (5:134167592 G>A), RS1000427395 (5:134149199 T>A), RS1000510106 (5:134163137 C>T), RS1000605080 (5:134153074 A>C), RS1000674601 (5:134172419 A>AT), RS1000737364 (5:134156585 A>G), RS1000992784 (5:134177705 C>A,T), RS1001035048 (5:134166870 C>A,T), RS1001045721 (5:134148905 A>C), RS1001154450 (5:134178878 A>C), RS1001571497 (5:134158993 CTTTA>C), RS1001602939 (5:134152353 T>C,G), RS1001655061 (5:134175544 T>C,G)

Disease associations

OMIM: gene MIM:601434 | disease phenotypes: MIM:148300

GenCC curated gene-disease

Mondo (1): keratoconus 1 (MONDO:0007851)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003155_48	Systemic lupus erythematosus	4.000000e-16
GCST003156_47	Systemic lupus erythematosus	7.000000e-10
GCST003622_50	Systemic lupus erythematosus	4.000000e-10
GCST90002395_459	Mean platelet volume	1.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563649	Keratoconus 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3885547 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885634 (PROTEIN-PROTEIN INTERACTION), CHEMBL5482973 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,018 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL238804	SELEXIPAG	4	1,018

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

ChEMBL bioactivities

20 potent at pChembl≥5 of 37 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.24	IC50	570	nM	CHEMBL5411495
5.96	IC50	1100	nM	CHEMBL5420161
5.77	IC50	1700	nM	CHEMBL5393726
5.64	IC50	2300	nM	CHEMBL5420913
5.62	IC50	2400	nM	CHEMBL5428364
5.62	IC50	2400	nM	CHEMBL5406988
5.57	IC50	2700	nM	CHEMBL5399928
5.55	IC50	2800	nM	CHEMBL5410031
5.55	IC50	2800	nM	CHEMBL5417549
5.48	IC50	3300	nM	CHEMBL5427761
5.38	IC50	4200	nM	CHEMBL5422656
5.28	IC50	5200	nM	CHEMBL5433202
5.27	IC50	5400	nM	CHEMBL5409004
5.24	IC50	5800	nM	CHEMBL5400880
5.17	IC50	6700	nM	CHEMBL5414066
5.09	IC50	8120	nM	CHEMBL5404378
5.07	IC50	8500	nM	CHEMBL5420818
5.07	IC50	8500	nM	CHEMBL5408533
5.00	IC50	9900	nM	CHEMBL5429197
5.00	IC50	1e+04	nM	CHEMBL5411594

PubChem BioAssay actives

20 with measured affinity, of 91 total; 20 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
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]-2,2-dimethylpropanamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	0.5700	uM
N-[[1-[5-[4-(hydroxymethyl)phenyl]-6-phenylpyrazin-2-yl]piperidin-4-yl]methyl]-2,2-dimethylpropanamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	1.1000	uM
tert-butyl 4-(5,6-diphenylpyrazin-2-yl)piperazine-1-carboxylate	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	1.7000	uM
tert-butyl N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]carbamate	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	2.3000	uM
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]morpholine-4-carboxamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	2.4000	uM
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]benzamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	2.4000	uM
2,2-dimethyl-N-[[1-[5-(4-methylsulfonylphenyl)-6-phenylpyrazin-2-yl]piperidin-4-yl]methyl]propanamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	2.7000	uM
2-chloro-N-[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]acetamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	2.8000	uM
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]propanamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	2.8000	uM
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]cyclopropanecarboxamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	3.3000	uM
N-[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]benzamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	4.2000	uM
N-[[1-[5-[4-(dimethylamino)phenyl]-6-phenylpyrazin-2-yl]piperidin-4-yl]methyl]-2,2-dimethylpropanamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	5.2000	uM
N-[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]acetamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	5.4000	uM
cyclopropyl-[4-(5,6-diphenylpyrazin-2-yl)piperazin-1-yl]methanone	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	5.8000	uM
N-[[1-[5-(4-fluorophenyl)-6-phenylpyrazin-2-yl]piperidin-4-yl]methyl]-2,2-dimethylpropanamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	6.7000	uM
N-[[1-[5-(furan-2-yl)-6-phenylpyrazin-2-yl]piperidin-4-yl]methyl]-2,2-dimethylpropanamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	8.1200	uM
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]cyclohexanecarboxamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	8.5000	uM
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]thiophene-2-carboxamide	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	8.5000	uM
2-chloro-1-[4-(5,6-diphenylpyrazin-2-yl)piperazin-1-yl]ethanone	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	9.9000	uM
1-[4-(5,6-diphenylpyrazin-2-yl)piperazin-1-yl]propan-1-one	1989939: Inhibition of GST-tagged Skp2/Skp1 (unknown origin)/His6-tagged Cks1 (unknown origin) interaction preincubated with Skp2/Skp1 for 10 mins followed by Cks1 addition measured after 20 mins by HTRF assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression	3
sodium arsenite	increases expression	2
Valproic Acid	increases methylation, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
coumarin	decreases phosphorylation	1
arsenic disulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
deguelin	decreases expression	1
7,3’-dihydroxy-4’-methoxyisoflavone	increases expression	1
monomethylarsonous acid	increases expression	1
dimethylarsinous acid	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	affects expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3760676	Binding	Inhibition of Cul-1/Skp1 protein interaction in human HCT116 cells after 24 hrs by immunoprecipitation assay	Antitumor Activity of Americanin A Isolated from the Seeds of Phytolacca americana by Regulating the ATM/ATR Signaling Pathway and the Skp2-p27 Axis in Human Colon Cancer Cells. — J Nat Prod

Clinical trials (associated diseases)

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