SKP2

Summary

SKP2 (S-phase kinase associated protein 2, HGNC:10901) is a protein-coding gene on chromosome 5p13.2, encoding S-phase kinase-associated protein 2 (Q13309). Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription.

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms.

Source: NCBI Gene 6502 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 46 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005983

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10901
Approved symbol	SKP2
Name	S-phase kinase associated protein 2
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FBXL1, FBL1, p45
Ensembl gene	ENSG00000145604
Ensembl biotype	protein_coding
OMIM	601436
Entrez	6502

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 11 protein_coding, 11 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000274254, ENST00000274255, ENST00000504386, ENST00000508514, ENST00000509692, ENST00000513151, ENST00000513263, ENST00000546211, ENST00000620197, ENST00000676559, ENST00000677537, ENST00000677861, ENST00000677886, ENST00000677905, ENST00000677911, ENST00000677984, ENST00000678129, ENST00000678149, ENST00000678260, ENST00000678270, ENST00000678537, ENST00000678580, ENST00000678948, ENST00000679015, ENST00000679258, ENST00000679283, ENST00000855793, ENST00000855794

RefSeq mRNA: 3 — MANE Select: NM_005983 NM_001243120, NM_005983, NM_032637

CCDS: CCDS3915, CCDS3916

Canonical transcript exons

ENST00000274255 — 10 exons

Exon	Start	End
ENSE00001006180	36163645	36163756
ENSE00001082238	36181818	36184319
ENSE00001852758	36152111	36152270
ENSE00003467798	36168313	36168447
ENSE00003482539	36170344	36170442
ENSE00003553233	36177185	36177292
ENSE00003563858	36166519	36166662
ENSE00003597130	36176965	36177016
ENSE00003606190	36152771	36153042
ENSE00003790054	36171603	36171733

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3301 / max 577.7592, expressed in 1753 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56121	21.1393	1751
56120	0.8037	500
56122	0.2650	162
56119	0.1221	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.86	gold quality
secondary oocyte	CL:0000655	99.78	gold quality
placenta	UBERON:0001987	94.21	gold quality
ventricular zone	UBERON:0003053	94.15	gold quality
embryo	UBERON:0000922	93.29	gold quality
gingival epithelium	UBERON:0001949	93.09	gold quality
gingiva	UBERON:0001828	92.30	gold quality
buccal mucosa cell	CL:0002336	91.91	gold quality
ganglionic eminence	UBERON:0004023	91.86	gold quality
cervix squamous epithelium	UBERON:0006922	91.42	silver quality
squamous epithelium	UBERON:0006914	91.13	gold quality
tibia	UBERON:0000979	91.11	gold quality
adrenal tissue	UBERON:0018303	91.02	gold quality
endothelial cell	CL:0000115	90.76	gold quality
esophagus squamous epithelium	UBERON:0006920	90.51	gold quality
trabecular bone tissue	UBERON:0002483	90.04	gold quality
tongue squamous epithelium	UBERON:0006919	89.68	gold quality
oviduct epithelium	UBERON:0004804	89.53	gold quality
tendon of biceps brachii	UBERON:0008188	89.43	gold quality
epithelium of esophagus	UBERON:0001976	89.06	gold quality
amniotic fluid	UBERON:0000173	88.91	gold quality
bone marrow	UBERON:0002371	87.75	gold quality
germinal epithelium of ovary	UBERON:0001304	87.68	gold quality
inferior olivary complex	UBERON:0002127	87.44	gold quality
cervix epithelium	UBERON:0004801	87.29	gold quality
pharyngeal mucosa	UBERON:0000355	87.10	gold quality
epithelium of nasopharynx	UBERON:0001951	86.82	gold quality
superficial temporal artery	UBERON:0001614	86.57	gold quality
mammalian vulva	UBERON:0000997	86.23	gold quality
endometrium	UBERON:0001295	85.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
RHOA	Activation

Upstream regulators (CollecTRI, top): E2F1, ELK1, EP300, ESR1, FOXM1, FOXO3, FOXP3, GABPA, GATA2, ID1, ING4, LEF1, MYC, MYCN, NFATC1, NFKB2, NFKB, NR4A3, RBPJ, RELA, RELB, SMAD7, SP1, STAT1, STAT3, TBXT, TCF4, TCF7L2, TP53, TP63, VDR, YBX1, ZNF143

miRNA regulators (miRDB)

108 targeting SKP2, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3686	99.90	70.53	2432

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex (PMID:11961546)
• The lower Cyclin A gene expression would predict drug resistance for acute leukemia patients. (PMID:12133445)
• SKP2 is a major determinant of p27 levels in prostate cancer cells; overexpression of SKP2 may be one of the mechanisms that allow prostate cancer cells to escape growth control mediated by p27. (PMID:12188931)
• expressed in lymphoma: correlation with p27(Kip1) and proliferation index (PMID:12351407)
• induction of Skp2 may be causally linked with decreased levels of p27 in prostate cancer and implicate PTEN in the regulation of Skp2 expression (PMID:12429629)
• The activity of the ubiquitin ligase complex Skp1-Cul1/Cdc53-F-box protein Skp2 (SCF(Skp2)) and the proteasome were necessary for p130 degradation. (PMID:12435635)
• S-phase kinase-associated protein 2 overexpression is associated with laryngeal squamous cell carcinomas (PMID:12579266)
• Skp2 mRNA expression level was high in squamous cell carcinomas of the lung and was inversely related with the p27(Kip1) protein level (PMID:12670508)
• Skp2 overexpression is associated with ovarian adenocarcinoma (PMID:12738731)
• negatively charged amino acid is required for Skp2-Cks1 interaction and ubiquitination of p27Kip1 (PMID:12813041)
• SKP2’s role does not include regulation of CDK9 expression (PMID:12861003)
• hepatocyte growth factor suppresses HepG2 cell proliferation by directly increasing p27 expression and indirectly decreasing Skp2 expression, and beta 1-integrin modulates responsiveness of hepatoma cells by increasing Skp2. (PMID:12883474)
• skp2 has a role in the downregulation of p27Kip1 by estrogens in breast cancer cells (PMID:12904306)
• SCFSkp2 complex plays an important role in cell-cycle progression by determining the abundance of p57Kip2 and that of the related CDK inhibitor p27Kip1. (PMID:12925736)
• increased p27 degradation through the ubiquitin-proteasome pathway could be regulated in pituitary tumors by changes in Skp2 expression (PMID:14558671)
• Skp2 may be involved in Merkel cell tumorigenesis, but other factors may also influence cell proliferation in these tumors. (PMID:14586067)
• Overexpression of Skp2 and Jab1 is associated with the reduction of p27(KIP1) expression, and may have a role in the progression of Oral Squamous Cell Carcinoma. (PMID:14707456)
• induction of Skp2 and Cks1 degradation in G1 represents a principal mechanism by which APC/C(Cdh1) prevents the unscheduled degradation of SCF(Skp2-Cks1) substrates and maintains the G1 state (PMID:15014502)
• F-box protein Skp2 is polyubiquitinated, and hence earmarked for destruction, by APC(CDH1) (PMID:15014503)
• Skp2 protein expression is a significant independent poor prognostic marler in non-small cell lung carcinoma. (PMID:15041716)
• the Skp2-p27kip1 pathway and the G1/S transition are regulated by RhoA, mDia, and ROCK (PMID:15096506)
• down-regulation of Skp2 induces tumor cell-cycle arrest with a fatty acid synthase blockade (PMID:15138278)
• Overexpression is associated with colorectal carcinogenesis and late metastasis to lymph nodes, whereas relative reduction of Skp2 is correlated with local invasion of primary carcinoma. (PMID:15201993)
• Amplification and overexpression of SKP2 are associated with metastasis of non-small-cell lung cancers to lymph nodes. (PMID:15215173)
• expression of p27, Skp2 & Ki67 was similar in normal secretory endometrium & endometrium from ovarian hyperstimulation; p27 is significantly lower while Skp2 and Ki67 are higher in endometrial carcinoma and endometrium from the proliferative phase (PMID:15220466)
• S-phase kinase-associated protein 2 may have a role in progression of acute myelogenous leukemia (PMID:15297415)
• SCFSkp2 is involved in controlling UBP43 protein levels and may play an important role in modulating type 1 IFN signaling (PMID:15342634)
• SCFSkp2 mediates regulation of p27 stability and is regulated by tuberin (PMID:15355997)
• Skp2 overexpression is closely associated with the suppression of p27 and the aggressiveness in NSCLC. (PMID:15483027)
• Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. (PMID:15491322)
• Downregulation of both Skp2 and p27 increased apoptosis synergistically, Skp2 in tumor cells suppresses apoptosis through Bcl-2 expression (PMID:15605273)
• Data suggest that p107, in addition to its interaction with E2F, inhibits cell proliferation through the control of Skp2 expression and the resulting stabilization of p27. (PMID:15631990)
• COX-2 contributes to the expression of Skp2 and poor survival in human gastric carcinomas (PMID:15645119)
• SKP2 plays an oncogenic role in lung cancer and that SKP2 silencing may be useful in the treatment of lung cancer (PMID:15735730)
• expression of Skp2, p27KIP1 and Ki-67 in 10 naevi, 15 superficial spreading melanomas, 10 nodular melanomas and 14 melanoma metastases (PMID:15736055)
• Skp2 expression might play an important role in the development and progression in non-small cell lung cancer (PMID:15756449)
• Skp2 siRNA inhibits the cell proliferation of oral squamous cell carcinoma cells (PMID:15767556)
• BCR-ABL cells show transcriptional up-regulation of Skp2. Expression of a p27(Kip1) mutant unable of being recognized by Skp2 results in inhibition of proliferation of BCR-ABL cells. (PMID:15833859)
• Skp2 is not required for the degradation of Cdt1 in S phase- this degradation is necessary for the optimum progression of cells through S phase (PMID:15855168)
• Skp2-SCF provides an unexpected and direct mechanistic link between DNA recombination and the cell cycle. (PMID:15949444)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	skp2	ENSDARG00000004937
mus_musculus	Skp2	ENSMUSG00000054115
rattus_norvegicus	Skp2	ENSRNOG00000059059
drosophila_melanogaster	CG15056	FBGN0030918
drosophila_melanogaster	CG8272	FBGN0033337
drosophila_melanogaster	CG9003	FBGN0033639
drosophila_melanogaster	Skp2	FBGN0037236
drosophila_melanogaster	CG14891	FBGN0038445
drosophila_melanogaster	CG5003	FBGN0039554
drosophila_melanogaster	FipoQ	FBGN0039667
caenorhabditis_elegans		WBGENE00007206
caenorhabditis_elegans		WBGENE00007208
caenorhabditis_elegans		WBGENE00007887
caenorhabditis_elegans		WBGENE00008177
caenorhabditis_elegans		WBGENE00009689
caenorhabditis_elegans	gadr-6	WBGENE00009823
caenorhabditis_elegans		WBGENE00010365
caenorhabditis_elegans	K05C4.9	WBGENE00010585
caenorhabditis_elegans		WBGENE00012655
caenorhabditis_elegans		WBGENE00015350
caenorhabditis_elegans		WBGENE00018561
caenorhabditis_elegans		WBGENE00018613
caenorhabditis_elegans		WBGENE00018766
caenorhabditis_elegans		WBGENE00019239
caenorhabditis_elegans		WBGENE00020884
caenorhabditis_elegans		WBGENE00021053
caenorhabditis_elegans		WBGENE00021180
caenorhabditis_elegans	zeel-1	WBGENE00021463
caenorhabditis_elegans		WBGENE00044459
caenorhabditis_elegans	gadr-5	WBGENE00045058

Paralogs (15): FBXL3 (ENSG00000005812), FBXL19 (ENSG00000099364), FBXL15 (ENSG00000107872), FBXL20 (ENSG00000108306), FBXL4 (ENSG00000112234), FBXL5 (ENSG00000118564), FBXL16 (ENSG00000127585), FBXL17 (ENSG00000145743), FBXL2 (ENSG00000153558), FBXL18 (ENSG00000155034), FBXL13 (ENSG00000161040), FBXL14 (ENSG00000171823), FBXL6 (ENSG00000182325), FBXL7 (ENSG00000183580), FBXL22 (ENSG00000197361)

Protein

Protein identifiers

S-phase kinase-associated protein 2 — Q13309 (reviewed: Q13309)

Alternative names: Cyclin-A/CDK2-associated protein p45, F-box protein Skp2, F-box/LRR-repeat protein 1, p45skp2

All UniProt accessions (15): A0A0A0MTL5, A0A7I2V2J7, A0A7I2V3U1, A0A7I2V413, A0A7I2V5B8, A0A7I2YQB7, A0A7I2YQC7, A0A7I2YQH6, A0A7P0S4R7, D6R9R7, Q13309, D6RAG5, D6RF40, D6RHY6, H0Y9I9

UniProt curated annotations — full annotation on UniProt →

Function. Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, NBN, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration. Following phosphorylation in response to DNA damage, mediates ‘Lys-63’-linked ubiquitination of NBN, promoting ATM recruitment to DNA damage sites and DNA repair via homologous recombination. Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus.

Subunit / interactions. Part of a SCF(SKP2) complex consisting of CUL1, RBX1, SKP1 and SKP2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts directly with CUL1 and SKP1. Interacts with CKS1. Interacts with ASB2 which is the substrate-recognition component of a probable ECS E3 ubiquitin-protein ligase complex; ASB2 is likely to bridge the formation of dimeric E3-ubiquitin-protein ligase complexes composed of an ECS complex and an SCF(SKP2) complex. Interacts with the cyclin-A-CDK2 complex. Interacts with ORC1, phosphorylated CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1, UBP43, MYC, TOB1, TAL1 and KMT2A/MLL1. Interacts with TRIM21. Interacts with cyclin-E. Interacts with IFI27; promotes the ubiquitin-mediated proteasomal degradation of hepatitis C virus/HCV non-structural protein NS5A. Interacts with CARM1. (Microbial infection) Interacts with hepatitis C virus/HCV non-structural protein NS5A; promotes the ubiquitin-mediated proteasomal degradation of NS5A.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylated on serine and threonine resudues in response to DNA damage, promoting ‘Lys-63’-linked ubiquitination of NBN. Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13. Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3.

Pathway. Protein modification; protein ubiquitination.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13309-1	1, SKP2-alpha	yes
Q13309-2	2, SKP2-beta
Q13309-4	3

RefSeq proteins (3): NP_001230049, NP_005974, NP_116026 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR006553	Leu-rich_rpt_Cys-con_subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036047	F-box-like_dom_sf	Homologous_superfamily

Pfam: PF12937

UniProt features (74 total): strand 20, helix 15, sequence conflict 11, repeat 10, modified residue 6, region of interest 3, splice variant 3, sequence variant 2, chain 1, domain 1, short sequence motif 1, turn 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
1FS1	X-RAY DIFFRACTION	1.8
2AST	X-RAY DIFFRACTION	2.3
7Z8V	ELECTRON MICROSCOPY	2.7
1FQV	X-RAY DIFFRACTION	2.8
1FS2	X-RAY DIFFRACTION	2.9
8OR3	ELECTRON MICROSCOPY	2.9
9QO4	ELECTRON MICROSCOPY	2.95
2ASS	X-RAY DIFFRACTION	3
7Z8T	ELECTRON MICROSCOPY	3
1LDK	X-RAY DIFFRACTION	3.1
7ZBZ	ELECTRON MICROSCOPY	3.1
8OR0	ELECTRON MICROSCOPY	3.1
7LUO	X-RAY DIFFRACTION	3.17
9QO0	ELECTRON MICROSCOPY	3.26
8CDK	ELECTRON MICROSCOPY	3.32
8BYA	ELECTRON MICROSCOPY	3.38
8CDJ	ELECTRON MICROSCOPY	3.4
7ZBW	ELECTRON MICROSCOPY	3.5
8BYL	ELECTRON MICROSCOPY	3.5
7B5L	ELECTRON MICROSCOPY	3.8
7B5R	ELECTRON MICROSCOPY	3.8
8OR4	ELECTRON MICROSCOPY	3.8
9QO2	ELECTRON MICROSCOPY	3.8
7B5M	ELECTRON MICROSCOPY	3.91
9QO5	ELECTRON MICROSCOPY	4
9QO3	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13309-F1	82.15	0.71

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 (6): 64, 68, 71, 72, 75, 179

Function

Pathways and Gene Ontology

Reactome pathways

40 pathways

ID	Pathway
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-5689880	Ub-specific processing proteases
R-HSA-68949	Orc1 removal from chromatin
R-HSA-69231	Cyclin D associated events in G1
R-HSA-8939902	Regulation of RUNX2 expression and activity
R-HSA-8951664	Neddylation
R-HSA-9687136	Aberrant regulation of mitotic exit in cancer due to RB1 defects
R-HSA-9708530	Regulation of BACH1 activity
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-392499	Metabolism of proteins
R-HSA-453276	Regulation of mitotic cell cycle
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-69052	Switching of origins to a post-replicative state
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69206	G1/S Transition
R-HSA-69236	G1 Phase
R-HSA-69239	Synthesis of DNA
R-HSA-69242	S Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69306	DNA Replication

MSigDB gene sets: 389 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, REACTOME_DNA_REPLICATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, HOFMANN_CELL_LYMPHOMA_UP, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (21): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), positive regulation of intracellular estrogen receptor signaling pathway (GO:0033148), regulation of apoptotic process (GO:0042981), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), innate immune response (GO:0045087), positive regulation of smooth muscle cell proliferation (GO:0048661), defense response to virus (GO:0051607), regulation of cell cycle (GO:0051726), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), cellular response to cell-matrix adhesion (GO:0071460), positive regulation of protein polyubiquitination (GO:1902916), positive regulation of double-strand break repair via homologous recombination (GO:1905168), protein polyubiquitination (GO:0000209), DNA double-strand break processing (GO:0000729), immune system process (GO:0002376), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), protein localization to site of double-strand break (GO:1990166)

GO Molecular Function (4): identical protein binding (GO:0042802), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), SCF ubiquitin ligase complex (GO:0019005), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Cell Cycle, Mitotic	2
APC/C-mediated degradation of cell cycle proteins	1
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Deubiquitination	1
Switching of origins to a post-replicative state	1
G1 Phase	1
Transcriptional regulation by RUNX2	1
Post-translational protein modification	1
Aberrant regulation of mitotic cell cycle due to RB1 defects	1
KEAP1-NFE2L2 pathway	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Regulation of mitotic cell cycle	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein polyubiquitination	3
cellular anatomical structure	3
mitotic cell cycle	2
mitotic cell cycle phase transition	2
protein ubiquitination	2
nuclear lumen	2
cell cycle G1/S phase transition	1
cell cycle G2/M phase transition	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
estrogen receptor signaling pathway	1
positive regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of intracellular estrogen receptor signaling pathway	1
apoptotic process	1
regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
immune response	1
defense response to symbiont	1
positive regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
defense response	1
response to virus	1
cell cycle	1
regulation of cellular process	1
cellular response to stimulus	1
positive regulation of protein ubiquitination	1
regulation of protein polyubiquitination	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
DNA metabolic process	1
double-strand break repair	1
5’-3’ DNA exonuclease activity	1
biological_process	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
protein binding	1
enzyme-substrate adaptor activity	1

Protein interactions and networks

STRING

3158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SKP2	SKP1	P34991	999
SKP2	RBX1	P62877	998
SKP2	CCNA2	P20248	998
SKP2	CUL1	Q13616	998
SKP2	CCNA1	P78396	997
SKP2	CKS1B	P33551	997
SKP2	CDK2	P24941	992
SKP2	BTRC	Q9Y297	975
SKP2	CDKN1B	P46527	948
SKP2	CCNF	P41002	939
SKP2	FBXW7	Q969H0	915
SKP2	CCNL2	Q96S94	880
SKP2	CUL2	Q13617	865
SKP2	EP300	Q09472	854
SKP2	MYC	P01106	851

IntAct

230 interactions, top by confidence:

A	B	Type	Score
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
CCNA2	CDK2	psi-mi:“MI:0914”(association)	0.980
SKP1	SKP2	psi-mi:“MI:2364”(proximity)	0.960
SKP2	SKP1	psi-mi:“MI:0914”(association)	0.960
SKP2	SKP1	psi-mi:“MI:0915”(physical association)	0.960
SKP1	SKP2	psi-mi:“MI:0915”(physical association)	0.960
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CKS1B	CDK1	psi-mi:“MI:0914”(association)	0.920
SKP2	CDK2	psi-mi:“MI:0914”(association)	0.900
CDK2	CCNB1	psi-mi:“MI:0914”(association)	0.890
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
SKP2	CKS1B	psi-mi:“MI:0915”(physical association)	0.860
CKS1B	SKP2	psi-mi:“MI:0915”(physical association)	0.860
SKP2	CKS1B	psi-mi:“MI:0914”(association)	0.860
CDK1	CCNB2	psi-mi:“MI:0914”(association)	0.840
SKP1	CKS1B	psi-mi:“MI:0914”(association)	0.830
CKS1B	SKP1	psi-mi:“MI:0915”(physical association)	0.830
SKP2	CUL1	psi-mi:“MI:0915”(physical association)	0.820
CUL1	SKP2	psi-mi:“MI:0915”(physical association)	0.820

BioGRID (854): CUL1 (Affinity Capture-Western), CDKN1A (Biochemical Activity), SKP2 (Affinity Capture-Western), CDKN1B (Biochemical Activity), SKP2 (Affinity Capture-RNA), ESR1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), RBX1 (Affinity Capture-Western), SKP2 (Affinity Capture-Western), SKP2 (Affinity Capture-Western), SKP2 (Affinity Capture-Western), SKP2 (Affinity Capture-Western), ESR1 (Biochemical Activity), SKP2 (Affinity Capture-Western)

ESM2 similar proteins: A0JM56, A0JPI9, A4IHG1, A5PK13, D3YY91, F1ND48, O35125, Q13309, Q15813, Q24K06, Q32KP2, Q32KS0, Q32L08, Q32NT4, Q3KQF4, Q3KRC6, Q3UGP9, Q498T9, Q4U2V3, Q5BKY1, Q5DU41, Q5FVQ9, Q5PQJ7, Q5QJ74, Q5R8X9, Q5RBD9, Q5U378, Q66JT1, Q68F79, Q6GQN5, Q6NSJ5, Q6NU09, Q6P9F7, Q6WRX3, Q6ZNQ3, Q8C5W3, Q8CDN9, Q8CIV8, Q8IY45, Q8IZ02

Diamond homologs: A1A5X2, Q13309, Q5BJ29, Q6PB97, Q6PCT2, Q9EPX5, Q9NXK8, Q9QZN1, Q9UJT9, Q9Z0Z3, A2VE78, A6H779, B8M7Q5, P34284, Q2YDQ5, Q58DG6, Q5R3Z8, Q5R6E1, Q8BH16, Q8C2S5, Q8N3Y1, Q96IG2, Q9CZV8, Q9FLX3, Q9QZH7, Q9UKA1, Q9UKC9, Q32PG9, Q5XGI3, Q6INS1, Q7TPD1, Q7TSL3, Q86XK2, Q8N531, B6Q4Z5, Q8BFZ4, Q8S8F2, Q9UKA2

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
SKP2	down-regulates	SMAD4	ubiquitination
SKP2	down-regulates	CDKN1A	ubiquitination
SKP2	down-regulates	CDKN1B	ubiquitination
TGFB1	down-regulates	SKP2
SKP2	“down-regulates quantity”	MYC	ubiquitination
SKP2	“form complex”	SCF-SKP2	binding
CDC14B	“down-regulates quantity by destabilization”	SKP2	dephosphorylation
SKP2	“down-regulates quantity by destabilization”	DAB2IP	ubiquitination
PIM1	“up-regulates activity”	SKP2	phosphorylation
SKP2	“down-regulates quantity by destabilization”	CDT1	binding
SKP2	“down-regulates quantity by destabilization”	CCNE1	binding
SKP2	“up-regulates activity”	“Cullin 1-RBX1-Skp1”	binding
SKP2	“down-regulates quantity by destabilization”	MYBL2	polyubiquitination
SKP2	“down-regulates quantity by destabilization”	CCND1	binding
SKP2	“down-regulates quantity by destabilization”	NUDT1	binding
SKP2	“down-regulates quantity by destabilization”	CYGB	binding
SKP2	up-regulates	“Cullin 1-RBX1-Skp1”	binding
AKT1	“down-regulates activity”	SKP2	phosphorylation
WNT7A	“down-regulates activity”	SKP2	binding
CDK2	“up-regulates quantity by stabilization”	SKP2	phosphorylation
SKP2	“down-regulates quantity by destabilization”	IDH1	ubiquitination
SKP2	“down-regulates quantity by destabilization”	IDH2	ubiquitination
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	SKP2	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
TP53 Regulates Transcription of Cell Cycle Genes	8	44.4×	5e-10
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	6	43.7×	1e-07
p53-Dependent G1 DNA Damage Response	6	43.7×	1e-07
p53-Dependent G1/S DNA damage checkpoint	6	43.7×	1e-07
G1/S DNA Damage Checkpoints	6	41.1×	2e-07
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	5	32.4×	8e-06
Regulation of APC/C activators between G1/S and early anaphase	10	31.5×	7e-11
G1/S Transition	13	30.9×	9e-14

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of DNA replication	6	28.8×	1e-05
G1/S transition of mitotic cell cycle	15	24.9×	3e-14
mitotic G2 DNA damage checkpoint signaling	6	22.0×	4e-05
G2/M transition of mitotic cell cycle	7	18.1×	2e-05
positive regulation of G1/S transition of mitotic cell cycle	5	16.6×	1e-03
regulation of mitotic cell cycle	8	15.9×	1e-05
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	5	15.5×	1e-03
intrinsic apoptotic signaling pathway	5	14.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1636 predictions. Top by Δscore:

Variant	Effect	Δscore
5:36152983:G:GT	donor_gain	1.0000
5:36153040:CAGGT:C	donor_loss	1.0000
5:36153041:AGG:A	donor_loss	1.0000
5:36153043:G:A	donor_loss	1.0000
5:36153044:T:G	donor_loss	1.0000
5:36163744:G:GA	donor_gain	1.0000
5:36163755:GC:G	donor_gain	1.0000
5:36163757:G:GG	donor_gain	1.0000
5:36166514:TATA:T	acceptor_loss	1.0000
5:36166516:TA:T	acceptor_loss	1.0000
5:36166517:A:C	acceptor_loss	1.0000
5:36168311:A:AG	acceptor_gain	1.0000
5:36168312:G:GG	acceptor_gain	1.0000
5:36168448:G:GG	donor_gain	1.0000
5:36177293:G:GG	donor_gain	1.0000
5:36181816:A:AG	acceptor_gain	1.0000
5:36181817:G:GG	acceptor_gain	1.0000
5:36195281:CC:C	acceptor_gain	1.0000
5:36195282:CC:C	acceptor_gain	1.0000
5:36153014:GCC:G	donor_gain	0.9900
5:36153043:G:GG	donor_gain	0.9900
5:36163743:T:TA	donor_gain	0.9900
5:36166517:A:AG	acceptor_gain	0.9900
5:36166518:G:GG	acceptor_gain	0.9900
5:36166518:GGTCT:G	acceptor_gain	0.9900
5:36166660:CAG:C	donor_loss	0.9900
5:36166661:AGGT:A	donor_loss	0.9900
5:36166662:G:GT	donor_loss	0.9900
5:36166663:G:GC	donor_loss	0.9900
5:36166664:T:C	donor_loss	0.9900

AlphaMissense

2759 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:36163743:T:A	W127R	0.999
5:36163743:T:C	W127R	0.999
5:36171614:T:C	L261P	0.999
5:36171695:T:C	L288P	0.999
5:36171707:G:A	G292D	0.999
5:36177007:T:C	L315P	0.999
5:36177186:G:C	D319H	0.999
5:36177187:A:C	D319A	0.999
5:36177187:A:T	D319V	0.999
5:36177250:T:C	L340P	0.999
5:36177258:A:C	S343R	0.999
5:36177260:T:A	S343R	0.999
5:36177260:T:G	S343R	0.999
5:36177262:G:C	R344P	0.999
5:36177264:T:C	C345R	0.999
5:36177266:C:G	C345W	0.999
5:36181858:T:C	F368L	0.999
5:36181860:T:A	F368L	0.999
5:36181860:T:G	F368L	0.999
5:36168410:A:C	S212R	0.998
5:36168412:C:A	S212R	0.998
5:36168412:C:G	S212R	0.998
5:36171625:T:A	W265R	0.998
5:36171625:T:C	W265R	0.998
5:36171707:G:T	G292V	0.998
5:36177189:A:C	S320R	0.998
5:36177191:T:A	S320R	0.998
5:36177191:T:G	S320R	0.998
5:36177265:G:A	C345Y	0.998
5:36181850:T:C	L365P	0.998

dbSNP variants (sampled 300 via entrez): RS1000139652 (5:36152468 T>C,G), RS1000168343 (5:36177818 T>C,G), RS1000193136 (5:36157133 G>A), RS1000251232 (5:36177078 G>T), RS1000425183 (5:36163512 G>A), RS1000465916 (5:36191816 A>C), RS1000477677 (5:36170774 G>A), RS1000488180 (5:36151990 A>G,T), RS1000513825 (5:36163128 A>C), RS1000593308 (5:36192172 A>G), RS1000618415 (5:36184916 C>T), RS1000689117 (5:36169905 G>C), RS1000905106 (5:36176358 T>C), RS1000969332 (5:36163434 A>G), RS1001047458 (5:36162273 C>G,T)

Disease associations

OMIM: gene MIM:601436 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL3632458 (SINGLE PROTEIN), CHEMBL3885557 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885558 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885634 (PROTEIN-PROTEIN INTERACTION), CHEMBL5482973 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193820 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193821 (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)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — E3 ubiquitin ligase components

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 14i [PMID: 37204466]	Inhibition	8.56	pIC50

ChEMBL bioactivities

77 potent at pChembl≥5 of 122 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.62	Kd	2.37	nM	CHEMBL5653589
8.58	ED50	2.609	nM	CHEMBL5653589
6.77	IC50	170	nM	CHEMBL3633440
6.27	IC50	540	nM	CHEMBL3633420
6.26	IC50	550	nM	CHEMBL3633421
6.24	IC50	580	nM	CHEMBL3633439
6.24	IC50	570	nM	CHEMBL5411495
6.17	IC50	680	nM	CHEMBL5418623
6.08	IC50	840	nM	CHEMBL3633414
5.96	IC50	1100	nM	CHEMBL5420161
5.95	IC50	1120	nM	CHEMBL5420161
5.94	IC50	1150	nM	CHEMBL3633429
5.92	IC50	1210	nM	CHEMBL3633445
5.83	IC50	1480	nM	CHEMBL6102830
5.78	IC50	1670	nM	CHEMBL3633441
5.77	IC50	1700	nM	CHEMBL5393726
5.76	IC50	1730	nM	CHEMBL3633422
5.76	IC50	1740	nM	CHEMBL3633430
5.71	IC50	1930	nM	CHEMBL6078575
5.68	IC50	2070	nM	CHEMBL6133069
5.66	IC50	2180	nM	CHEMBL1487635
5.66	IC50	2200	nM	CHEMBL3633431
5.66	IC50	2200	nM	CHEMBL3633435
5.64	IC50	2300	nM	CHEMBL5420913
5.64	IC50	2280	nM	CHEMBL6102638
5.62	IC50	2400	nM	CHEMBL5428364
5.62	IC50	2400	nM	CHEMBL5406988
5.62	IC50	2370	nM	CHEMBL5406988
5.61	IC50	2450	nM	CHEMBL3633444
5.57	IC50	2700	nM	CHEMBL5399928
5.57	IC50	2710	nM	CHEMBL6078521
5.56	IC50	2760	nM	CHEMBL5410031
5.55	IC50	2800	nM	CHEMBL5410031
5.55	IC50	2800	nM	CHEMBL5417549
5.49	IC50	3210	nM	CHEMBL6078063
5.48	IC50	3300	nM	CHEMBL5427761
5.46	IC50	3490	nM	CHEMBL6083130
5.45	IC50	3570	nM	CHEMBL3633428
5.45	IC50	3530	nM	CHEMBL6102145
5.38	IC50	4200	nM	CHEMBL5422656
5.38	IC50	4120	nM	CHEMBL6074432
5.38	IC50	4170	nM	CHEMBL5422656
5.36	Kd	4381	nM	CHEMBL3752910
5.34	IC50	4610	nM	CHEMBL6101857
5.33	IC50	4640	nM	CHEMBL6132832
5.33	IC50	4640	nM	CHEMBL6103326
5.32	ED50	4824	nM	CHEMBL3752910
5.31	IC50	4860	nM	CHEMBL5593463
5.28	IC50	5200	nM	CHEMBL5433202
5.27	IC50	5400	nM	CHEMBL5409004

PubChem BioAssay actives

46 with measured affinity, of 290 total; 45 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149399: Binding affinity to human SKP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0024	uM
N-(5-pyridin-3-ylquinolin-8-yl)-3-(trifluoromethyl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	0.1700	uM
4-methyl-N-(5-phenylquinolin-8-yl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	0.5400	uM
N-[5-(furan-2-yl)quinolin-8-yl]-4-methylbenzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	0.5500	uM
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
4-methoxy-N-(5-pyridin-3-ylquinolin-8-yl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	0.5800	uM
N-(5-bromoquinolin-8-yl)-4-methylbenzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	0.8400	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
N-[6-(4-methoxyphenoxy)quinolin-8-yl]-4-methylbenzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	1.1500	uM
N-(5-pyridin-4-ylquinolin-8-yl)pyridine-3-sulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	1.2100	uM
N-(5-pyridin-3-ylquinolin-8-yl)pyridine-3-sulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	1.6700	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
4-methyl-N-(5-pyridin-3-ylquinolin-8-yl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	1.7300	uM
N-[6-(3-cyanophenoxy)quinolin-8-yl]-4-methylbenzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	1.7400	uM
4-methyl-N-quinolin-8-ylbenzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	2.1800	uM
N-(5-phenylquinolin-8-yl)methanesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	2.2000	uM
N-(5-phenylquinolin-8-yl)pyridine-3-sulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	2.2000	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
4-methoxy-N-(5-pyridin-4-ylquinolin-8-yl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	2.4500	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-[6-(3,5-difluorophenoxy)quinolin-8-yl]-4-methylbenzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	3.5700	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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149399: Binding affinity to human SKP2 incubated for 45 mins by Kinobead based pull down assay	kd	4.3809	uM
2-[(4-bromophenyl)methylsulfanyl]-7-(2,4-dimethoxyphenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine	2118666: Inhibition of GST-tagged SKP2 (unknown origin) binding to His6-tagged CKS1 (unknown origin) preincubated with SKP2 for 10 mins followed by CKS1 addition for 20 mins and measured after by HTRF method	ic50	4.8600	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
4-methyl-N-(5-thiophen-3-ylquinolin-8-yl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	5.5400	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-[4-[(5-pyridin-4-ylquinolin-8-yl)sulfamoyl]phenyl]acetamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	6.5500	uM
N-(5-phenylquinolin-8-yl)-3-(trifluoromethyl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	6.7000	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-(5-pyridin-3-ylquinolin-8-yl)cyclopropanesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	7.1600	uM
N-[4-[(5-phenylquinolin-8-yl)sulfamoyl]phenyl]acetamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	7.6000	uM
N-[5-(1-benzothiophen-2-yl)quinolin-8-yl]-4-methylbenzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	7.8400	uM
4-methoxy-N-(5-phenylquinolin-8-yl)benzenesulfonamide	1256275: Inhibition of Cks1-Skp2 (unknown origin) interaction after 30 mins by ELISA	ic50	8.0200	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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, decreases methylation, affects cotreatment	9
sodium arsenite	decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression	4
Tretinoin	decreases response to substance, decreases expression, increases degradation, increases ubiquitination, increases expression	4
Cyclosporine	decreases expression	4
Troglitazone	decreases response to substance, decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation	3
cobaltous chloride	decreases expression	2
Bortezomib	decreases expression, increases reaction	2
Arsenic Trioxide	decreases expression	2
Arsenic	increases reaction, affects methylation, decreases expression	2
Calcitriol	decreases expression, affects cotreatment	2
Cannabidiol	decreases expression	2
Copper	affects binding, decreases expression	2
Doxorubicin	affects expression, affects response to substance	2
Estradiol	increases expression, decreases reaction, increases degradation, increases response to substance, affects cotreatment (+1 more)	2
Formaldehyde	decreases expression	2
Quercetin	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
tert-Butylhydroperoxide	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
geraniol	decreases expression	1
arsenite	affects expression	1

ChEMBL screening assays

45 unique, capped per target: 45 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5342852	Binding	Binding affinity to Skp2 in human PC-3 cells assessed as thermal stability incubated for 4 hrs followed by heat treatment at 57 to 68 degreeC for 3 mins by CETSA	Discovery of Novel 1,3-Diphenylpyrazine Derivatives as Potent S-Phase Kinase-Associated Protein 2 (Skp2) Inhibitors for the Treatment of Cancer. — J Med Chem

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7DM	Abcam A-549 SKP2 KO	Cancer cell line	Male
CVCL_C7EA	Abcam HCT 116 SKP2 KO	Cancer cell line	Male
CVCL_C7EQ	Abcam THP-1 SKP2 KO	Cancer cell line	Male
CVCL_D8AD	Ubigene A-549 SKP2 KO	Cancer cell line	Male
CVCL_D8V6	Ubigene HCT 116 SKP2 KO	Cancer cell line	Male
CVCL_D9RN	Ubigene HEK293 SKP2 KO	Transformed cell line	Female
CVCL_E0NG	Ubigene HeLa SKP2 KO	Cancer cell line	Female
CVCL_TL39	HAP1 SKP2 (-) 1	Cancer cell line	Male
CVCL_TL40	HAP1 SKP2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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