TISIDB

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	-
Domain	PF00888 Cullin family PF10557 Cullin protein neddylation domain
Function	Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. Seems to be involved in proteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor.

> Gene Ontology [ TOP ]
Biological Process	GO:0000082 G1/S transition of mitotic cell cycle GO:0006816 calcium ion transport GO:0007050 cell cycle arrest GO:0038127 ERBB signaling pathway GO:0038128 ERBB2 signaling pathway GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044843 cell cycle G1/S phase transition GO:0045786 negative regulation of cell cycle GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0072511 divalent inorganic cation transport GO:0097193 intrinsic apoptotic signaling pathway
Molecular Function	GO:0004842 ubiquitin-protein transferase activity GO:0005216 ion channel activity GO:0005261 cation channel activity GO:0005262 calcium channel activity GO:0015085 calcium ion transmembrane transporter activity GO:0015267 channel activity GO:0019787 ubiquitin-like protein transferase activity GO:0022803 passive transmembrane transporter activity GO:0022838 substrate-specific channel activity GO:0031625 ubiquitin protein ligase binding GO:0044389 ubiquitin-like protein ligase binding GO:0046873 metal ion transmembrane transporter activity GO:0061630 ubiquitin protein ligase activity GO:0061659 ubiquitin-like protein ligase activity GO:0072509 divalent inorganic cation transmembrane transporter activity
Cellular Component	GO:0000151 ubiquitin ligase complex GO:0031461 cullin-RING ubiquitin ligase complex GO:0031466 Cul5-RING ubiquitin ligase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04120 Ubiquitin mediated proteolysis
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983168: Antigen processing R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-1643685: Disease R-HSA-8863795: Downregulation of ERBB2 signaling R-HSA-162906: HIV Infection R-HSA-162909: Host Interactions of HIV factors R-HSA-168256: Immune System R-HSA-5663205: Infectious disease R-HSA-162582: Signal Transduction R-HSA-1227986: Signaling by ERBB2 R-HSA-180585: Vif-mediated degradation of APOBEC3G

> KEGG and Reactome Pathway

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KEGG

hsa04120 Ubiquitin mediated proteolysis

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-983168: Antigen processing
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1643685: Disease
R-HSA-8863795: Downregulation of ERBB2 signaling
R-HSA-162906: HIV Infection
R-HSA-162909: Host Interactions of HIV factors
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-162582: Signal Transduction
R-HSA-1227986: Signaling by ERBB2
R-HSA-180585: Vif-mediated degradation of APOBEC3G

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CUL5 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CUL5 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.53	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CUL5 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.005	0.987
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.129	0.925
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.105	0.914
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.301	0.353
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.262	0.878
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.356	0.859
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.123	0.727
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.076	0.963
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.187	0.919
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.001	0.999
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.417	0.788
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.013	0.845

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CUL5 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	21.4	0	21.4	0.081
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	0	30	0.528
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	1.4	6	0.177
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	1.7	5.7	0.231
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CUL5. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CUL5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CUL5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CUL5. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CUL5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CUL5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CUL5
Name	cullin 5
Aliases	VACM-1; VACM1; CUL-5; Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1); Vasopressin-activated ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CUL5 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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