TISIDB

Summary
Symbol	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
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	Cytoplasmic vesicle, secretory vesicle, acrosome inner membrane Single-pass type I membrane protein Note=Inner acrosomal membrane of spermatozoa. Internalized upon binding of Measles virus, Herpesvirus 6 or Neisseria gonorrhoeae, which results in an increased susceptibility of infected cells to complement-mediated injury. In cancer cells or cells infected by Neisseria, shedding leads to a soluble peptide.
Domain	PF00084 Sushi repeat (SCR repeat)
Function	Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity. ; FUNCTION: (Microbial infection) A number of viral and bacterial pathogens seem to bind MCP in order to exploit its immune regulation property and directly induce an immunosuppressive phenotype in T-cells.; FUNCTION: (Microbial infection) Acts as a receptor for Adenovirus subgroup B2 and Ad3. ; FUNCTION: (Microbial infection) Acts as a receptor for cultured Measles virus. ; FUNCTION: (Microbial infection) Acts as a receptor for Herpesvirus 6/HHV-6. ; FUNCTION: (Microbial infection) May act as a receptor for pathogenic bacteria Neisseria and Streptococcus pyogenes (PubMed:7708671, PubMed:9379894, PubMed:11260136, PubMed:11971006).

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002285 lymphocyte activation involved in immune response GO:0002286 T cell activation involved in immune response GO:0002292 T cell differentiation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002455 humoral immune response mediated by circulating immunoglobulin GO:0002456 T cell mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002521 leukocyte differentiation GO:0002526 acute inflammatory response GO:0002673 regulation of acute inflammatory response GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002699 positive regulation of immune effector process GO:0002920 regulation of humoral immune response GO:0006956 complement activation GO:0006958 complement activation, classical pathway GO:0006959 humoral immune response GO:0007159 leukocyte cell-cell adhesion GO:0007219 Notch signaling pathway GO:0007338 single fertilization GO:0008593 regulation of Notch signaling pathway GO:0009566 fertilization GO:0016064 immunoglobulin mediated immune response GO:0016485 protein processing GO:0019058 viral life cycle GO:0019724 B cell mediated immunity GO:0022407 regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0030098 lymphocyte differentiation GO:0030217 T cell differentiation GO:0030260 entry into host cell GO:0030449 regulation of complement activation GO:0032613 interleukin-10 production GO:0032653 regulation of interleukin-10 production GO:0032733 positive regulation of interleukin-10 production GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0035581 sequestering of extracellular ligand from receptor GO:0042098 T cell proliferation GO:0042102 positive regulation of T cell proliferation GO:0042110 T cell activation GO:0042129 regulation of T cell proliferation GO:0043379 memory T cell differentiation GO:0043380 regulation of memory T cell differentiation GO:0043382 positive regulation of memory T cell differentiation GO:0044409 entry into host GO:0045066 regulatory T cell differentiation GO:0045580 regulation of T cell differentiation GO:0045582 positive regulation of T cell differentiation GO:0045589 regulation of regulatory T cell differentiation GO:0045591 positive regulation of regulatory T cell differentiation GO:0045619 regulation of lymphocyte differentiation GO:0045621 positive regulation of lymphocyte differentiation GO:0045785 positive regulation of cell adhesion GO:0046651 lymphocyte proliferation GO:0046718 viral entry into host cell GO:0050670 regulation of lymphocyte proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050727 regulation of inflammatory response GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050870 positive regulation of T cell activation GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0051604 protein maturation GO:0051701 interaction with host GO:0051806 entry into cell of other organism involved in symbiotic interaction GO:0051828 entry into other organism involved in symbiotic interaction GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070613 regulation of protein processing GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0071593 lymphocyte aggregation GO:0071604 transforming growth factor beta production GO:0071634 regulation of transforming growth factor beta production GO:0071636 positive regulation of transforming growth factor beta production GO:0072376 protein activation cascade GO:1900115 extracellular regulation of signal transduction GO:1900116 extracellular negative regulation of signal transduction GO:1902105 regulation of leukocyte differentiation GO:1902107 positive regulation of leukocyte differentiation GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion GO:1903317 regulation of protein maturation GO:1903706 regulation of hemopoiesis GO:1903708 positive regulation of hemopoiesis GO:2000257 regulation of protein activation cascade
Molecular Function	GO:0001618 virus receptor activity GO:0045296 cadherin binding GO:0050839 cell adhesion molecule binding
Cellular Component	GO:0001669 acrosomal vesicle GO:0002079 inner acrosomal membrane GO:0002080 acrosomal membrane GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction GO:0030141 secretory granule GO:0030659 cytoplasmic vesicle membrane GO:0030667 secretory granule membrane GO:0097223 sperm part GO:0098589 membrane region GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04610 Complement and coagulation cascades
Reactome	R-HSA-166658: Complement cascade R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-977606: Regulation of Complement cascade

Summary
Symbol	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD46 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

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Literatures describing the relation between CD46 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23474221	Breast Carcinoma; Lung Carcinoma; Ovarian Carcinoma	Inhibit immunity	The therapeutic potential of anticancer antibodies is limited by the resistance of tumor cells to complement-mediated attack, primarily through the over-expression of membrane complement regulatory proteins (mCRPs: CD46, CD55 and CD59). Delivery of chemically stabilized anti-mCRP siRNAs using cationic lipoplexes, AtuPLEXes, to HER2-over-expressing BT474, SK-BR-3 (breast), SKOV3 (ovarian) and Calu-3 (lung) cancer cells reduced mCRPs expression by 85-95%.

Summary
Symbol	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
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 CD46 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	NA/NS	NA/NS
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	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
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 CD46 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	-0.139	0.685
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.006	0.998
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.229	0.902
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.211	0.528
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.003	0.999
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.472	0.864
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.097	0.843
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.198	0.927
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.063	0.98
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.065	0.975
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	0.704	0.819
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.006	0.944

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD46 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
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	3.7	2.7	1	1
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	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD46. 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	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD46. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD46. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD46. 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	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD46 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD46 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD46
Name	CD46 molecule, complement regulatory protein
Aliases	TRA2.10; MGC26544; antigen identified by monoclonal antibody TRA-2-10; membrane cofactor protein (CD46, trop ......
Chromosomal Location	1q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD46 collected from DrugBank database.

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

Browse CD46