TISIDB

Summary
Symbol	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
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	Cell membrane Lipid-anchor Note=Present and active in lipid rafts. Membrane location is required for the phosphorylation of CD79A and CD79B (By similarity).
Domain	PF07714 Protein tyrosine kinase PF00017 SH2 domain PF00018 SH3 domain
Function	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose.

> Gene Ontology [ TOP ]
Biological Process	GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002790 peptide secretion GO:0002791 regulation of peptide secretion GO:0002793 positive regulation of peptide secretion GO:0006909 phagocytosis GO:0009306 protein secretion GO:0009914 hormone transport GO:0010817 regulation of hormone levels GO:0015833 peptide transport GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0023061 signal release GO:0030072 peptide hormone secretion GO:0030073 insulin secretion GO:0030100 regulation of endocytosis GO:0032024 positive regulation of insulin secretion GO:0038083 peptidyl-tyrosine autophosphorylation GO:0042886 amide transport GO:0043254 regulation of protein complex assembly GO:0046777 protein autophosphorylation GO:0046879 hormone secretion GO:0046883 regulation of hormone secretion GO:0046887 positive regulation of hormone secretion GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050764 regulation of phagocytosis GO:0050796 regulation of insulin secretion GO:0050851 antigen receptor-mediated signaling pathway GO:0050853 B cell receptor signaling pathway GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0060627 regulation of vesicle-mediated transport GO:0071800 podosome assembly GO:0071801 regulation of podosome assembly GO:0090087 regulation of peptide transport GO:0090276 regulation of peptide hormone secretion GO:0090277 positive regulation of peptide hormone secretion GO:1902115 regulation of organelle assembly GO:1903532 positive regulation of secretion by cell GO:1904951 positive regulation of establishment of protein localization
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity
Cellular Component	GO:0009898 cytoplasmic side of plasma membrane GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0031234 extrinsic component of cytoplasmic side of plasma membrane GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983695: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers R-HSA-168256: Immune System R-HSA-983705: Signaling by the B Cell Receptor (BCR)

Summary
Symbol	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between BLK 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	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
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

[ TOP ]

Statistical results of BLK 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	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
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

[ TOP ]

Points in the above scatter plot represent the expression difference of BLK 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	0.44	0.414
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.579	0.0628
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.404	0.585
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.112	0.852
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.135	0.923
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.081	0.961
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.988	0.2
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.139	0.297
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.05	0.384
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.129	0.0304
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	0.775	0.264
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.223	0.508

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of BLK 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	7.4	2.7	4.7	0.294
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	3.4	4	0.587
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	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of BLK. 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	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of BLK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by BLK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of BLK. 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	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of BLK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between BLK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Aliases	MGC10442; B lymphoid tyrosine kinase; MODY11; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk; ......
Chromosomal Location	8p23-p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting BLK collected from DrugBank database.

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

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