TISIDB

Summary
Symbol	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
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	Cytoplasm, perinuclear region Golgi apparatus, trans-Golgi network Cell junction, focal adhesion Note=Localizes to the perinuclear area and to the trans-Golgi network. Also seen on the plasma membrane, probably at focal adhesions.
Domain	PF00069 Protein kinase domain PF10409 C2 domain of PTEN tumour-suppressor protein
Function	Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1.

> Gene Ontology [ TOP ]
Biological Process	GO:0006892 post-Golgi vesicle-mediated transport GO:0006896 Golgi to vacuole transport GO:0006898 receptor-mediated endocytosis GO:0007009 plasma membrane organization GO:0007029 endoplasmic reticulum organization GO:0007030 Golgi organization GO:0007034 vacuolar transport GO:0007041 lysosomal transport GO:0010721 negative regulation of cell development GO:0010975 regulation of neuron projection development GO:0010977 negative regulation of neuron projection development GO:0016482 cytosolic transport GO:0031345 negative regulation of cell projection organization GO:0032984 macromolecular complex disassembly GO:0034067 protein localization to Golgi apparatus GO:0043241 protein complex disassembly GO:0043624 cellular protein complex disassembly GO:0045665 negative regulation of neuron differentiation GO:0048193 Golgi vesicle transport GO:0050768 negative regulation of neurogenesis GO:0051261 protein depolymerization GO:0051961 negative regulation of nervous system development GO:0072318 clathrin coat disassembly GO:0072319 vesicle uncoating GO:0072583 clathrin-dependent endocytosis GO:0072600 establishment of protein localization to Golgi GO:0072657 protein localization to membrane GO:0072659 protein localization to plasma membrane GO:0090002 establishment of protein localization to plasma membrane GO:0090150 establishment of protein localization to membrane GO:0090160 Golgi to lysosome transport GO:1990778 protein localization to cell periphery
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0030332 cyclin binding
Cellular Component	GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-421837: Clathrin derived vesicle budding R-HSA-8856828: Clathrin-mediated endocytosis R-HSA-432722: Golgi Associated Vesicle Biogenesis R-HSA-199991: Membrane Trafficking R-HSA-5653656: Vesicle-mediated transport R-HSA-199992: trans-Golgi Network Vesicle Budding

Summary
Symbol	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GAK 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	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
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 GAK 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	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
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 GAK 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	0.023	0.937
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.205	0.919
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.189	0.898
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.332	0.331
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.261	0.919
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.427	0.899
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.14	0.69
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.283	0.849
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.075	0.966
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.865	0.585
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	0.834	0.717
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.065	0.257

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GAK 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	5.9	-5.9	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	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	14.8	2.7	12.1	0.0439
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	14.8	3.4	11.4	0.0746
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	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	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	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
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	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GAK. 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	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GAK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GAK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GAK. 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	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GAK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GAK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GAK
Name	cyclin G associated kinase
Aliases	DNAJC26; auxilin-2; DNAJ26; Cyclin-G-associated kinase
Chromosomal Location	4p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GAK collected from DrugBank database.

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

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