TISIDB

Summary
Symbol	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
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	Nucleus Nucleus speckle
Domain	PF00069 Protein kinase domain
Function	Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3. Has pro-survival function and negatively regulates the apoptotic process. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000375 RNA splicing, via transesterification reactions GO:0000377 RNA splicing, via transesterification reactions with bulged adenosine as nucleophile GO:0000380 alternative mRNA splicing, via spliceosome GO:0000381 regulation of alternative mRNA splicing, via spliceosome GO:0000398 mRNA splicing, via spliceosome GO:0006397 mRNA processing GO:0006476 protein deacetylation GO:0007623 circadian rhythm GO:0008380 RNA splicing GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0018108 peptidyl-tyrosine phosphorylation GO:0018209 peptidyl-serine modification GO:0018210 peptidyl-threonine modification GO:0018212 peptidyl-tyrosine modification GO:0030330 DNA damage response, signal transduction by p53 class mediator GO:0033119 negative regulation of RNA splicing GO:0035601 protein deacylation GO:0042770 signal transduction in response to DNA damage GO:0043484 regulation of RNA splicing GO:0043516 regulation of DNA damage response, signal transduction by p53 class mediator GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator GO:0046777 protein autophosphorylation GO:0048024 regulation of mRNA splicing, via spliceosome GO:0048025 negative regulation of mRNA splicing, via spliceosome GO:0048511 rhythmic process GO:0050684 regulation of mRNA processing GO:0050686 negative regulation of mRNA processing GO:0072331 signal transduction by p53 class mediator GO:0090311 regulation of protein deacetylation GO:0090312 positive regulation of protein deacetylation GO:0098732 macromolecule deacylation GO:1901796 regulation of signal transduction by p53 class mediator GO:1901797 negative regulation of signal transduction by p53 class mediator GO:1902532 negative regulation of intracellular signal transduction GO:1903311 regulation of mRNA metabolic process GO:1903312 negative regulation of mRNA metabolic process GO:2001020 regulation of response to DNA damage stimulus GO:2001021 negative regulation of response to DNA damage stimulus
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0004712 protein serine/threonine/tyrosine kinase activity GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity GO:0043621 protein self-association GO:0048156 tau protein binding
Cellular Component	GO:0016604 nuclear body GO:0016607 nuclear speck

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-1538133: G0 and Early G1 R-HSA-453279: Mitotic G1-G1/S phases

Summary
Symbol	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DYRK1A 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	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
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 DYRK1A 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: 0.54	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	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
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 DYRK1A 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	0.135	0.527
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.131	0.938
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.134	0.917
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.158	0.615
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.15	0.953
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.549	0.863
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.134	0.729
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.073	0.968
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.365	0.856
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.678	0.553
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	1.251	0.459
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.134	0.0097

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of DYRK1A 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	1.4	2.3	0.469
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	1.7	2	0.532
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	11.1	6.2	4.9	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	25	14.3	10.7	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	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DYRK1A. 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	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DYRK1A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DYRK1A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DYRK1A. 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	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DYRK1A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DYRK1A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DYRK1A
Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
Aliases	DYRK1; DYRK; MNBH; HP86; MNB; MRD7; MNB/DYRK protein kinase; dual specificity YAK1-related kinase; hMNB; mnb ......
Chromosomal Location	21q22.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DYRK1A collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting DYRK1A.

ID	Name	Drug Type	Targets	#Targets
DB07608	N-(5-{[(2S)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1H-indazol-3-yl)benzamide	Small Molecule	DYRK1A	1

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