TISIDB

Summary
Symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
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	Isoform 1: Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: Isoform 2: Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: Isoform 3: Secreted ; SUBCELLULAR LOCATION: Isoform 4: Cell membrane; Single-pass type I membrane protein.
Domain	PF00754 F5/8 type C domain PF07714 Protein tyrosine kinase
Function	Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11.

> Gene Ontology [ TOP ]
Biological Process	GO:0001558 regulation of cell growth GO:0001763 morphogenesis of a branching structure GO:0001952 regulation of cell-matrix adhesion GO:0002011 morphogenesis of an epithelial sheet GO:0007160 cell-matrix adhesion GO:0007423 sensory organ development GO:0007565 female pregnancy GO:0007566 embryo implantation GO:0007589 body fluid secretion GO:0007595 lactation GO:0010715 regulation of extracellular matrix disassembly GO:0010810 regulation of cell-substrate adhesion GO:0014812 muscle cell migration GO:0014909 smooth muscle cell migration GO:0016049 cell growth GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0022612 gland morphogenesis GO:0022617 extracellular matrix disassembly GO:0030198 extracellular matrix organization GO:0030879 mammary gland development GO:0031589 cell-substrate adhesion GO:0032941 secretion by tissue GO:0035239 tube morphogenesis GO:0038063 collagen-activated tyrosine kinase receptor signaling pathway GO:0038065 collagen-activated signaling pathway GO:0038083 peptidyl-tyrosine autophosphorylation GO:0043062 extracellular structure organization GO:0043583 ear development GO:0044319 wound healing, spreading of cells GO:0044706 multi-multicellular organism process GO:0046777 protein autophosphorylation GO:0048732 gland development GO:0048754 branching morphogenesis of an epithelial tube GO:0050878 regulation of body fluid levels GO:0060443 mammary gland morphogenesis GO:0060444 branching involved in mammary gland duct morphogenesis GO:0060562 epithelial tube morphogenesis GO:0060603 mammary gland duct morphogenesis GO:0060749 mammary gland alveolus development GO:0061138 morphogenesis of a branching epithelium GO:0061180 mammary gland epithelium development GO:0061302 smooth muscle cell-matrix adhesion GO:0061377 mammary gland lobule development GO:0090504 epiboly GO:0090505 epiboly involved in wound healing GO:1903053 regulation of extracellular matrix organization
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004714 transmembrane receptor protein tyrosine kinase activity GO:0005518 collagen binding GO:0019199 transmembrane receptor protein kinase activity GO:0038062 protein tyrosine kinase collagen receptor activity GO:0038064 collagen receptor activity
Cellular Component	GO:0043235 receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1474244: Extracellular matrix organization R-HSA-3000171: Non-integrin membrane-ECM interactions

Summary
Symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DDR1 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 DDR1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29489427	Urothelial Carcinoma	Resistant to immunotherapy	We examined the relationship between DDR alterations and response to PD-1/PD-L1 blockade. A higher response rate was observed in patients whose tumors harbored known or likely deleterious DDR alterations (80%) compared with DDR alterations of unknown significance (54%) and in those whose tumors were wild-type for DDR genes (19%; P < .001). DDR alterations are independently associated with response to PD-1/PD-L1 blockade in patients with metastatic urothelial carcinoma.

Summary
Symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
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 DDR1 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	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
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 DDR1 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	1.173	0.0113
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.46	0.716
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.711	0.0234
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.437	0.317
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1.076	0.696
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.373	0.913
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.121	0.826
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.662	0.707
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.375	0.837
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.057	0.978
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	-0.319	0.915
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.007	0.951

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of DDR1 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	3.7	6.8	-3.1	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	8.5	-4.8	0.66
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	22.2	6.2	16	0.53
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
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	7.9	3.7	4.2	0.636
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	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	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DDR1. 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	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DDR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DDR1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DDR1. 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	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DDR1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DDR1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Aliases	RTK6; CD167; NTRK4; PTK3A; EDDR1; discoidin domain receptor family, member 1; DDR; HGK2; MCK10; PTK3; TRKE; ......
Chromosomal Location	6p21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DDR1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting DDR1.

ID	Name	Drug Type	Targets	#Targets
DB00619	Imatinib	Small Molecule	ABL1, CSF1R, DDR1, KIT, NTRK1, PDGFRA, PDGFRB	7

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