DDR1 (Discoidin Domain Receptor Tyrosine Kinase 1): Collagen Receptor, Cancer, and Fibrosis Gene
DDR1 encodes a collagen-activated receptor tyrosine kinase involved in cell adhesion, proliferation, and matrix remodeling, with implications in cancer progression and fibrotic diseases.
Gene Information Card
| Symbol | DDR1 |
|---|---|
| Full Name | Discoidin Domain Receptor Tyrosine Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 780 ncbi.nlm.nih.gov/gene/780 |
| Ensembl ID | ENSG00000204580 |
| UniProt ID | Q08345 |
| OMIM ID | 600408 |
| HGNC ID | 2730 |
| Aliases | CAK, DDR, EDDR1, NEP, NTRK4, PTK3A, RTK6, TRKE |
Description
DDR1 (Discoidin Domain Receptor Tyrosine Kinase 1) is a member of the discoidin domain receptor (DDR) family of receptor tyrosine kinases (RTKs). Unlike most RTKs that bind soluble growth factors, DDR1 is activated by native collagens (types I-V), which are major components of the extracellular matrix (ECM). Upon collagen binding, DDR1 undergoes autophosphorylation and activates downstream signaling pathways, including MAPK, PI3K/AKT, and NF-κB. DDR1 plays a critical role in cell adhesion, migration, proliferation, differentiation, and matrix remodeling. It is widely expressed in epithelial cells, and its dysregulation is implicated in various cancers, fibrotic diseases (e.g., pulmonary fibrosis, liver fibrosis), atherosclerosis, and inflammatory conditions. DDR1 has also been identified as a receptor for the collagen domain of C1q, linking it to immune and complement pathways. Alternative splicing produces multiple isoforms (DDR1a, DDR1b, DDR1c, DDR1d, DDR1e) with distinct functions and tissue distributions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | DDR1 overexpression promotes tumor cell invasion, proliferation, and metastasis via collagen-induced signaling (MAPK, PI3K/AKT). It also contributes to a reactive tumor microenvironment and drug resistance. | COSMIC, PubMed (multiple studies) |
| Pulmonary Fibrosis | DDR1 activation by collagen in lung fibroblasts and epithelial cells drives myofibroblast differentiation and excessive ECM deposition, leading to fibrosis. | PubMed, ClinVar |
| Liver Fibrosis | DDR1 is upregulated in hepatic stellate cells and promotes collagen production and fibrogenesis in chronic liver disease. | PubMed |
| Atherosclerosis | DDR1 in vascular smooth muscle cells and macrophages contributes to plaque formation and vascular remodeling. | PubMed |
| Inflammatory Bowel Disease (IBD) | DDR1 expression is altered in intestinal epithelium, affecting mucosal healing and inflammation. | PubMed |
| Renal Fibrosis | DDR1 mediates tubular epithelial cell injury and interstitial fibrosis in chronic kidney disease. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.9 | Low |
| Breast | 12.3 | Medium |
| Colon | 10.1 | Medium |
| Kidney | 9.5 | Low |
| Liver | 4.2 | Low |
| Lung | 11.8 | Medium |
| Ovary | 13.5 | Medium |
| Pancreas | 7.8 | Low |
| Skin | 15.2 | Medium |
| Stomach | 9.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 18.5 | High expression; collagen-induced signaling |
| MCF7 (Breast Carcinoma) | 22.1 | High expression; promotes invasion |
| HepG2 (Liver Carcinoma) | 6.3 | Low expression |
| HeLa (Cervical Carcinoma) | 14.7 | Medium expression |
| K562 (Leukemia) | 3.2 | Low expression |
| HT-29 (Colon Carcinoma) | 16.8 | Medium-high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1654C>T (p.Arg552Cys) | Missense | Rare (<0.01%) | Potential alteration in kinase domain; functional impact unclear |
| c.2071A>G (p.Thr691Ala) | Missense | Rare (<0.01%) | Located in kinase domain; may affect catalytic activity |
| c.244G>A (p.Val82Met) | Missense | Rare (<0.01%) | In discoidin domain; may affect collagen binding |
| c.1129G>A (p.Asp377Asn) | Missense | Rare (<0.01%) | In extracellular domain; potential impact on ligand binding |
| c.2542C>T (p.Arg848Trp) | Missense | Rare (<0.01%) | In kinase domain; potential gain-of-function in some cancers |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in DDR1 are rare and not well characterized. Complete knockout in mice is viable but leads to defects in mammary gland development, cochlear hair cell function, and vascular integrity. In humans, no clear loss-of-function disease phenotype has been established, suggesting functional redundancy with DDR2 or other RTKs.
Gain of Function (GOF)
Gain-of-function mutations or overexpression of DDR1 are common in cancers. These mutations often lead to constitutive or enhanced collagen-independent activation, promoting tumor cell survival, invasion, and metastasis. Specific activating mutations have been reported in the kinase domain in some solid tumors.
Dominant Negative (DN)
Dominant-negative effects have been observed with certain DDR1 splice variants (e.g., DDR1d and DDR1e) that lack the kinase domain. These isoforms can dimerize with full-length DDR1 and inhibit its signaling, potentially acting as endogenous regulators. Pathogenic dominant-negative mutations are not well documented.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Focal adhesion (KEGG: hsa04510)
• ECM-receptor interaction (KEGG: hsa04512)
• Rap1 signaling pathway (KEGG: hsa04015)
• Ras signaling pathway (KEGG: hsa04014)
• NF-kappa B signaling pathway (KEGG: hsa04064)
Protein Summary
DDR1 is a single-pass type I transmembrane receptor tyrosine kinase. The protein consists of an extracellular region containing a discoidin (DS) domain and a DS-like domain, which mediate collagen binding, followed by a transmembrane helix and an intracellular tyrosine kinase domain. Collagen binding induces receptor dimerization and autophosphorylation of specific tyrosine residues in the kinase domain, creating docking sites for downstream signaling molecules. DDR1 signaling regulates cell adhesion, migration, proliferation, and matrix remodeling. It is expressed as multiple isoforms (a-e) generated by alternative splicing, which differ in the juxtamembrane region and kinase domain. DDR1 is a key mediator of cellular responses to the extracellular matrix and is implicated in tissue development, wound healing, and pathological conditions such as cancer and fibrosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DDR1 Knockout HEK293 Cell Line | EDJ-KQ2579 | Human | 780 | Details Get a Quote |
| DDR1 Knockout HeLa Cell Line | EDJ-KQ18335 | Human | 780 | Details Get a Quote |
| DDR1 Knockout A-549 Cell Line | EDJ-KQ23264 | Human | 780 | Details Get a Quote |
| DDR1 Knockout HCT 116 Cell Line | EDJ-KQ23265 | Human | 780 | Details Get a Quote |
| Ddr1 Knockout CT26 Cell Line | EDJ-KZ180 | Mouse | 12305 | Details Get a Quote |
| DDR1 Overexpression HEK293T Stable Cell Line | EDJ-GQ118 | Human | 780 | Details Get a Quote |
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