Discoidin domain-containing receptor 2

Function

Tyrosine kinase involved in the regulation of tissues remodeling. It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing.

Classification

Family (Pfam)

PF21114 DDR1-2_DS-like, PF00754 F5_F8_type_C, PF07714 PK_Tyr_Ser-Thr

InterPro

DDR1-2_DS-like, FA58C, Galactose-bd-like_sf, Kinase-like_dom_sf, Prot_kinase_dom, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_2_CS

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 5

• 2WUH X-ray 1.60A
• 2Z4F NMR
• 6FER X-ray 2.87A
• 7AYM X-ray 2.12A
• 7AZB X-ray 2.62A

A predicted model is available from AlphaFold.

Gene Ontology · 43

• GO:0016324 apical plasma membrane
• GO:0005925 focal adhesion
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0005524 ATP binding
• GO:0005518 collagen binding
• GO:0038062 protein tyrosine kinase collagen receptor activity
• GO:0004714 transmembrane receptor protein tyrosine kinase activity
• GO:0031214 biomineral tissue development
• GO:0007155 cell adhesion
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:1904385 cellular response to angiotensin
• GO:0071456 cellular response to hypoxia
• GO:0071560 cellular response to transforming growth factor beta stimulus
• GO:0035988 chondrocyte proliferation
• GO:0030199 collagen fibril organization
• GO:0038063 collagen-activated tyrosine kinase receptor signaling pathway
• GO:0003416 endochondral bone growth
• GO:0043066 negative regulation of apoptotic process
• GO:1901299 negative regulation of hydrogen peroxide-mediated programmed cell death
• GO:0001503 ossification
• GO:0018108 peptidyl-tyrosine phosphorylation
• GO:0032967 positive regulation of collagen biosynthetic process
• GO:0070374 positive regulation of ERK1 and ERK2 cascade
• GO:0090091 positive regulation of extracellular matrix disassembly
• GO:0010763 positive regulation of fibroblast migration
• GO:0048146 positive regulation of fibroblast proliferation
• GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
• GO:2000491 positive regulation of hepatic stellate cell activation
• GO:1904899 positive regulation of hepatic stellate cell proliferation
• GO:0010976 positive regulation of neuron projection development
• GO:0045669 positive regulation of osteoblast differentiation
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0045860 positive regulation of protein kinase activity
• GO:1904754 positive regulation of vascular associated smooth muscle cell migration
• GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
• GO:0090303 positive regulation of wound healing
• GO:0046777 protein autophosphorylation
• GO:0030500 regulation of bone mineralization
• GO:0010715 regulation of extracellular matrix disassembly
• GO:0034103 regulation of tissue remodeling
• GO:0035994 response to muscle stretch
• GO:0007165 signal transduction

Disease associations

• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome MONDO:0010077
• warburg-cinotti syndrome MONDO:0032579

Drugs targeting this protein · 1

• REGORAFENIB inhibitor

Related proteins · sequence + function similarity

• Discoidin domain-containing receptor 2 0.99
• Discoidin domain-containing receptor tyrosine kinase B 0.87
• Discoidin domain-containing receptor A 0.81
• Ephrin type-B receptor 2 0.74
• Ephrin type-B receptor 2 0.74
• Ephrin type-B receptor 2 0.74
• Ephrin type-B receptor 2 0.73
• Ephrin type-B receptor 5 0.73
• Ephrin type-B receptor 1-A 0.73
• Fibroblast growth factor receptor 0.73
• Ephrin type-B receptor 1-B 0.73
• Ephrin type-B receptor 1 0.73

Co-cited proteins · studied together in the literature

• Discoidin domain-containing receptor 2 1 shared papers
• Epithelial discoidin domain-containing receptor 1 1 shared papers
• SHC-transforming protein 1 1 shared papers
• Proto-oncogene tyrosine-protein kinase Src 1 shared papers
• Proto-oncogene tyrosine-protein kinase Src 1 shared papers

Literature · 23 cited papers

• Recurrent, activating variants in the receptor tyrosine kinase DDR2 cause Warburg-Cinotti syndrome. Am. J. Hum. Genet. · 2018
• Novel DDR2 mutation identified by whole exome sequencing in a Moroccan patient with spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type. Am. J. Med. Genet. A · 2016
• Transmembrane collagen receptors. Annu. Rev. Cell Dev. Biol. · 2011
• An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation. J. Bone Miner. Res. · 2011
• Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation. J. Bone Miner. Res. · 2010
• Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients. Hum. Mol. Genet. · 2010
• Crystallographic insight into collagen recognition by discoidin domain receptor 2. Structure · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications. Am. J. Hum. Genet. · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. J. Biol. Chem. · 2008
• Structural basis of the collagen-binding mode of discoidin domain receptor 2. EMBO J. · 2007
• … and 11 more in the literature graph