Tyrosine kinase that functions as 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. ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein] Present in an inactive state in the absence of collagen binding and phosphorylation by SRC. Tyrosine phosphorylation enhances the affinity for ATP and the catalytic activity. Binds hydroxyproline-rich sequence motifs in fibrillar, glycosylated collagen, such as the GQOGVMGFO motif, where O stands for hydroxyproline. Interacts with SRC. Interacts (tyrosine phosphorylated) with SHC1. Widely expressed. Detected in lung, ovary, skin and in testis Leydig cells (at protein level). Widely expressed. Detected at high levels in heart, lung, skeletal muscle, central nervous system (CNS) and kidney, and at lower levels in brain and testis. Detected in chondrocytes in tibia growth plates of young mice. Up-regulated during osteoblast differentiation (in vitro). Up-regulated in cartilage from mice with osteoarthritis. N-glycosylated. Tyrosine phosphorylated in response to collagen binding. Phosphorylated by SRC; this is required for activation and subsequent autophosphorylation on additional tyrosine residues (By similarity). Defects in Ddr2 are the cause of the smallie (sli) phenotype. Smallie mice show distinct dwarfing, with reduced body mass and reduced bone mineral content. Mice also have mild craniofacial deformities, such as protuberant eyes and snub noses. Smallie mice have a reduced life span, with about half of them dying within 6 months. Matings between male and female smallie mice do not yield any offspring. The levels of circulating steroid hormones remain at a level corresponding to prepubertal wild-type mice. Adult testes exhibit much reduced numbers of spermatids with atrophy of spermatogonia, Sertoli and Leydig cells. Ovaries show an absence of corpora lutea. Mice are born at the expected Mendelian rate, but fail to thrive, resulting in much reduced adult body weight and dwarfing. They exhibit shortening of long bones, irregular growth of flat bones and a shortened snout. Young mice show shortened growth plates in long bones and impaired chondrocyte proliferation. Likewise, cultured fibroblasts from mutant mice show reduced proliferation. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. According to PubMed:18483174 Ddr2 is required for male and female fertility, since smallie mice with a 150 kb deletion that extends into the Ddr2 gene are sterile. Smallie males have defects in spermatogenesis (PubMed:19681157). On the other hand, the fertility status of mice with a targeted disruption of the Ddr2 gene has not been mentioned (PubMed:11375938). Thus, the infertility of smallie mice may be due to some additional, not yet identified defect.