Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol DDR2 contributors: mct/pgu - updated : 15-01-2019
HGNC name discoidin domain receptor tyrosine kinase 2
HGNC id 2731
Corresponding disease
BPCVAO blepharophimosis, corneal vascularization, acro-osteolysis
SEMD5 spondyloepimetaphyseal dysplasia, type 5
Location 1q23.3      Physical location : 162.602.227 - 162.750.237
Synonym name
  • discoidin domain receptor family, member 2
  • hydroxyaryl-protein kinase
  • neurotrophic tyrosine kinase receptor related 3
  • tyrosylprotein kinase
  • cell migration-inducing protein 20
  • migration-inducing gene 16 protein
  • CD167 antigen-like family member B
    • Synonym symbol(s) PTK10, TRKR, TRKS, Tyro10, NTRKR3, TKT, MIG20a
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 155.31 kb     19 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 3252 94.3 855 - 2018 29709482
  • encoding the same isoform than variant 2
  • a 21 aa signal peptide of 2.4 kda
  • a 834 aa mature peptide of 94.4 kda
    • 18 splicing 3172 94.3 855 - 2018 29709482
  • differing in the 5' UTR compared to variant 1
  • encoding the same isoform than variant 1
  • a 21 aa signal peptide of 2.4 kda
  • a 834 aa mature peptide of 94.4 kda
    • 18 - 9290 - 855 - 2018 29709482
    18 - 9274 - 855 - 2018 29709482
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
     vessel   highly
    Digestivestomach   moderately
    Endocrineadrenal gland   highly
    Respiratoryrespiratory tracttrachea  highly
    Skin/Tegumentskin     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectiveinterstitial  predominantly Homo sapiens
    Muscular   moderately
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificchondrocyte Homo sapiens
    not specificfibroblast Homo sapiens
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text predominantly in umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • a N terminal extracellular discoidin domains, similar to the dictyostelium discoideum lectin discoid 1 and the milk fat globule membrane protein of mouse, and a domain unique to the DDRs (stalk region)
  • an hydrophilic proline/glycine rich region
  • interrupted by a predicted transmembrane segment (TM)
  • an F5/8 type C domain
  • a transmembrane region followed by a large cytoplasmic juxtamembrane domain
  • 14 tyrosine residues: four located in the extracellular juxtamembrane region, and the rest located in the kinase domain of the receptor
  • a C terminal kinase domain
    • conjugated GlycoP , PhosphoP
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Ddr2 (96.5 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • insulin receptor subfamily
    • CATEGORY adhesion , enzyme , receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • integral protein
  • single-pass type I membrane protein
    • basic FUNCTION
  • acting as a tyrosine kinase receptor for fibrillar collagen mediating fibroblast migration and proliferation
  • contributing to cutaneous wound healing
  • plays an important role in bone growth, and interaction of DDR2 with collagen is essential for proper skeletal growth
  • a critical role for type I collagen-dependent DDR2 signaling in the regulation of EMT
  • required for normal fibroblast spreading and migration independent of adhesion ligand and collagen activation of DDR2 tyrosine kinase
  • participates in hypoxia-induced breast cancer metastasis through the regulation of cell migration, invasion, and EMT
  • is a receptor tyrosine kinase that promotes the differentiation of bone-depositing cells, osteoblasts, and bone formation
  • DDR2 functions as an inhibitor of osteoclastogenesis, as well as a promoter of osteoblastogenesis
  • is critical for skeletal development and differentiation of marrow progenitor cells to osteoblasts while suppressing marrow adipogenesis
  • important for maintenance of osteoblast activity and suppression of marrow adipogenesis
  • DDR2 is likely a microenvironment sensor that regulates fibroblast migration in a collagen-rich environment
  • is a collagen-binding receptor tyrosine kinase that initiates delayed and sustained tyrosine phosphorylation signalling
  • DDR2 localisation is independent of integrin activation and the key DDR2 signalling effector SHC1
  • collagen-responsive receptor tyrosine kinase that regulates connective-tissue formation
  • is an important regulator of bone growth and resorption, both as a promoter of osteoblastogenesis and as an inhibitor of osteoclastogenesis
  • activated DDR2 has likely a role in the migration or function of melanocytes
  • DDR1 and DDR2 are receptor tyrosine kinases that signal in response to collagen
  • oligomeric form of DDR2 extracellular domain (ECD) displayed enhanced binding to collagen and inhibition of fibrillogenesis
    • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text
  • positive regulation of cell proliferation
    • PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • interaction with collagen II in the proliferative zone of the growth plate is responsible for controlling chondrocyte proliferation
  • DDR2 is also a receptor for another collagen type with relevance to bone growth, collagen X
  • DDR2 is involved in the collagen I-induced IL12A production via NFKB1 and JNK pathway
  • CBLB, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway
  • DDR2 mediates collagen-induced activation of MMP14 in human fibroblasts
  • SHC1 is a key validated downstream effector of DDR2 signalling and is essential for multiple biological functions such as axon regeneration
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SEMD5 , BPCVAO
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a powerful biomarker that can predict poor prognosis as well as peritoneal dissemination (PD)
    • Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerative 
    DDR1 and DDR2 inhibition is a potential target to clear neurotoxic proteins and reduce inflammation in neurodegeneration
    cancerdigestivecolon
    might be an effective therapeutic target for colorectal cancer
    osteoarticularboneostéoporosis
    DDR2 may be therapeutic for patients with osteoporosis
    cancerreproductivebreast
    may serve as an accessible therapeutic target for the treatment of breast cancer
    ANIMAL & CELL MODELS