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FLASH GENE
Symbol DDR1 contributors: mct/shn - updated : 14-06-2015
HGNC name discoidin domain receptor tyrosine kinase 1
HGNC id 2730
Location 6p21.3      Physical location : 2.144.847 - 30.867.931
Synonym name
  • epithelial discoidin domain receptor 1
  • discoidin domain receptor family, member 1
  • kinase, neurotrophic tyrosine kinase receptor type 4
  • protein tyrosine kinase 3A
  • CD167 antigen-like family member A
  • discoidin domain receptor 1
  • PTK3A protein tyrosine kinase 3A
  • cell adhesion kinase
  • mammary carcinoma kinase 10
  • neuroepithelial tyrosine kinase
  • neurotrophic tyrosine kinase
  • receptor, type 4
  • protein-tyrosine kinase RTK-6
  • tyrosine kinase DDR
  • tyrosine-protein kinase CAK
  • Synonym symbol(s) CAK, EDDR1, NTRK4, PTK3A, RTK6, DDR, NEP, PTK3, TRKE, CD167, MCK10
    EC.number 2.7.10.1, 2.7.1.114
    DNA
    TYPE functioning gene
    STRUCTURE 15.61 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - DDR1 - D6S1615 - D5S1454 - cen
    Physical map
    LOC346173 6p21.32 similar to Succinyl-CoA ligase [ADP-forming] beta-chain, mitochondrial precursor (Succinyl-CoA synthetase, betaA chain) (SCS-betaA) (ATP-specific succinyl-CoA synthetase beta subunit) RANP1 6p21.32 RAN, member RAS oncogene family pseudogene 1 HLA-E 6p21.3 major histocompatibility complex, class I, E GNL1 6p21.3 guanine nucleotide binding protein-like 1 PRR3 6p21.32 proline-rich polypeptide 3 ABCF1 6p21.33 ATP-binding cassette, sub-family F (GCN20), member 1 PPP1R10 6p21.3 protein phosphatase 1, regulatory subunit 10 MRPS18B 6p21.3 mitochondrial ribosomal protein S18B C6orf134 6p21.32 chromosome 6 open reading frame 134 C6orf136 6p21.32 chromosome 6 open reading frame 136 DHX16 6p21.3 DEAH (Asp-Glu-Ala-His) box polypeptide 16 KIAA1949 6p21.3 KIAA1949 protein NRM 6p21.31 nurim (nuclear envelope membrane protein) MDC1 6pter-p21.3 mediator of DNA damage checkpoint 1 OK/SW-cl.56 6p21.32 beta 5-tubulin FLOT1 6p21.3 flotillin 1 IER3 6p21.3 immediate early response 3 DDR1 6p21.3 discoidin domain receptor family, member 1 VARS2L 6p21.33 valyl-tRNA synthetase 2-like GTF2H4 6p21.3 general transcription factor IIH, polypeptide 4, 52kDa LOC389376 6 similar to GSGL541 DPCR1 6p21.32 similar to GSGL541 LOC389377 6 similar to KMQK697 C6orf15 6p21.3 chromosome 6 open reading frame 15 PSORS1C1 6p21.3 psoriasis susceptibility 1 candidate 1 CDSN 6p21.3 corneodesmosin PSORS1C2 6p21.3 psoriasis susceptibility 1 candidate 2 C6orf18 6p21.3 chromosome 6 open reading frame 18 TCF19 6p21.3 transcription factor 19 (SC1) POU5F1 6p21.31 POU domain, class 5, transcription factor 1 LOC253018 6p21.32 hypothetical protein LOC253018 LOC391911 6 similar to HLA-B-associated transcript 1A; HLA-B associated transcript 1A; HLA-B associated transcript 1; Nuclear RNA helicase
    RNA
    TRANSCRIPTS type messenger
    text
  • an A2RE-like sequence (PMID:22077590)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 splicing 3877 101 913 widely 2008 18065762
  • also known as DDR1b
  • lacking an alternate in-frame segment compared to variant 3
  • being the predominant isoform
  • 19 splicing 3840 97 876 widely 2008 18065762
  • also known as DDR1a
  • lacking two alternate in-frame segments compared to variant 3
  • lacking an internal coding exon
  • 17 splicing 3678 101.7 919 widely 2008 18065762
  • also known as DDR1c
  • 17 splicing 3801 - 894 - 2008 18065762
    15 splicing 3304 - 508 - 2008 18065762
    14 splicing 3222 - 767 - 2008 18065762
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately Homo sapiens
    Digestivemouth   highly
    Lymphoid/Immunespleen   highly Homo sapiens
     thymus   moderately Homo sapiens
    Nervousbrainforebraincerebral cortex   Homo sapiens
    Reproductivefemale systemplacenta  moderately Homo sapiens
     male systemtestis  moderately
    Respiratorylung    
    Skin/Tegumentskin     Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentralwhite matter   Homo sapiens
    Nervouscentralgray matter   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
     epithelial cell
    Nervousoligodendrocyte Homo sapiens
    cell lineage myelin oligodendrocytes (
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 18 aa signal peptide
  • a N terminal discoidin domain, similar to the Dictyostelium discoideum lectin discoid 1 necessary for collagen binding
  • an hydrophilic proline/glycine rich region interrupted by a predicted transmembrane segment
  • a C terminal kinase domain
  • an F5/8 type C domain
  • a protein kinase domain
  • conjugated GlycoP
    mono polymer dimer
    HOMOLOGY
    interspecies ortholog to Ddr1, Rattus norvegicus
    ortholog to Ddr1, Mus musculus
    ortholog to DDR1, Pan troglodytes
    ortholog to ddr1, Danio rerio
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • insulin receptor subfamily
  • discoidin domains receptor family
  • CATEGORY adhesion , enzyme , receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,nuclear envelope,int
    text
  • single-pass type I membrane
  • integral to plasma membrane
  • basic FUNCTION
  • may be involved in cell-cell interactions and recognition
  • receptor tyrosine kinase that acts as a collagen IV adhesion receptor
  • plays an important role as a collagen receptor, mediating intimal thickening after vascular injury
  • a key mediator of the stromal-epithelial interaction during ductal morphogenesis in the mammary gland
  • central mediator of smooth muscle cell migration
  • required for cell-mediated calcification of the matrix
  • mediates an important mechanism for atherosclerotic calcification
  • regulates the stabilization of cell surface E-cadherin and E-cadherin-mediated cell aggregation
  • its expression increases epithelial plasticity
  • promotes cell-cell adhesion and differentiation through stabilization of E-cadherin, which is mediated by CDC42 inactivation
  • promotes E-cadherin-mediated adhesion
  • exerts prosurvival effect, at least in part, through the functional interaction with NOTCH1
  • acts as a novel upstream regulator for Notch1 signaling, that Notch1 functions as an important effector for DDR1-mediated survival in both the TP53-dependent and p53-independent responses to genotoxic stress
  • nonintegrin tyrosine kinase receptor for collagen implicated in cell adhesion, proliferation, and extracellular matrix remodeling
  • plays an important role in the pathogenesis of renal disease via enhanced inflammation
  • DDR1 and DDR2 are receptor tyrosine kinases that signal in response to collagen
  • while DDR1b clusters co-localized with non-fibrillar collagen, DDR1b/DDR2 filamentous structures associated with collagen fibrils
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • existing as a disulfide-linked dimer in transfected as well as endogenously expressing cells
  • could be an important constituent of myelin
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
    ATP
    protein
  • collagen type I
  • direct TP53 target gene and can be functionally activated/phosphorylated in a TP53-dependent manner
  • Nck2 and Shp-2
  • kidney and brain protein protein KIBRA
  • DDR1 stabilized E-cadherin through inactivation of CDC42
  • NOTCH1 protein is an interacting partner of DDR1 receptor
  • cell & other
    REGULATION
    activated by collagen type I, II, III, IV and V
    by TP53
    triple-helical collagen
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast, ovarian, esophageal, child brain tumors
    constitutional     --over  
    strongly increased in the obstructed kidney
    tumoral somatic mutation      
    occasionally mutated in lung cancer and leukemia
    Susceptibility to schizophrenia
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousurinary 
    Inhibition of DDR1 expression or activity may represent a novel therapeutic target against the progression of renal diseases
    immunologyinflammatory 
    blockade of collagen-receptor DDR1 might serve as an important new therapeutic concept in progressive fibrotic and inflammatory diseases in the future
    neurologyneurodegenerative 
    DDR1 and DDR2 inhibition is a potential target to clear neurotoxic proteins and reduce inflammation in neurodegeneration
    ANIMAL & CELL MODELS
  • DDR1-null mice have smooth muscle cells that display reduced attachment to collagen, reduced proliferation on collagen, reduced migration toward collagen, reduced MMP2 and MMP2 expression, and targeted disruption of the DDR1 gene reduced neointimal growth after carotid injury
  • DDR1-null mice are viable but smaller in size, mutant females were unable to bear offspring, and unable unable to lactate which is caused by hyperproliferation and abnormal branching of mammary ducts
  • mice DDR1(-/-) smooth muscle cell exhibited impaired attachment to and migration toward a type I collagen substrate and MMP-2 and MMP-9 activities were concomitantly reduced