Human Gene DDR1 (uc011gup.2) Description and Page Index
  Description: Homo sapiens discoidin domain receptor tyrosine kinase 1 (DDR1), transcript variant 2, mRNA.
RefSeq Summary (NM_013993): Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011].
Transcript (Including UTRs)
   Position: chr6_mann_hap4:2,200,400-2,216,014 Size: 15,615 Total Exon Count: 19 Strand: +
Coding Region
   Position: chr6_mann_hap4:2,204,592-2,215,154 Size: 10,563 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDMicroarray
RNA StructureProtein StructureOther SpeciesmRNA DescriptionsOther NamesModel Information
Methods
Data last updated: 2013-06-14

+  Sequence and Links to Tools and Databases
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-  Comments and Description Text from UniProtKB
  ID: DDR1_HUMAN
DESCRIPTION: RecName: Full=Epithelial discoidin domain-containing receptor 1; Short=Epithelial discoidin domain receptor 1; EC=2.7.10.1; AltName: Full=CD167 antigen-like family member A; AltName: Full=Cell adhesion kinase; AltName: Full=Discoidin receptor tyrosine kinase; AltName: Full=HGK2; AltName: Full=Mammary carcinoma kinase 10; Short=MCK-10; AltName: Full=Protein-tyrosine kinase 3A; AltName: Full=Protein-tyrosine kinase RTK-6; AltName: Full=TRK E; AltName: Full=Tyrosine kinase DDR; AltName: Full=Tyrosine-protein kinase CAK; AltName: CD_antigen=CD167a; Flags: Precursor;
FUNCTION: Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SUBUNIT: Homodimer. Interacts (via PPxY motif) with WWC1 (via WW domains) in a collagen-regulated manner. Forms a tripartite complex with WWC1 and PRKCZ, but predominantly in the absence of collagen. Interacts (tyrosine phosphorylated) with SHC1. Interacts with SRC. Interacts with MYH9. Interacts with CDH1. Interacts with PTPN11. Interacts with NCK2.
INTERACTION: O43639:NCK2; NbExp=3; IntAct=EBI-711879, EBI-713635; Q06124:PTPN11; NbExp=4; IntAct=EBI-711879, EBI-297779;
SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein.
SUBCELLULAR LOCATION: Isoform 2: Cell membrane; Single-pass type I membrane protein.
SUBCELLULAR LOCATION: Isoform 3: Secreted (Potential).
SUBCELLULAR LOCATION: Isoform 4: Cell membrane; Single-pass type I membrane protein.
TISSUE SPECIFICITY: Detected in T-47D, MDA-MB-175 and HBL-100 breast carcinoma cells, A-431 epidermoid carcinoma cells, SW48 and SNU-C2B colon carcinoma cells and Hs 294T melanoma cells (at protein level). Expressed at low levels in most adult tissues and is highest in the brain, lung, placenta and kidney. Lower levels of expression are detected in melanocytes, heart, liver, skeletal muscle and pancreas. Abundant in breast carcinoma cell lines. In the colonic mucosa, expressed in epithelia but not in the connective tissue of the lamina propria. In the thyroid gland, expressed in the epithelium of the thyroid follicles. In pancreas, expressed in the islets of Langerhans cells, but not in the surrounding epithelial cells of the exocrine pancreas. In kidney, expressed in the epithelia of the distal tubules. Not expressed in connective tissue, endothelial cells, adipose tissue, muscle cells or cells of hematopoietic origin.
DOMAIN: The Gly/Pro-rich domains may be required for an unusual geometry of interaction with ligand or substrates.
PTM: Autophosphorylated in response to fibrillar collagen binding.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
SIMILARITY: Contains 1 F5/8 type C domain.
SIMILARITY: Contains 1 protein kinase domain.
SEQUENCE CAUTION: Sequence=ACF47649.1; Type=Erroneous termination; Positions=287; Note=Translated as Cys; Sequence=BAE06103.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/DDR1ID40280ch6p21.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database: DDR1
CDC HuGE Published Literature: DDR1
Positive Disease Associations: Behcet Syndrome , Psoriasis , schizophrenia
Related Studies:
  1. Behcet Syndrome
    Elaine F Remmers et al. Nature genetics 2010, , Nature genetics. [PubMed 20622878]
  2. Psoriasis
    , , . [PubMed 0]
  3. Psoriasis
    , , . [PubMed 0]
           more ... click here to view the complete list

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  Microarray Expression Data
 
Expression ratio colors:

GNF Expression Atlas 2 Data from U133A and GNF1H Chips

      
      
      
     
    
     
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GNF Expression Atlas 1 Human Data on Affy U95 Chips

      
    
     
      
    
    
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -115.90271-0.428 Picture PostScript Text
3' UTR -319.80860-0.372 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000421 - Coagulation_fac_5/8-C_type_dom
IPR008979 - Galactose-bd-like
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_dom
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR008266 - Tyr_kinase_AS
IPR020635 - Tyr_kinase_cat_dom
IPR002011 - Tyr_kinase_rcpt_2_CS

Pfam Domains:
PF00069 - Protein kinase domain
PF00754 - F5/8 type C domain
PF07714 - Protein tyrosine kinase

SCOP Domains:
49785 - Galactose-binding domain-like
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure

3ZOS
- X-ray Chimera

4AG4
- X-ray Chimera

4BKI
- X-ray Chimera
To conserve bandwidth, only the images from the first 3 structures are shown.
4BKJ - X-ray Chimera
Chimera help

ModBase Predicted Comparative 3D Structure on Q08345
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
Jackson LabRGD    
Protein Sequence     
Alignment     

-  Descriptions from all associated GenBank mRNAs
  AK291621 - Homo sapiens cDNA FLJ75091 complete cds, highly similar to Homo sapiens discoidin domain receptor family, member 1 (DDR1),transcript variant 2, mRNA.
BC008716 - Homo sapiens discoidin domain receptor tyrosine kinase 1, mRNA (cDNA clone MGC:8681 IMAGE:2964574), complete cds.
BC013400 - Homo sapiens discoidin domain receptor tyrosine kinase 1, mRNA (cDNA clone MGC:3909 IMAGE:2964574), complete cds.
L20817 - Homo sapiens tyrosine protein kinase (CAK) gene, complete cds.
L57508 - Homo sapiens Cak receptor kinase mRNA, complete cds.
BC070070 - Homo sapiens discoidin domain receptor tyrosine kinase 1, mRNA (cDNA clone MGC:87336 IMAGE:5262509), complete cds.
AB210021 - Homo sapiens mRNA for DDR1 variant protein, partial cds, clone: fk11093.
L11315 - Homo sapiens receptor tyrosine kinase mRNA, complete cds.
AK294793 - Homo sapiens cDNA FLJ56035 complete cds, highly similar to Epithelial discoidin domain-containing receptor 1 precursor (EC 2.7.10.1).
AK295643 - Homo sapiens cDNA FLJ54797 complete cds, highly similar to Epithelial discoidin domain-containing receptor 1 precursor (EC 2.7.10.1).
Z29093 - H.sapiens EDDR1 gene for receptor tyrosine kinase.
X74979 - H.sapiens TRK E mRNA.
EU826614 - Homo sapiens soluble DDR1 variant 2 (DDR1) mRNA, complete cds, alternatively spliced.
EU826613 - Homo sapiens soluble DDR1 variant 1 (DDR1) mRNA, complete cds, alternatively spliced.
CU687028 - Synthetic construct Homo sapiens gateway clone IMAGE:100022861 5' read DDR1 mRNA.
AB463012 - Synthetic construct DNA, clone: pF1KB2260, Homo sapiens DDR1 gene for discoidin domain receptor tyrosine kinase 1, without stop codon, in Flexi system.
AK130776 - Homo sapiens cDNA FLJ27266 fis, clone TMS00356, highly similar to Epithelial discoidin domain receptor 1 precursor (EC 2.7.1.112).
AF353182 - Homo sapiens discoidin domain receptor DDR1d (DDR1) mRNA, partial cds, alternatively spliced.
AF353183 - Homo sapiens discoidin domain receptor DDR1e (DDR1) mRNA, partial cds, alternatively spliced.

-  Other Names for This Gene
  Alternate Gene Symbols: B5A975, B5A976, B7Z2K0, CAK, DDR1_HUMAN, EDDR1, NEP, NM_013993, NP_054699, NTRK4, PTK3A, Q08345, Q14196, Q16562, Q2L6H3, Q4LE50, Q5ST11, Q5ST12, Q6NSK4, Q9UD35, Q9UD36, Q9UD37, Q9UD86, Q9UDL2, RTK6, TRKE
UCSC ID: uc011gup.2
RefSeq Accession: NM_013993
Protein: Q08345 (aka DDR1_HUMAN