Discoidin domain-containing receptor 2

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Discoidin domain receptor tyrosine kinase 2

Rendering based on PDB 2WUH.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DDR2 ; MIG20a; NTRKR3; TKT; TYRO10
External IDs OMIM191311 MGI1345277 HomoloGene68505 ChEMBL: 5122 GeneCards: DDR2 Gene
EC number 2.7.10.1
RNA expression pattern
PBB GE DDR2 205168 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4921 18214
Ensembl ENSG00000162733 ENSMUSG00000026674
UniProt Q16832 Q62371
RefSeq (mRNA) NM_001014796 NM_022563
RefSeq (protein) NP_001014796 NP_072075
Location (UCSC) Chr 1:
162.6 – 162.75 Mb
Chr 1:
169.97 – 170.11 Mb
PubMed search [1] [2]

Discoidin domain-containing receptor 2, also known as CD167b (cluster of differentiation 167b), is a protein that in humans is encoded by the DDR2 gene.[1] Discoidin domain-containing receptor 2 is a receptor tyrosine kinase (RTK).

Function[edit]

RTKs play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation, and metabolism. In several cases the biochemical mechanism by which RTKs transduce signals across the membrane has been shown to be ligand induced receptor oligomerization and subsequent intracellular phosphorylation. In the case of DDR2, the ligand is collagen which binds to its extracellular discoidin domain. [2] This autophosphorylation leads to phosphorylation of cytosolic targets as well as association with other molecules, which are involved in pleiotropic effects of signal transduction. DDR2 has been associated with a number of diseases including fibrosis and cancer. [3]

Structure[edit]

RTKs have a tripartite structure with extracellular, transmembrane, and cytoplasmic regions. This gene encodes a member of a novel subclass of RTKs and contains a distinct extracellular region encompassing a factor VIII-like domain.[1]

Gene[edit]

Alternative splicing in the 5' UTR of the DDR2 gene results in multiple transcript variants encoding the same protein.[1]

Interactions[edit]

DDR2 (gene) has been shown to interact with SHC1[4] and phosphorylate Shp2.[5] DDR2 also interacts with Integrin α1β1 and α2β1 by promoting their adhesion to collagen. [6]

References[edit]

  1. ^ a b c "Entrez Gene: DDR2 discoidin domain receptor family, member 2". 
  2. ^ Fu HL, Valiathan RR, Arkwright R, Sohail A, Mihai C, Kumarasiri M, Mahasenan KV, Mobashery S, Huang P, Agarwal G, Fridman R (March 2013). "Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling.". J. Biol Chem. 288 (11): 7430–9. doi:10.1074/jbc.R112.444158. PMID 23335507. 
  3. ^ Leitinger B (May 2011). "Transmembrane collagen receptors.". Annu Rev Cell Dev Biol. 27: 265–90. doi:10.1146/annurev-cellbio-092910-154013. PMID 21568710. 
  4. ^ Ikeda K, Wang LH, Torres R, Zhao H, Olaso E, Eng FJ, Labrador P, Klein R, Lovett D, Yancopoulos GD, Friedman SL, Lin HC (May 2002). "Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen". J. Biol. Chem. 277 (21): 19206–12. doi:10.1074/jbc.M201078200. PMID 11884411. 
  5. ^ Iwai LK, Payne LS, Luczynski MT, Chang F, Xu H, Clinton RW, Paul A, Esposito EA, Gridley S, Leitinger B, Naegle KM, Huang PH (July 2013). "Phosphoproteomics of Collagen Receptor Networks Reveals SHP-2 Phosphorylation Downstream of Wildtype DDR2 and its Lung Cancer Mutants". Biochem. J. 454 (3): 501–13. doi:10.1042/BJ20121750. PMID 23822953. 
  6. ^ Xu H, Bihan D, Chang F, Huang PH, Farndale RW, Leitinger B (Dec 2012). "Discoidin domain receptors promote α1β1- and α2β1-integrin mediated cell adhesion to collagen by enhancing integrin activation". PLoS One 7 (12): e52209. doi:10.1371/journal.pone.0052209. PMID 23284937. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.