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Discoidin domain-containing receptor 2

From Wikipedia, the free encyclopedia
DDR2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDDR2, MIG20a, NTRKR3, TKT, TYRO10, discoidin domain receptor tyrosine kinase 2, WRCN
External IDsOMIM: 191311; MGI: 1345277; HomoloGene: 68505; GeneCards: DDR2; OMA:DDR2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001014796
NM_006182
NM_001354982
NM_001354983

NM_022563

RefSeq (protein)

NP_001014796
NP_006173
NP_001341911
NP_001341912

NP_072075

Location (UCSC)Chr 1: 162.63 – 162.79 MbChr 1: 169.8 – 169.94 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] Discoidin domain-containing receptor 2 is a receptor tyrosine kinase (RTK).

Function

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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.[6] 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.[7]

Structure

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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.[5]

Gene

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

Interactions

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DDR2 (gene) has been shown to interact with SHC1[8] and phosphorylate Shp2.[9] DDR2 also interacts with Integrin α1β1 and α2β1 by promoting their adhesion to collagen.[10]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162733Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026674Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c "Entrez Gene: DDR2 discoidin domain receptor family, member 2".
  6. ^ 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): 7430–7. doi:10.1074/jbc.R112.444158. PMC 3597784. PMID 23335507.
  7. ^ Leitinger B (May 2011). "Transmembrane collagen receptors". Annu. Rev. Cell Dev. Biol. 27: 265–90. doi:10.1146/annurev-cellbio-092910-154013. PMID 21568710.
  8. ^ 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.
  9. ^ 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 wild-type DDR2 and its lung cancer mutants". Biochem. J. 454 (3): 501–13. doi:10.1042/BJ20121750. PMC 3893797. PMID 23822953.
  10. ^ 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. Bibcode:2012PLoSO...752209X. doi:10.1371/journal.pone.0052209. PMC 3527415. PMID 23284937.

Further reading

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