Discoidin domain-containing receptor 2

Discoidin domain receptor tyrosine kinase 2
Rendering based on PDB 2WUH​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2WUH​, 2Z4F​
Identifiers
Symbols	DDR2 ; MIG20a; NTRKR3; TKT; TYRO10
External IDs	OMIM: 191311 MGI: 1345277 HomoloGene: 68505 ChEMBL: 5122 GeneCards: DDR2 Gene
EC number	2.7.10.1
Gene ontology Molecular function • transmembrane receptor protein tyrosine kinase activity • protein binding • collagen binding • ATP binding • protein tyrosine kinase collagen receptor activity Cellular component • plasma membrane • integral component of plasma membrane • focal adhesion • apical plasma membrane • extracellular exosome Biological process • ossification • endochondral bone growth • cell adhesion • signal transduction • regulation of extracellular matrix disassembly • positive regulation of fibroblast migration • peptidyl-tyrosine phosphorylation • extracellular matrix organization • collagen fibril organization • regulation of bone mineralization • biomineral tissue development • chondrocyte proliferation • collagen-activated tyrosine kinase receptor signaling pathway • positive regulation of osteoblast differentiation • positive regulation of protein kinase activity • protein autophosphorylation • positive regulation of fibroblast proliferation • positive regulation of sequence-specific DNA binding transcription factor activity • positive regulation of extracellular matrix disassembly Sources: Amigo / QuickGO
RNA expression pattern
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: 162.63 – 162.79 Mb	Chr 1: 169.97 – 170.11 Mb
PubMed search

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

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

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

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

Interactions

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

1. "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): 7430–7. doi:10.1074/jbc.R112.444158. PMC 3597784. 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 wild-type DDR2 and its lung cancer mutants". Biochem. J. 454 (3): 501–13. doi:10.1042/BJ20121750. PMC 3893797. 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. PMC 3527415. PMID 23284937.

Further reading

• Lapsys NM, Layfield R, Baker E, Callen DF, Sutherland GR, Abedinia M, Nixon PF, Mattick JS (1992). "Chromosomal location of the human transketolase gene". Cytogenet. Cell Genet. 61 (4): 274–5. doi:10.1159/000133421. PMID 1486804.
• Abedinia M, Layfield R, Jones SM, Nixon PF, Mattick JS (1992). "Nucleotide and predicted amino acid sequence of a cDNA clone encoding part of human transketolase". Biochem. Biophys. Res. Commun. 183 (3): 1159–66. doi:10.1016/S0006-291X(05)80312-2. PMID 1567394.
• Edelhoff S, Sweetser DA, Disteche CM (1995). "Mapping of the NEP receptor tyrosine kinase gene to human chromosome 6p21.3 and mouse chromosome 17C". Genomics 25 (1): 309–11. doi:10.1016/0888-7543(95)80144-B. PMID 7774938.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Karn T, Holtrich U, Bräuninger A, Böhme B, Wolf G, Rübsamen-Waigmann H, Strebhardt K (1993). "Structure, expression and chromosomal mapping of TKT from man and mouse: a new subclass of receptor tyrosine kinases with a factor VIII-like domain". Oncogene 8 (12): 3433–40. PMID 8247548.
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M (1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Vogel W, Gish GD, Alves F, Pawson T (1997). "The discoidin domain receptor tyrosine kinases are activated by collagen". Mol. Cell 1 (1): 13–23. doi:10.1016/S1097-2765(00)80003-9. PMID 9659899.
• Mohan RR, Mohan RR, Wilson SE (2001). "Discoidin domain receptor (DDR) 1 and 2: collagen-activated tyrosine kinase receptors in the cornea". Exp. Eye Res. 72 (1): 87–92. doi:10.1006/exer.2000.0932. PMID 11133186.
• Ikeda K, Wang LH, Torres R, Zhao H, Olaso E, Eng FJ, Labrador P, Klein R, Lovett D, Yancopoulos GD, Friedman SL, Lin HC (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.
• Faraci E, Eck M, Gerstmayer B, Bosio A, Vogel WF (2003). "An extracellular matrix-specific microarray allowed the identification of target genes downstream of discoidin domain receptors". Matrix Biol. 22 (4): 373–81. doi:10.1016/S0945-053X(03)00053-2. PMID 12935821.
• Ferri N, Carragher NO, Raines EW (2004). "Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis". Am. J. Pathol. 164 (5): 1575–85. doi:10.1016/S0002-9440(10)63716-9. PMC 1615659. PMID 15111304.
• Leitinger B, Steplewski A, Fertala A (2004). "The D2 period of collagen II contains a specific binding site for the human discoidin domain receptor, DDR2". J. Mol. Biol. 344 (4): 993–1003. doi:10.1016/j.jmb.2004.09.089. PMID 15544808.
• Wall SJ, Werner E, Werb Z, DeClerck YA (2005). "Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by fibrillar collagen". J. Biol. Chem. 280 (48): 40187–94. doi:10.1074/jbc.M508226200. PMC 2768768. PMID 16186104.
• Yang K, Kim JH, Kim HJ, Park IS, Kim IY, Yang BS (2005). "Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation". J. Biol. Chem. 280 (47): 39058–66. doi:10.1074/jbc.M506921200. PMID 16186108.
• Leitinger B, Kwan AP (2006). "The discoidin domain receptor DDR2 is a receptor for type X collagen". Matrix Biol. 25 (6): 355–64. doi:10.1016/j.matbio.2006.05.006. PMID 16806867.
• Zhang W, Ding T, Zhang J, Su J, Li F, Liu X, Ma W, Yao L (2006). "Expression of discoidin domain receptor 2 (DDR2) extracellular domain in pichia pastoris and functional analysis in synovial fibroblasts and NIT3T3 cells". Mol. Cell. Biochem. 290 (1-2): 43–53. doi:10.1007/s11010-006-9136-4. PMID 16967187.
• Ford CE, Lau SK, Zhu CQ, Andersson T, Tsao MS, Vogel WF (2007). "Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma". Br. J. Cancer 96 (5): 808–14. doi:10.1038/sj.bjc.6603614. PMC 2360060. PMID 17299390.
• Xu L, Servais J, Polur I, Kim D, Lee PL, Chung K, Li Y (2010). "Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice". Arthritis Rheum. 62 (9): 2736–44. doi:10.1002/art.27582. PMC 2946478. PMID 20518074.

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