View source for Biology:Discoidin domain-containing receptor 2

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Discoidin domain-containing receptor 2''', also known as '''CD167b''' ([[Biology:Cluster of differentiation|cluster of differentiation]] 167b), is a protein that in humans is encoded by the DDR2 [[Biology:Gene|gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DDR2 discoidin domain receptor family, member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4921}}</ref>  Discoidin domain-containing receptor 2 is a [[Biology:Receptor tyrosine kinase|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 [[Biology:Signal transduction|transduce signals]] across the membrane has been shown to be ligand induced receptor oligomerization and subsequent intracellular [[Biology:Phosphorylation|phosphorylation]]. In the case of DDR2, the ligand is [[Biology:Collagen|collagen]] which binds to its extracellular discoidin domain.<ref name="pmid23335507">{{cite journal | vauthors = Fu HL, Valiathan RR, Arkwright R, Sohail A, Mihai C, Kumarasiri M, Mahasenan KV, Mobashery S, Huang P, Agarwal G, Fridman R | title = Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling | journal = J. Biol. Chem. | volume = 288 | issue = 11 | pages = 7430–7  | date = March 2013 | pmid = 23335507 | pmc = 3597784 | doi = 10.1074/jbc.R112.444158 | doi-access = free }}</ref> This [[Biology:Autophosphorylation|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 [[Medicine:Fibrosis|fibrosis]] and [[Medicine:Cancer|cancer]].<ref name="pmid21568710">{{cite journal | vauthors = Leitinger B | title = Transmembrane collagen receptors | journal = Annu. Rev. Cell Dev. Biol. | volume = 27 | pages = 265–90  | date = May 2011 | pmid = 21568710 | doi = 10.1146/annurev-cellbio-092910-154013 }}</ref>

== 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 [[Biology:Factor VIII|factor VIII]]-like domain.<ref name="entrez"/>

== Gene ==

Alternative splicing in the 5' UTR of the DDR2 gene results in multiple transcript variants encoding the same protein.<ref name="entrez"/>

== Interactions ==

DDR2 (gene) has been shown to interact with SHC1<ref name="pmid11884411">{{cite journal | vauthors = Ikeda K, Wang LH, Torres R, Zhao H, Olaso E, Eng FJ, Labrador P, Klein R, Lovett D, Yancopoulos GD, Friedman SL, Lin HC | title = Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen | journal = J. Biol. Chem. | volume = 277 | issue = 21 | pages = 19206–12  | date = May 2002 | pmid = 11884411 | doi = 10.1074/jbc.M201078200 | doi-access = free }}</ref> and phosphorylate Shp2.<ref name="pmid23822953">{{cite journal | vauthors = Iwai LK, Payne LS, Luczynski MT, Chang F, Xu H, Clinton RW, Paul A, Esposito EA, Gridley S, Leitinger B, Naegle KM, Huang PH | title = Phosphoproteomics of collagen receptor networks reveals SHP-2 phosphorylation downstream of wild-type DDR2 and its lung cancer mutants | journal = Biochem. J. | volume = 454 | issue = 3 | pages = 501–13  | date = July 2013 | pmid = 23822953 | pmc = 3893797 | doi = 10.1042/BJ20121750 }}</ref>  DDR2 also interacts with [[Biology:Integrin|Integrin]] α<sub>1</sub>β<sub>1</sub> and α<sub>2</sub>β<sub>1</sub> by promoting their adhesion to collagen.<ref name="pmid23284937">{{cite journal | vauthors = Xu H, Bihan D, Chang F, Huang PH, Farndale RW, Leitinger B | title = Discoidin domain receptors promote α1β1- and α2β1-integrin mediated cell adhesion to collagen by enhancing integrin activation | journal = PLOS ONE | volume = 7 | issue = 12 | pages = e52209  | date = Dec 2012 | pmid = 23284937 | pmc = 3527415 | doi = 10.1371/journal.pone.0052209 | bibcode = 2012PLoSO...752209X | doi-access = free }}</ref>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Lapsys NM, Layfield R, Baker E, Callen DF, Sutherland GR, Abedinia M, Nixon PF, Mattick JS | title = Chromosomal location of the human transketolase gene | journal = Cytogenet. Cell Genet. | volume = 61 | issue = 4 | pages = 274–5 | year = 1992 | pmid = 1486804 | doi = 10.1159/000133421 }}
* {{cite journal | vauthors = Abedinia M, Layfield R, Jones SM, Nixon PF, Mattick JS | title = Nucleotide and predicted amino acid sequence of a cDNA clone encoding part of human transketolase | journal = Biochem. Biophys. Res. Commun. | volume = 183 | issue = 3 | pages = 1159–66 | year = 1992 | pmid = 1567394 | doi = 10.1016/S0006-291X(05)80312-2 }}
* {{cite journal | vauthors = Edelhoff S, Sweetser DA, Disteche CM | title = Mapping of the NEP receptor tyrosine kinase gene to human chromosome 6p21.3 and mouse chromosome 17C | journal = Genomics | volume = 25 | issue = 1 | pages = 309–11 | year = 1995 | pmid = 7774938 | doi = 10.1016/0888-7543(95)80144-B }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Karn T, Holtrich U, Bräuninger A, Böhme B, Wolf G, Rübsamen-Waigmann H, Strebhardt K | title = Structure, expression and chromosomal mapping of TKT from man and mouse: a new subclass of receptor tyrosine kinases with a factor VIII-like domain | journal = Oncogene | volume = 8 | issue = 12 | pages = 3433–40 | year = 1993 | pmid = 8247548 }}
* {{cite journal | vauthors = 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 | title = Generation and analysis of 280,000 human expressed sequence tags | journal = Genome Res. | volume = 6 | issue = 9 | pages = 807–28 | year = 1996 | pmid = 8889549 | doi = 10.1101/gr.6.9.807 | doi-access = free }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Vogel W, Gish GD, Alves F, Pawson T | title = The discoidin domain receptor tyrosine kinases are activated by collagen | journal = Mol. Cell | volume = 1 | issue = 1 | pages = 13–23 | year = 1997 | pmid = 9659899 | doi = 10.1016/S1097-2765(00)80003-9 | doi-access = free }}
* {{cite journal | vauthors = Mohan RR, Mohan RR, Wilson SE | title = Discoidin domain receptor (DDR) 1 and 2: collagen-activated tyrosine kinase receptors in the cornea | journal = Exp. Eye Res. | volume = 72 | issue = 1 | pages = 87–92 | year = 2001 | pmid = 11133186 | doi = 10.1006/exer.2000.0932 }}
* {{cite journal | vauthors = Ikeda K, Wang LH, Torres R, Zhao H, Olaso E, Eng FJ, Labrador P, Klein R, Lovett D, Yancopoulos GD, Friedman SL, Lin HC | title = Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen | journal = J. Biol. Chem. | volume = 277 | issue = 21 | pages = 19206–12 | year = 2002 | pmid = 11884411 | doi = 10.1074/jbc.M201078200 | doi-access = free }}
* {{cite journal | vauthors = Faraci E, Eck M, Gerstmayer B, Bosio A, Vogel WF | title = An extracellular matrix-specific microarray allowed the identification of target genes downstream of discoidin domain receptors | journal = Matrix Biol. | volume = 22 | issue = 4 | pages = 373–81 | year = 2003 | pmid = 12935821 | doi = 10.1016/S0945-053X(03)00053-2 }}
* {{cite journal | vauthors = Ferri N, Carragher NO, Raines EW | title = Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis | journal = Am. J. Pathol. | volume = 164 | issue = 5 | pages = 1575–85 | year = 2004 | pmid = 15111304 | pmc = 1615659 | doi = 10.1016/S0002-9440(10)63716-9 }}
* {{cite journal | vauthors = Leitinger B, Steplewski A, Fertala A | title = The D2 period of collagen II contains a specific binding site for the human discoidin domain receptor, DDR2 | journal = J. Mol. Biol. | volume = 344 | issue = 4 | pages = 993–1003 | year = 2004 | pmid = 15544808 | doi = 10.1016/j.jmb.2004.09.089 }}
* {{cite journal | vauthors = Wall SJ, Werner E, Werb Z, DeClerck YA | title = Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by fibrillar collagen | journal = J. Biol. Chem. | volume = 280 | issue = 48 | pages = 40187–94 | year = 2005 | pmid = 16186104 | pmc = 2768768 | doi = 10.1074/jbc.M508226200 | doi-access = free }}
* {{cite journal | vauthors = Yang K, Kim JH, Kim HJ, Park IS, Kim IY, Yang BS | title = Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation | journal = J. Biol. Chem. | volume = 280 | issue = 47 | pages = 39058–66 | year = 2005 | pmid = 16186108 | doi = 10.1074/jbc.M506921200 | doi-access = free }}
* {{cite journal | vauthors = Leitinger B, Kwan AP | title = The discoidin domain receptor DDR2 is a receptor for type X collagen | journal = Matrix Biol. | volume = 25 | issue = 6 | pages = 355–64 | year = 2006 | pmid = 16806867 | doi = 10.1016/j.matbio.2006.05.006 }}
* {{cite journal | vauthors = Zhang W, Ding T, Zhang J, Su J, Li F, Liu X, Ma W, Yao L | title = Expression of discoidin domain receptor 2 (DDR2) extracellular domain in pichia pastoris and functional analysis in synovial fibroblasts and NIT3T3 cells | journal = Mol. Cell. Biochem. | volume = 290 | issue = 1–2 | pages = 43–53 | year = 2006 | pmid = 16967187 | doi = 10.1007/s11010-006-9136-4 | s2cid = 19400659 }}
* {{cite journal | vauthors = Ford CE, Lau SK, Zhu CQ, Andersson T, Tsao MS, Vogel WF | title = Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma | journal = Br. J. Cancer | volume = 96 | issue = 5 | pages = 808–14 | year = 2007 | pmid = 17299390 | pmc = 2360060 | doi = 10.1038/sj.bjc.6603614 }}
* {{cite journal | vauthors = Xu L, Servais J, Polur I, Kim D, Lee PL, Chung K, Li Y | title = Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice | journal = Arthritis Rheum. | volume = 62 | issue = 9 | pages = 2736–44 | year = 2010 | pmid = 20518074 | pmc = 2946478 | doi = 10.1002/art.27582 }}
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{{NLM content}}
{{Clusters of differentiation}}
{{Tyrosine kinases}}
{{Enzymes}}

[[Category:Clusters of differentiation]]

{{Sourceattribution|Discoidin domain-containing receptor 2}}