Discoidin domain-containing receptor 2

DDR2

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
2WUH, 2Z4F

Identifiers

Aliases

DDR2, MIG20a, NTRKR3, TKT, TYRO10, discoidin domain receptor tyrosine kinase 2

External IDs

MGI: 1345277 HomoloGene: 68505 GeneCards: DDR2

Targeted by Drug

sorafenib^[1]

Gene ontology
Molecular function	• transferase activity • nucleotide binding • protein kinase activity • kinase activity • protein binding • transmembrane receptor protein tyrosine kinase activity • protein tyrosine kinase collagen receptor activity • protein tyrosine kinase activity • ATP binding • collagen binding
Cellular component	• integral component of membrane • membrane • focal adhesion • plasma membrane • integral component of plasma membrane • extracellular exosome • apical plasma membrane
Biological process	• collagen-activated tyrosine kinase receptor signaling pathway • ossification • phosphorylation • collagen fibril organization • transmembrane receptor protein tyrosine kinase signaling pathway • regulation of bone mineralization • positive regulation of fibroblast proliferation • biomineral tissue development • positive regulation of sequence-specific DNA binding transcription factor activity • extracellular matrix organization • regulation of extracellular matrix disassembly • positive regulation of extracellular matrix disassembly • protein phosphorylation • cell adhesion • positive regulation of osteoblast differentiation • chondrocyte proliferation • positive regulation of cell proliferation • protein autophosphorylation • peptidyl-tyrosine phosphorylation • endochondral bone growth • positive regulation of fibroblast migration • signal transduction • positive regulation of protein kinase activity
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_006182


NM_022563

RefSeq (protein)


NP_001014796.1 NP_006173.2


NP_072075.2

Location (UCSC)

Chr 1: 162.63 – 162.79 Mb

Chr 1: 169.97 – 170.11 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/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.^[4] 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.^[5] 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.^[6]

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.^[4]

Gene

Alternative splicing in the 5' UTR of the DDR2 gene results in multiple transcript variants encoding the same protein.^[4]

Interactions

DDR2 (gene) has been shown to interact with SHC1^[7] and phosphorylate Shp2.^[8] DDR2 also interacts with Integrin α₁β₁ and α₂β₁ by promoting their adhesion to collagen.^[9]

References

↑ "Drugs that physically interact with Discoidin domain-containing receptor 2 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
1 2 3 "Entrez Gene: DDR2 discoidin domain receptor family, member 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.
↑ Leitinger B (May 2011). "Transmembrane collagen receptors". Annu. Rev. Cell Dev. Biol. 27: 265–90. doi:10.1146/annurev-cellbio-092910-154013. PMID 21568710.
↑ 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.
↑ 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.
↑ 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.

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.

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1-50	CD1 a-c 1A 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50

51-100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100

101-150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150

151-200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200

201-250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249

251-300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299

301-350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

Protein kinases: tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

Growth factor receptors

EGF receptor family	EGFR ERBB2 ERBB3 ERBB4

Insulin receptor family	IGF1R INSR INSRR

PDGF receptor family	CSF1R FLT3 KIT PDGFR (PDGFRA PDGFRB)

FGF receptor family	FGFR1 FGFR2 FGFR3 FGFR4

VEGF receptors family	VEGFR1 VEGFR2 VEGFR3

HGF receptor family	MET RON

Trk receptor family	NTRK1 NTRK2 NTRK3

EPH receptor family

LTK receptor family

TIE receptor family

ROR receptor family

ROR1
ROR2

DDR receptor family

DDR1
DDR2

PTK7 receptor family

PTK7

RYK receptor family

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AATYK
AATYK2

AXL receptor family

RET receptor family

uncategorised

STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family	ABL1 ARG

ACK family	ACK1 TNK1

CSK family	CSK MATK

FAK family	FAK PYK2

FES family	FES FER

FRK family	FRK BRK SRMS

JAK family	JAK1 JAK2 JAK3 TYK2

SRC-A family	SRC FGR FYN YES1

SRC-B family	BLK HCK LCK LYN

TEC family	TEC BMX BTK ITK TXK

SYK family	SYK ZAP70

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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