Discoidin domain-containing receptor 2

Details

Name

Discoidin domain-containing receptor 2

Synonyms

• 2.7.10.1
• CD167 antigen-like family member B
• Discoidin domain receptor 2
• Discoidin domain-containing receptor tyrosine kinase 2
• Neurotrophic tyrosine kinase, receptor-related 3
• NTRKR3
• Receptor protein-tyrosine kinase TKT
• TKT
• TYRO10
• Tyrosine-protein kinase TYRO10

Gene Name

DDR2

Organism

Humans

Amino acid sequence

>lcl|BSEQ0017522|Discoidin domain-containing receptor 2
MILIPRMLLVLFLLLPILSSAKAQVNPAICRYPLGMSGGQIPDEDITASSQWSESTAAKY
GRLDSEEGDGAWCPEIPVEPDDLKEFLQIDLHTLHFITLVGTQGRHAGGHGIEFAPMYKI
NYSRDGTRWISWRNRHGKQVLDGNSNPYDIFLKDLEPPIVARFVRFIPVTDHSMNVCMRV
ELYGCVWLDGLVSYNAPAGQQFVLPGGSIIYLNDSVYDGAVGYSMTEGLGQLTDGVSGLD
DFTQTHEYHVWPGYDYVGWRNESATNGYIEIMFEFDRIRNFTTMKVHCNNMFAKGVKIFK
EVQCYFRSEASEWEPNAISFPLVLDDVNPSARFVTVPLHHRMASAIKCQYHFADTWMMFS
EITFQSDAAMYNNSEALPTSPMAPTTYDPMLKVDDSNTRILIGCLVAIIFILLAIIVIIL
WRQFWQKMLEKASRRMLDDEMTVSLSLPSDSSMFNNNRSSSPSEQGSNSTYDRIFPLRPD
YQEPSRLIRKLPEFAPGEEESGCSGVVKPVQPSGPEGVPHYAEADIVNLQGVTGGNTYSV
PAVTMDLLSGKDVAVEEFPRKLLTFKEKLGEGQFGEVHLCEVEGMEKFKDKDFALDVSAN
QPVLVAVKMLRADANKNARNDFLKEIKIMSRLKDPNIIHLLAVCITDDPLCMITEYMENG
DLNQFLSRHEPPNSSSSDVRTVSYTNLKFMATQIASGMKYLSSLNFVHRDLATRNCLVGK
NYTIKIADFGMSRNLYSGDYYRIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWET
FTFCQEQPYSQLSDEQVIENTGEFFRDQGRQTYLPQPAICPDSVYKLMLSCWRRDTKNRP
SFQEIHLLLLQQGDE

Number of residues

855

Molecular Weight

96735.44

Theoretical pI

Not Available

GO Classification

Functions

ATP binding / collagen binding / protein tyrosine kinase collagen receptor activity / transmembrane receptor protein tyrosine kinase activity

Processes

biomineral tissue development / cell adhesion / chondrocyte proliferation / collagen fibril organization / collagen-activated tyrosine kinase receptor signaling pathway / endochondral bone developmental growth / extracellular matrix organization / ossification / peptidyl-tyrosine phosphorylation / positive regulation of extracellular matrix disassembly / positive regulation of fibroblast migration / positive regulation of fibroblast proliferation / positive regulation of osteoblast differentiation / positive regulation of protein kinase activity / positive regulation of sequence-specific DNA binding transcription factor activity / protein autophosphorylation / regulation of bone mineralization / regulation of extracellular matrix disassembly / signal transduction

Components

apical plasma membrane / extracellular exosome / focal adhesion / integral component of plasma membrane / plasma membrane

General Function

Transmembrane receptor protein tyrosine kinase activity

Specific Function

Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing.

Pfam Domain Function

• PK_Tyr_Ser-Thr (PF07714)
• F5_F8_type_C (PF00754)

Transmembrane Regions

400-421

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0017523|Discoidin domain-containing receptor 2 (DDR2)
ATGATCCTGATTCCCAGAATGCTCTTGGTGCTGTTCCTGCTGCTGCCTATCTTGAGTTCT
GCAAAAGCTCAGGTTAATCCAGCTATATGCCGCTATCCTCTGGGCATGTCAGGAGGCCAG
ATTCCAGATGAGGACATCACAGCTTCCAGTCAGTGGTCAGAGTCCACAGCTGCCAAATAT
GGAAGGCTGGACTCAGAAGAAGGGGATGGAGCCTGGTGCCCTGAGATTCCAGTGGAACCT
GATGACCTGAAGGAGTTTCTGCAGATTGACTTGCACACCCTCCATTTTATCACTCTGGTG
GGGACCCAGGGGCGCCATGCAGGAGGTCATGGCATCGAGTTTGCCCCCATGTACAAGATC
AATTACAGTCGGGATGGCACTCGCTGGATCTCTTGGCGGAACCGTCATGGGAAACAGGTG
CTGGATGGAAATAGTAACCCCTATGACATTTTCCTAAAGGACTTGGAGCCGCCCATTGTA
GCCAGATTTGTCCGGTTCATTCCAGTCACCGACCACTCCATGAATGTGTGTATGAGAGTG
GAGCTTTACGGCTGTGTCTGGCTAGATGGCTTGGTGTCTTACAATGCTCCAGCTGGGCAG
CAGTTTGTACTCCCTGGAGGTTCCATCATTTATCTGAATGATTCTGTCTATGATGGAGCT
GTTGGATACAGCATGACAGAAGGGCTAGGCCAATTGACCGATGGTGTGTCTGGCCTGGAC
GATTTCACCCAGACCCATGAATACCACGTGTGGCCCGGCTATGACTATGTGGGCTGGCGG
AACGAGAGTGCCACCAATGGCTACATTGAGATCATGTTTGAATTTGACCGCATCAGGAAT
TTCACTACCATGAAGGTCCACTGCAACAACATGTTTGCTAAAGGTGTGAAGATCTTTAAG
GAGGTACAGTGCTACTTCCGCTCTGAAGCCAGTGAGTGGGAACCTAATGCCATTTCCTTC
CCCCTTGTCCTGGATGACGTCAACCCCAGTGCTCGGTTTGTCACGGTGCCTCTCCACCAC
CGAATGGCCAGTGCCATCAAGTGTCAATACCATTTTGCAGATACCTGGATGATGTTCAGT
GAGATCACCTTCCAATCAGATGCTGCAATGTACAACAACTCTGAAGCCCTGCCCACCTCT
CCTATGGCACCCACAACCTATGATCCAATGCTTAAAGTTGATGACAGCAACACTCGGATC
CTGATTGGCTGCTTGGTGGCCATCATCTTTATCCTCCTGGCCATCATTGTCATCATCCTC
TGGAGGCAGTTCTGGCAGAAAATGCTGGAGAAGGCTTCTCGGAGGATGCTGGATGATGAA
ATGACAGTCAGCCTTTCCCTGCCAAGTGATTCTAGCATGTTCAACAATAACCGCTCCTCA
TCACCTAGTGAACAAGGGTCCAACTCGACTTACGATCGCATCTTTCCCCTTCGCCCTGAC
TACCAGGAGCCATCCAGGCTGATACGAAAACTCCCAGAATTTGCTCCAGGGGAGGAGGAG
TCAGGCTGCAGCGGTGTTGTGAAGCCAGTCCAGCCCAGTGGCCCTGAGGGGGTGCCCCAC
TATGCAGAGGCTGACATAGTGAACCTCCAAGGAGTGACAGGAGGCAACACATACTCAGTG
CCTGCCGTCACCATGGACCTGCTCTCAGGAAAAGATGTGGCTGTGGAGGAGTTCCCCAGG
AAACTCCTAACTTTCAAAGAGAAGCTGGGAGAAGGACAGTTTGGGGAGGTTCATCTCTGT
GAAGTGGAGGGAATGGAAAAATTCAAAGACAAAGATTTTGCCCTAGATGTCAGTGCCAAC
CAGCCTGTCCTGGTGGCTGTGAAAATGCTCCGAGCAGATGCCAACAAGAATGCCAGGAAT
GATTTTCTTAAGGAGATAAAGATCATGTCTCGGCTCAAGGACCCAAACATCATCCATCTA
TTAGCTGTGTGTATCACTGATGACCCTCTCTGTATGATCACTGAATACATGGAGAATGGA
GATCTCAATCAGTTTCTTTCCCGCCACGAGCCCCCTAATTCTTCCTCCAGCGATGTACGC
ACTGTCAGTTACACCAATCTGAAGTTTATGGCTACCCAAATTGCCTCTGGCATGAAGTAC
CTTTCCTCTCTTAATTTTGTTCACCGAGATCTGGCCACACGAAACTGTTTAGTGGGTAAG
AACTACACAATCAAGATAGCTGACTTTGGAATGAGCAGGAACCTGTACAGTGGTGACTAT
TACCGGATCCAGGGCCGGGCAGTGCTCCCTATCCGCTGGATGTCTTGGGAGAGTATCTTG
CTGGGCAAGTTCACTACAGCAAGTGATGTGTGGGCCTTTGGGGTTACTTTGTGGGAGACT
TTCACCTTTTGTCAAGAACAGCCCTATTCCCAGCTGTCAGATGAACAGGTTATTGAGAAT
ACTGGAGAGTTCTTCCGAGACCAAGGGAGGCAGACTTACCTCCCTCAACCAGCCATTTGT
CCTGACTCTGTGTATAAGCTGATGCTCAGCTGCTGGAGAAGAGATACGAAGAACCGTCCC
TCATTCCAAGAAATCCACCTTCTGCTCCTTCAACAAGGCGACGAGTGA

Chromosome Location

1

Locus

Not Available

External Identifiers

Resource	Link
UniProtKB ID	Q16832
UniProtKB Entry Name	DDR2_HUMAN
HGNC ID	HGNC:2731

General References

1. Karn T, Holtrich U, Brauninger A, Bohme B, Wolf G, Rubsamen-Waigmann H, Strebhardt K: 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. 1993 Dec;8(12):3433-40. [Article]
2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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5. Vogel W, Gish GD, Alves F, Pawson T: The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell. 1997 Dec;1(1):13-23. [Article]
6. Yang K, Kim JH, Kim HJ, Park IS, Kim IY, Yang BS: Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation. J Biol Chem. 2005 Nov 25;280(47):39058-66. Epub 2005 Sep 26. [Article]
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8. Xu L, Peng H, Glasson S, Lee PL, Hu K, Ijiri K, Olsen BR, Goldring MB, Li Y: Increased expression of the collagen receptor discoidin domain receptor 2 in articular cartilage as a key event in the pathogenesis of osteoarthritis. Arthritis Rheum. 2007 Aug;56(8):2663-73. [Article]
9. Konitsiotis AD, Raynal N, Bihan D, Hohenester E, Farndale RW, Leitinger B: Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. J Biol Chem. 2008 Mar 14;283(11):6861-8. doi: 10.1074/jbc.M709290200. Epub 2008 Jan 16. [Article]
10. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
11. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
12. Lin KL, Chou CH, Hsieh SC, Hwa SY, Lee MT, Wang FF: Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation. J Bone Miner Res. 2010 Nov;25(11):2489-503. doi: 10.1002/jbmr.159. [Article]
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14. Vogel WF, Abdulhussein R, Ford CE: Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal. 2006 Aug;18(8):1108-16. Epub 2006 Feb 28. [Article]
15. Leitinger B: Transmembrane collagen receptors. Annu Rev Cell Dev Biol. 2011;27:265-90. doi: 10.1146/annurev-cellbio-092910-154013. Epub 2011 May 13. [Article]
16. Ichikawa O, Osawa M, Nishida N, Goshima N, Nomura N, Shimada I: Structural basis of the collagen-binding mode of discoidin domain receptor 2. EMBO J. 2007 Sep 19;26(18):4168-76. Epub 2007 Aug 16. [Article]
17. Carafoli F, Bihan D, Stathopoulos S, Konitsiotis AD, Kvansakul M, Farndale RW, Leitinger B, Hohenester E: Crystallographic insight into collagen recognition by discoidin domain receptor 2. Structure. 2009 Dec 9;17(12):1573-81. doi: 10.1016/j.str.2009.10.012. [Article]
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20. Bargal R, Cormier-Daire V, Ben-Neriah Z, Le Merrer M, Sosna J, Melki J, Zangen DH, Smithson SF, Borochowitz Z, Belostotsky R, Raas-Rothschild A: Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications. Am J Hum Genet. 2009 Jan;84(1):80-4. doi: 10.1016/j.ajhg.2008.12.004. Epub 2008 Dec 24. [Article]
21. Ali BR, Xu H, Akawi NA, John A, Karuvantevida NS, Langer R, Al-Gazali L, Leitinger B: Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients. Hum Mol Genet. 2010 Jun 1;19(11):2239-50. doi: 10.1093/hmg/ddq103. Epub 2010 Mar 10. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB08896	Regorafenib	approved	yes	inhibitor	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details
DB00619	Imatinib	approved	unknown	antagonist	Details