Q16832 (DDR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Discoidin domain-containing receptor 2
Short name=Discoidin domain receptor 2
EC=2.7.10.1

Alternative name(s):
CD167 antigen-like family member B
Discoidin domain-containing receptor tyrosine kinase 2
Neurotrophic tyrosine kinase, receptor-related 3
Receptor protein-tyrosine kinase TKT
Tyrosine-protein kinase TYRO10
CD_antigen=CD167b

Gene names

Name:	DDR2
Synonyms:	NTRKR3, TKT, TYRO10

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	855 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.13 Ref.14 Ref.18
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.7 Ref.18
Enzyme regulation	Present in an inactive state in the absence of collagen binding and phosphorylation by SRC. Tyrosine phosphorylation enhances the affinity for ATP and the catalytic activity. Ref.7
Subunit structure	Binds hydroxyproline-rich sequence motifs in fibrillar, glycosylated collagen, such as the GQOGVMGFO motif, where O stands for hydroxyproline. Interacts with SRC. Interacts (tyrosine phosphorylated) with SHC1. Ref.7 Ref.10 Ref.17
Subcellular location	Cell membrane; Single-pass type I membrane protein Ref.6 Ref.10 Ref.22.
Tissue specificity	Detected in osteocytes, osteoblastic cells in subchondral bone, bone lining cells, tibia and cartilage (at protein level). Detected at high levels in heart and lung, and at low levels in brain, placenta, liver, skeletal muscle, pancreas, and kidney. Ref.1 Ref.9 Ref.13
Induction	Up-regulated during osteoblast differentiation (in vitro). Up-regulated in cartilage from osteoarthritis patients. Ref.6 Ref.7 Ref.9 Ref.13
Post-translational modification	N-glycosylated. Ref.22 Tyrosine phosphorylated in response to collagen binding. Phosphorylated by SRC; this is required for activation and subsequent autophosphorylation on additional tyrosine residues. Ref.6 Ref.7 Ref.8 Ref.10 Ref.18
Involvement in disease	Spondyloepimetaphyseal dysplasia short limb-hand type (SEMD-SL) [MIM:271665]: A bone disease characterized by short-limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.22
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. Contains 1 F5/8 type C domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Osteogenesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	biomineral tissue development Inferred from sequence or structural similarity. Source: UniProtKB cell adhesion Traceable author statement Ref.6. Source: ProtInc chondrocyte proliferation Inferred from sequence or structural similarity. Source: UniProtKB collagen fibril organization Inferred from sequence or structural similarity. Source: UniProtKB endochondral bone growth Inferred from sequence or structural similarity. Source: UniProtKB ossification Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.18. Source: UniProtKB positive regulation of extracellular matrix disassembly Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of fibroblast migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of osteoblast differentiation Inferred from mutant phenotype Ref.13. Source: UniProtKB positive regulation of protein kinase activity Inferred from mutant phenotype Ref.13. Source: UniProtKB positive regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype Ref.13. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.7. Source: UniProtKB regulation of bone mineralization Inferred from mutant phenotype Ref.13. Source: UniProtKB
Cellular_component	integral to plasma membrane Traceable author statement Ref.6. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW collagen binding Inferred from direct assay Ref.18. Source: UniProtKB protein tyrosine kinase collagen receptor activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSP90AB1	P08238	2	EBI-1381484,EBI-352572

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 855

834

Discoidin domain-containing receptor 2

PRO_0000016746

Regions

Topological domain

22 – 399

378

Extracellular Potential

Transmembrane

400 – 421

22

Helical; Potential

Topological domain

422 – 855

434

Cytoplasmic Potential

Domain

30 – 185

156

F5/8 type C

Domain

563 – 849

287

Protein kinase

Nucleotide binding

569 – 577

9

ATP By similarity

Sites

Active site

710

1

Proton acceptor By similarity

Binding site

608

1

ATP Probable

Amino acid modifications

Modified residue

461

1

Phosphoserine

Modified residue

471

1

Phosphotyrosine; by SRC and autocatalysis By similarity

Modified residue

674

1

Phosphoserine

Modified residue

736

1

Phosphotyrosine; by SRC and autocatalysis

Modified residue

740

1

Phosphotyrosine; by SRC and autocatalysis

Modified residue

741

1

Phosphotyrosine; by SRC and autocatalysis

Glycosylation

121

1

N-linked (GlcNAc...) Potential

Glycosylation

213

1

N-linked (GlcNAc...) Potential

Glycosylation

261

1

N-linked (GlcNAc...) Potential

Glycosylation

280

1

N-linked (GlcNAc...) Potential

Glycosylation

372

1

N-linked (GlcNAc...) Potential

Disulfide bond

30 ↔ 185

Ref.17 Ref.18

Disulfide bond

73 ↔ 177

Ref.17 Ref.18

Natural variations

Natural variant

105

1

R → S in a lung large cell carcinoma sample; somatic mutation. Ref.19 Ref.20

VAR_041498

Natural variant

113

1

E → K in SEMD-SL; abolishes collagen binding. Ref.22

VAR_065719

Natural variant

441

1

M → I. Ref.20
Corresponds to variant rs34722354 [ dbSNP | Ensembl ].

VAR_041499

Natural variant

478

1

R → C. Ref.20
Corresponds to variant rs34869543 [ dbSNP | Ensembl ].

VAR_041500

Natural variant

543

1

V → F. Ref.20
Corresponds to variant rs55973200 [ dbSNP | Ensembl ].

VAR_041501

Natural variant

713

1

T → I in SEMD-SL; causes retention in an intracellular compartment and thereby abolishes signaling in response collagen binding. Ref.21 Ref.22

VAR_063050

Natural variant

726

1

I → R in SEMD-SL; causes retention in an intracellular compartment and thereby abolishes signaling in response collagen binding. Ref.21 Ref.22

VAR_063051

Natural variant

752

1

R → C in SEMD-SL; causes retention in an intracellular compartment and thereby abolishes signaling in response collagen binding. Ref.21 Ref.22

VAR_063052

Experimental info

Mutagenesis

52

1

W → A: Abolishes collagen binding. Ref.18 Ref.22

Mutagenesis

608

1

K → A: Abolishes kinase activity. Ref.7

Mutagenesis

736

1

Y → F: Reduces autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-740 and F-741. Ref.7

Mutagenesis

740

1

Y → F: Promotes autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-736 and F-741. Ref.7

Mutagenesis

741

1

Y → F: Reduces autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-736 and F-740. Ref.7

Sequence conflict

642

1

A → S in CAA52777. Ref.1

Secondary structure

1

.

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855

Helix Strand Turn

Details...

Turn

27 – 29

3

Beta strand

33 – 35

3

Turn

36 – 38

3

Beta strand

39 – 41

3

Helix

43 – 45

3

Beta strand

46 – 49

4

Helix

54 – 56

3

Helix

58 – 60

3

Beta strand

70 – 72

3

Beta strand

87 – 103

17

Helix

107 – 109

3

Beta strand

116 – 128

13

Beta strand

139 – 142

4

Beta strand

145 – 149

5

Beta strand

151 – 169

19

Beta strand

171 – 174

4

Beta strand

178 – 186

9

Sequences

	Sequence		Length	Mass (Da)
	Q16832 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 78662021BC53E1A0	FASTA	855	96,736
	10 20 30 40 50 60 MILIPRMLLV LFLLLPILSS AKAQVNPAIC RYPLGMSGGQ IPDEDITASS QWSESTAAKY 70 80 90 100 110 120 GRLDSEEGDG AWCPEIPVEP DDLKEFLQID LHTLHFITLV GTQGRHAGGH GIEFAPMYKI 130 140 150 160 170 180 NYSRDGTRWI SWRNRHGKQV LDGNSNPYDI FLKDLEPPIV ARFVRFIPVT DHSMNVCMRV 190 200 210 220 230 240 ELYGCVWLDG LVSYNAPAGQ QFVLPGGSII YLNDSVYDGA VGYSMTEGLG QLTDGVSGLD 250 260 270 280 290 300 DFTQTHEYHV WPGYDYVGWR NESATNGYIE IMFEFDRIRN FTTMKVHCNN MFAKGVKIFK 310 320 330 340 350 360 EVQCYFRSEA SEWEPNAISF PLVLDDVNPS ARFVTVPLHH RMASAIKCQY HFADTWMMFS 370 380 390 400 410 420 EITFQSDAAM YNNSEALPTS PMAPTTYDPM LKVDDSNTRI LIGCLVAIIF ILLAIIVIIL 430 440 450 460 470 480 WRQFWQKMLE KASRRMLDDE MTVSLSLPSD SSMFNNNRSS SPSEQGSNST YDRIFPLRPD 490 500 510 520 530 540 YQEPSRLIRK LPEFAPGEEE SGCSGVVKPV QPSGPEGVPH YAEADIVNLQ GVTGGNTYSV 550 560 570 580 590 600 PAVTMDLLSG KDVAVEEFPR KLLTFKEKLG EGQFGEVHLC EVEGMEKFKD KDFALDVSAN 610 620 630 640 650 660 QPVLVAVKML RADANKNARN DFLKEIKIMS RLKDPNIIHL LAVCITDDPL CMITEYMENG 670 680 690 700 710 720 DLNQFLSRHE PPNSSSSDVR TVSYTNLKFM ATQIASGMKY LSSLNFVHRD LATRNCLVGK 730 740 750 760 770 780 NYTIKIADFG MSRNLYSGDY YRIQGRAVLP IRWMSWESIL LGKFTTASDV WAFGVTLWET 790 800 810 820 830 840 FTFCQEQPYS QLSDEQVIEN TGEFFRDQGR QTYLPQPAIC PDSVYKLMLS CWRRDTKNRP 850 SFQEIHLLLL QQGDE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure, expression and chromosomal mapping of TKT from man and mouse: a new subclass of receptor tyrosine kinases with a factor VIII-like domain." Karn T., Holtrich U., Braeuninger A., Boehme B., Wolf G., Ruebsamen-Waigmann H., Strebhardt K. Oncogene 8:3433-3440(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Heart and Thymus.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hair follicle dermal papilla and Uterus.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[6]	"The discoidin domain receptor tyrosine kinases are activated by collagen." Vogel W., Gish G.D., Alves F., Pawson T. Mol. Cell 1:13-23(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS COLLAGEN RECEPTOR AND IN UP-REGULATION OF MMP1, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[7]	"Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation." Yang K., Kim J.H., Kim H.J., Park I.S., Kim I.Y., Yang B.S. J. Biol. Chem. 280:39058-39066(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REGULATION OF MMP1 AND MMP2, PHOSPHORYLATION BY SRC, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, ENZYME REGULATION, INTERACTION WITH SHC1, MUTAGENESIS OF LYS-608; TYR-736; TYR-740 AND TYR-741.
[8]	"Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by fibrillar collagen." Wall S.J., Werner E., Werb Z., DeClerck Y.A. J. Biol. Chem. 280:40187-40194(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS COLLAGEN RECEPTOR, PHOSPHORYLATION.
[9]	"Increased expression of the collagen receptor discoidin domain receptor 2 in articular cartilage as a key event in the pathogenesis of osteoarthritis." Xu L., Peng H., Glasson S., Lee P.L., Hu K., Ijiri K., Olsen B.R., Goldring M.B., Li Y. Arthritis Rheum. 56:2663-2673(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UP-REGULATION OF MMP13, INDUCTION, TISSUE SPECIFICITY.
[10]	"Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen." Konitsiotis A.D., Raynal N., Bihan D., Hohenester E., Farndale R.W., Leitinger B. J. Biol. Chem. 283:6861-6868(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS COLLAGEN RECEPTOR, SUBCELLULAR LOCATION, PHOSPHORYLATION, SUBUNIT.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation." Lin K.L., Chou C.H., Hsieh S.C., Hwa S.Y., Lee M.T., Wang F.F. J. Bone Miner. Res. 25:2489-2503(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN OSTEOBLAST DIFFERENTIATION VIA ACTIVATION OF RUNX2, INDUCTION, TISSUE SPECIFICITY.
[14]	"An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation." Zhang Y., Su J., Yu J., Bu X., Ren T., Liu X., Yao L. J. Bone Miner. Res. 26:604-617(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN OSTEOBLAST DIFFERENTIATION AND CHONDROCYTE MATURATION VIA ACTIVATION OF RUNX2.
[15]	"Sensing extracellular matrix: an update on discoidin domain receptor function." Vogel W.F., Abdulhussein R., Ford C.E. Cell. Signal. 18:1108-1116(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[16]	"Transmembrane collagen receptors." Leitinger B. Annu. Rev. Cell Dev. Biol. 27:265-290(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[17]	"Structural basis of the collagen-binding mode of discoidin domain receptor 2." Ichikawa O., Osawa M., Nishida N., Goshima N., Nomura N., Shimada I. EMBO J. 26:4168-4176(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 22-186, INTERACTION WITH COLLAGEN, DISULFIDE BONDS.
[18]	"Crystallographic insight into collagen recognition by discoidin domain receptor 2." Carafoli F., Bihan D., Stathopoulos S., Konitsiotis A.D., Kvansakul M., Farndale R.W., Leitinger B., Hohenester E. Structure 17:1573-1581(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-190 IN COMPLEX WITH COLLAGEN PEPTIDE, DISULFIDE BONDS, MUTAGENESIS OF TRP-52, FUNCTION IN COLLAGEN BINDING, CATALYTIC ACTIVITY, PHOSPHORYLATION.
[19]	"Somatic mutations of the protein kinase gene family in human lung cancer." Davies H., Hunter C., Smith R., Stephens P., Greenman C., Bignell G., Teague J., Butler A., Edkins S., Stevens C., Parker A., O'Meara S., Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J. , Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R., Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A., Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S., Yates A., Brasseur F., Cooper C.S., Flanagan A.M., Green A., Knowles M., Leung S.Y., Looijenga L.H., Malkowicz B., Pierotti M.A., Teh B.T., Yuen S.T., Lakhani S.R., Easton D.F., Weber B.L., Goldstraw P., Nicholson A.G., Wooster R., Stratton M.R., Futreal P.A. Cancer Res. 65:7591-7595(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-105.
[20]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-105; ILE-441; CYS-478 AND PHE-543.
[21]	"Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications." Bargal R., Cormier-Daire V., Ben-Neriah Z., Le Merrer M., Sosna J., Melki J., Zangen D.H., Smithson S.F., Borochowitz Z., Belostotsky R., Raas-Rothschild A. Am. J. Hum. Genet. 84:80-84(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SEMD-SL ILE-713; ARG-726 AND CYS-752.
[22]	"Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients." Ali B.R., Xu H., Akawi N.A., John A., Karuvantevida N.S., Langer R., Al-Gazali L., Leitinger B. Hum. Mol. Genet. 19:2239-2250(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SEMD-SL LYS-113, CHARACTERIZATION OF VARIANTS SEMD-SL LYS-113; ILE-713; ARG-726 AND CYS-752, MUTAGENESIS OF TRP-52, GLYCOSYLATION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X74764 mRNA. Translation: CAA52777.1.
AK314388 mRNA. Translation: BAG37013.1.
AK095975 mRNA. Translation: BAG53183.1.
AL445197 Genomic DNA. Translation: CAI15941.1.
CH471067 Genomic DNA. Translation: EAW90713.1.
BC052998 mRNA. Translation: AAH52998.1.

IPI

IPI00004409.

PIR

S42621.

RefSeq

NP_001014796.1. NM_001014796.1.
NP_006173.2. NM_006182.2.

UniGene

Hs.275757.
Hs.593833.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WUH	X-ray	1.60	A	26-190	[»]
2Z4F	NMR	-	A	26-186	[»]

ProteinModelPortal

Q16832.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39699N.

IntAct

Q16832. 1 interaction.

MINT

MINT-233614.

STRING

9606.ENSP00000356898.

PTM databases

PhosphoSite

Q16832.

Polymorphism databases

DMDM

215273969.

Proteomic databases

PaxDb

Q16832.

PRIDE

Q16832.

Protocols and materials databases

DNASU

4921.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367921; ENSP00000356898; ENSG00000162733.
ENST00000367922; ENSP00000356899; ENSG00000162733.

GeneID

4921.

KEGG

hsa:4921.

UCSC

uc001gcf.3. human.

Organism-specific databases

CTD

4921.

GeneCards

GC01P162601.

HGNC

HGNC:2731. DDR2.

MIM

191311. gene.
271665. phenotype.

neXtProt

NX_Q16832.

Orphanet

93358. Spondyloepimetaphyseal dysplasia - short limb - abnormal calcification.

PharmGKB

PA27196.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000043102.

HOVERGEN

HBG005461.

InParanoid

Q16832.

KO

K05125.

OMA

FSEITFQ.

OrthoDB

EOG4KWJS6.

PhylomeDB

Q16832.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

SignaLink

Q16832.

Gene expression databases

ArrayExpress

Q16832.

Bgee

Q16832.

CleanEx

HS_DDR2.
HS_TKT.

Genevestigator

Q16832.

GermOnline

ENSG00000162733. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.260. 1 hit.

InterPro

IPR000421. Coagulation_fac_5/8-C_type_dom.
IPR008979. Galactose-bd-like.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]

Pfam

PF00754. F5_F8_type_C. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PRINTS

PR00109. TYRKINASE.

SMART

SM00231. FA58C. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF49785. Gal_bind_like. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS01285. FA58C_1. 1 hit.
PS01286. FA58C_2. 1 hit.
PS50022. FA58C_3. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16832.

ChEMBL

CHEMBL5122.

EvolutionaryTrace

Q16832.

GenomeRNAi

4921.

NextBio

18949.

SOURCE

Search...

Entry information

Entry name

DDR2_HUMAN

Accession

Primary (citable) accession number: Q16832
Secondary accession number(s): Q7Z730

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	May 29, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.