Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q16832 (DDR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length855 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processOsteogenesis
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Dwarfism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbiomineral 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

collagen-activated tyrosine kinase receptor signaling pathway

Inferred from direct assay Ref.7. Source: UniProtKB

endochondral bone growth

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular matrix organization

Traceable author statement. Source: Reactome

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

regulation of extracellular matrix disassembly

Traceable author statement Ref.15. Source: UniProtKB

signal transduction

Traceable author statement Ref.6. Source: ProtInc

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.6. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

collagen binding

Inferred from direct assay Ref.18. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.17PubMed 22939624. Source: IntAct

protein tyrosine kinase collagen receptor activity

Inferred from direct assay Ref.6. Source: UniProtKB

transmembrane receptor protein tyrosine kinase activity

Inferred from direct assay Ref.18. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

COL11A2P139422EBI-1381484,EBI-2515504
HSP90AB1P082382EBI-1381484,EBI-352572

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 855834Discoidin domain-containing receptor 2
PRO_0000016746

Regions

Topological domain22 – 399378Extracellular Potential
Transmembrane400 – 42122Helical; Potential
Topological domain422 – 855434Cytoplasmic Potential
Domain30 – 185156F5/8 type C
Domain563 – 849287Protein kinase
Nucleotide binding569 – 5779ATP By similarity

Sites

Active site7101Proton acceptor By similarity
Binding site6081ATP Probable

Amino acid modifications

Modified residue4611Phosphoserine
Modified residue4711Phosphotyrosine; by SRC and autocatalysis By similarity
Modified residue6741Phosphoserine
Modified residue7361Phosphotyrosine; by SRC and autocatalysis Ref.7
Modified residue7401Phosphotyrosine; by SRC and autocatalysis Ref.7
Modified residue7411Phosphotyrosine; by SRC and autocatalysis Ref.7
Glycosylation1211N-linked (GlcNAc...) Potential
Glycosylation2131N-linked (GlcNAc...) Potential
Glycosylation2611N-linked (GlcNAc...) Potential
Glycosylation2801N-linked (GlcNAc...) Potential
Glycosylation3721N-linked (GlcNAc...) Potential
Disulfide bond30 ↔ 185 Ref.17 Ref.18
Disulfide bond73 ↔ 177 Ref.17 Ref.18

Natural variations

Natural variant1051R → S in a lung large cell carcinoma sample; somatic mutation. Ref.19 Ref.20
VAR_041498
Natural variant1131E → K in SEMD-SL; abolishes collagen binding. Ref.22
VAR_065719
Natural variant4411M → I. Ref.20
Corresponds to variant rs34722354 [ dbSNP | Ensembl ].
VAR_041499
Natural variant4781R → C. Ref.20
Corresponds to variant rs34869543 [ dbSNP | Ensembl ].
VAR_041500
Natural variant5431V → F. Ref.20
Corresponds to variant rs55973200 [ dbSNP | Ensembl ].
VAR_041501
Natural variant7131T → 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 variant7261I → 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 variant7521R → 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

Mutagenesis521W → A: Abolishes collagen binding. Ref.18 Ref.22
Mutagenesis6081K → A: Abolishes kinase activity. Ref.7
Mutagenesis7361Y → F: Reduces autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-740 and F-741. Ref.7
Mutagenesis7401Y → F: Promotes autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-736 and F-741. Ref.7
Mutagenesis7411Y → F: Reduces autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-736 and F-740. Ref.7
Sequence conflict6421A → S in CAA52777. Ref.1

Secondary structure

................................ 855
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16832 [UniParc].

Last modified November 25, 2008. Version 2.
Checksum: 78662021BC53E1A0

FASTA85596,736
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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 AT TYR-736; TYR-740 AND TYR-741, 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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS1241.1.
PIRS42621.
RefSeqNP_001014796.1. NM_001014796.1.
NP_006173.2. NM_006182.2.
XP_006711407.1. XM_006711344.1.
UniGeneHs.275757.
Hs.593833.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WUHX-ray1.60A26-190[»]
2Z4FNMR-A26-186[»]
ProteinModelPortalQ16832.
SMRQ16832. Positions 26-369, 459-851.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110975. 6 interactions.
DIPDIP-39699N.
IntActQ16832. 2 interactions.
MINTMINT-233614.
STRING9606.ENSP00000356898.

Chemistry

BindingDBQ16832.
ChEMBLCHEMBL5122.
GuidetoPHARMACOLOGY1844.

PTM databases

PhosphoSiteQ16832.

Polymorphism databases

DMDM215273969.

Proteomic databases

MaxQBQ16832.
PaxDbQ16832.
PRIDEQ16832.

Protocols and materials databases

DNASU4921.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367921; ENSP00000356898; ENSG00000162733.
ENST00000367922; ENSP00000356899; ENSG00000162733.
GeneID4921.
KEGGhsa:4921.
UCSCuc001gcf.3. human.

Organism-specific databases

CTD4921.
GeneCardsGC01P162601.
HGNCHGNC:2731. DDR2.
MIM191311. gene.
271665. phenotype.
neXtProtNX_Q16832.
Orphanet93358. Spondyloepimetaphyseal dysplasia - short limb - abnormal calcification.
PharmGKBPA27196.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000043102.
HOVERGENHBG005461.
InParanoidQ16832.
KOK05125.
OMAASAIKCQ.
OrthoDBEOG77Q4W2.
PhylomeDBQ16832.
TreeFamTF317840.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_118779. Extracellular matrix organization.
SignaLinkQ16832.

Gene expression databases

ArrayExpressQ16832.
BgeeQ16832.
CleanExHS_DDR2.
HS_TKT.
GenevestigatorQ16832.

Family and domain databases

Gene3D2.60.120.260. 1 hit.
InterProIPR000421. Coagulation_fac_5/8-C_type_dom.
IPR008979. Galactose-bd-like.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamPF00754. F5_F8_type_C. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00231. FA58C. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS01285. 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]
ProtoNetSearch...

Other

EvolutionaryTraceQ16832.
GeneWikiDiscoidin_domain-containing_receptor_2.
GenomeRNAi4921.
NextBio18949.
PROQ16832.
SOURCESearch...

Entry information

Entry nameDDR2_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries