DDR2_HUMAN » Discoidin domain-containing receptor 2

DDR2_HUMAN » Discoidin domain-containing receptor 2
Magnify DDR2_HUMAN » Discoidin domain-containing receptor 2Enlarged view of image
3D view in GLMol or JMol

gray dot

Download Coordinates

gray dot

Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
DDR2_HUMAN » Discoidin domain-containing receptor 2 » Discoidin domain receptor 2; 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;
Hydrophobic Thickness 32.8 ± 2.0 Å
Tilt Angle 0 ± 2°
ΔGtransfer -45.8 kcal/mol
ΔGfold -30.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 400-424 (395-432)
Pathways none
PDB 2z4f (26-186), 2wuh (A=26-190)
OPM 2wuh
Complexes none
Interactions

CADH1, Complex: CADH1:DDR2

CADH2, Complex: CADH2:DDR2

Domains

AA: 45-182, PDBID: 2WUH, Subunit A, Seq Identity:100%, F5/8 type C domain

AA: 563-849, PDBID: 3ZOS, Subunit B, Seq Identity:68%, Protein tyrosine kinase

UniProt annotation for DDR2_HUMAN » Discoidin domain-containing receptor 2
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.

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

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.

SUBUNIT: 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.

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.

INDUCTION: Up-regulated during osteoblast differentiation (in vitro). Up-regulated in cartilage from osteoarthritis patients.

DISEASE: Spondyloepimetaphyseal dysplasia short limb-hand type (SEMD-SL) OMIM: 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.

UniProt features for DDR2_HUMAN » Discoidin domain-containing receptor 2
SIGNAL 1 21 Potential.
CHAIN 22 855 Discoidin domain-containing receptor 2.
DOMAIN 30 185 F5/8 type C.
DOMAIN 563 849 Protein kinase.
ACT_SITE 710 710 Proton acceptor (By similarity).
DISULFID 30 185
DISULFID 73 177
Amino Acid Sequence for DDR2_HUMAN » Discoidin domain-containing receptor 2
MILIPRMLLV LFLLLPILSS AKAQVNPAIC RYPLGMSGGQ IPDEDITASS QWSESTAAKY GRLDSEEGDG AWCPEIPVEP DDLKEFLQID LHTLHFITLV GTQGRHAGGH GIEFAPMYKI NYSRDGTRWI SWRNRHGKQV LDGNSNPYDI FLKDLEPPIV ARFVRFIPVT DHSMNVCMRV ELYGCVWLDG LVSYNAPAGQ QFVLPGGSII YLNDSVYDGA VGYSMTEGLG QLTDGVSGLD DFTQTHEYHV WPGYDYVGWR NESATNGYIE IMFEFDRIRN FTTMKVHCNN MFAKGVKIFK EVQCYFRSEA SEWEPNAISF PLVLDDVNPS ARFVTVPLHH RMASAIKCQY HFADTWMMFS EITFQSDAAM YNNSEALPTS PMAPTTYDPM LKVDDSNTRI LIGCLVAIIF ILLAIIVIIL WRQFWQKMLE KASRRMLDDE MTVSLSLPSD SSMFNNNRSS SPSEQGSNST YDRIFPLRPD YQEPSRLIRK LPEFAPGEEE SGCSGVVKPV QPSGPEGVPH YAEADIVNLQ GVTGGNTYSV PAVTMDLLSG KDVAVEEFPR KLLTFKEKLG EGQFGEVHLC EVEGMEKFKD KDFALDVSAN QPVLVAVKML RADANKNARN DFLKEIKIMS RLKDPNIIHL LAVCITDDPL CMITEYMENG DLNQFLSRHE PPNSSSSDVR TVSYTNLKFM ATQIASGMKY LSSLNFVHRD LATRNCLVGK NYTIKIADFG MSRNLYSGDY YRIQGRAVLP IRWMSWESIL LGKFTTASDV WAFGVTLWET FTFCQEQPYS QLSDEQVIEN TGEFFRDQGR QTYLPQPAIC PDSVYKLMLS CWRRDTKNRP SFQEIHLLLL QQGDE