DDR1_HUMAN » Epithelial discoidin domain-containing receptor 1

DDR1_HUMAN » Epithelial discoidin domain-containing receptor 1
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
DDR1_HUMAN » Epithelial discoidin domain-containing receptor 1 » Epithelial discoidin domain receptor 1; CD167 antigen-like family member A;Cell adhesion kinase;Discoidin receptor tyrosine kinase;HGK2;Mammary carcinoma kinase 10;MCK-10; Protein-tyrosine kinase 3A;Protein-tyrosine kinase RTK-6;TRK E;Tyrosine kinase DDR;
Hydrophobic Thickness 33.2 ± 1.8 Å
Tilt Angle 4 ± 3°
ΔGtransfer -46.3 kcal/mol
ΔGfold -31.7 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 415-443 (415-451)
Pathways none
PDB 3zos (601-913), 4bkj (601-913), 4ckr (601-913), 4ag4 (A=29-367)
OPM none
Complexes none
Interactions

CADH1, Complex: CADH1:DDR1

CADH2, Complex: CADH2:DDR1

Domains

AA: 46-182, PDBID: 4AG4, Subunit A, Seq Identity:100%, F5/8 type C domain

AA: 610-905, PDBID: 3ZOS, Subunit B, Seq Identity:100%, Protein tyrosine kinase

UniProt annotation for DDR1_HUMAN » Epithelial discoidin domain-containing receptor 1
FUNCTION: Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11.

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

ENZYME REGULATION: Inhibited by the multi-targeted cancer drugs imatinib and ponatinib.

SUBUNIT: Homodimer. Interacts (via PPxY motif) with WWC1 (via WW domains) in a collagen-regulated manner. Forms a tripartite complex with WWC1 and PRKCZ, but predominantly in the absence of collagen. Interacts (tyrosine phosphorylated) with SHC1. Interacts with SRC. Interacts with MYH9. Interacts with CDH1. Interacts with PTPN11. Interacts with NCK2.

TISSUE SPECIFICITY: Detected in T-47D, MDA-MB-175 and HBL-100 breast carcinoma cells, A-431 epidermoid carcinoma cells, SW48 and SNU-C2B colon carcinoma cells and Hs 294T melanoma cells (at protein level). Expressed at low levels in most adult tissues and is highest in the brain, lung, placenta and kidney. Lower levels of expression are detected in melanocytes, heart, liver, skeletal muscle and pancreas. Abundant in breast carcinoma cell lines. In the colonic mucosa, expressed in epithelia but not in the connective tissue of the lamina propria. In the thyroid gland, expressed in the epithelium of the thyroid follicles. In pancreas, expressed in the islets of Langerhans cells, but not in the surrounding epithelial cells of the exocrine pancreas. In kidney, expressed in the epithelia of the distal tubules. Not expressed in connective tissue, endothelial cells, adipose tissue, muscle cells or cells of hematopoietic origin.

DOMAIN: The Gly/Pro-rich domains may be required for an unusual geometry of interaction with ligand or substrates.

UniProt features for DDR1_HUMAN » Epithelial discoidin domain-containing receptor 1
SIGNAL 1 18 Potential.
CHAIN 19 913 Epithelial discoidin domain-containing receptor 1.
DOMAIN 31 185 F5/8 type C.
DOMAIN 610 905 Protein kinase.
REGION 192 367 DS-like domain.
MOTIF 481 484 PPxY motif.
ACT_SITE 766 766 Proton acceptor (By similarity).
DISULFID 31 185
DISULFID 74 177
DISULFID 303 348
Amino Acid Sequence for DDR1_HUMAN » Epithelial discoidin domain-containing receptor 1
MGPEALSSLL LLLLVASGDA DMKGHFDPAK CRYALGMQDR TIPDSDISAS SSWSDSTAAR HSRLESSDGD GAWCPAGSVF PKEEEYLQVD LQRLHLVALV GTQGRHAGGL GKEFSRSYRL RYSRDGRRWM GWKDRWGQEV ISGNEDPEGV VLKDLGPPMV ARLVRFYPRA DRVMSVCLRV ELYGCLWRDG LLSYTAPVGQ TMYLSEAVYL NDSTYDGHTV GGLQYGGLGQ LADGVVGLDD FRKSQELRVW PGYDYVGWSN HSFSSGYVEM EFEFDRLRAF QAMQVHCNNM HTLGARLPGG VECRFRRGPA MAWEGEPMRH NLGGNLGDPR ARAVSVPLGG RVARFLQCRF LFAGPWLLFS EISFISDVVN NSSPALGGTF PPAPWWPPGP PPTNFSSLEL EPRGQQPVAK AEGSPTAILI GCLVAIILLL LLIIALMLWR LHWRRLLSKA ERRVLEEELT VHLSVPGDTI LINNRPGPRE PPPYQEPRPR GNPPHSAPCV PNGSALLLSN PAYRLLLATY ARPPRGPGPP TPAWAKPTNT QAYSGDYMEP EKPGAPLLPP PPQNSVPHYA EADIVTLQGV TGGNTYAVPA LPPGAVGDGP PRVDFPRSRL RFKEKLGEGQ FGEVHLCEVD SPQDLVSLDF PLNVRKGHPL LVAVKILRPD ATKNARNDFL KEVKIMSRLK DPNIIRLLGV CVQDDPLCMI TDYMENGDLN QFLSAHQLED KAAEGAPGDG QAAQGPTISY PMLLHVAAQI ASGMRYLATL NFVHRDLATR NCLVGENFTI KIADFGMSRN LYAGDYYRVQ GRAVLPIRWM AWECILMGKF TTASDVWAFG VTLWEVLMLC RAQPFGQLTD EQVIENAGEF FRDQGRQVYL SRPPACPQGL YELMLRCWSR ESEQRPPFSQ LHRFLAEDAL NTV