Epithelial discoidin domain-containing receptor 1

Details

Name
Epithelial discoidin domain-containing receptor 1
Synonyms
  • 2.7.10.1
  • CAK
  • CD167 antigen-like family member A
  • Cell adhesion kinase
  • Discoidin receptor tyrosine kinase
  • EDDR1
  • Epithelial discoidin domain receptor 1
  • HGK2
  • Mammary carcinoma kinase 10
  • MCK-10
  • NEP
  • NTRK4
  • Protein-tyrosine kinase 3A
  • Protein-tyrosine kinase RTK-6
  • PTK3A
  • RTK6
  • TRK E
  • TRKE
  • Tyrosine kinase DDR
  • Tyrosine-protein kinase CAK
Gene Name
DDR1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002236|Epithelial discoidin domain-containing receptor 1
MGPEALSSLLLLLLVASGDADMKGHFDPAKCRYALGMQDRTIPDSDISASSSWSDSTAAR
HSRLESSDGDGAWCPAGSVFPKEEEYLQVDLQRLHLVALVGTQGRHAGGLGKEFSRSYRL
RYSRDGRRWMGWKDRWGQEVISGNEDPEGVVLKDLGPPMVARLVRFYPRADRVMSVCLRV
ELYGCLWRDGLLSYTAPVGQTMYLSEAVYLNDSTYDGHTVGGLQYGGLGQLADGVVGLDD
FRKSQELRVWPGYDYVGWSNHSFSSGYVEMEFEFDRLRAFQAMQVHCNNMHTLGARLPGG
VECRFRRGPAMAWEGEPMRHNLGGNLGDPRARAVSVPLGGRVARFLQCRFLFAGPWLLFS
EISFISDVVNNSSPALGGTFPPAPWWPPGPPPTNFSSLELEPRGQQPVAKAEGSPTAILI
GCLVAIILLLLLIIALMLWRLHWRRLLSKAERRVLEEELTVHLSVPGDTILINNRPGPRE
PPPYQEPRPRGNPPHSAPCVPNGSALLLSNPAYRLLLATYARPPRGPGPPTPAWAKPTNT
QAYSGDYMEPEKPGAPLLPPPPQNSVPHYAEADIVTLQGVTGGNTYAVPALPPGAVGDGP
PRVDFPRSRLRFKEKLGEGQFGEVHLCEVDSPQDLVSLDFPLNVRKGHPLLVAVKILRPD
ATKNARNDFLKEVKIMSRLKDPNIIRLLGVCVQDDPLCMITDYMENGDLNQFLSAHQLED
KAAEGAPGDGQAAQGPTISYPMLLHVAAQIASGMRYLATLNFVHRDLATRNCLVGENFTI
KIADFGMSRNLYAGDYYRVQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEVLMLC
RAQPFGQLTDEQVIENAGEFFRDQGRQVYLSRPPACPQGLYELMLRCWSRESEQRPPFSQ
LHRFLAEDALNTV
Number of residues
913
Molecular Weight
101126.72
Theoretical pI
6.81
GO Classification
Functions
ATP binding / collagen binding / metal ion binding / protein tyrosine kinase collagen receptor activity / transmembrane receptor protein tyrosine kinase activity
Processes
cell adhesion / collagen-activated tyrosine kinase receptor signaling pathway / extracellular matrix organization / female pregnancy / lactation / peptidyl-tyrosine autophosphorylation / protein autophosphorylation / regulation of extracellular matrix disassembly / smooth muscle cell migration / smooth muscle cell-matrix adhesion / wound healing, spreading of cells
Components
extracellular exosome / extracellular space / integral component of plasma membrane / plasma membrane / receptor complex
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
418-438
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010785|Epithelial discoidin domain-containing receptor 1 (DDR1)
ATGGGACCAGAGGCCCTGTCATCTTTACTGCTGCTGCTCTTGGTGGCAAGTGGAGATGCT
GACATGAAGGGACATTTTGATCCTGCCAAGTGCCGCTATGCCCTGGGCATGCAGGACCGG
ACCATCCCAGACAGTGACATCTCTGCTTCCAGCTCCTGGTCAGATTCCACTGCCGCCCGC
CACAGCAGGTTGGAGAGCAGTGACGGGGATGGGGCCTGGTGCCCCGCAGGGTCGGTGTTT
CCCAAGGAGGAGGAGTACTTGCAGGTGGATCTACAACGACTGCACCTGGTGGCTCTGGTG
GGCACCCAGGGACGGCATGCCGGGGGCCTGGGCAAGGAGTTCTCCCGGAGCTACCGGCTG
CGTTACTCCCGGGATGGTCGCCGCTGGATGGGCTGGAAGGACCGCTGGGGTCAGGAGGTG
ATCTCAGGCAATGAGGACCCTGAGGGAGTGGTGCTGAAGGACCTTGGGCCCCCCATGGTT
GCCCGACTGGTTCGCTTCTACCCCCGGGCTGACCGGGTCATGAGCGTCTGTCTGCGGGTA
GAGCTCTATGGCTGCCTCTGGAGGGATGGACTCCTGTCTTACACCGCCCCTGTGGGGCAG
ACAATGTATTTATCTGAGGCCGTGTACCTCAACGACTCCACCTATGACGGACATACCGTG
GGCGGACTGCAGTATGGGGGTCTGGGCCAGCTGGCAGATGGTGTGGTGGGGCTGGATGAC
TTTAGGAAGAGTCAGGAGCTGCGGGTCTGGCCAGGCTATGACTATGTGGGATGGAGCAAC
CACAGCTTCTCCAGTGGCTATGTGGAGATGGAGTTTGAGTTTGACCGGCTGAGGGCCTTC
CAGGCTATGCAGGTCCACTGTAACAACATGCACACGCTGGGAGCCCGTCTGCCTGGCGGG
GTGGAATGTCGCTTCCGGCGTGGCCCTGCCATGGCCTGGGAGGGGGAGCCCATGCGCCAC
AACCTAGGGGGCAACCTGGGGGACCCCAGAGCCCGGGCTGTCTCAGTGCCCCTTGGCGGC
CGTGTGGCTCGCTTTCTGCAGTGCCGCTTCCTCTTTGCGGGGCCCTGGTTACTCTTCAGC
GAAATCTCCTTCATCTCTGATGTGGTGAACAATTCCTCTCCGGCACTGGGAGGCACCTTC
CCGCCAGCCCCCTGGTGGCCGCCTGGCCCACCTCCCACCAACTTCAGCAGCTTGGAGCTG
GAGCCCAGAGGCCAGCAGCCCGTGGCCAAGGCCGAGGGGAGCCCGACCGCCATCCTCATC
GGCTGCCTGGTGGCCATCATCCTGCTCCTGCTGCTCATCATTGCCCTCATGCTCTGGCGG
CTGCACTGGCGCAGGCTCCTCAGCAAGGCTGAACGGAGGGTGTTGGAAGAGGAGCTGACG
GTTCACCTCTCTGTCCCTGGGGACACTATCCTCATCAACAACCGCCCAGGTCCTAGAGAG
CCACCCCCGTACCAGGAGCCCCGGCCTCGTGGGAATCCGCCCCACTCCGCTCCCTGTGTC
CCCAATGGCTCTGGTGCACCTGTGTGA
Chromosome Location
6
Locus
6p21.3
External Identifiers
ResourceLink
UniProtKB IDQ08345
UniProtKB Entry NameDDR1_HUMAN
GenBank Protein ID306475
GenBank Gene IDL20817
GenAtlas IDDDR1
HGNC IDHGNC:2730
General References
  1. Di Marco E, Cutuli N, Guerra L, Cancedda R, De Luca M: Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal human tissues. J Biol Chem. 1993 Nov 15;268(32):24290-5. [PubMed:8226977]
  2. Johnson JD, Edman JC, Rutter WJ: A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5677-81. [PubMed:8390675]
  3. Laval S, Butler R, Shelling AN, Hanby AM, Poulsom R, Ganesan TS: Isolation and characterization of an epithelial-specific receptor tyrosine kinase from an ovarian cancer cell line. Cell Growth Differ. 1994 Nov;5(11):1173-83. [PubMed:7848919]
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  5. Sakuma S, Saya H, Tada M, Nakao M, Fujiwara T, Roth JA, Sawamura Y, Shinohe Y, Abe H: Receptor protein tyrosine kinase DDR is up-regulated by p53 protein. FEBS Lett. 1996 Dec 2;398(2-3):165-9. [PubMed:8977099]
  6. Playford MP, Butler RJ, Wang XC, Katso RM, Cooke IE, Ganesan TS: The genomic structure of discoidin receptor tyrosine kinase. Genome Res. 1996 Jul;6(7):620-7. [PubMed:8796349]
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  14. Alves F, Vogel W, Mossie K, Millauer B, Hofler H, Ullrich A: Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer. Oncogene. 1995 Feb 2;10(3):609-18. [PubMed:7845687]
  15. Weiner TM, Liu ET, Craven RJ, Cance WG: Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors. Ann Surg Oncol. 1994 Jan;1(1):18-27. [PubMed:7834423]
  16. Lee ST, Strunk KM, Spritz RA: A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. Oncogene. 1993 Dec;8(12):3403-10. [PubMed:8247543]
  17. 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. [PubMed:9659899]
  18. Hou G, Vogel WF, Bendeck MP: Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression. Circ Res. 2002 Jun 14;90(11):1147-9. [PubMed:12065315]
  19. Koo DH, McFadden C, Huang Y, Abdulhussein R, Friese-Hamim M, Vogel WF: Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1. FEBS Lett. 2006 Jan 9;580(1):15-22. Epub 2005 Dec 1. [PubMed:16337946]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00619ImatinibapprovedunknownantagonistDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails