DDR1_RAT
ID DDR1_RAT Reviewed; 910 AA.
AC Q63474;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Epithelial discoidin domain-containing receptor 1;
DE Short=Epithelial discoidin domain receptor 1;
DE EC=2.7.10.1;
DE AltName: Full=CD167 antigen-like family member A;
DE AltName: Full=Cell adhesion kinase;
DE AltName: Full=Discoidin receptor tyrosine kinase;
DE AltName: Full=Protein-tyrosine kinase 3;
DE AltName: Full=Tyrosine kinase DDR;
DE AltName: Full=Tyrosine-protein kinase CAK;
DE AltName: CD_antigen=CD167a;
DE Flags: Precursor;
GN Name=Ddr1; Synonyms=Eddr1, Ptk3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8127887; DOI=10.1073/pnas.91.5.1819;
RA Sanchez M.P., Tapley P., Saini S.S., He B., Pulido D., Barbacid M.;
RT "Multiple tyrosine protein kinases in rat hippocampal neurons: isolation of
RT Ptk-3, a receptor expressed in proliferative zones of the developing
RT brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:1819-1823(1994).
CC -!- FUNCTION: Tyrosine kinase that functions as cell surface receptor for
CC fibrillar collagen and regulates cell attachment to the extracellular
CC matrix, remodeling of the extracellular matrix, cell migration,
CC differentiation, survival and cell proliferation. Collagen binding
CC triggers a signaling pathway that involves SRC and leads to the
CC activation of MAP kinases. Regulates remodeling of the extracellular
CC matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and
CC MMP9, and thereby facilitates cell migration and wound healing.
CC Promotes smooth muscle cell migration, and thereby contributes to
CC arterial wound healing. Also plays a role in tumor cell invasion.
CC Phosphorylates PTPN11. Required for normal blastocyst implantation
CC during pregnancy, for normal mammary gland differentiation and normal
CC lactation. Required for normal ear morphology and normal hearing (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Homodimer. Interacts (via PPxY motif) with WWC1 (via WW
CC domains) in a collagen-regulated manner. Forms a tripartite complex
CC with WWC1 and PRKCZ, but predominantly in the absence of collagen.
CC Interacts (tyrosine phosphorylated) with SHC1. Interacts with SRC.
CC Interacts with MYH9. Interacts with CDH1. Interacts with PTPN11.
CC Interacts with NCK2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Various embryonic and adult tissues; also
CC proliferative zones of the developing brain; hippocampal neurons.
CC -!- PTM: Autophosphorylated in response to fibrillar collagen binding.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; L26525; AAA21089.1; -; Genomic_DNA.
DR PIR; A53137; A53137.
DR AlphaFoldDB; Q63474; -.
DR SMR; Q63474; -.
DR STRING; 10116.ENSRNOP00000001102; -.
DR BindingDB; Q63474; -.
DR ChEMBL; CHEMBL4295859; -.
DR GlyGen; Q63474; 4 sites.
DR iPTMnet; Q63474; -.
DR PhosphoSitePlus; Q63474; -.
DR jPOST; Q63474; -.
DR PaxDb; Q63474; -.
DR UCSC; RGD:2252; rat.
DR RGD; 2252; Ddr1.
DR eggNOG; KOG1094; Eukaryota.
DR InParanoid; Q63474; -.
DR PhylomeDB; Q63474; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-3000171; Non-integrin membrane-ECM interactions.
DR PRO; PR:Q63474; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0005903; C:brush border; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0038062; F:protein tyrosine kinase collagen receptor activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0061564; P:axon development; ISO:RGD.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; ISO:RGD.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IEP:RGD.
DR GO; GO:0043583; P:ear development; ISO:RGD.
DR GO; GO:0007566; P:embryo implantation; ISO:RGD.
DR GO; GO:0007595; P:lactation; IEA:UniProtKB-KW.
DR GO; GO:0060749; P:mammary gland alveolus development; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1990138; P:neuron projection extension; ISO:RGD.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:RGD.
DR GO; GO:0001558; P:regulation of cell growth; ISO:RGD.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; ISO:RGD.
DR GO; GO:0010715; P:regulation of extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; IEP:RGD.
DR GO; GO:0014909; P:smooth muscle cell migration; ISS:UniProtKB.
DR GO; GO:0061302; P:smooth muscle cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB.
DR CDD; cd00057; FA58C; 1.
DR InterPro; IPR034299; DDR1/DDR2.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR PANTHER; PTHR24416:SF295; PTHR24416:SF295; 1.
DR Pfam; PF00754; F5_F8_type_C; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00231; FA58C; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01285; FA58C_1; 1.
DR PROSITE; PS01286; FA58C_2; 1.
DR PROSITE; PS50022; FA58C_3; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Calcium; Cell membrane; Disulfide bond; Glycoprotein; Kinase;
KW Lactation; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Pregnancy; Receptor; Reference proteome; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..910
FT /note="Epithelial discoidin domain-containing receptor 1"
FT /id="PRO_0000016745"
FT TOPO_DOM 22..414
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 436..910
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..186
FT /note="F5/8 type C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 607..902
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 193..368
FT /note="DS-like domain"
FT /evidence="ECO:0000250"
FT REGION 467..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 478..481
FT /note="PPxY motif"
FT ACT_SITE 763
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 234
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 256
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 361
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 362
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 613..621
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 652
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 481
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 510
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 517
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 737
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 789
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 793
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 794
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT CARBOHYD 212
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 391
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 75..178
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 304..349
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
SQ SEQUENCE 910 AA; 101165 MW; 7E7FFA1DCB029806 CRC64;
MGTGTLSSLL LLLLLVTIGD ADMKGHFDPA KCRYALGMQD RTIPDSDISV SSSWSDSTAA
RHSRLESSDG DGAWCPAGPV FPKEEEYLQV DLRRLHLVAL VGTQGRHAGG LGKEFSRSYR
LRYSRDGRRW MDWKDRWGQE VISGNEDPGG VVLKDLGPPM VARLVRFYPR ADRVMSVCLR
VELYGCLWRD GLLSYTAPVG QTMQLSEMVY LNDSTYDGYT AGGLQYGGLG QLADGVVGLD
DFRQSQELRV WPGYDYVGWS NHSFPSGYVE MEFEFDRLRS FQTMQVHCNN MHTLGARLPG
GVECRFKRGP AMAWEGEPVH HALGGSLGDP RARAISVPLG GHVGRFLQCR FLFAGPWLLF
SEISFISDVV NDSSDTFPPA PWWPPGPPPT NFSSLELEPR GQQPVAKAEG SPTAILIGCL
VAIILLLLLI IALMLWRLHW RRLLSKAERR VLEEELTVHL SVPGDTILIN NRPGPREPPP
YQEPRPRGTP THSAPCVPNG SALLLSNPAY RLLLATYARP PRGPGPPTPA WAKPTNTQAC
SGDYMEPEKP GAPLLPPPPQ NSVPHYAEAD IVTLQGVTGG NTYAVPALPP GAVGDGPPRV
DFPRSRLRFK EKLGEGQFGE VHLCEVEDPQ DLVTSDFPIS VQKGHPLLVA VKILRPDATK
NARNDFLKEV KIMSRLKDLN IIRLLGVCVQ DDPLCMITDY MENGDLNQFL SAHQLENKVT
QGLPGDRESD QGPTISYPML LHVGAQIASG MRYLATLNFV HRDLATRNCL VGENFTIKIA
DFGMSRNLYA GDYYRVQGRA VLPIRWMAWE CILMGKFTTA SDVWAFGVTL WEVLMLCRSQ
PFGQLTDEQV IENAGEFFRD QGRQVYLSRP PACPQTLYEL MLRCWSREPE QRPPFSQLHR
FLADDALNTV
