DDR1_MOUSE
ID DDR1_MOUSE Reviewed; 911 AA.
AC Q03146;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 196.
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 MPK-6;
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=Cak, Eddr1, Mpk6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RX PubMed=8622863;
RA Perez J.L., Jing S.Q., Wong T.W.;
RT "Identification of two isoforms of the Cak receptor kinase that are
RT coexpressed in breast tumor cell lines.";
RL Oncogene 12:1469-1477(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 766-822.
RC STRAIN=C57BL/6J; TISSUE=Embryonic brain;
RX PubMed=1281307;
RA Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A.,
RA Wilkinson D.G., Charnay P.;
RT "An Eph-related receptor protein tyrosine kinase gene segmentally expressed
RT in the developing mouse hindbrain.";
RL Oncogene 7:2499-2506(1992).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=11283268; DOI=10.1128/mcb.21.8.2906-2917.2001;
RA Vogel W.F., Aszodi A., Alves F., Pawson T.;
RT "Discoidin domain receptor 1 tyrosine kinase has an essential role in
RT mammary gland development.";
RL Mol. Cell. Biol. 21:2906-2917(2001).
RN [4]
RP FUNCTION.
RX PubMed=12065315; DOI=10.1161/01.res.0000022166.74073.f8;
RA Hou G., Vogel W.F., Bendeck M.P.;
RT "Tyrosine kinase activity of discoidin domain receptor 1 is necessary for
RT smooth muscle cell migration and matrix metalloproteinase expression.";
RL Circ. Res. 90:1147-1149(2002).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=15200417; DOI=10.1111/j.1523-1755.2004.00712.x;
RA Gross O., Beirowski B., Harvey S.J., McFadden C., Chen D., Tam S.,
RA Thorner P.S., Smyth N., Addicks K., Bloch W., Ninomiya Y., Sado Y.,
RA Weber M., Vogel W.F.;
RT "DDR1-deficient mice show localized subepithelial GBM thickening with focal
RT loss of slit diaphragms and proteinuria.";
RL Kidney Int. 66:102-111(2004).
RN [6]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=18026164; DOI=10.1038/labinvest.3700692;
RA Meyer zum Gottesberge A.M., Gross O., Becker-Lendzian U., Massing T.,
RA Vogel W.F.;
RT "Inner ear defects and hearing loss in mice lacking the collagen receptor
RT DDR1.";
RL Lab. Invest. 88:27-37(2008).
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, but
CC also tumor cell invasion. Promotes smooth muscle cell migration, and
CC thereby contributes to arterial wound healing. Phosphorylates PTPN11
CC (By similarity). Required for normal blastocyst implantation during
CC pregnancy, for normal mammary gland differentiation and normal
CC lactation. Required for normal ear morphology and normal hearing.
CC {ECO:0000250, ECO:0000269|PubMed:12065315}.
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; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=CAK I;
CC IsoId=Q03146-1; Sequence=Displayed;
CC Name=2; Synonyms=CAK II;
CC IsoId=Q03146-2; Sequence=VSP_002954;
CC -!- TISSUE SPECIFICITY: Detected in the cochlea and the organ of Corti in
CC the inner ear. Isoform 1 is predominant and is expressed in developing
CC embryo and adult brain. Isoform 2 is expressed in various epithelial
CC cells. {ECO:0000269|PubMed:18026164}.
CC -!- PTM: Autophosphorylated in response to fibrillar collagen binding.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate, but
CC female mice are dwarfs and most of them are unable to bear offspring,
CC due to defects in blastocyte implantation in the uterus. About one
CC fifth can bear offspring, but for these the mammary gland fails to
CC undergo proper differentiation during pregnancy, with
CC hyperproliferation and abnormal branching of the mammary ducts, leading
CC to a lactation defect. In addition, mice exhibit hearing loss, due to
CC alterations of the inner ear. Mice display poor calcification of the
CC fibula. They also exhibit defects in the structure of the slit
CC diaphragm in kidney glomeruli, leading to proteinuria, but do not show
CC overt signs of kidney dysfunction. {ECO:0000269|PubMed:11283268,
CC ECO:0000269|PubMed:15200417, ECO:0000269|PubMed:18026164}.
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; L57509; AAB05209.1; -; mRNA.
DR EMBL; X57240; CAA40516.1; -; mRNA.
DR CCDS; CCDS28703.1; -. [Q03146-1]
DR CCDS; CCDS37603.1; -. [Q03146-2]
DR PIR; S30502; S30502.
DR RefSeq; NP_001185760.1; NM_001198831.1. [Q03146-1]
DR RefSeq; NP_001185762.1; NM_001198833.1. [Q03146-1]
DR RefSeq; NP_031610.1; NM_007584.2. [Q03146-1]
DR RefSeq; NP_766550.1; NM_172962.1. [Q03146-2]
DR RefSeq; XP_006523596.1; XM_006523533.1.
DR RefSeq; XP_006523597.1; XM_006523534.1. [Q03146-1]
DR RefSeq; XP_006523598.1; XM_006523535.3. [Q03146-1]
DR RefSeq; XP_006523599.1; XM_006523536.3. [Q03146-1]
DR RefSeq; XP_006523600.1; XM_006523537.1. [Q03146-1]
DR RefSeq; XP_011244561.1; XM_011246259.1. [Q03146-1]
DR AlphaFoldDB; Q03146; -.
DR SMR; Q03146; -.
DR BioGRID; 198447; 13.
DR IntAct; Q03146; 1.
DR MINT; Q03146; -.
DR STRING; 10090.ENSMUSP00000113062; -.
DR ChEMBL; CHEMBL4523274; -.
DR GlyGen; Q03146; 4 sites.
DR iPTMnet; Q03146; -.
DR PhosphoSitePlus; Q03146; -.
DR MaxQB; Q03146; -.
DR PaxDb; Q03146; -.
DR PRIDE; Q03146; -.
DR ProteomicsDB; 279178; -. [Q03146-1]
DR ProteomicsDB; 279179; -. [Q03146-2]
DR Antibodypedia; 48090; 761 antibodies from 43 providers.
DR DNASU; 12305; -.
DR Ensembl; ENSMUST00000003628; ENSMUSP00000003628; ENSMUSG00000003534. [Q03146-1]
DR Ensembl; ENSMUST00000097333; ENSMUSP00000094945; ENSMUSG00000003534. [Q03146-2]
DR Ensembl; ENSMUST00000117301; ENSMUSP00000112570; ENSMUSG00000003534. [Q03146-1]
DR Ensembl; ENSMUST00000119825; ENSMUSP00000113062; ENSMUSG00000003534. [Q03146-1]
DR Ensembl; ENSMUST00000166980; ENSMUSP00000133047; ENSMUSG00000003534. [Q03146-1]
DR GeneID; 12305; -.
DR KEGG; mmu:12305; -.
DR UCSC; uc008cih.2; mouse. [Q03146-1]
DR CTD; 780; -.
DR MGI; MGI:99216; Ddr1.
DR VEuPathDB; HostDB:ENSMUSG00000003534; -.
DR eggNOG; KOG1094; Eukaryota.
DR GeneTree; ENSGT00940000159733; -.
DR HOGENOM; CLU_008873_2_0_1; -.
DR InParanoid; Q03146; -.
DR OMA; QILRCHF; -.
DR PhylomeDB; Q03146; -.
DR TreeFam; TF317840; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-3000171; Non-integrin membrane-ECM interactions.
DR BioGRID-ORCS; 12305; 5 hits in 76 CRISPR screens.
DR ChiTaRS; Ddr1; mouse.
DR PRO; PR:Q03146; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q03146; protein.
DR Bgee; ENSMUSG00000003534; Expressed in ciliary body and 259 other tissues.
DR ExpressionAtlas; Q03146; baseline and differential.
DR Genevisible; Q03146; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005903; C:brush border; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005518; F:collagen binding; IDA:MGI.
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:0061564; P:axon development; IMP:MGI.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IDA:MGI.
DR GO; GO:0043583; P:ear development; IMP:MGI.
DR GO; GO:0007566; P:embryo implantation; IMP:MGI.
DR GO; GO:0007595; P:lactation; IEA:UniProtKB-KW.
DR GO; GO:0060749; P:mammary gland alveolus development; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:1990138; P:neuron projection extension; IMP:MGI.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0001558; P:regulation of cell growth; IMP:MGI.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IMP:MGI.
DR GO; GO:0010715; P:regulation of extracellular matrix disassembly; IMP:UniProtKB.
DR GO; GO:0014909; P:smooth muscle cell migration; IMP:UniProtKB.
DR GO; GO:0061302; P:smooth muscle cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0044319; P:wound healing, spreading of cells; IMP: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 Alternative splicing; ATP-binding; Calcium; Cell membrane; Disulfide bond;
KW Glycoprotein; Kinase; Lactation; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Pregnancy; Receptor;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..911
FT /note="Epithelial discoidin domain-containing receptor 1"
FT /id="PRO_0000016743"
FT TOPO_DOM 22..415
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..911
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 608..903
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 193..369
FT /note="DS-like domain"
FT /evidence="ECO:0000250"
FT REGION 468..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 479..482
FT /note="PPxY motif"
FT COMPBIAS 474..494
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 764
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 255
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 257
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
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 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 614..622
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 653
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 482
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 511
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 518
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 738
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 790
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 MOD_RES 795
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT CARBOHYD 213
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 392
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 305..350
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT VAR_SEQ 503..539
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8622863"
FT /id="VSP_002954"
SQ SEQUENCE 911 AA; 101161 MW; DBB7FE03DDD79510 CRC64;
MGTGTLSSLL LLLLLVTIGD ADMKGHFDPA KCRYALGMQD RTIPDSDISV SSSWSDSTAA
RHSRLESSDG DGAWCPAGPV FPKEEEYLQV DLRRLHLVAL VGTQGRHAGG LGKEFSRSYR
LRYSRDGRRW MDWKDRWGQE VISGNEDPGG VVLKDLGPPM VARLVRFYPR ADRVMSVCLR
VELYGCLWRD GLLSYTAPVG QTMQLSEVMV HLNDSTYDGY TAGGLQYGGL GQLADGVVGL
DDFRQSQELR VWPGYDYVGW SNQSFPTGYV EMEFEFDRLR TFQTMQVHCN NMHTLGARLP
GGVECRFKRG PAMAWEGEPV RHALGGSLGD PRARAISVPL GGHVGRFLQC RFLFAGPWLL
FSEISFISDV VNDSSDTFPP APWWPPGPPP TNFSSLELEP RGQQPVAKAE GSPTAILIGC
LVAIILLLLL IIALMLWRLH WRRLLSKAER RVLEEELTVH LSVPGDTILI NNRPGPREPP
PYQEPRPRGT PPHSAPCVPN GSALLLSNPA YRLLLATYAR PPRGPGPPTP AWAKPTNTQA
CSGDYMEPEK PGAPLLPPPP QNSVPHYAEA DIVTLQGVTG GNTYAVPALP PGAVGDGPPR
VDFPRSRLRF KEKLGEGQFG EVHLCEVEDP QDLVSSDFPI SVHKGHPLLV AVKILRPDAT
KNARNDFLKE VKIMSRLKDP NIIRLLGVCV QDDPLCMITD YMENGDLNQF LSARQLENKA
TQGLSGDTES DQGPTISYPM LLHVGAQIAS GMRYLATLNF VHRDLATRNC LVGENFTIKI
ADFGMSRNLY AGDYYRVQGR AVLPIRWMAW ECILMGKFTT ASDVWAFGVT LWEVLMLCRS
QPFGQLTDEQ VIENAGEFFR DQGRQVYLSR PPACPQTLYE LMLRCWSREP EQRPPFAQLH
RFLADDALNT V
