DDR1_PANTR
ID DDR1_PANTR Reviewed; 909 AA.
AC Q7YR43;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
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=Discoidin receptor tyrosine kinase;
DE AltName: Full=Tyrosine kinase DDR;
DE AltName: CD_antigen=CD167a;
DE Flags: Precursor;
GN Name=DDR1; Synonyms=EDDR1;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12799463; DOI=10.1073/pnas.1230533100;
RA Anzai T., Shiina T., Kimura N., Yanagiya K., Kohara S., Shigenari A.,
RA Yamagata T., Kulski J.K., Naruse T.K., Fujimori Y., Fukuzumi Y.,
RA Yamazaki M., Tashiro H., Iwamoto C., Umehara Y., Imanishi T., Meyer A.,
RA Ikeo K., Gojobori T., Bahram S., Inoko H.;
RT "Comparative sequencing of human and chimpanzee MHC class I regions unveils
RT insertions/deletions as the major path to genomic divergence.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7708-7713(2003).
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 -!- DOMAIN: The Gly/Pro-rich domains may be required for an unusual
CC geometry of interaction with ligand or substrates.
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; BA000041; BAC78172.1; -; Genomic_DNA.
DR RefSeq; NP_001038967.1; NM_001045502.1.
DR AlphaFoldDB; Q7YR43; -.
DR SMR; Q7YR43; -.
DR STRING; 9598.ENSPTRP00000030612; -.
DR PaxDb; Q7YR43; -.
DR GeneID; 462548; -.
DR KEGG; ptr:462548; -.
DR CTD; 780; -.
DR eggNOG; KOG1094; Eukaryota.
DR HOGENOM; CLU_008873_2_0_1; -.
DR InParanoid; Q7YR43; -.
DR OrthoDB; 227725at2759; -.
DR TreeFam; TF317840; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
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:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; IEA:UniProtKB-KW.
DR GO; GO:0007595; P:lactation; IEA:UniProtKB-KW.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010715; P:regulation of extracellular matrix disassembly; ISS:UniProtKB.
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: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 3: Inferred from homology;
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..18
FT /evidence="ECO:0000255"
FT CHAIN 19..909
FT /note="Epithelial discoidin domain-containing receptor 1"
FT /id="PRO_0000016744"
FT TOPO_DOM 21..413
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..909
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..181
FT /note="F5/8 type C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 606..901
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 45..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..363
FT /note="DS-like domain"
FT /evidence="ECO:0000250"
FT REGION 466..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 477..480
FT /note="PPxY motif"
FT COMPBIAS 45..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..492
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 762
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 207
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 249
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 251
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 356
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 612..620
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 651
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 480
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 509
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 516
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 736
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 788
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08345"
FT MOD_RES 792
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 CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 70..173
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 299..344
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
SQ SEQUENCE 909 AA; 100642 MW; 5E30275EE6D0D931 CRC64;
MGPEALSSLL LLLLVASGDA DMKGHFDPAK CRYALGMQDR TIPDSDISAS SSWSDSTAAR
HSSDGDGAWC PAGSVFPKEE EYLQVDLQRL HLVALVGTQG RHAGGLGKEF SRSYRLRYSR
DGRRWMGWKD RWGQEVISGN EDPEGVVLKD LGPPMVARLV RFYPRADRVM SVCLRVELYG
CLWRDGLLSY TAPVGQTMYL SEAVYLNDST YDGHTVGGLQ YGGLGQLADG VVGLDDFRKS
QELRVWPGYD YVGWSNHSFS SGYVEMEFEF DRLRAFQAMQ VHCNNMHTLG ARLPGGVECR
FRRGPAMAWE GEPMRHNLGG NLGDPRARAV SVPLGGRVAR FLQCRFLFAG PWLLFSEISF
ISDVVNNSSP ALGGTFPPAP WWPPGPPPTN FSSLELEPRG QQPVAKAEGS PTAILIGCLV
AIILLLLLII ALMLWRLHWR RLLSKAERRV LEEELTVHLS VPGDTILINN RPGPREPPPY
QEPRPRGNPP HSAPCVPNGS ALLLSNPAYR LLLATYARPP RGPGPPTPAW AKPTNTQAYS
GDYMEPEKPG APLLPPPPQN SVPHYAEADI VTLQGVTGGN TYAVPALPPG AVGDGPPRVD
FPRSRLRFKE KLGEGQFGEV HLCEVDSPQD LVSLDFPLNV RKGHPLLVAV KILRPDATKN
ARNDFLKEVK IMSRLKDPNI IRLLGVCVQD DPLCMITDYM ENGDLNQFLS AHQLEDKAAE
GAPGDGQAAQ GPTISYPMLL HVAAQIASGM RYLATLNFVH RDLATRNCLV GENFTIKIAD
FGMSRNLYAG DYYRVQGRAV LPIRWMAWEC ILMGKFTTAS DVWAFGVTLW EVLMLCRAQP
FGQLTDEQVI ENAGEFFRDQ GRQVYLSRPP ACPQGLYELM LRCWSRESEQ RPPFSQLHRF
LAEDALNTV
