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Protein

Epithelial discoidin domain-containing receptor 1

Gene

Ddr1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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, but also tumor cell invasion. Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Phosphorylates PTPN11 (By similarity). Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing.By similarity1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi213Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi232Calcium 1By similarity1
Metal bindingi232Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi235Calcium 2By similarity1
Metal bindingi237Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi255Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi257Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi362Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi363Calcium 2By similarity1
Binding sitei653ATPPROSITE-ProRule annotation1
Active sitei764Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi614 – 622ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • axon development Source: MGI
  • branching involved in mammary gland duct morphogenesis Source: MGI
  • collagen-activated tyrosine kinase receptor signaling pathway Source: MGI
  • ear development Source: MGI
  • embryo implantation Source: MGI
  • lactation Source: UniProtKB-KW
  • mammary gland alveolus development Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • neuron projection extension Source: MGI
  • peptidyl-tyrosine autophosphorylation Source: MGI
  • peptidyl-tyrosine phosphorylation Source: MGI
  • protein autophosphorylation Source: MGI
  • regulation of cell growth Source: MGI
  • regulation of cell-matrix adhesion Source: MGI
  • regulation of extracellular matrix disassembly Source: UniProtKB
  • smooth muscle cell-matrix adhesion Source: UniProtKB
  • smooth muscle cell migration Source: UniProtKB
  • wound healing, spreading of cells Source: UniProtKB

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processLactation, Pregnancy
LigandATP-binding, Calcium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 3474
ReactomeiR-MMU-3000171 Non-integrin membrane-ECM interactions

Names & Taxonomyi

Protein namesi
Recommended name:
Epithelial discoidin domain-containing receptor 1 (EC:2.7.10.1)
Short name:
Epithelial discoidin domain receptor 1
Alternative name(s):
CD167 antigen-like family member A
Cell adhesion kinase
Discoidin receptor tyrosine kinase
Protein-tyrosine kinase MPK-6
Tyrosine kinase DDR
Tyrosine-protein kinase CAK
CD_antigen: CD167a
Gene namesi
Name:Ddr1
Synonyms:Cak, Eddr1, Mpk6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:99216 Ddr1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 415ExtracellularSequence analysisAdd BLAST394
Transmembranei416 – 436HelicalSequence analysisAdd BLAST21
Topological domaini437 – 911CytoplasmicSequence analysisAdd BLAST475

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are born at the expected Mendelian rate, but female mice are dwarfs and most of them are unable to bear offspring, due to defects in blastocyte implantation in the uterus. About one fifth can bear offspring, but for these the mammary gland fails to undergo proper differentiation during pregnancy, with hyperproliferation and abnormal branching of the mammary ducts, leading to a lactation defect. In addition, mice exhibit hearing loss, due to alterations of the inner ear. Mice display poor calcification of the fibula. They also exhibit defects in the structure of the slit diaphragm in kidney glomeruli, leading to proteinuria, but do not show overt signs of kidney dysfunction.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001674320 – 911Epithelial discoidin domain-containing receptor 1Add BLAST892

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 186PROSITE-ProRule annotation
Disulfide bondi75 ↔ 178PROSITE-ProRule annotation
Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi262N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi305 ↔ 350PROSITE-ProRule annotation
Glycosylationi372N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi392N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei482Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei511Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei518Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei738Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei790Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei794Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei795Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated in response to fibrillar collagen binding.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ03146
PaxDbiQ03146
PRIDEiQ03146

PTM databases

iPTMnetiQ03146
PhosphoSitePlusiQ03146

Expressioni

Tissue specificityi

Detected in the cochlea and the organ of Corti in the inner ear. Isoform 1 is predominant and is expressed in developing embryo and adult brain. Isoform 2 is expressed in various epithelial cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000003534
CleanExiMM_DDR1
ExpressionAtlasiQ03146 baseline and differential
GenevisibleiQ03146 MM

Interactioni

Subunit structurei

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 (By similarity).By similarity

Protein-protein interaction databases

IntActiQ03146 1 interactor.
MINTiQ03146
STRINGi10090.ENSMUSP00000003628

Structurei

3D structure databases

ProteinModelPortaliQ03146
SMRiQ03146
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 186F5/8 type CPROSITE-ProRule annotationAdd BLAST155
Domaini608 – 903Protein kinasePROSITE-ProRule annotationAdd BLAST296

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni193 – 369DS-like domainBy similarityAdd BLAST177

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi479 – 482PPxY motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi379 – 413Gly/Pro-richAdd BLAST35
Compositional biasi474 – 599Gly/Pro-richAdd BLAST126

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1094 Eukaryota
ENOG410XQAI LUCA
GeneTreeiENSGT00760000118818
HOGENOMiHOG000043102
HOVERGENiHBG005461
InParanoidiQ03146
KOiK05124
OMAiGVECRFK
OrthoDBiEOG091G05Y8
PhylomeDBiQ03146
TreeFamiTF317840

Family and domain databases

Gene3Di2.60.120.2601 hit
InterProiView protein in InterPro
IPR029553 DDR1
IPR000421 FA58C
IPR008979 Galactose-bd-like_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR002011 Tyr_kinase_rcpt_2_CS
PANTHERiPTHR24416:SF333 PTHR24416:SF333, 1 hit
PfamiView protein in Pfam
PF00754 F5_F8_type_C, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00231 FA58C, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01285 FA58C_1, 1 hit
PS01286 FA58C_2, 1 hit
PS50022 FA58C_3, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS00239 RECEPTOR_TYR_KIN_II, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q03146-1) [UniParc]FASTAAdd to basket
Also known as: CAK I

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGTGTLSSLL LLLLLVTIGD ADMKGHFDPA KCRYALGMQD RTIPDSDISV
60 70 80 90 100
SSSWSDSTAA RHSRLESSDG DGAWCPAGPV FPKEEEYLQV DLRRLHLVAL
110 120 130 140 150
VGTQGRHAGG LGKEFSRSYR LRYSRDGRRW MDWKDRWGQE VISGNEDPGG
160 170 180 190 200
VVLKDLGPPM VARLVRFYPR ADRVMSVCLR VELYGCLWRD GLLSYTAPVG
210 220 230 240 250
QTMQLSEVMV HLNDSTYDGY TAGGLQYGGL GQLADGVVGL DDFRQSQELR
260 270 280 290 300
VWPGYDYVGW SNQSFPTGYV EMEFEFDRLR TFQTMQVHCN NMHTLGARLP
310 320 330 340 350
GGVECRFKRG PAMAWEGEPV RHALGGSLGD PRARAISVPL GGHVGRFLQC
360 370 380 390 400
RFLFAGPWLL FSEISFISDV VNDSSDTFPP APWWPPGPPP TNFSSLELEP
410 420 430 440 450
RGQQPVAKAE GSPTAILIGC LVAIILLLLL IIALMLWRLH WRRLLSKAER
460 470 480 490 500
RVLEEELTVH LSVPGDTILI NNRPGPREPP PYQEPRPRGT PPHSAPCVPN
510 520 530 540 550
GSALLLSNPA YRLLLATYAR PPRGPGPPTP AWAKPTNTQA CSGDYMEPEK
560 570 580 590 600
PGAPLLPPPP QNSVPHYAEA DIVTLQGVTG GNTYAVPALP PGAVGDGPPR
610 620 630 640 650
VDFPRSRLRF KEKLGEGQFG EVHLCEVEDP QDLVSSDFPI SVHKGHPLLV
660 670 680 690 700
AVKILRPDAT KNARNDFLKE VKIMSRLKDP NIIRLLGVCV QDDPLCMITD
710 720 730 740 750
YMENGDLNQF LSARQLENKA TQGLSGDTES DQGPTISYPM LLHVGAQIAS
760 770 780 790 800
GMRYLATLNF VHRDLATRNC LVGENFTIKI ADFGMSRNLY AGDYYRVQGR
810 820 830 840 850
AVLPIRWMAW ECILMGKFTT ASDVWAFGVT LWEVLMLCRS QPFGQLTDEQ
860 870 880 890 900
VIENAGEFFR DQGRQVYLSR PPACPQTLYE LMLRCWSREP EQRPPFAQLH
910
RFLADDALNT V
Length:911
Mass (Da):101,161
Last modified:November 1, 1997 - v2
Checksum:iDBB7FE03DDD79510
GO
Isoform 2 (identifier: Q03146-2) [UniParc]FASTAAdd to basket
Also known as: CAK II

The sequence of this isoform differs from the canonical sequence as follows:
     503-539: Missing.

Show »
Length:874
Mass (Da):97,207
Checksum:iA649B2FCE360BA5B
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002954503 – 539Missing in isoform 2. 1 PublicationAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L57509 mRNA Translation: AAB05209.1
X57240 mRNA Translation: CAA40516.1
CCDSiCCDS28703.1 [Q03146-1]
CCDS37603.1 [Q03146-2]
PIRiS30502
RefSeqiNP_001185760.1, NM_001198831.1 [Q03146-1]
NP_001185762.1, NM_001198833.1 [Q03146-1]
NP_031610.1, NM_007584.2 [Q03146-1]
NP_766550.1, NM_172962.1 [Q03146-2]
XP_006523596.1, XM_006523533.1
XP_006523597.1, XM_006523534.1 [Q03146-1]
XP_006523598.1, XM_006523535.3 [Q03146-1]
XP_006523599.1, XM_006523536.3 [Q03146-1]
XP_006523600.1, XM_006523537.1 [Q03146-1]
XP_011244561.1, XM_011246259.1 [Q03146-1]
UniGeneiMm.5021

Genome annotation databases

EnsembliENSMUST00000003628; ENSMUSP00000003628; ENSMUSG00000003534 [Q03146-1]
ENSMUST00000097333; ENSMUSP00000094945; ENSMUSG00000003534 [Q03146-2]
ENSMUST00000117301; ENSMUSP00000112570; ENSMUSG00000003534 [Q03146-1]
ENSMUST00000119825; ENSMUSP00000113062; ENSMUSG00000003534 [Q03146-1]
ENSMUST00000166980; ENSMUSP00000133047; ENSMUSG00000003534 [Q03146-1]
GeneIDi12305
KEGGimmu:12305
UCSCiuc008cih.2 mouse [Q03146-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDDR1_MOUSE
AccessioniPrimary (citable) accession number: Q03146
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: November 1, 1997
Last modified: March 28, 2018
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome