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Q03146 (DDR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Epithelial discoidin domain-containing receptor 1

Short name=Epithelial discoidin domain receptor 1
EC=2.7.10.1
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 names
Name:Ddr1
Synonyms:Cak, Eddr1, Mpk6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length911 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

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, 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. Ref.4

Catalytic activity

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

Subunit structure

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.

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

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. Ref.6

Post-translational modification

Autophosphorylated in response to fibrillar collagen binding By similarity.

Disruption phenotype

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. Ref.3 Ref.5 Ref.6

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 1 F5/8 type C domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processLactation
Pregnancy
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Calcium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbranching involved in mammary gland duct morphogenesis

Inferred from mutant phenotype Ref.3. Source: MGI

collagen-activated tyrosine kinase receptor signaling pathway

Inferred from mutant phenotype Ref.4. Source: UniProtKB

ear development

Inferred from mutant phenotype Ref.3. Source: MGI

embryo implantation

Inferred from mutant phenotype Ref.3. Source: MGI

lactation

Inferred from electronic annotation. Source: UniProtKB-KW

mammary gland alveolus development

Inferred from mutant phenotype Ref.3. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 12397034. Source: MGI

peptidyl-tyrosine autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 12397034. Source: MGI

regulation of cell growth

Inferred from mutant phenotype PubMed 12397034. Source: MGI

regulation of cell-matrix adhesion

Inferred from mutant phenotype PubMed 12397034. Source: MGI

regulation of extracellular matrix disassembly

Inferred from mutant phenotype Ref.4. Source: UniProtKB

smooth muscle cell migration

Inferred from mutant phenotype Ref.4. Source: UniProtKB

smooth muscle cell-matrix adhesion

Inferred from mutant phenotype Ref.4. Source: UniProtKB

wound healing, spreading of cells

Inferred from mutant phenotype Ref.4. Source: UniProtKB

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 12397034. Source: MGI

receptor complex

Inferred from sequence orthology PubMed 23382219. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

collagen binding

Inferred from mutant phenotype Ref.4. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein tyrosine kinase collagen receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q03146-1)

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.
Isoform 2 (identifier: Q03146-2)

Also known as: CAK II;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 911892Epithelial discoidin domain-containing receptor 1
PRO_0000016743

Regions

Topological domain22 – 415394Extracellular Potential
Transmembrane416 – 43621Helical; Potential
Topological domain437 – 911475Cytoplasmic Potential
Domain32 – 186155F5/8 type C
Domain608 – 903296Protein kinase
Nucleotide binding614 – 6229ATP By similarity
Region193 – 369177DS-like domain By similarity
Motif479 – 4824PPxY motif
Compositional bias379 – 41335Gly/Pro-rich
Compositional bias474 – 599126Gly/Pro-rich

Sites

Active site7641Proton acceptor By similarity
Metal binding2131Calcium 1; via carbonyl oxygen By similarity
Metal binding2321Calcium 1 By similarity
Metal binding2321Calcium 2; via carbonyl oxygen By similarity
Metal binding2351Calcium 2 By similarity
Metal binding2371Calcium 2; via carbonyl oxygen By similarity
Metal binding2551Calcium 1; via carbonyl oxygen By similarity
Metal binding2571Calcium 1; via carbonyl oxygen By similarity
Metal binding3621Calcium 2; via carbonyl oxygen By similarity
Metal binding3631Calcium 2 By similarity
Binding site6531ATP By similarity

Amino acid modifications

Modified residue5111Phosphotyrosine; by autocatalysis By similarity
Modified residue7381Phosphotyrosine; by autocatalysis By similarity
Modified residue7901Phosphotyrosine; by autocatalysis By similarity
Modified residue7941Phosphotyrosine; by autocatalysis By similarity
Modified residue7951Phosphotyrosine; by autocatalysis By similarity
Glycosylation2131N-linked (GlcNAc...) Potential
Glycosylation2621N-linked (GlcNAc...) Potential
Glycosylation3721N-linked (GlcNAc...) Potential
Glycosylation3921N-linked (GlcNAc...) Potential
Disulfide bond32 ↔ 186 By similarity
Disulfide bond75 ↔ 178 By similarity
Disulfide bond305 ↔ 350 By similarity

Natural variations

Alternative sequence503 – 53937Missing in isoform 2.
VSP_002954

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CAK I) [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: DBB7FE03DDD79510

FASTA911101,161
        10         20         30         40         50         60 
MGTGTLSSLL LLLLLVTIGD ADMKGHFDPA KCRYALGMQD RTIPDSDISV SSSWSDSTAA 

        70         80         90        100        110        120 
RHSRLESSDG DGAWCPAGPV FPKEEEYLQV DLRRLHLVAL VGTQGRHAGG LGKEFSRSYR 

       130        140        150        160        170        180 
LRYSRDGRRW MDWKDRWGQE VISGNEDPGG VVLKDLGPPM VARLVRFYPR ADRVMSVCLR 

       190        200        210        220        230        240 
VELYGCLWRD GLLSYTAPVG QTMQLSEVMV HLNDSTYDGY TAGGLQYGGL GQLADGVVGL 

       250        260        270        280        290        300 
DDFRQSQELR VWPGYDYVGW SNQSFPTGYV EMEFEFDRLR TFQTMQVHCN NMHTLGARLP 

       310        320        330        340        350        360 
GGVECRFKRG PAMAWEGEPV RHALGGSLGD PRARAISVPL GGHVGRFLQC RFLFAGPWLL 

       370        380        390        400        410        420 
FSEISFISDV VNDSSDTFPP APWWPPGPPP TNFSSLELEP RGQQPVAKAE GSPTAILIGC 

       430        440        450        460        470        480 
LVAIILLLLL IIALMLWRLH WRRLLSKAER RVLEEELTVH LSVPGDTILI NNRPGPREPP 

       490        500        510        520        530        540 
PYQEPRPRGT PPHSAPCVPN GSALLLSNPA YRLLLATYAR PPRGPGPPTP AWAKPTNTQA 

       550        560        570        580        590        600 
CSGDYMEPEK PGAPLLPPPP QNSVPHYAEA DIVTLQGVTG GNTYAVPALP PGAVGDGPPR 

       610        620        630        640        650        660 
VDFPRSRLRF KEKLGEGQFG EVHLCEVEDP QDLVSSDFPI SVHKGHPLLV AVKILRPDAT 

       670        680        690        700        710        720 
KNARNDFLKE VKIMSRLKDP NIIRLLGVCV QDDPLCMITD YMENGDLNQF LSARQLENKA 

       730        740        750        760        770        780 
TQGLSGDTES DQGPTISYPM LLHVGAQIAS GMRYLATLNF VHRDLATRNC LVGENFTIKI 

       790        800        810        820        830        840 
ADFGMSRNLY AGDYYRVQGR AVLPIRWMAW ECILMGKFTT ASDVWAFGVT LWEVLMLCRS 

       850        860        870        880        890        900 
QPFGQLTDEQ VIENAGEFFR DQGRQVYLSR PPACPQTLYE LMLRCWSREP EQRPPFAQLH 

       910 
RFLADDALNT V 

« Hide

Isoform 2 (CAK II) [UniParc].

Checksum: A649B2FCE360BA5B
Show »

FASTA87497,207

References

[1]"Identification of two isoforms of the Cak receptor kinase that are coexpressed in breast tumor cell lines."
Perez J.L., Jing S.Q., Wong T.W.
Oncogene 12:1469-1477(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6.
[2]"An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain."
Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P.
Oncogene 7:2499-2506(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 766-822.
Strain: C57BL/6.
Tissue: Embryonic brain.
[3]"Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development."
Vogel W.F., Aszodi A., Alves F., Pawson T.
Mol. Cell. Biol. 21:2906-2917(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[4]"Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression."
Hou G., Vogel W.F., Bendeck M.P.
Circ. Res. 90:1147-1149(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"DDR1-deficient mice show localized subepithelial GBM thickening with focal loss of slit diaphragms and proteinuria."
Gross O., Beirowski B., Harvey S.J., McFadden C., Chen D., Tam S., Thorner P.S., Smyth N., Addicks K., Bloch W., Ninomiya Y., Sado Y., Weber M., Vogel W.F.
Kidney Int. 66:102-111(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[6]"Inner ear defects and hearing loss in mice lacking the collagen receptor DDR1."
Meyer zum Gottesberge A.M., Gross O., Becker-Lendzian U., Massing T., Vogel W.F.
Lab. Invest. 88:27-37(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L57509 mRNA. Translation: AAB05209.1.
X57240 mRNA. Translation: CAA40516.1.
PIRS30502.
RefSeqNP_001185760.1. NM_001198831.1.
NP_001185762.1. NM_001198833.1.
NP_031610.1. NM_007584.2.
NP_766550.1. NM_172962.1.
XP_006523596.1. XM_006523533.1.
XP_006523597.1. XM_006523534.1.
XP_006523598.1. XM_006523535.1.
XP_006523599.1. XM_006523536.1.
XP_006523600.1. XM_006523537.1.
UniGeneMm.5021.

3D structure databases

ProteinModelPortalQ03146.
SMRQ03146. Positions 31-369, 599-911.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ03146. 1 interaction.
MINTMINT-5170014.

PTM databases

PhosphoSiteQ03146.

Proteomic databases

PaxDbQ03146.
PRIDEQ03146.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000003628; ENSMUSP00000003628; ENSMUSG00000003534. [Q03146-1]
ENSMUST00000097333; ENSMUSP00000094945; ENSMUSG00000003534. [Q03146-2]
ENSMUST00000117301; ENSMUSP00000112570; ENSMUSG00000003534. [Q03146-1]
ENSMUST00000119825; ENSMUSP00000113062; ENSMUSG00000003534. [Q03146-1]
ENSMUST00000166980; ENSMUSP00000133047; ENSMUSG00000003534. [Q03146-1]
GeneID12305.
KEGGmmu:12305.
UCSCuc008cih.2. mouse. [Q03146-1]

Organism-specific databases

CTD780.
MGIMGI:99216. Ddr1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117362.
HOGENOMHOG000043102.
HOVERGENHBG005461.
InParanoidQ03146.
KOK05124.
OMAFLQCRFL.
OrthoDBEOG77Q4W2.
PhylomeDBQ03146.
TreeFamTF317840.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressQ03146.
BgeeQ03146.
CleanExMM_DDR1.
GenevestigatorQ03146.

Family and domain databases

Gene3D2.60.120.260. 1 hit.
InterProIPR000421. Coagulation_fac_5/8-C_type_dom.
IPR008979. Galactose-bd-like.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamPF00754. F5_F8_type_C. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00231. FA58C. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS01285. 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.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDDR1. mouse.
NextBio280834.
PROQ03146.
SOURCESearch...

Entry information

Entry nameDDR1_MOUSE
AccessionPrimary (citable) accession number: Q03146
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot