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Q03146

- DDR1_MOUSE

UniProt

Q03146 - DDR1_MOUSE

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Protein

Epithelial discoidin domain-containing receptor 1

Gene
Ddr1, Cak, Eddr1, Mpk6
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - 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.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi213 – 2131Calcium 1; via carbonyl oxygen By similarity
Metal bindingi232 – 2321Calcium 1 By similarity
Metal bindingi232 – 2321Calcium 2; via carbonyl oxygen By similarity
Metal bindingi235 – 2351Calcium 2 By similarity
Metal bindingi237 – 2371Calcium 2; via carbonyl oxygen By similarity
Metal bindingi255 – 2551Calcium 1; via carbonyl oxygen By similarity
Metal bindingi257 – 2571Calcium 1; via carbonyl oxygen By similarity
Metal bindingi362 – 3621Calcium 2; via carbonyl oxygen By similarity
Metal bindingi363 – 3631Calcium 2 By similarity
Binding sitei653 – 6531ATP By similarity
Active sitei764 – 7641Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi614 – 6229ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. collagen binding Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW
  4. protein tyrosine kinase collagen receptor activity Source: UniProtKB

GO - Biological processi

  1. branching involved in mammary gland duct morphogenesis Source: MGI
  2. collagen-activated tyrosine kinase receptor signaling pathway Source: UniProtKB
  3. ear development Source: MGI
  4. embryo implantation Source: MGI
  5. lactation Source: UniProtKB-KW
  6. mammary gland alveolus development Source: MGI
  7. negative regulation of cell proliferation Source: MGI
  8. peptidyl-tyrosine autophosphorylation Source: UniProtKB
  9. peptidyl-tyrosine phosphorylation Source: MGI
  10. regulation of cell growth Source: MGI
  11. regulation of cell-matrix adhesion Source: MGI
  12. regulation of extracellular matrix disassembly Source: UniProtKB
  13. smooth muscle cell-matrix adhesion Source: UniProtKB
  14. smooth muscle cell migration Source: UniProtKB
  15. wound healing, spreading of cells Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Lactation, Pregnancy

Keywords - Ligandi

ATP-binding, Calcium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.
ReactomeiREACT_196607. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 17

Organism-specific databases

MGIiMGI:99216. Ddr1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 415394Extracellular Reviewed predictionAdd
BLAST
Transmembranei416 – 43621Helical; Reviewed predictionAdd
BLAST
Topological domaini437 – 911475Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: MGI
  3. receptor complex Source: MGI
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919 Reviewed predictionAdd
BLAST
Chaini20 – 911892Epithelial discoidin domain-containing receptor 1PRO_0000016743Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi32 ↔ 186 By similarity
Disulfide bondi75 ↔ 178 By similarity
Glycosylationi213 – 2131N-linked (GlcNAc...) Reviewed prediction
Glycosylationi262 – 2621N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi305 ↔ 350 By similarity
Glycosylationi372 – 3721N-linked (GlcNAc...) Reviewed prediction
Glycosylationi392 – 3921N-linked (GlcNAc...) Reviewed prediction
Modified residuei482 – 4821Phosphotyrosine; by autocatalysis By similarity
Modified residuei511 – 5111Phosphotyrosine; by autocatalysis By similarity
Modified residuei518 – 5181Phosphotyrosine; by autocatalysis By similarity
Modified residuei738 – 7381Phosphotyrosine; by autocatalysis By similarity
Modified residuei790 – 7901Phosphotyrosine; by autocatalysis By similarity
Modified residuei794 – 7941Phosphotyrosine; by autocatalysis By similarity
Modified residuei795 – 7951Phosphotyrosine; by autocatalysis By similarity

Post-translational modificationi

Autophosphorylated in response to fibrillar collagen binding By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ03146.
PRIDEiQ03146.

PTM databases

PhosphoSiteiQ03146.

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

ArrayExpressiQ03146.
BgeeiQ03146.
CleanExiMM_DDR1.
GenevestigatoriQ03146.

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.

Protein-protein interaction databases

IntActiQ03146. 1 interaction.
MINTiMINT-5170014.

Structurei

3D structure databases

ProteinModelPortaliQ03146.
SMRiQ03146. Positions 31-369, 599-911.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 186155F5/8 type CAdd
BLAST
Domaini608 – 903296Protein kinaseAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni193 – 369177DS-like domain By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi479 – 4824PPxY motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi379 – 41335Gly/Pro-richAdd
BLAST
Compositional biasi474 – 599126Gly/Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 F5/8 type C domain.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00750000117362.
HOGENOMiHOG000043102.
HOVERGENiHBG005461.
InParanoidiQ03146.
KOiK05124.
OMAiCRFLFAG.
OrthoDBiEOG77Q4W2.
PhylomeDBiQ03146.
TreeFamiTF317840.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
InterProiIPR000421. Coagulation_fac_5/8-C_type_dom.
IPR029566. DDR1.
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]
PANTHERiPTHR24416:SF65. PTHR24416:SF65. 1 hit.
PfamiPF00754. F5_F8_type_C. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00231. FA58C. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS01285. 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]

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. Align

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

MGTGTLSSLL LLLLLVTIGD ADMKGHFDPA KCRYALGMQD RTIPDSDISV    50
SSSWSDSTAA RHSRLESSDG DGAWCPAGPV FPKEEEYLQV DLRRLHLVAL 100
VGTQGRHAGG LGKEFSRSYR LRYSRDGRRW MDWKDRWGQE VISGNEDPGG 150
VVLKDLGPPM VARLVRFYPR ADRVMSVCLR VELYGCLWRD GLLSYTAPVG 200
QTMQLSEVMV HLNDSTYDGY TAGGLQYGGL GQLADGVVGL DDFRQSQELR 250
VWPGYDYVGW SNQSFPTGYV EMEFEFDRLR TFQTMQVHCN NMHTLGARLP 300
GGVECRFKRG PAMAWEGEPV RHALGGSLGD PRARAISVPL GGHVGRFLQC 350
RFLFAGPWLL FSEISFISDV VNDSSDTFPP APWWPPGPPP TNFSSLELEP 400
RGQQPVAKAE GSPTAILIGC LVAIILLLLL IIALMLWRLH WRRLLSKAER 450
RVLEEELTVH LSVPGDTILI NNRPGPREPP PYQEPRPRGT PPHSAPCVPN 500
GSALLLSNPA YRLLLATYAR PPRGPGPPTP AWAKPTNTQA CSGDYMEPEK 550
PGAPLLPPPP QNSVPHYAEA DIVTLQGVTG GNTYAVPALP PGAVGDGPPR 600
VDFPRSRLRF KEKLGEGQFG EVHLCEVEDP QDLVSSDFPI SVHKGHPLLV 650
AVKILRPDAT KNARNDFLKE VKIMSRLKDP NIIRLLGVCV QDDPLCMITD 700
YMENGDLNQF LSARQLENKA TQGLSGDTES DQGPTISYPM LLHVGAQIAS 750
GMRYLATLNF VHRDLATRNC LVGENFTIKI ADFGMSRNLY AGDYYRVQGR 800
AVLPIRWMAW ECILMGKFTT ASDVWAFGVT LWEVLMLCRS QPFGQLTDEQ 850
VIENAGEFFR DQGRQVYLSR PPACPQTLYE LMLRCWSREP EQRPPFAQLH 900
RFLADDALNT V 911
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei503 – 53937Missing in isoform 2. VSP_002954Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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. [Q03146-1]
XP_006523597.1. XM_006523534.1. [Q03146-1]
XP_006523598.1. XM_006523535.1. [Q03146-1]
XP_006523599.1. XM_006523536.1. [Q03146-1]
XP_006523600.1. XM_006523537.1. [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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L57509 mRNA. Translation: AAB05209.1 .
X57240 mRNA. Translation: CAA40516.1 .
CCDSi CCDS28703.1. [Q03146-1 ]
CCDS37603.1. [Q03146-2 ]
PIRi S30502.
RefSeqi NP_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. [Q03146-1 ]
XP_006523597.1. XM_006523534.1. [Q03146-1 ]
XP_006523598.1. XM_006523535.1. [Q03146-1 ]
XP_006523599.1. XM_006523536.1. [Q03146-1 ]
XP_006523600.1. XM_006523537.1. [Q03146-1 ]
UniGenei Mm.5021.

3D structure databases

ProteinModelPortali Q03146.
SMRi Q03146. Positions 31-369, 599-911.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q03146. 1 interaction.
MINTi MINT-5170014.

PTM databases

PhosphoSitei Q03146.

Proteomic databases

PaxDbi Q03146.
PRIDEi Q03146.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000003628 ; ENSMUSP00000003628 ; ENSMUSG00000003534 . [Q03146-1 ]
ENSMUST00000097333 ; ENSMUSP00000094945 ; ENSMUSG00000003534 . [Q03146-2 ]
ENSMUST00000117301 ; ENSMUSP00000112570 ; ENSMUSG00000003534 . [Q03146-1 ]
ENSMUST00000119825 ; ENSMUSP00000113062 ; ENSMUSG00000003534 . [Q03146-1 ]
ENSMUST00000166980 ; ENSMUSP00000133047 ; ENSMUSG00000003534 . [Q03146-1 ]
GeneIDi 12305.
KEGGi mmu:12305.
UCSCi uc008cih.2. mouse. [Q03146-1 ]

Organism-specific databases

CTDi 780.
MGIi MGI:99216. Ddr1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00750000117362.
HOGENOMi HOG000043102.
HOVERGENi HBG005461.
InParanoidi Q03146.
KOi K05124.
OMAi CRFLFAG.
OrthoDBi EOG77Q4W2.
PhylomeDBi Q03146.
TreeFami TF317840.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 3474.
Reactomei REACT_196607. Non-integrin membrane-ECM interactions.

Miscellaneous databases

ChiTaRSi DDR1. mouse.
NextBioi 280834.
PROi Q03146.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q03146.
Bgeei Q03146.
CleanExi MM_DDR1.
Genevestigatori Q03146.

Family and domain databases

Gene3Di 2.60.120.260. 1 hit.
InterProi IPR000421. Coagulation_fac_5/8-C_type_dom.
IPR029566. DDR1.
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 ]
PANTHERi PTHR24416:SF65. PTHR24416:SF65. 1 hit.
Pfami PF00754. F5_F8_type_C. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR00109. TYRKINASE.
SMARTi SM00231. FA58C. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiDDR1_MOUSE
AccessioniPrimary (citable) accession number: Q03146
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: November 1, 1997
Last modified: September 3, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi