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Protein

Dickkopf-related protein 1

Gene

Dkk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:18524778). Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti-apoptotic activity (PubMed:26206087). Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning (PubMed:18505822).3 Publications

GO - Molecular functioni

GO - Biological processi

  • cell morphogenesis involved in differentiation Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • endoderm development Source: MGI
  • endoderm formation Source: MGI
  • face morphogenesis Source: MGI
  • forebrain development Source: MGI
  • hair follicle development Source: MGI
  • head morphogenesis Source: MGI
  • learning or memory Source: ARUK-UCL
  • limb development Source: UniProtKB
  • mesoderm formation Source: MGI
  • modulation of age-related behavioral decline Source: ARUK-UCL
  • motor learning Source: ParkinsonsUK-UCL
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of BMP signaling pathway Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment Source: MGI
  • negative regulation of cardiac muscle cell differentiation Source: MGI
  • negative regulation of mesodermal cell fate specification Source: MGI
  • negative regulation of ossification Source: UniProtKB
  • negative regulation of pathway-restricted SMAD protein phosphorylation Source: MGI
  • negative regulation of peptidyl-serine phosphorylation Source: MGI
  • negative regulation of protein binding Source: MGI
  • negative regulation of skeletal muscle tissue development Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • negative regulation of Wnt-Frizzled-LRP5/6 complex assembly Source: MGI
  • negative regulation of Wnt signaling pathway Source: MGI
  • positive regulation of gene expression Source: ARUK-UCL
  • positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • positive regulation of JUN kinase activity Source: MGI
  • positive regulation of midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • positive regulation of tau-protein kinase activity Source: ARUK-UCL
  • regulation of endodermal cell fate specification Source: MGI
  • regulation of receptor internalization Source: MGI
  • regulation of synapse organization Source: ParkinsonsUK-UCL
  • regulation of synaptic transmission, glutamatergic Source: ParkinsonsUK-UCL
  • regulation of Wnt signaling pathway Source: MGI
  • response to retinoic acid Source: MGI
  • Wnt signaling pathway involved in somitogenesis Source: MGI

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.

Names & Taxonomyi

Protein namesi
Recommended name:
Dickkopf-related protein 1
Short name:
Dickkopf-1
Short name:
Dkk-1
Short name:
mDkk-1
Gene namesi
Name:Dkk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1329040. Dkk1.

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Triple knockout mice KREM1/KREM2/DKK1 exhibit enhanced growth of ectopic digits.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi210H → E: 50% reduced binding to LRP6. 1 Publication1
Mutagenesisi217K → E: 50% reduced binding to LRP6. 1 Publication1
Mutagenesisi242R → E: 50% reduced binding to LRP6. 1 Publication1
Mutagenesisi267H → E: 43% reduced binding to LRP6. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3745589.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000000721932 – 272Dickkopf-related protein 1Add BLAST241

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi62O-linked (GalNAc...) serineBy similarity1
Disulfide bondi86 ↔ 98By similarity
Disulfide bondi92 ↔ 114By similarity
Disulfide bondi117 ↔ 131By similarity
Disulfide bondi124 ↔ 136By similarity
Disulfide bondi130 ↔ 141By similarity
Disulfide bondi195 ↔ 207By similarity
Disulfide bondi201 ↔ 216By similarity
Disulfide bondi206 ↔ 243By similarity
Disulfide bondi226 ↔ 251By similarity
Disulfide bondi245 ↔ 269By similarity
Glycosylationi262N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO54908.
PRIDEiO54908.

PTM databases

PhosphoSitePlusiO54908.

Expressioni

Developmental stagei

Expressed in the developing brain, cochlea and limb buds.2 Publications

Gene expression databases

BgeeiENSMUSG00000024868.
CleanExiMM_DKK1.
GenevisibleiO54908. MM.

Interactioni

Subunit structurei

Interacts (via the C-termianl Cys-rich domain) with LRP5 (via beta-propeller regions 3 and 4); the interaction, enhanced by MESD and or KREMEN, antagonizes Wnt-mediated signaling. Interacts with LRP6 (PubMed:18524778). Forms a ternary complex with LRP6 and KREM1. Interacts with KREM1 (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199226. 8 interactors.
CORUMiO54908.
STRINGi10090.ENSMUSP00000025803.

Structurei

3D structure databases

ProteinModelPortaliO54908.
SMRiO54908.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni86 – 141DKK-type Cys-1Add BLAST56
Regioni195 – 269DKK-type Cys-2Add BLAST75

Domaini

The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.

Sequence similaritiesi

Belongs to the dickkopf family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IRWP. Eukaryota.
ENOG4111FNB. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG000441.
InParanoidiO54908.
KOiK02165.
OMAiYHTKGQE.
OrthoDBiEOG091G0H13.
TreeFamiTF330916.

Family and domain databases

InterProiView protein in InterPro
IPR006796. Dickkopf_N.
PfamiView protein in Pfam
PF04706. Dickkopf_N. 1 hit.

Sequencei

Sequence statusi: Complete.

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

O54908-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMVVCAAAAV RFLAVFTMMA LCSLPLLGAS ATLNSVLINS NAIKNLPPPL
60 70 80 90 100
GGAGGQPGSA VSVAPGVLYE GGNKYQTLDN YQPYPCAEDE ECGSDEYCSS
110 120 130 140 150
PSRGAAGVGG VQICLACRKR RKRCMRHAMC CPGNYCKNGI CMPSDHSHFP
160 170 180 190 200
RGEIEESIIE NLGNDHNAAA GDGYPRRTTL TSKIYHTKGQ EGSVCLRSSD
210 220 230 240 250
CAAGLCCARH FWSKICKPVL KEGQVCTKHK RKGSHGLEIF QRCYCGEGLA
260 270
CRIQKDHHQA SNSSRLHTCQ RH
Length:272
Mass (Da):29,298
Last modified:October 3, 2012 - v2
Checksum:iADFAC3E7B8858A9E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7A → P in AAC02426 (PubMed:9450748).Curated1
Sequence conflicti126R → T in AAC02426 (PubMed:9450748).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030433 mRNA. Translation: AAC02426.1.
JN966751 mRNA. Translation: AFI61654.1.
AK141693 mRNA. Translation: BAE24802.1.
AK144119 mRNA. Translation: BAE25711.1.
AC103405 Genomic DNA. No translation available.
CH466534 Genomic DNA. Translation: EDL41707.1.
BC050189 mRNA. Translation: AAH50189.1.
CCDSiCCDS29744.1.
RefSeqiNP_034181.2. NM_010051.3.
UniGeneiMm.214717.

Genome annotation databases

EnsembliENSMUST00000025803; ENSMUSP00000025803; ENSMUSG00000024868.
GeneIDi13380.
KEGGimmu:13380.
UCSCiuc008hen.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiDKK1_MOUSE
AccessioniPrimary (citable) accession number: O54908
Secondary accession number(s): Q80UL5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 3, 2012
Last modified: September 27, 2017
This is version 123 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families