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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 LRP5/6.1 Publication

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
  • extracellular negative regulation of signal transduction Source: MGI
  • face morphogenesis Source: MGI
  • forebrain development Source: MGI
  • hair follicle development Source: MGI
  • head morphogenesis Source: MGI
  • mesoderm formation Source: MGI
  • motor learning Source: ParkinsonsUK-UCL
  • 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 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: ParkinsonsUK-UCL
  • negative regulation of Wnt signaling pathway Source: MGI
  • positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • positive regulation of midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-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
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1329040. Dkk1.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: MGI
  • extracellular space Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi210 – 2101H → E: 50% reduced binding to LRP6. 1 Publication
Mutagenesisi217 – 2171K → E: 50% reduced binding to LRP6. 1 Publication
Mutagenesisi242 – 2421R → E: 50% reduced binding to LRP6. 1 Publication
Mutagenesisi267 – 2671H → E: 43% reduced binding to LRP6. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131Sequence analysisAdd
BLAST
Chaini32 – 272241Dickkopf-related protein 1PRO_0000007219Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi62 – 621O-linked (GalNAc...)By similarity
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
Glycosylationi262 – 2621N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO54908.
PRIDEiO54908.

Expressioni

Gene expression databases

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 (By similarity). Interacts with LRP6.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199226. 8 interactions.
STRINGi10090.ENSMUSP00000025803.

Structurei

3D structure databases

ProteinModelPortaliO54908.
SMRiO54908. Positions 188-272.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni86 – 14156DKK-type Cys-1Add
BLAST
Regioni195 – 26975DKK-type Cys-2Add
BLAST

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.
OrthoDBiEOG7K3TMT.
TreeFamiTF330916.

Family and domain databases

InterProiIPR006796. Dickkopf_N.
[Graphical view]
PfamiPF04706. Dickkopf_N. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71A → P in AAC02426 (PubMed:9450748).Curated
Sequence conflicti126 – 1261R → T in AAC02426 (PubMed:9450748).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliO54908.
SMRiO54908. Positions 188-272.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199226. 8 interactions.
STRINGi10090.ENSMUSP00000025803.

Proteomic databases

PaxDbiO54908.
PRIDEiO54908.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi22943.
MGIiMGI:1329040. Dkk1.

Phylogenomic databases

eggNOGiENOG410IRWP. Eukaryota.
ENOG4111FNB. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG000441.
InParanoidiO54908.
KOiK02165.
OMAiYHTKGQE.
OrthoDBiEOG7K3TMT.
TreeFamiTF330916.

Enzyme and pathway databases

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

Miscellaneous databases

PROiO54908.
SOURCEiSearch...

Gene expression databases

CleanExiMM_DKK1.
GenevisibleiO54908. MM.

Family and domain databases

InterProiIPR006796. Dickkopf_N.
[Graphical view]
PfamiPF04706. Dickkopf_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction."
    Glinka A., Wu W., Delius H., Monaghan A.P., Blumenstock C., Niehrs C.
    Nature 391:357-362(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Molecular cloning and bioinformatic analysis of DKK1."
    Hu L., Jiang G., Yang J., Liu S.
    Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Trophoblast stem cell.
  7. "Function and biological roles of the Dickkopf family of Wnt modulators."
    Niehrs C.
    Oncogene 25:7469-7481(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW OF THE DKK FAMILY.
  8. "Structural insight into the mechanisms of Wnt signaling antagonism by Dkk."
    Chen L., Wang K., Shao Y., Huang J., Li X., Shan J., Wu D., Zheng J.J.
    J. Biol. Chem. 283:23364-23370(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, INTERACTION WITH LRP5 AND LRP6, MUTAGENESIS OF HIS-210; LYS-217; ARG-242 AND HIS-267.

Entry informationi

Entry nameiDKK1_MOUSE
AccessioniPrimary (citable) accession number: O54908
Secondary accession number(s): Q80UL5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 3, 2012
Last modified: June 8, 2016
This is version 114 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.