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Protein

Dickkopf-related protein 1

Gene

DKK1

Organism
Homo sapiens (Human)
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. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease.1 Publication

GO - Molecular functioni

  • co-receptor binding Source: ParkinsonsUK-UCL
  • growth factor activity Source: ProtInc
  • low-density lipoprotein particle receptor binding Source: MGI
  • receptor antagonist activity Source: BHF-UCL
  • signal transducer activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000107984-MONOMER.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.
SignaLinkiO94907.
SIGNORiO94907.

Names & Taxonomyi

Protein namesi
Recommended name:
Dickkopf-related protein 1
Short name:
Dickkopf-1
Short name:
Dkk-1
Short name:
hDkk-1
Alternative name(s):
SK
Gene namesi
Name:DKK1
ORF Names:UNQ492/PRO1008
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:2891. DKK1.

Subcellular locationi

GO - Cellular componenti

  • early endosome membrane Source: Reactome
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi22943.
MalaCardsiDKK1.
OpenTargetsiENSG00000107984.
Orphaneti85193. Idiopathic juvenile osteoporosis.
PharmGKBiPA27345.

Chemistry databases

ChEMBLiCHEMBL6024.

Polymorphism and mutation databases

BioMutaiDKK1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 311 PublicationAdd BLAST31
ChainiPRO_000000721832 – 266Dickkopf-related protein 1Add BLAST235

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi61O-linked (GalNAc...)1 Publication1
Disulfide bondi85 ↔ 97
Disulfide bondi91 ↔ 111
Disulfide bondi114 ↔ 128
Disulfide bondi121 ↔ 133
Disulfide bondi127 ↔ 138
Disulfide bondi189 ↔ 201
Disulfide bondi195 ↔ 210
Disulfide bondi200 ↔ 237
Disulfide bondi220 ↔ 245
Disulfide bondi239 ↔ 263
Glycosylationi256N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO94907.
PaxDbiO94907.
PeptideAtlasiO94907.
PRIDEiO94907.

PTM databases

iPTMnetiO94907.
PhosphoSitePlusiO94907.

Miscellaneous databases

PMAP-CutDBO94907.

Expressioni

Tissue specificityi

Placenta.

Gene expression databases

BgeeiENSG00000107984.
CleanExiHS_DKK1.
ExpressionAtlasiO94907. baseline and differential.
GenevisibleiO94907. HS.

Organism-specific databases

HPAiHPA018995.

Interactioni

Subunit structurei

Interacts with LRP6. 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.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LRP6O755813EBI-742864,EBI-910915
MDFIQ997503EBI-742864,EBI-724076

GO - Molecular functioni

  • co-receptor binding Source: ParkinsonsUK-UCL
  • growth factor activity Source: ProtInc
  • low-density lipoprotein particle receptor binding Source: MGI
  • receptor antagonist activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi116599. 15 interactors.
DIPiDIP-46461N.
IntActiO94907. 5 interactors.
MINTiMINT-1196808.
STRINGi9606.ENSP00000363081.

Chemistry databases

BindingDBiO94907.

Structurei

Secondary structure

1266
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi192 – 194Combined sources3
Beta strandi199 – 204Combined sources6
Beta strandi207 – 212Combined sources6
Beta strandi218 – 220Combined sources3
Helixi226 – 231Combined sources6
Beta strandi243 – 247Combined sources5
Beta strandi261 – 265Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S2KX-ray2.80C178-266[»]
3S8VX-ray3.10X183-266[»]
3SOQX-ray1.90Z38-44[»]
5FWWX-ray3.50C182-266[»]
ProteinModelPortaliO94907.
SMRiO94907.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni85 – 138DKK-type Cys-1Add BLAST54
Regioni189 – 263DKK-type Cys-2Add BLAST75

Domaini

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

Sequence similaritiesi

Belongs to the dickkopf family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IRWP. Eukaryota.
ENOG4111FNB. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG000441.
InParanoidiO94907.
KOiK02165.
OMAiYHTKGQE.
OrthoDBiEOG091G0H13.
PhylomeDBiO94907.
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.

O94907-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMALGAAGAT RVFVAMVAAA LGGHPLLGVS ATLNSVLNSN AIKNLPPPLG
60 70 80 90 100
GAAGHPGSAV SAAPGILYPG GNKYQTIDNY QPYPCAEDEE CGTDEYCASP
110 120 130 140 150
TRGGDAGVQI CLACRKRRKR CMRHAMCCPG NYCKNGICVS SDQNHFRGEI
160 170 180 190 200
EETITESFGN DHSTLDGYSR RTTLSSKMYH TKGQEGSVCL RSSDCASGLC
210 220 230 240 250
CARHFWSKIC KPVLKEGQVC TKHRRKGSHG LEIFQRCYCG EGLSCRIQKD
260
HHQASNSSRL HTCQRH
Length:266
Mass (Da):28,672
Last modified:May 1, 1999 - v1
Checksum:i5E878B2CCE4236BA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF127563 mRNA. Translation: AAD21087.1.
AF177394 mRNA. Translation: AAF02674.1.
AB020315 Genomic DNA. Translation: BAA34651.1.
AF261158, AF261157 Genomic DNA. Translation: AAG15544.1.
AY359005 mRNA. Translation: AAQ89364.1.
AK314902 mRNA. Translation: BAG37416.1.
CH471083 Genomic DNA. Translation: EAW54144.1.
BC001539 mRNA. Translation: AAH01539.1.
CCDSiCCDS7246.1.
RefSeqiNP_036374.1. NM_012242.2.
UniGeneiHs.40499.

Genome annotation databases

EnsembliENST00000373970; ENSP00000363081; ENSG00000107984.
GeneIDi22943.
KEGGihsa:22943.
UCSCiuc001jjr.4. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF127563 mRNA. Translation: AAD21087.1.
AF177394 mRNA. Translation: AAF02674.1.
AB020315 Genomic DNA. Translation: BAA34651.1.
AF261158, AF261157 Genomic DNA. Translation: AAG15544.1.
AY359005 mRNA. Translation: AAQ89364.1.
AK314902 mRNA. Translation: BAG37416.1.
CH471083 Genomic DNA. Translation: EAW54144.1.
BC001539 mRNA. Translation: AAH01539.1.
CCDSiCCDS7246.1.
RefSeqiNP_036374.1. NM_012242.2.
UniGeneiHs.40499.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S2KX-ray2.80C178-266[»]
3S8VX-ray3.10X183-266[»]
3SOQX-ray1.90Z38-44[»]
5FWWX-ray3.50C182-266[»]
ProteinModelPortaliO94907.
SMRiO94907.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116599. 15 interactors.
DIPiDIP-46461N.
IntActiO94907. 5 interactors.
MINTiMINT-1196808.
STRINGi9606.ENSP00000363081.

Chemistry databases

BindingDBiO94907.
ChEMBLiCHEMBL6024.

PTM databases

iPTMnetiO94907.
PhosphoSitePlusiO94907.

Polymorphism and mutation databases

BioMutaiDKK1.

Proteomic databases

MaxQBiO94907.
PaxDbiO94907.
PeptideAtlasiO94907.
PRIDEiO94907.

Protocols and materials databases

DNASUi22943.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373970; ENSP00000363081; ENSG00000107984.
GeneIDi22943.
KEGGihsa:22943.
UCSCiuc001jjr.4. human.

Organism-specific databases

CTDi22943.
DisGeNETi22943.
GeneCardsiDKK1.
HGNCiHGNC:2891. DKK1.
HPAiHPA018995.
MalaCardsiDKK1.
MIMi605189. gene.
neXtProtiNX_O94907.
OpenTargetsiENSG00000107984.
Orphaneti85193. Idiopathic juvenile osteoporosis.
PharmGKBiPA27345.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IRWP. Eukaryota.
ENOG4111FNB. LUCA.
GeneTreeiENSGT00390000007000.
HOGENOMiHOG000246998.
HOVERGENiHBG000441.
InParanoidiO94907.
KOiK02165.
OMAiYHTKGQE.
OrthoDBiEOG091G0H13.
PhylomeDBiO94907.
TreeFamiTF330916.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000107984-MONOMER.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.
SignaLinkiO94907.
SIGNORiO94907.

Miscellaneous databases

ChiTaRSiDKK1. human.
GeneWikiiDKK1.
GenomeRNAii22943.
PMAP-CutDBO94907.
PROiO94907.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107984.
CleanExiHS_DKK1.
ExpressionAtlasiO94907. baseline and differential.
GenevisibleiO94907. HS.

Family and domain databases

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

Entry informationi

Entry nameiDKK1_HUMAN
AccessioniPrimary (citable) accession number: O94907
Secondary accession number(s): B2RC19
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 1999
Last modified: November 2, 2016
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.