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Protein

Dickkopf-related protein 1

Gene

DKK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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:22000856). 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 (PubMed:17143291). Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti-apoptotic activity (By similarity).1 PublicationBy similarity1 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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000107984.9
HGNCiHGNC:2891 DKK1
MIMi605189 gene
neXtProtiNX_O94907

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

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...) serine1 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...) asparagine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO94907
MaxQBiO94907
PaxDbiO94907
PeptideAtlasiO94907
PRIDEiO94907
ProteomicsDBi50543

PTM databases

iPTMnetiO94907
PhosphoSitePlusiO94907

Miscellaneous databases

PMAP-CutDBiO94907

Expressioni

Tissue specificityi

Placenta.

Gene expression databases

BgeeiENSG00000107984 Expressed in 141 organ(s), highest expression level in decidua
CleanExiHS_DKK1
ExpressionAtlasiO94907 baseline and differential
GenevisibleiO94907 HS

Interactioni

Subunit structurei

Interacts with LRP6 (PubMed:11448771, PubMed:17804805, PubMed:20093360, PubMed:22000856). 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 (PubMed:19746449). Forms a ternary complex with LRP6 and KREM1 (PubMed:27524201). Interacts with KREM1 (PubMed:17804805).6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116599, 15 interactors
DIPiDIP-46461N
ELMiO94907
IntActiO94907, 7 interactors
MINTiO94907
STRINGi9606.ENSP00000363081

Chemistry databases

BindingDBiO94907

Structurei

Secondary structure

1266
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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.

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

Similar proteinsi

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[»]
5GJEelectron microscopy21.00C182-266[»]
ProteinModelPortaliO94907
SMRiO94907
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116599, 15 interactors
DIPiDIP-46461N
ELMiO94907
IntActiO94907, 7 interactors
MINTiO94907
STRINGi9606.ENSP00000363081

Chemistry databases

BindingDBiO94907
ChEMBLiCHEMBL6024

PTM databases

iPTMnetiO94907
PhosphoSitePlusiO94907

Polymorphism and mutation databases

BioMutaiDKK1

Proteomic databases

EPDiO94907
MaxQBiO94907
PaxDbiO94907
PeptideAtlasiO94907
PRIDEiO94907
ProteomicsDBi50543

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
EuPathDBiHostDB:ENSG00000107984.9
GeneCardsiDKK1
HGNCiHGNC:2891 DKK1
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

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-CutDBiO94907
PROiPR:O94907
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107984 Expressed in 141 organ(s), highest expression level in decidua
CleanExiHS_DKK1
ExpressionAtlasiO94907 baseline and differential
GenevisibleiO94907 HS

Family and domain databases

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

Entry informationi

Entry nameiDKK1_HUMAN
AccessioniPrimary (citable) accession number: O94907
Secondary accession number(s): B2RC19
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 1999
Last modified: October 10, 2018
This is version 167 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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