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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 (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
  • signal transducer activity Source: ProtInc

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.

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.

PTM databases

iPTMnetiO94907.
PhosphoSitePlusiO94907.

Miscellaneous databases

PMAP-CutDBiO94907.

Expressioni

Tissue specificityi

Placenta.

Gene expression databases

BgeeiENSG00000107984.
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

Show more details

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.
ELMiO94907.
IntActiO94907. 6 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[»]
5GJEelectron microscopy21.00C182-266[»]
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

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

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: September 27, 2017
This is version 158 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. 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