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Browse DKK1

Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted.
Domain PF04706 Dickkopf N-terminal cysteine-rich region
Function

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).

> Gene Ontology
 
Biological Process GO:0001101 response to acid chemical
GO:0001704 formation of primary germ layer
GO:0001706 endoderm formation
GO:0001707 mesoderm formation
GO:0001708 cell fate specification
GO:0001710 mesodermal cell fate commitment
GO:0001711 endodermal cell fate commitment
GO:0001714 endodermal cell fate specification
GO:0001756 somitogenesis
GO:0001759 organ induction
GO:0001933 negative regulation of protein phosphorylation
GO:0001942 hair follicle development
GO:0002090 regulation of receptor internalization
GO:0003002 regionalization
GO:0003007 heart morphogenesis
GO:0003128 heart field specification
GO:0003129 heart induction
GO:0003156 regulation of animal organ formation
GO:0003306 Wnt signaling pathway involved in heart development
GO:0003307 regulation of Wnt signaling pathway involved in heart development
GO:0003308 negative regulation of Wnt signaling pathway involved in heart development
GO:0006898 receptor-mediated endocytosis
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007270 neuron-neuron synaptic transmission
GO:0007369 gastrulation
GO:0007389 pattern specification process
GO:0007492 endoderm development
GO:0007498 mesoderm development
GO:0007501 mesodermal cell fate specification
GO:0007507 heart development
GO:0007517 muscle organ development
GO:0007519 skeletal muscle tissue development
GO:0007611 learning or memory
GO:0007612 learning
GO:0008544 epidermis development
GO:0009952 anterior/posterior pattern specification
GO:0009996 negative regulation of cell fate specification
GO:0010092 specification of animal organ identity
GO:0010171 body morphogenesis
GO:0010453 regulation of cell fate commitment
GO:0010454 negative regulation of cell fate commitment
GO:0010470 regulation of gastrulation
GO:0010720 positive regulation of cell development
GO:0014706 striated muscle tissue development
GO:0016055 Wnt signaling pathway
GO:0016202 regulation of striated muscle tissue development
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0021953 central nervous system neuron differentiation
GO:0022404 molting cycle process
GO:0022405 hair cycle process
GO:0030100 regulation of endocytosis
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030326 embryonic limb morphogenesis
GO:0030509 BMP signaling pathway
GO:0030510 regulation of BMP signaling pathway
GO:0030514 negative regulation of BMP signaling pathway
GO:0030900 forebrain development
GO:0030901 midbrain development
GO:0031128 developmental induction
GO:0031333 negative regulation of protein complex assembly
GO:0031623 receptor internalization
GO:0032091 negative regulation of protein binding
GO:0032526 response to retinoic acid
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033137 negative regulation of peptidyl-serine phosphorylation
GO:0035051 cardiocyte differentiation
GO:0035107 appendage morphogenesis
GO:0035108 limb morphogenesis
GO:0035113 embryonic appendage morphogenesis
GO:0035249 synaptic transmission, glutamatergic
GO:0035282 segmentation
GO:0035987 endodermal cell differentiation
GO:0042303 molting cycle
GO:0042326 negative regulation of phosphorylation
GO:0042633 hair cycle
GO:0042659 regulation of cell fate specification
GO:0042661 regulation of mesodermal cell fate specification
GO:0042662 negative regulation of mesodermal cell fate specification
GO:0042663 regulation of endodermal cell fate specification
GO:0042692 muscle cell differentiation
GO:0042693 muscle cell fate commitment
GO:0043112 receptor metabolic process
GO:0043254 regulation of protein complex assembly
GO:0043393 regulation of protein binding
GO:0043588 skin development
GO:0044708 single-organism behavior
GO:0045165 cell fate commitment
GO:0045666 positive regulation of neuron differentiation
GO:0045843 negative regulation of striated muscle tissue development
GO:0045992 negative regulation of embryonic development
GO:0045995 regulation of embryonic development
GO:0048259 regulation of receptor-mediated endocytosis
GO:0048332 mesoderm morphogenesis
GO:0048333 mesodermal cell differentiation
GO:0048634 regulation of muscle organ development
GO:0048635 negative regulation of muscle organ development
GO:0048641 regulation of skeletal muscle tissue development
GO:0048642 negative regulation of skeletal muscle tissue development
GO:0048645 animal organ formation
GO:0048736 appendage development
GO:0048738 cardiac muscle tissue development
GO:0050769 positive regulation of neurogenesis
GO:0050803 regulation of synapse structure or activity
GO:0050804 modulation of synaptic transmission
GO:0050807 regulation of synapse organization
GO:0050808 synapse organization
GO:0050890 cognition
GO:0051098 regulation of binding
GO:0051100 negative regulation of binding
GO:0051146 striated muscle cell differentiation
GO:0051147 regulation of muscle cell differentiation
GO:0051148 negative regulation of muscle cell differentiation
GO:0051153 regulation of striated muscle cell differentiation
GO:0051154 negative regulation of striated muscle cell differentiation
GO:0051962 positive regulation of nervous system development
GO:0051966 regulation of synaptic transmission, glutamatergic
GO:0055007 cardiac muscle cell differentiation
GO:0055024 regulation of cardiac muscle tissue development
GO:0055026 negative regulation of cardiac muscle tissue development
GO:0060070 canonical Wnt signaling pathway
GO:0060173 limb development
GO:0060323 head morphogenesis
GO:0060324 face development
GO:0060325 face morphogenesis
GO:0060389 pathway-restricted SMAD protein phosphorylation
GO:0060393 regulation of pathway-restricted SMAD protein phosphorylation
GO:0060394 negative regulation of pathway-restricted SMAD protein phosphorylation
GO:0060537 muscle tissue development
GO:0060538 skeletal muscle organ development
GO:0060627 regulation of vesicle-mediated transport
GO:0060795 cell fate commitment involved in formation of primary germ layer
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0060911 cardiac cell fate commitment
GO:0060914 heart formation
GO:0060923 cardiac muscle cell fate commitment
GO:0061053 somite development
GO:0061311 cell surface receptor signaling pathway involved in heart development
GO:0061316 canonical Wnt signaling pathway involved in heart development
GO:0061317 canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment
GO:0061743 motor learning
GO:0071542 dopaminergic neuron differentiation
GO:0071772 response to BMP
GO:0071773 cellular response to BMP stimulus
GO:0090081 regulation of heart induction by regulation of canonical Wnt signaling pathway
GO:0090082 positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090101 negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090244 Wnt signaling pathway involved in somitogenesis
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090288 negative regulation of cellular response to growth factor stimulus
GO:0090381 regulation of heart induction
GO:0098773 skin epidermis development
GO:0098883 synapse disassembly
GO:0100012 regulation of heart induction by canonical Wnt signaling pathway
GO:0198738 cell-cell signaling by wnt
GO:1900115 extracellular regulation of signal transduction
GO:1900116 extracellular negative regulation of signal transduction
GO:1901295 regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment
GO:1901296 negative regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment
GO:1901321 positive regulation of heart induction
GO:1901861 regulation of muscle tissue development
GO:1901862 negative regulation of muscle tissue development
GO:1903224 regulation of endodermal cell differentiation
GO:1904338 regulation of dopaminergic neuron differentiation
GO:1904340 positive regulation of dopaminergic neuron differentiation
GO:1904701 Wnt-Frizzled-LRP5/6 complex assembly
GO:1904711 regulation of Wnt-Frizzled-LRP5/6 complex assembly
GO:1904723 negative regulation of Wnt-Frizzled-LRP5/6 complex assembly
GO:1904948 midbrain dopaminergic neuron differentiation
GO:1904956 regulation of midbrain dopaminergic neuron differentiation
GO:1904958 positive regulation of midbrain dopaminergic neuron differentiation
GO:1905066 regulation of canonical Wnt signaling pathway involved in heart development
GO:1905067 negative regulation of canonical Wnt signaling pathway involved in heart development
GO:1905207 regulation of cardiocyte differentiation
GO:1905208 negative regulation of cardiocyte differentiation
GO:2000027 regulation of organ morphogenesis
GO:2000380 regulation of mesoderm development
GO:2000381 negative regulation of mesoderm development
GO:2000542 negative regulation of gastrulation
GO:2000725 regulation of cardiac muscle cell differentiation
GO:2000726 negative regulation of cardiac muscle cell differentiation
GO:2000826 regulation of heart morphogenesis
Molecular Function GO:0008083 growth factor activity
GO:0030545 receptor regulator activity
GO:0030547 receptor inhibitor activity
GO:0039706 co-receptor binding
GO:0048019 receptor antagonist activity
GO:0050750 low-density lipoprotein particle receptor binding
GO:0070325 lipoprotein particle receptor binding
Cellular Component GO:0005769 early endosome
GO:0010008 endosome membrane
GO:0031901 early endosome membrane
GO:0044440 endosomal part
> KEGG and Reactome Pathway
 
KEGG hsa04310 Wnt signaling pathway
Reactome R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-5339717: Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling
R-HSA-3772470: Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-2892245: POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation
R-HSA-162582: Signal Transduction
R-HSA-4791275: Signaling by WNT in cancer
R-HSA-195721: Signaling by Wnt
R-HSA-201681: TCF dependent signaling in response to WNT
R-HSA-452723: Transcriptional regulation of pluripotent stem cells
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between DKK1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between DKK1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27045006Lung CarcinomaInhibit immunity (T cell function)Here, we demonstrate that stroma-derived Dickkopf-1 (Dkk1) targets β-catenin in MDSCs, thus exerting immune suppressive effects during tumor progression. Mice bearing extraskeletal tumors show significantly elevated levels of Dkk1 in bone microenvironment relative to tumor site. Strikingly, Dkk1 neutralization decreases tumor growth and MDSC numbers by rescuing β-catenin in these cells and restores T cell recruitment at the tumor site.
27015306Lung Carcinoma; Breast CarcinomaInhibit immunityThrough expression of the WNT inhibitor DKK1, LCC cells self-impose a slow-cycling state with broad downregulation of ULBP ligands for NK cells and evasion of NK-cell-mediated clearance.
22049519Plasma Cell MyelomaPromote immunity; Immunotherapy targetWe used DKK1-DNA vaccine in the murine MOPC-21 myeloma model, and the results clearly showed that active vaccination using the DKK1 vaccine not only was able to protect mice from developing myeloma, but it was also therapeutic against established myeloma. Mechanistic studies revealed that DKK1 vaccine elicited a strong DKK1- and tumor-specific CD4+ and CD8+ immune responses, and treatment with B7H1 or OX40 Abs significantly reduced the numbers of IL-10-expressing and Foxp3+ regulatory T cells in vaccinated mice.
20551066Lung CarcinomaInhibit immunityUsing an original ELISA system, high levels of DKK1 protein were found in serologic samples from 906 patients with cancers of the pancreas, stomach, liver, bile duct, breast, and cervix, which also showed elevated expression levels of DKK1. Additionally, anti-DKK1 antibody inhibited the invasive activity and the growth of cancer cells in vitro and suppressed the growth of engrafted tumors in vivo. Tumor tissues treated with anti-DKK1 displayed significant fibrotic changes and a decrease in viable cancer cells without apparent toxicity in mice.
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of DKK1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of DKK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.8240.247
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.5710.627
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-1.0230.331
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.5180.525
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 591.1930.418
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3450.831
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.5830.496
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.7970.514
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.3760.771
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.5530.622
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.3960.333
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4160.18
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of DKK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DKK1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DKK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DKK1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DKK1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of DKK1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between DKK1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolDKK1
Namedickkopf WNT signaling pathway inhibitor 1
Aliases SK; DKK-1; dickkopf (Xenopus laevis) homolog 1; dickkopf 1 homolog (Xenopus laevis); dickkopf 1 homolog; dic ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting DKK1 collected from DrugBank database.
> Drugs from DrugBank database
 

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