DKK1 [The Human Chemical-Genetic Interaction Map Project]

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======= DKK1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: DKK1
  * **<color #00a2e8>Official Name</color>**: dickkopf WNT signaling pathway inhibitor 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=22943|22943]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O94907|O94907]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=DKK1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DKK1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605189|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000250|UniProtKB:O54908, ECO:0000269|PubMed:22000856, ECO:0000303|PubMed:17143291}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Dickkopf N|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of Wnt signaling pathway, calcium modulating pathway|
|regulation of Wnt-Frizzled-LRP5/6 complex assembly|
|negative regulation of Wnt-Frizzled-LRP5/6 complex assembly|
|negative regulation of presynapse assembly|
|positive regulation of Wnt signaling pathway, calcium modulating pathway|
|negative regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment|
|negative regulation of canonical Wnt signaling pathway involved in heart development|
|positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway|
|regulation of canonical Wnt signaling pathway involved in heart development|
|regulation of endodermal cell fate specification|
|regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment|
|regulation of heart induction by regulation of canonical Wnt signaling pathway|
|positive regulation of midbrain dopaminergic neuron differentiation|
|positive regulation of dopaminergic neuron differentiation|
|negative regulation of mesodermal cell fate specification|
|regulation of endodermal cell differentiation|
|negative regulation of mesodermal cell differentiation|
|negative regulation of mesoderm formation|
|Wnt signaling pathway involved in somitogenesis|
|regulation of midbrain dopaminergic neuron differentiation|
|positive regulation of heart induction|
|negative regulation of Wnt signaling pathway involved in heart development|
|motor learning|
|regulation of Wnt signaling pathway involved in heart development|
|regulation of heart induction|
|negative regulation of cell fate specification|
|positive regulation of tau-protein kinase activity|
|regulation of mesodermal cell differentiation|
|negative regulation of synapse assembly|
|negative regulation of gastrulation|
|regulation of mesodermal cell fate specification|
|regulation of mesoderm formation|
|negative regulation of mesoderm development|
|positive regulation of Wnt signaling pathway, planar cell polarity pathway|
|modulation of age-related behavioral decline|
|regulation of dopaminergic neuron differentiation|
|regulation of tau-protein kinase activity|
|negative regulation of pathway-restricted SMAD protein phosphorylation|
|synapse pruning|
|negative regulation of skeletal muscle tissue development|
|regulation of cell fate specification|
|negative regulation of cell fate commitment|
|positive regulation of non-canonical Wnt signaling pathway|
|co-receptor binding|
|regulation of Wnt signaling pathway, planar cell polarity pathway|
|negative regulation of cardiac muscle cell differentiation|
|regulation of mesoderm development|
|low-density lipoprotein particle receptor binding|
|negative regulation of cardiocyte differentiation|
|regulation of non-canonical Wnt signaling pathway|
|negative regulation of synapse organization|
|negative regulation of embryonic development|
|negative regulation of peptidyl-serine phosphorylation|
|receptor antagonist activity|
|regulation of cell fate commitment|
|regulation of presynapse assembly|
|regulation of presynapse organization|
|face morphogenesis|
|negative regulation of cardiac muscle tissue development|
|regulation of cardiac muscle cell differentiation|
|regulation of animal organ formation|
|regulation of gastrulation|
|head morphogenesis|
|negative regulation of striated muscle cell differentiation|
|regulation of heart morphogenesis|
|body morphogenesis|
|endoderm formation|
|negative regulation of striated muscle tissue development|
|face development|
|regulation of skeletal muscle tissue development|
|negative regulation of muscle organ development|
|negative regulation of BMP signaling pathway|
|regulation of cardiocyte differentiation|
|negative regulation of muscle tissue development|
|regulation of receptor internalization|
|negative regulation of muscle cell differentiation|
|negative regulation of signaling receptor activity|
|regulation of pathway-restricted SMAD protein phosphorylation|
|somitogenesis|
|mesoderm formation|
|mesoderm morphogenesis|
|regulation of synaptic transmission, glutamatergic|
|hair follicle development|
|positive regulation of JUN kinase activity|
|endoderm development|
|skin epidermis development|
|negative regulation of ossification|
|hair cycle process|
|molting cycle process|
|regulation of cardiac muscle tissue development|
|positive regulation of animal organ morphogenesis|
|somite development|
|regulation of JUN kinase activity|
|regulation of BMP signaling pathway|
|hair cycle|
|positive regulation of neuron death|
|molting cycle|
|segmentation|
|regulation of receptor-mediated endocytosis|
|regulation of striated muscle cell differentiation|
|negative regulation of protein binding|
|regulation of synapse assembly|
|response to retinoic acid|
|regulation of establishment of planar polarity|
|formation of primary germ layer|
|negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|mesoderm development|
|embryonic appendage morphogenesis|
|embryonic limb morphogenesis|
|regulation of embryonic development|
|negative regulation of protein complex assembly|
|regulation of striated muscle tissue development|
|regulation of muscle tissue development|
|regulation of muscle organ development|
|regulation of peptidyl-serine phosphorylation|
|positive regulation of JNK cascade|
|learning|
|negative regulation of cellular response to growth factor stimulus|
|limb morphogenesis|
|appendage morphogenesis|
|early endosome membrane|
|regulation of muscle cell differentiation|
|negative regulation of neuron projection development|
|gastrulation|
|growth factor activity|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|negative regulation of binding|
|regulation of signaling receptor activity|
|negative regulation of canonical Wnt signaling pathway|
|positive regulation of Wnt signaling pathway|
|limb development|
|regulation of morphogenesis of an epithelium|
|appendage development|
|negative regulation of cell projection organization|
|regulation of JNK cascade|
|regulation of ossification|
|regulation of endocytosis|
|negative regulation of Wnt signaling pathway|
|anterior/posterior pattern specification|
|regulation of synapse organization|
|regulation of protein binding|
|negative regulation of neuron differentiation|
|regulation of synapse structure or activity|
|regulation of stress-activated MAPK cascade|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of stress-activated protein kinase signaling cascade|
|regulation of animal organ morphogenesis|
|learning or memory|
|positive regulation of MAP kinase activity|
|synapse organization|
|regulation of cellular response to growth factor stimulus|
|aging|
|regulation of canonical Wnt signaling pathway|
|negative regulation of neurogenesis|
|cognition|
|regulation of neuron death|
|negative regulation of nervous system development|
|regionalization|
|negative regulation of cell development|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|response to acid chemical|
|Wnt signaling pathway|
|cell-cell signaling by wnt|
|regulation of Wnt signaling pathway|
|positive regulation of neuron differentiation|
|regulation of binding|
|skin development|
|forebrain development|
|cellular component disassembly|
|negative regulation of protein phosphorylation|
|epidermis development|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|pattern specification process|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|negative regulation of phosphorylation|
|regulation of protein complex assembly|
|positive regulation of neurogenesis|
|regulation of neuron projection development|
|regulation of protein serine/threonine kinase activity|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cell development|
|positive regulation of MAPK cascade|
|regulation of vesicle-mediated transport|
|cell morphogenesis involved in differentiation|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|tissue morphogenesis|
|embryonic morphogenesis|
|behavior|
|positive regulation of kinase activity|
|negative regulation of protein modification process|
|chordate embryonic development|
|embryo development ending in birth or egg hatching|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|negative regulation of cellular component organization|
|regulation of cell projection organization|
|negative regulation of cell differentiation|
|cell morphogenesis|
|regulation of cellular response to stress|
|brain development|
|regulation of MAPK cascade|
|head development|
|regulation of protein kinase activity|
|regulation of neurogenesis|
|cellular component morphogenesis|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|regulation of kinase activity|
|negative regulation of apoptotic process|
|anatomical structure formation involved in morphogenesis|
|negative regulation of programmed cell death|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|regulation of transferase activity|
|embryo development|
|central nervous system development|
|negative regulation of cell death|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|negative regulation of cellular protein metabolic process|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|negative regulation of protein metabolic process|
|epithelium development|
|cell-cell signaling|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|nervous system process|
|negative regulation of cellular macromolecule biosynthetic process|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|extracellular space|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|extracellular region|
|system process|
|positive regulation of gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp209|Deguelin 0.15μM R05 exp209]]|-1.8|
|[[:results:exp448|Ammonium tetrathiomolybdate 10μM R08 exp448]]|1.75|
|[[:results:exp280|Daidzin 10μM R06 exp280]]|1.78|
|[[:results:exp477|DKK1 89ng/ml R08 exp477]]|1.83|
|[[:results:exp430|Rifampicin 30μM R08 exp430]]|1.9|
|[[:results:exp156|UNC2400 2μM R03 exp156]]|1.9|
|[[:results:exp242|Radicicol 0.16μM R05 exp242]]|1.91|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:prim1|PRIM1]]|0.401|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 12781
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -3.8 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='DKK1 Expression in NALM6 Cells: -3.8'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>