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    DKK2 dickkopf WNT signaling pathway inhibitor 2 [ Homo sapiens (human) ]

    Gene ID: 27123, updated on 10-Dec-2024

    Summary

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    Official Symbol
    DKK2provided by HGNC
    Official Full Name
    dickkopf WNT signaling pathway inhibitor 2provided by HGNC
    Primary source
    HGNC:HGNC:2892
    See related
    Ensembl:ENSG00000155011 MIM:605415; AllianceGenome:HGNC:2892
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DKK-2
    Summary
    This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. It can act as either an agonist or antagonist of Wnt/beta-catenin signaling, depending on the cellular context and the presence of the co-factor kremen 2. Activity of this protein is also modulated by binding to the Wnt co-receptor LDL-receptor related protein 6 (LRP6). [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in lung (RPKM 4.8), ovary (RPKM 3.0) and 14 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DKK2 in Genome Data Viewer
    Location:
    4q25
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (106921802..107036313, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (110226876..110341391, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (107842959..107957470, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377356 Neighboring gene ACTR6 pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:107898921-107899694 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:107899695-107900466 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:107994239-107994739 Neighboring gene vomeronasal 1 receptor 22 pseudogene Neighboring gene vomeronasal 1 receptor 23 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Elevated Dickkopf-2 levels contribute to the abnormal phenotype of human osteoarthritic osteoblasts. Chan TF, et al. J Bone Miner Res, 2011 Jul. PMID 21312269
    2. Selective Retention of an Inactive Allele of the DKK2 Tumor Suppressor Gene in Hepatocellular Carcinoma. Lin YF, et al. PLoS Genet, 2016 May. PMID 27203079, Free PMC Article
    3. Dickkopf 2 promotes proliferation and invasion via Wnt signaling in prostate cancer. Xu W, et al. Mol Med Rep, 2016 Sep. PMID 27431620
    4. Wnt antagonist gene DKK2 is epigenetically silenced and inhibits renal cancer progression through apoptotic and cell cycle pathways. Hirata H, et al. Clin Cancer Res, 2009 Sep 15. PMID 19755393
    5. Dickkopf-related protein 2 induces G0/G1 arrest and apoptosis through suppressing Wnt/β-catenin signaling and is frequently methylated in breast cancer. Mu J, et al. Oncotarget, 2017 Jun 13. PMID 28467796, Free PMC Article

    See all (55) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. DKK2 promotes the progression of oral squamous cell carcinoma through the PI3K/AKT signaling pathway.
      Title: DKK2 promotes the progression of oral squamous cell carcinoma through the PI3K/AKT signaling pathway.
    2. G Protein-Coupled Estrogen Receptor Correlates With Dkk2 Expression and Has Prognostic Impact in Ovarian Cancer Patients.
      Title: G Protein-Coupled Estrogen Receptor Correlates With Dkk2 Expression and Has Prognostic Impact in Ovarian Cancer Patients.
    3. miR4833p promotes the osteogenesis of human osteoblasts by targeting Dikkopf 2 (DKK2) and the Wnt signaling pathway.
      Title: miR‑483‑3p promotes the osteogenesis of human osteoblasts by targeting Dikkopf 2 (DKK2) and the Wnt signaling pathway.
    4. Dickkopf 2-Expressing Adenovirus Increases the Survival of Random-Pattern Flaps and Promotes Vasculogenesis in a Rat Model.
      Title: Dickkopf 2-Expressing Adenovirus Increases the Survival of Random-Pattern Flaps and Promotes Vasculogenesis in a Rat Model.
    5. RNAM EXPRESSION AND DNA METHYLATION OF DKK2 GENE IN COLORECTAL CANCER.
      Title: RNAM EXPRESSION AND DNA METHYLATION OF DKK2 GENE IN COLORECTAL CÂNCER.
    6. AWPPH inhibits GC cell proliferation and invasion via miR-203a/DKK2 axis.
      Title: Up-regulation of long non-coding RNA AWPPH inhibits proliferation and invasion of gastric cancer cells via miR-203a/DKK2 axis.
    7. We then confirmed these results and demonstrated that a higher expression of DKK2 imparts the recruitment of CD8(+) T cells. Our work suggested that DKK2 imparts tumor immune evasion and is associated with poor prognosis in pancreatic ductal adenocarcinoma.
      Title: DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma.
    8. Here, the authors found that Dickkopf associated protein 2 (DKK2), a secretory protein highly expressed in metastatic colorectal cancer tissues, could stimulate angiogenesis via a classic VEGF/VEGFR independent pathway.
      Title: Tumor-secreted dickkopf2 accelerates aerobic glycolysis and promotes angiogenesis in colorectal cancer.
    9. the critical role of MEG3-miR-4261-DKK2-Wnt/beta-catenin signalling axis in ESCC
      Title: Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling.
    10. Study confirmed the low DKK1 expression in patients with grade 1 breast cancer and a high DKK1 expression in ER-negative breast cancer. DKK2 may be a potential prognostic biomarker for the Normal-like subtype of breast cancer.
      Title: Prognostic value of DKK2 from the Dickkopf family in human breast cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (37)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables co-receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables receptor antagonist activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of canonical Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of canonical Wnt signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    dickkopf-related protein 2
    Names
    dickkopf 2 homolog
    dickkopf homolog 2
    dickkopf-2
    hDkk-2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_014421.3 → NP_055236.1  dickkopf-related protein 2 precursor

      Status: REVIEWED

      Source sequence(s)
      AF177395, AP001819, AY358414
      Consensus CDS
      CCDS3675.1
      UniProtKB/Swiss-Prot
      A0AVE9, B2R6S7, Q9UBU2, Q9UIU3
      Related
      ENSP00000285311.3, ENST00000285311.8
      Conserved Domains (1) summary
      pfam04706
      Location:78 → 128
      Dickkopf_N; Dickkopf N-terminal cysteine-rich region

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      106921802..107036313 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      110226876..110341391 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UBU2.1 GenPept UniProtKB/Swiss-Prot:Q9UBU2

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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