DKK4 dickkopf WNT signaling pathway inhibitor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DKK4provided by HGNC
Official Full Name: dickkopf WNT signaling pathway inhibitor 4provided by HGNC
Primary source: HGNC:HGNC:2894
See related: Ensembl:ENSG00000104371 MIM:605417; AllianceGenome:HGNC:2894
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-4
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. Activity of this protein is modulated by binding to the Wnt co-receptor and the co-factor kremen 2. [provided by RefSeq, Jul 2008]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 8p11.21

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (42374063..42391322, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (42644359..42661636, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (42231581..42234747, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sensitization of hepatocellular carcinoma cells towards doxorubicin and sorafenib is facilitated by glucosedependent alterations in reactive oxygen species, P-glycoprotein and DKK4.
Title: Sensitization of hepatocellular carcinoma cells towards doxorubicin and sorafenib is facilitated by glucosedependent alterations in reactive oxygen species, P-glycoprotein and DKK4.
The data implied that DLX3 regulated Wnt/beta-catenin pathway through histone modification of DKK4 during the osteogenic differentiation of bone marrow mesenchymal stem cells.
Title: DLX3 regulates osteogenic differentiation of bone marrow mesenchymal stem cells via Wnt/β-catenin pathway mediated histone methylation of DKK4.
Dkk4 CRD2 mediates high-affinity binding to both the E1E2 region of low-density lipoprotein receptor-related protein 6 (LRP6 E1E2) and the Kremen1 (Krm1) extracellular domain.
Title: Structural and functional analysis of Dickkopf 4 (Dkk4): New insights into Dkk evolution and regulation of Wnt signaling by Dkk and Kremen proteins.
Data suggest a critical role of dickkopf 4 (DKK4) in docetaxel resistance of the lung adenocarcinoma A549 (A549/DTX) cells.
Title: DKK4-knockdown enhances chemosensitivity of A549/DTX cells to docetaxel.
in NOD/SCID mice supplemented with high glucose, HepG2 xenografted tumors grew rapidly in which elevated levels of beta-catenin, c-Myc and decreased levels of DKK4 were detected. Knockdown of DKK4 by shRNA promotes proliferation of HCC cells in NG, which is suppressed by treating cells exogenously with recombinant DKK4 protein. Our in vitro and in vivo results indicate an important functional role of DKK4 in glucose fa...
Title: Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4.
Our results indicated that DKK4 might be contributed to predicting EOC progression and prognosis. DKK4 could promote the invasion of EOC through JNK activation.
Title: Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion.
We found that TCF7L1 recruits the C-terminal binding protein (CtBP) and histone deacetylase 1 (HDAC1) to the DKK4 promoter to repress DKK4 gene expression. In the absence of TCF7L1, TCF7L2 and beta-catenin occupancy at the DKK4 promoter is stimulated and DKK4 expression is increased. These findings uncover a critical role for TCF7L1 in repressing DKK4 gene expression to promote the oncogenic potential of CRCs.
Title: TCF7L1 recruits CtBP and HDAC1 to repress DICKKOPF4 gene expression in human colorectal cancer cells.
DKK4 expression is significantly upregulated in human masticatory mucosa during wound healing
Title: Human gingiva transcriptome during wound healing.
DKK4 may have function on the development and progression of pancreatic cancer.
Title: Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq.
The recurrence of benign tumors of mammary gland occurred predominantly in women-carriers of mutant alleles with polymorphism rs8190924 of gene GSR and AA rs3763511of gene DKK4.
Title: [MODERN METHODS OF PROGNOSTICATION OF THE RECURRENCES OCCURRENCE AFTER SURGICAL TREATMENT OF THE MAMMARY GLAND BENIGN TUMORS].

Submit: New GeneRIF Correction See all GeneRIFs (26)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:483963

NoName (e-PCR)
- UniSTS:480686

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables co-receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables molecular_function	ND No biological Data available 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 Wnt signaling pathway	NAS Non-traceable Author Statement more info	PubMed
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	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of hair follicle placode formation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cellular_component	ND No biological Data available more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: dickkopf-related protein 4

Names: dickkopf-4; hDkk-4

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)

NM_014420.3 → NP_055235.1 dickkopf-related protein 4 precursor

See identical proteins and their annotated locations for NP_055235.1

Status: REVIEWED

Source sequence(s)

AC107885, AF177397, BX105775

Consensus CDS

CCDS6130.1

UniProtKB/Swiss-Prot

Q3KNX0, Q9UBT3, Q9Y4C3

Related

ENSP00000220812.2, ENST00000220812.3

Conserved Domains (2) summary

pfam06607
Location:145 → 202

Prokineticin; Prokineticin

pfam04706
Location:41 → 91

Dickkopf_N; Dickkopf N-terminal cysteine-rich region

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

42374063..42391322 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017013316.2 → XP_016868805.1 dickkopf-related protein 4 isoform X1

UniProtKB/Swiss-Prot

Q3KNX0, Q9UBT3, Q9Y4C3

Conserved Domains (2) summary

pfam06607
Location:145 → 202

Prokineticin; Prokineticin

pfam04706
Location:41 → 91

Dickkopf_N; Dickkopf N-terminal cysteine-rich region
XM_011544488.3 → XP_011542790.1 dickkopf-related protein 4 isoform X1

See identical proteins and their annotated locations for XP_011542790.1

UniProtKB/Swiss-Prot

Q3KNX0, Q9UBT3, Q9Y4C3

Conserved Domains (2) summary

pfam06607
Location:145 → 202

Prokineticin; Prokineticin

pfam04706
Location:41 → 91

Dickkopf_N; Dickkopf N-terminal cysteine-rich region

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

42644359..42661636 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054360295.1 → XP_054216270.1 dickkopf-related protein 4 isoform X1

UniProtKB/Swiss-Prot

Q3KNX0, Q9UBT3, Q9Y4C3
XM_054360296.1 → XP_054216271.1 dickkopf-related protein 4 isoform X1

UniProtKB/Swiss-Prot

Q3KNX0, Q9UBT3, Q9Y4C3