NKD2 NKD inhibitor of WNT signaling pathway 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NKD2provided by HGNC
Official Full Name: NKD inhibitor of WNT signaling pathway 2provided by HGNC
Primary source: HGNC:HGNC:17046
See related: Ensembl:ENSG00000145506 MIM:607852; AllianceGenome:HGNC:17046
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: Naked2
Summary: This gene encodes a member of a family of proteins that function as negative regulators of Wnt receptor signaling through interaction with Dishevelled family members. The encoded protein participates in the delivery of transforming growth factor alpha-containing vesicles to the cell membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]
Expression: Broad expression in lung (RPKM 6.0), skin (RPKM 2.9) and 15 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5p15.33

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (1008802..1038943)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (914423..943101)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (1008917..1039058)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

NKD2 Trigger NF-kappaB Signaling Pathway and Facilitates Thyroid Cancer Cell Proliferation.
Title: NKD2 Trigger NF-κB Signaling Pathway and Facilitates Thyroid Cancer Cell Proliferation.
NKD2 mediates stimulation-dependent ORAI1 trafficking to augment Ca(2+) entry in T cells.
Title: NKD2 mediates stimulation-dependent ORAI1 trafficking to augment Ca(2+) entry in T cells.
LINC00922 regulates epithelial-mesenchymal transition, invasive and migratory capacities in breast cancer through promoting NKD2 methylation.
Title: LINC00922 regulates epithelial-mesenchymal transition, invasive and migratory capacities in breast cancer through promoting NKD2 methylation.
NKD2 phosphorylation by PKA promotes cell-surface delivery of TGFalpha and increased EGFR activation.
Title: Protein kinase A-mediated phosphorylation of naked cuticle homolog 2 stimulates cell-surface delivery of transforming growth factor-α for epidermal growth factor receptor transactivation.
The experiments in vitro suggested that knockdown of ZFAS1 repressed bladder cancer cell proliferation via up-regulating KLF2 and NKD2 expression, and inhibited cell migration and invasion via down-regulating ZEB1 and ZEB2 expression.
Title: ZFAS1 functions as an oncogenic long non-coding RNA in bladder cancer.
Reduced expression of NKD2 correlated with hyperactivation of the Wnt/beta-catenin pathway and doxorubicin resistance in hepatocellular carcinoma cells
Title: Low expression of NKD2 is associated with enhanced cell proliferation and poor prognosis in human hepatocellular carcinoma.
ZFAS1 over-expression confers an oncogenic function in gastric cancer and this function is partly dependent on repressing KLF2 and NKD2
Title: Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression.
NKD2 is frequently methylated in human esophageal cancer, and the expression of NKD2 is regulated by promoter region methylation. NKD2 suppresses esophageal cancer progression by inhibiting Wnt signaling both in vitro and in vivo.
Title: Silencing NKD2 by Promoter Region Hypermethylation Promotes Esophageal Cancer Progression by Activating Wnt Signaling.
NKD2 is the key molecular marker to study the progression of osteosarcoma development, and it may be used for better prognosis of the disease in early stage
Title: NKD2 a novel marker to study the progression of osteosarcoma development.
curcumin significantly inhibited the proliferation of colorectal cancer cells and upregulated the expression of NKD2 in SW620 colorectal cancer cells.
Title: Curcumin inhibits tumor epithelial‑mesenchymal transition by downregulating the Wnt signaling pathway and upregulating NKD2 expression in colon cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

D10S18 (e-PCR)
- UniSTS:147999

RH98721 (e-PCR)
- UniSTS:91832

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase binding	IPI Inferred from Physical Interaction more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables growth factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables molecular adaptor activity	EXP Inferred from Experiment more info	PubMed
enables myosin heavy chain binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Golgi vesicle fusion to target membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in exocytosis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of 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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cell periphery	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in exocytic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in lateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein naked cuticle homolog 2

Names: Dvl-binding protein NKD2; NKD2, WNT signaling pathway inhibitor; naked cuticle homolog 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)

NM_001271082.2 → NP_001258011.1 protein naked cuticle homolog 2 isoform 2

See identical proteins and their annotated locations for NP_001258011.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC116351

Consensus CDS

CCDS59486.1

UniProtKB/Swiss-Prot

Q969F2

Related

ENSP00000274150.4, ENST00000274150.4
NM_033120.4 → NP_149111.1 protein naked cuticle homolog 2 isoform 1

See identical proteins and their annotated locations for NP_149111.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC116351

Consensus CDS

CCDS3859.1

UniProtKB/Swiss-Prot

Q969F2, Q96EK8, Q9BSN0

Related

ENSP00000296849.5, ENST00000296849.10