NEK4 NIMA related kinase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NEK4provided by HGNC
Official Full Name: NIMA related kinase 4provided by HGNC
Primary source: HGNC:HGNC:11399
See related: Ensembl:ENSG00000114904 MIM:601959; AllianceGenome:HGNC:11399
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: NRK2; STK2; pp12301
Summary: The protein encoded by this gene is a serine/threonine protein kinase required for normal entry into replicative senescence. The encoded protein also is involved in cell cycle arrest in response to double-stranded DNA damage. Finally, this protein plays a role in maintaining cilium integrity, and defects in this gene have been associated with ciliopathies. [provided by RefSeq, Jan 2017]
Expression: Broad expression in testis (RPKM 13.9), thyroid (RPKM 5.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.1

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (52708444..52770940, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (52741355..52803847, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (52742460..52804956, complement)

Chromosome 3 - NC_000003.12 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?

Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.
Title: Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.
NRK-2 deficiency promotes post-MI scar expansion, rapid LV chamber dilatation, cardiac dysfunction and fibrosis possibly due to increased p38alpha activation.
Title: Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling.
this study demonstrates NEK4 as a novel kinase involved in regulation of Epithelial-to-mesenchymal transition.
Title: NEK4 kinase regulates EMT to promote lung cancer metastasis.
High NEK4 expression is associated with lung cancer and colorectal cancer.
Title: Inhibition of never in mitosis A (NIMA)-related kinase-4 reduces survivin expression and sensitizes cancer cells to TRAIL-induced cell death.
Nek4 as a novel regulator of replicative senescence and the response to double-stranded DNA damage.
Title: Nek4 regulates entry into replicative senescence and the response to DNA damage in human fibroblasts.
Nek4 interaction with both RPGRIP1 and the RPGRIP1L is involved in cilium assembly.
Title: The ciliopathy-associated protein homologs RPGRIP1 and RPGRIP1L are linked to cilium integrity through interaction with Nek4 serine/threonine kinase.
Observational study of gene-disease association. (HuGE Navigator)
Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
Data show that after Taxol treatment, Nek4 promoted microtubule outgrowth, whereas Nek4 deficiency impaired G(2)-M arrest and decreased formation of mitotic-like asters.
Title: Nek4 status differentially alters sensitivity to distinct microtubule poisons.
Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.

Submit: New GeneRIF Correction

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
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. 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

SHGC-77006 (e-PCR)
- UniSTS:48174

D3S3128 (e-PCR)
- UniSTS:152399

RH102821 (e-PCR)
- UniSTS:97155

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables manganese ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA damage response	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cellular senescence	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in ciliary basal body	IEA Inferred from Electronic Annotation more info
located_in ciliary plasm	IEA Inferred from Electronic Annotation more info
located_in ciliary rootlet	IEA Inferred from Electronic Annotation more info
located_in ciliary transition zone	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: serine/threonine-protein kinase Nek4

Names: NIMA (never in mitosis gene a)-related kinase 4; never in mitosis A-related kinase 4; nimA-related protein kinase 4; serine/threonine kinase 2; serine/threonine protein kinase-2; serine/threonine-protein kinase NRK2

NP_001180462.1

EC 2.7.11.1

NP_001335341.1

EC 2.7.11.1

NP_001335342.1

EC 2.7.11.1

NP_001335343.1

EC 2.7.11.1

NP_003148.2

EC 2.7.11.1

XP_011532341.1

EC 2.7.11.1

XP_011532342.1

EC 2.7.11.1

XP_016862574.1

EC 2.7.11.1

XP_016862575.1

EC 2.7.11.1

XP_047304728.1

EC 2.7.11.1

XP_047304730.1

EC 2.7.11.1

XP_054203612.1

EC 2.7.11.1

XP_054203613.1

EC 2.7.11.1

XP_054203614.1

EC 2.7.11.1

XP_054203615.1

EC 2.7.11.1

XP_054203616.1

EC 2.7.11.1

XP_054203617.1

EC 2.7.11.1

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.

Genomic

NG_053026.1 RefSeqGene

Range

5010..67506

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001193533.3 → NP_001180462.1 serine/threonine-protein kinase Nek4 isoform 2

See identical proteins and their annotated locations for NP_001180462.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate, in-frame, 5' coding region segment, compared to variant 1. The resulting protein (isoform 2) has a shorter N-terminus when it is compared to isoform 1.

Source sequence(s)

AC104446, AK294165, DB073127, L20321

Consensus CDS

CCDS54593.1

UniProtKB/TrEMBL

E7EX48

Related

ENSP00000437703.1, ENST00000535191.5

Conserved Domains (2) summary

smart00220
Location:31 → 172

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:5 → 172

PKc_like; Protein Kinases, catalytic domain
NM_001348412.2 → NP_001335341.1 serine/threonine-protein kinase Nek4 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC006254, AC104446

UniProtKB/TrEMBL

A0A059V7J1

Conserved Domains (1) summary

cd08223
Location:5 → 261

STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4
NM_001348413.2 → NP_001335342.1 serine/threonine-protein kinase Nek4 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon and differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (4) lacks an alternate internal segment and has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AC006254

Consensus CDS

CCDS87089.1

UniProtKB/TrEMBL

A0A059V7J1

Related

ENSP00000373227.4, ENST00000383721.8

Conserved Domains (1) summary

cd08223
Location:5 → 261

STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4
NM_001348414.2 → NP_001335343.1 serine/threonine-protein kinase Nek4 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AC006254, AC104446

UniProtKB/TrEMBL

E7EX48

Conserved Domains (1) summary

cl21453
Location:1 → 179

PKc_like; Protein Kinases, catalytic domain
NM_003157.6 → NP_003148.2 serine/threonine-protein kinase Nek4 isoform 1

See identical proteins and their annotated locations for NP_003148.2

Status: REVIEWED

Description

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

Source sequence(s)

AC104446, BC015515, DB073127, L20321

Consensus CDS

CCDS2863.1

UniProtKB/Swiss-Prot

A5YM70, B2R633, B7Z200, P51957, Q6P576

UniProtKB/TrEMBL

A0A059V7J1

Related

ENSP00000233027.5, ENST00000233027.10

Conserved Domains (2) summary

smart00220
Location:6 → 261

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd08223
Location:5 → 261

STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4

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

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

52708444..52770940 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448772.1 → XP_047304728.1 serine/threonine-protein kinase Nek4 isoform X4

UniProtKB/TrEMBL

A0A059V7J1
XM_011534039.4 → XP_011532341.1 serine/threonine-protein kinase Nek4 isoform X2

UniProtKB/TrEMBL

A0A059V7J1

Related

ENSP00000419666.1, ENST00000461689.5

Conserved Domains (2) summary

smart00220
Location:6 → 261

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd08223
Location:5 → 261

STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4
XM_017007086.2 → XP_016862575.1 serine/threonine-protein kinase Nek4 isoform X3

UniProtKB/TrEMBL

A0A059V7J1
XM_017007085.2 → XP_016862574.1 serine/threonine-protein kinase Nek4 isoform X1

UniProtKB/TrEMBL

A0A059V7J1
XM_047448774.1 → XP_047304730.1 serine/threonine-protein kinase Nek4 isoform X6
XM_011534040.4 → XP_011532342.1 serine/threonine-protein kinase Nek4 isoform X5

UniProtKB/TrEMBL

E7EX48

Conserved Domains (2) summary

smart00220
Location:6 → 261

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd08223
Location:5 → 261

STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

52741355..52803847 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054347640.1 → XP_054203615.1 serine/threonine-protein kinase Nek4 isoform X4

UniProtKB/TrEMBL

A0A059V7J1
XM_054347638.1 → XP_054203613.1 serine/threonine-protein kinase Nek4 isoform X2

UniProtKB/TrEMBL

A0A059V7J1
XM_054347637.1 → XP_054203612.1 serine/threonine-protein kinase Nek4 isoform X1

UniProtKB/TrEMBL

A0A059V7J1
XM_054347639.1 → XP_054203614.1 serine/threonine-protein kinase Nek4 isoform X3

UniProtKB/TrEMBL

A0A059V7J1
XM_054347642.1 → XP_054203617.1 serine/threonine-protein kinase Nek4 isoform X6
XM_054347641.1 → XP_054203616.1 serine/threonine-protein kinase Nek4 isoform X5

UniProtKB/TrEMBL

E7EX48