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NEK3 NIMA related kinase 3 [ Homo sapiens (human) ]

Gene ID: 4752, updated on 3-Apr-2024

Summary

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Official Symbol
NEK3provided by HGNC
Official Full Name
NIMA related kinase 3provided by HGNC
Primary source
HGNC:HGNC:7746
See related
Ensembl:ENSG00000136098 MIM:604044; AllianceGenome:HGNC:7746
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
HSPK36
Summary
This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein differs from other NimA family members in that it is not cell cycle regulated and is found primarily in the cytoplasm. The kinase is activated by prolactin stimulation, leading to phosphorylation of VAV2 guanine nucleotide exchange factor, paxillin, and activation of the RAC1 GTPase. Two functional alleles for this gene have been identified in humans. The reference genome assembly (GRCh38) represents a functional allele that is associated with the inclusion of an additional coding exon in protein-coding transcripts, compared to an alternate functional allele that lacks the exon. [provided by RefSeq, Sep 2019]
Annotation information
Note: Available sequence data supports two haplotypes in the human population that differ by a 1 nt indel (rs3837575) at the end of exon 10. Both haplotypes appear to encode functional proteins via alternative splicing of exon 11. The GRCh38 reference assembly includes the extra nt and expresses a full-length protein that includes exon 11, whereas haplotypes that lack the extra nt express a full-length protein lacking exon 11. [30 Sep 2019]
Expression
Broad expression in testis (RPKM 10.8), placenta (RPKM 6.5) and 24 other tissues See more
Orthologs
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Genomic context

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See NEK3 in Genome Data Viewer
Location:
13q14.3
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (52132647..52159860, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (51347476..51374692, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (52706783..52733732, complement)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene ALG11 alpha-1,2-mannosyltransferase Neighboring gene UTP14C small subunit processome component Neighboring gene NIMA related kinase 5 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:52653033-52653791 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:52653792-52654549 Neighboring gene Sharpr-MPRA regulatory region 10224 Neighboring gene Sharpr-MPRA regulatory region 2352 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:52696487-52696693 Neighboring gene uncharacterized LOC101929657 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:52706487-52707686 Neighboring gene uncharacterized LOC124903176 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5381 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5382 Neighboring gene Sharpr-MPRA regulatory region 2809 Neighboring gene mitochondrial ribosomal protein S31 pseudogene 5 Neighboring gene thrombospondin type 1 domain containing 1 pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:52764223-52764724 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7787 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7788 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7789 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:52796837-52797005 Neighboring gene TPTE2 pseudogene 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Overexpression of NEK3 is associated with poor prognosis in patients with gastric cancer. Cao Y, et al. Medicine (Baltimore), 2018 Jan. PMID 29504992, Free PMC Article
  2. Identification of NEK3 Kinase Threonine 165 as a Novel Regulatory Phosphorylation Site That Modulates Focal Adhesion Remodeling Necessary for Breast Cancer Cell Migration. Harrington KM, et al. J Biol Chem, 2016 Oct 7. PMID 27489110, Free PMC Article
  3. Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells. Miller SL, et al. Oncogene, 2007 Jul 12. PMID 17297458
  4. Is there any association between nek3 and cancers with frequent 13q14 deletion? Hernández M, et al. Cancer Invest, 2006 Nov. PMID 17118778
  5. Molecular cloning and characterization of the human NIMA-related protein kinase 3 gene (NEK3). Kimura M, et al. Cytogenet Cell Genet, 2001. PMID 12063396

See all (27) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. the NEK protein kinases emerge as important proteins in thyroid cancer development and may help to identify malignancy and aggressiveness features during diagnosis.
    Title: Expression of the NEK family in normal and cancer tissue: an immunohistochemical study.
  2. NEK3 kinase phosphorylates SNAP29 on its serine 105. NEK3-mediated phosphorylation determines membrane localization of SNAP29. Membrane-associated SNAP29 regulates Golgi and focal adhesion structures.
    Title: NEK3-mediated SNAP29 phosphorylation modulates its membrane association and SNARE fusion dependent processes.
  3. The data demonstrate that NEK3 is overexpressed in gastric cancer, which promotes the malignancy of gastric cancer
    Title: Overexpression of NEK3 is associated with poor prognosis in patients with gastric cancer.
  4. these data support a modulatory role for phosphorylation at NEK3 Thr-165 in focal adhesion maturation and/or turnover to promote breast cancer cell migration.
    Title: Identification of NEK3 Kinase Threonine 165 as a Novel Regulatory Phosphorylation Site That Modulates Focal Adhesion Remodeling Necessary for Breast Cancer Cell Migration.
  5. EHD2 interacts with Nek3 [NIMA (never in mitosis in Aspergillus nidulans)-related kinase 3], a serine/threonine kinase.
    Title: EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity.
  6. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  7. Nek3 contributes to prolactin-mediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation.
    Title: Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells.
  8. Nek3 insertion/deletion polymorphism with alterations at 13q14 is associated with cancers
    Title: Is there any association between nek3 and cancers with frequent 13q14 deletion?
  9. Molecular cloning and characterization of the human NIMA-related protein kinase 3 gene (NEK3).
    Title: Molecular cloning and characterization of the human NIMA-related protein kinase 3 gene (NEK3).
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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC29949

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in establishment of cell polarity IEA
Inferred from Electronic Annotation
more info
  
involved_in mitotic cell cycle NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in neuron projection morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of tubulin deacetylation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in axon IEA
Inferred from Electronic Annotation
more info
  
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in nucleus NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
serine/threonine-protein kinase Nek3
Names
HSPK 36
NIMA (never in mitosis gene a)-related kinase 3
glycogen synthase A kinase
hydroxyalkyl-protein kinase
never in mitosis A-related kinase 3
nimA-related protein kinase 3
phosphorylase B kinase kinase
NP_001139571.1
NP_001411183.1
NP_001411184.1
NP_001411186.1
NP_001411188.1
NP_001411193.1
NP_001411194.1
NP_001411195.1
NP_001411197.1
NP_001411198.1
NP_001411199.1
NP_001411200.1
NP_002489.1
NP_689933.1

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.

mRNA and Protein(s)

  1. NM_001146099.1 → NP_001139571.1  serine/threonine-protein kinase Nek3 isoform b

    See identical proteins and their annotated locations for NP_001139571.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon in the central coding region, compared to variant 1. The resulting isoform (b) lacks an internal segment, compared to isoform a. This variant represents an alternate haplotype that lacks an 'A' at position 1253. This haplotype is not encoded by the reference assembly.
    Source sequence(s)
    AB072828, AI026881, DA733733, DB185803
    UniProtKB/TrEMBL
    Q6ZN64
    Conserved Domains (1) summary
    cd08219
    Location:3 → 257
    STKc_Nek3; Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3

  2. NM_001424254.1 → NP_001411183.1  serine/threonine-protein kinase Nek3 isoform c

    Status: REVIEWED

    Source sequence(s)
    AL139082, KF459684

  3. NM_001424255.1 → NP_001411184.1  serine/threonine-protein kinase Nek3 isoform d

    Status: REVIEWED

    Source sequence(s)
    AL139082, KF459684

  4. NM_001424257.1 → NP_001411186.1  serine/threonine-protein kinase Nek3 isoform d

    Status: REVIEWED

    Source sequence(s)
    AL139082, KF459684

  5. NM_001424259.1 → NP_001411188.1  serine/threonine-protein kinase Nek3 isoform e

    Status: REVIEWED

    Source sequence(s)
    AL139082, KF459684

  6. NM_001424264.1 → NP_001411193.1  serine/threonine-protein kinase Nek3 isoform f

    Status: REVIEWED

    Source sequence(s)
    AL139082, KF459684

  7. NM_001424265.1 → NP_001411194.1  serine/threonine-protein kinase Nek3 isoform a

    Status: REVIEWED

    Source sequence(s)
    AL139082, KF459684
    UniProtKB/Swiss-Prot
    A8K2J4, P51956, Q5TAP2, Q8J023, Q8WUN5

  8. NM_001424266.1 → NP_001411195.1  serine/threonine-protein kinase Nek3 isoform a

    Status: REVIEWED

    Source sequence(s)
    AL139082, KF459684
    UniProtKB/Swiss-Prot
    A8K2J4, P51956, Q5TAP2, Q8J023, Q8WUN5

  9. NM_001424268.1 → NP_001411197.1  serine/threonine-protein kinase Nek3 isoform b

    Status: REVIEWED

    Source sequence(s)
    CP068265

  10. NM_001424269.1 → NP_001411198.1  serine/threonine-protein kinase Nek3 isoform b

    Status: REVIEWED

    Source sequence(s)
    CP068265

  11. NM_001424270.1 → NP_001411199.1  serine/threonine-protein kinase Nek3 isoform g

    Status: REVIEWED

    Source sequence(s)
    CP068265

  12. NM_001424271.1 → NP_001411200.1  serine/threonine-protein kinase Nek3 isoform h

    Status: REVIEWED

    Source sequence(s)
    CP068265

  13. NM_002498.3 → NP_002489.1  serine/threonine-protein kinase Nek3 isoform a

    See identical proteins and their annotated locations for NP_002489.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 encode the same isoform (a).
    Source sequence(s)
    AL139082, BC019916
    Consensus CDS
    CCDS73576.1
    UniProtKB/Swiss-Prot
    A8K2J4, P51956, Q5TAP2, Q8J023, Q8WUN5
    UniProtKB/TrEMBL
    Q5JPB0
    Related
    ENSP00000480328.1, ENST00000610828.5
    Conserved Domains (1) summary
    cd08219
    Location:3 → 257
    STKc_Nek3; Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3

  14. NM_152720.3 → NP_689933.1  serine/threonine-protein kinase Nek3 isoform a

    See identical proteins and their annotated locations for NP_689933.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (a).
    Source sequence(s)
    AI209040, AK131359, AK290259, AL139082, H15146
    Consensus CDS
    CCDS73576.1
    UniProtKB/Swiss-Prot
    A8K2J4, P51956, Q5TAP2, Q8J023, Q8WUN5
    UniProtKB/TrEMBL
    Q5JPB0
    Related
    ENSP00000484443.1, ENST00000618534.4
    Conserved Domains (1) summary
    cd08219
    Location:3 → 257
    STKc_Nek3; Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3

RNA

  1. NR_027415.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) represents the splice pattern of variant 1 but without the extra 'A' found in the GRCh38 haplotype. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AL139082, AW364762, BM675414, BX395059, CV029372, DA407862, DB185803

  2. NR_164641.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) represents the splice pattern of variant 3 but with the extra 'A' found in the GRCh38 haplotype. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AL139082, KF459684

  3. NR_172104.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) represents the splice pattern of variant 2 but without the extra 'A' found in the GRCh38 haplotype. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AL139082, KF459684

  4. NR_188248.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    CP068265

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

  1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    52132647..52159860 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    51347476..51374692 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51956.2 GenPept UniProtKB/Swiss-Prot:P51956

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