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MAP3K14 mitogen-activated protein kinase kinase kinase 14 [ Homo sapiens (human) ]

Gene ID: 9020, updated on 2-Nov-2024

Summary

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Official Symbol
MAP3K14provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase 14provided by HGNC
Primary source
HGNC:HGNC:6853
See related
Ensembl:ENSG00000006062 MIM:604655; AllianceGenome:HGNC:6853
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
HS; NIK; HSNIK; IMD112; FTDCR1B
Summary
This gene encodes mitogen-activated protein kinase kinase kinase 14, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-kappaB activity. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in lymph node (RPKM 11.1), spleen (RPKM 8.5) and 25 other tissues See more
Orthologs
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Genomic context

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See MAP3K14 in Genome Data Viewer
Location:
17q21.31
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (45263119..45317020, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (46116902..46170784, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (43340486..43394386, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene formin like 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:43322845-43323015 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12292 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8616 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12293 Neighboring gene MAP3K14 antisense RNA 1 Neighboring gene EF-hand calcium binding domain 15, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43333269-43334029 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8617 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43339293-43339898 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43339899-43340502 Neighboring gene spermatogenesis associated 32 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:43344006-43345205 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43350360-43351334 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:43367837-43368040 Neighboring gene Sharpr-MPRA regulatory region 11783 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12295 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12296 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8619 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12297 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12298 Neighboring gene RNA, 5S ribosomal pseudogene 443 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:43414932-43415093 Neighboring gene OCT4 hESC enhancer GRCh37_chr17:43427135-43427636 Neighboring gene uncharacterized LOC105371796

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 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. Expression of NF-κB-inducing kinase in breast carcinoma tissue and its clinical significance. Zhang X, et al. Int J Clin Exp Pathol, 2015. PMID 26823811, Free PMC Article
  2. Signaling molecules of the NF-kappa B pathway shuttle constitutively between cytoplasm and nucleus. Birbach A, et al. J Biol Chem, 2002 Mar 29. PMID 11801607
  3. Conditional Activation of NF-κB Inducing Kinase (NIK) in the Osteolineage Enhances Both Basal and Loading-Induced Bone Formation. Davis JL, et al. J Bone Miner Res, 2019 Nov. PMID 31246323, Free PMC Article
  4. NIK-IKK complex interaction controls NF-κB-dependent inflammatory activation of endothelium in response to LTβR ligation. Kucharzewska P, et al. J Cell Sci, 2019 Apr 3. PMID 30837284
  5. The non-canonical NF-κB pathway and its contribution to β-cell failure in diabetes. Meyerovich K, et al. J Mol Endocrinol, 2018 Aug. PMID 29728424

See all (177) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NIK-mediated reactivation of SIX2 enhanced the CSC-like traits of hepatocellular carcinoma cells through suppressing ubiquitin-proteasome system.
    Title: NIK-mediated reactivation of SIX2 enhanced the CSC-like traits of hepatocellular carcinoma cells through suppressing ubiquitin-proteasome system.
  2. Transcriptional induction of NF-kappaB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells.
    Title: Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells.
  3. EDA2R-NIK signalling promotes muscle atrophy linked to cancer cachexia.
    Title: EDA2R-NIK signalling promotes muscle atrophy linked to cancer cachexia.
  4. NIK/MAP3K14 in hepatocytes orchestrates NASH to hepatocellular carcinoma progression via JAK2/STAT5 inhibition.
    Title: NIK/MAP3K14 in hepatocytes orchestrates NASH to hepatocellular carcinoma progression via JAK2/STAT5 inhibition.
  5. Impairment of a NIK-SIX Feedback Axis Results in Dysregulation of Intestinal Immune Homeostasis and Promotes Early-onset Fatal Spontaneous Colitis.
    Title: Impairment of a NIK-SIX Feedback Axis Results in Dysregulation of Intestinal Immune Homeostasis and Promotes Early-onset Fatal Spontaneous Colitis.
  6. NIK promotes metabolic adaptation of glioblastoma cells to bioenergetic stress.
    Title: NIK promotes metabolic adaptation of glioblastoma cells to bioenergetic stress.
  7. Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome.
    Title: Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome.
  8. Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor small ka, Cyrillicb Activation in Preeclampsia.
    Title: Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia.
  9. A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes.
    Title: A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes.
  10. Conditional Activation of NF-kappaB Inducing Kinase (NIK) in the Osteolineage Enhances Both Basal and Loading-Induced Bone Formation.
    Title: Conditional Activation of NF-κB Inducing Kinase (NIK) in the Osteolineage Enhances Both Basal and Loading-Induced Bone Formation.
Submit: New GeneRIF Correction See all GeneRIFs (77)

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

Associated conditions

Description Tests
Immunodeficiency 112
MedGen: C5830633 OMIM: 620449 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
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)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of mitogen-activated protein kinase kinase kinase 14 (MAP3K14) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat enhances the capacity of NF-kappaB-inducing kinase (NIK) to accelerate degradation of IkappaB PubMed

Go to the HIV-1, Human Interaction Database

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 ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables MAP kinase kinase kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity EXP
Inferred from Experiment
more info
 PubMed 
enables protein serine/threonine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in canonical NF-kappaB signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in defense response to virus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in immune response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in non-canonical NF-kappaB signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in non-canonical NF-kappaB signal transduction ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in non-canonical NF-kappaB signal transduction TAS
Traceable Author Statement
more info
  
involved_in protein phosphorylation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in fibrillar center IDA
Inferred from Direct Assay
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
mitogen-activated protein kinase kinase kinase 14
Names
NF-kappa-beta-inducing kinase
serine/threonine-protein kinase NIK
NP_003945.2
XP_011523743.1
XP_047292953.1
XP_047292954.1
XP_054173658.1
XP_054173659.1
XP_054173660.1

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

  1. NG_033823.1 RefSeqGene

    Range
    5029..58930
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1222

mRNA and Protein(s)

  1. NM_003954.5 → NP_003945.2  mitogen-activated protein kinase kinase kinase 14

    See identical proteins and their annotated locations for NP_003945.2

    Status: REVIEWED

    Source sequence(s)
    AK290203, CR749592, HY287427, Y10256
    Consensus CDS
    CCDS74079.1
    UniProtKB/Swiss-Prot
    A8K2D8, D3DX67, Q8IYN1, Q99558
    Related
    ENSP00000478552.1, ENST00000344686.8
    Conserved Domains (2) summary
    smart00220
    Location:406 → 665
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd13991
    Location:393 → 660
    STKc_NIK; Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK)

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_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    45263119..45317020 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047436997.1 → XP_047292953.1  mitogen-activated protein kinase kinase kinase 14 isoform X1

  2. XM_011525441.3 → XP_011523743.1  mitogen-activated protein kinase kinase kinase 14 isoform X2

    See identical proteins and their annotated locations for XP_011523743.1

    UniProtKB/Swiss-Prot
    A8K2D8, D3DX67, Q8IYN1, Q99558
    Related
    ENSP00000480974.3, ENST00000617331.3
    Conserved Domains (2) summary
    smart00220
    Location:406 → 665
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd13991
    Location:393 → 660
    STKc_NIK; Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK)

  3. XM_047436998.1 → XP_047292954.1  mitogen-activated protein kinase kinase kinase 14 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    46116902..46170784 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054317683.1 → XP_054173658.1  mitogen-activated protein kinase kinase kinase 14 isoform X1

  2. XM_054317685.1 → XP_054173660.1  mitogen-activated protein kinase kinase kinase 14 isoform X2

    UniProtKB/Swiss-Prot
    A8K2D8, D3DX67, Q8IYN1, Q99558

  3. XM_054317684.1 → XP_054173659.1  mitogen-activated protein kinase kinase kinase 14 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99558.2 GenPept UniProtKB/Swiss-Prot:Q99558

Gene LinkOut

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Chemical Information
Molecular Biology Databases
Research Materials
Miscellaneous