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

    Gene ID: 9020, updated on 9-Dec-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
    mouse all
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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
    • 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)

    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 JUN 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 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
    		  
    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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