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 a... See more...

Aliases for MAP3K14 Gene

Aliases for MAP3K14 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 14 2 3 4 5
  • Serine/Threonine-Protein Kinase NIK 3 4
  • NF-Kappa-Beta-Inducing Kinase 3 4
  • NIK 3 4
  • Serine/Threonine Protein-Kinase 2
  • EC 2.7.11.25 4
  • FTDCR1B 3
  • HSNIK 3
  • HsNIK 4
  • HS 3

External Ids for MAP3K14 Gene

Previous GeneCards Identifiers for MAP3K14 Gene

  • GC17M042870
  • GC17M045504
  • GC17M043351
  • GC17M043815
  • GC17M040696
  • GC17M039101
  • GC17M043341
  • GC17M043370
  • GC17M043433
  • GC17M043466
  • GC17M043534

Summaries for MAP3K14 Gene

Entrez Gene Summary for MAP3K14 Gene

  • 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]

GeneCards Summary for MAP3K14 Gene

MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14) is a Protein Coding gene. Diseases associated with MAP3K14 include Nik Deficiency and Pancreatic Ductal Adenocarcinoma. Among its related pathways are RANK Signaling in Osteoclasts and CLEC7A (Dectin-1) signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is STK10.

UniProtKB/Swiss-Prot Summary for MAP3K14 Gene

  • Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.

Gene Wiki entry for MAP3K14 Gene

Additional gene information for MAP3K14 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP3K14 Gene

Genomics for MAP3K14 Gene

GeneHancer (GH) Regulatory Elements for MAP3K14 Gene

Promoters and enhancers for MAP3K14 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP3K14 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MAP3K14 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • LCR-F1
  • Pax-4a
  • Sox5

Genomic Locations for MAP3K14 Gene

Genomic Locations for MAP3K14 Gene
chr17:45,263,119-45,317,064
(GRCh38/hg38)
Size:
53,946 bases
Orientation:
Minus strand
chr17:43,340,488-43,394,414
(GRCh37/hg19)
Size:
53,927 bases
Orientation:
Minus strand

Genomic View for MAP3K14 Gene

Genes around MAP3K14 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP3K14 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP3K14 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K14 Gene

Proteins for MAP3K14 Gene

  • Protein details for MAP3K14 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99558-M3K14_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 14
    Protein Accession:
    Q99558
    Secondary Accessions:
    • A8K2D8
    • D3DX67
    • Q8IYN1

    Protein attributes for MAP3K14 Gene

    Size:
    947 amino acids
    Molecular mass:
    104042 Da
    Quaternary structure:
    • Interacts with TRAF2, TRAF5, TRAF6, IKKA and NFKB2/P100 (By similarity). Interacts with TRAF3 and PELI3. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with ZFP91. Interacts with NLRP12; this interaction promotes proteasomal degradation of MAP3K14.

    Three dimensional structures from OCA and Proteopedia for MAP3K14 Gene

neXtProt entry for MAP3K14 Gene

Post-translational modifications for MAP3K14 Gene

  • Autophosphorylated. Phosphorylation at Thr-559 is required to activates its kinase activity and 'Lys-63'-linked polyubiquitination. Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization.
  • Ubiquitinated. Undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. 'Lys-48'-linked polyubiquitination leads to its degradation by the proteasome, while 'Lys-63'-linked polyubiquitination stabilizes and activates it.
  • Ubiquitination at Lys106
  • Modification sites at PhosphoSitePlus

Other Protein References for MAP3K14 Gene

Antibody Products

  • Santa Cruz Biotechnology (SCBT) Antibodies for MAP3K14

No data available for DME Specific Peptides for MAP3K14 Gene

Domains & Families for MAP3K14 Gene

Gene Families for MAP3K14 Gene

Protein Domains for MAP3K14 Gene

Suggested Antigen Peptide Sequences for MAP3K14 Gene

GenScript: Design optimal peptide antigens:
  • Serine/threonine-protein kinase NIK (M3K14_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99558

UniProtKB/Swiss-Prot:

M3K14_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
genes like me logo Genes that share domains with MAP3K14: view

Function for MAP3K14 Gene

Molecular function for MAP3K14 Gene

UniProtKB/Swiss-Prot Function:
Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.25;.

Enzyme Numbers (IUBMB) for MAP3K14 Gene

Phenotypes From GWAS Catalog for MAP3K14 Gene

Gene Ontology (GO) - Molecular Function for MAP3K14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA,IDA 15001576
GO:0004674 protein serine/threonine kinase activity EXP,IBA 21873635
GO:0004704 NF-kappaB-inducing kinase activity ISS,IEA --
GO:0004709 MAP kinase kinase kinase activity IEA --
genes like me logo Genes that share ontologies with MAP3K14: view
genes like me logo Genes that share phenotypes with MAP3K14: view

Animal Models for MAP3K14 Gene

MGI Knock Outs for MAP3K14:

Animal Model Products

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP3K14 Gene

Localization for MAP3K14 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP3K14 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MAP3K14 gene
Compartment Confidence
nucleus 4
cytosol 4

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Vesicles (2)
  • Nucleoli fibrillar center (1)
  • Nucleus (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MAP3K14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001650 fibrillar center IDA --
GO:0005634 nucleus IDA --
GO:0005737 cytoplasm IBA 21873635
GO:0005829 cytosol TAS --
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with MAP3K14: view

Pathways & Interactions for MAP3K14 Gene

PathCards logo

SuperPathways for MAP3K14 Gene

SuperPathway Contained pathways
1 TNFR1 Pathway
.87
.87
.56
.55
.46
.42
.42
.35
2 4-1BB Pathway
.54
.54
.48
.42
.42
.37
3 Apoptosis Modulation and Signaling
.31
4 RANK Signaling in Osteoclasts
.92
.92
.45
5 CDK-mediated phosphorylation and removal of Cdc6
genes like me logo Genes that share pathways with MAP3K14: view

SIGNOR curated interactions for MAP3K14 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP3K14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000186 activation of MAPKK activity IEA --
GO:0006468 protein phosphorylation IEA --
GO:0006955 immune response ISS,IEA --
GO:0007249 I-kappaB kinase/NF-kappaB signaling ISS,IEA --
genes like me logo Genes that share ontologies with MAP3K14: view

Drugs & Compounds for MAP3K14 Gene

(11) Drugs for MAP3K14 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation 0

(8) Additional Compounds for MAP3K14 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
genes like me logo Genes that share compounds with MAP3K14: view

Transcripts for MAP3K14 Gene

mRNA/cDNA for MAP3K14 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K14 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9
SP1:
SP2: -
SP3: -
SP4:

Relevant External Links for MAP3K14 Gene

GeneLoc Exon Structure for
MAP3K14
ECgene alternative splicing isoforms for
MAP3K14

Expression for MAP3K14 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MAP3K14 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP3K14 Gene

This gene is overexpressed in Muscle - Skeletal (x4.4).

Protein differential expression in normal tissues from HIPED for MAP3K14 Gene

This gene is overexpressed in Gallbladder (16.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MAP3K14 Gene



NURSA nuclear receptor signaling pathways regulating expression of MAP3K14 Gene:

MAP3K14

SOURCE GeneReport for Unigene cluster for MAP3K14 Gene:

Hs.404183

mRNA Expression by UniProt/SwissProt for MAP3K14 Gene:

Q99558-M3K14_HUMAN
Tissue specificity: Weakly expressed in testis, small intestine, spleen, thymus, peripheral blood leukocytes, prostate, ovary and colon.
genes like me logo Genes that share expression patterns with MAP3K14: view

No data available for Protein tissue co-expression partners , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP3K14 Gene

Orthologs for MAP3K14 Gene

This gene was present in the common ancestor of chordates.

Orthologs for MAP3K14 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP3K14 32
  • 99.54 (n)
cow
(Bos Taurus)
Mammalia MAP3K14 32
  • 87.99 (n)
dog
(Canis familiaris)
Mammalia MAP3K14 32
  • 87.65 (n)
mouse
(Mus musculus)
Mammalia Map3k14 17 32
  • 84.4 (n)
rat
(Rattus norvegicus)
Mammalia Map3k14 32
  • 84.36 (n)
chicken
(Gallus gallus)
Aves MAP3K14 32
  • 66.29 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia map3k14 32
  • 55.85 (n)
zebrafish
(Danio rerio)
Actinopterygii si:dkey-260c8.4 32
  • 56.05 (n)
Species where no ortholog for MAP3K14 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MAP3K14 Gene

ENSEMBL:
Gene Tree for MAP3K14 (if available)
TreeFam:
Gene Tree for MAP3K14 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MAP3K14: view image

Paralogs for MAP3K14 Gene

(1) SIMAP similar genes for MAP3K14 Gene using alignment to 1 proteins:

  • M3K14_HUMAN
genes like me logo Genes that share paralogs with MAP3K14: view

Variants for MAP3K14 Gene

Sequence variations from dbSNP and Humsavar for MAP3K14 Gene

SNP ID Clin Chr 17 pos Variation AA Info Type
rs113278485 likely-benign, NIK deficiency 45,286,703(-) T/C/G coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs11574819 benign, NIK deficiency, - 45,287,272(-) C/T coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs11574820 likely-benign, NIK deficiency, - 45,286,819(-) G/A coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs11867907 benign, NIK deficiency, - 45,267,712(-) G/A coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs148344770 benign, NIK deficiency 45,286,809(-) G/C coding_sequence_variant, missense_variant, non_coding_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for MAP3K14 Gene

Variant ID Type Subtype PubMed ID
dgv1472n106 CNV deletion 24896259
esv3309064 CNV mobile element insertion 20981092
esv3336642 CNV insertion 20981092
esv3422273 CNV insertion 20981092
esv3640660 CNV loss 21293372
nsv1070831 CNV deletion 25765185
nsv1146669 OTHER inversion 26484159
nsv953904 CNV deletion 24416366

Additional Variant Information for MAP3K14 Gene

Human Gene Mutation Database (HGMD)
MAP3K14
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP3K14

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Variation tolerance for MAP3K14 Gene

Disorders for MAP3K14 Gene

MalaCards: The human disease database

(3) MalaCards diseases for MAP3K14 Gene - From: HGMD, LncRNADisease, Orphanet, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
nik deficiency
  • primary immunodeficiency with multifaceted aberrant lymphoid immunity
pancreatic ductal adenocarcinoma
  • ductal adenocarcinoma of the pancreas
t-cell leukemia
  • leukemia t-cell
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP3K14

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MAP3K14: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP3K14 Gene

Publications for MAP3K14 Gene

  1. MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. (PMID: 9020361) Malinin NL … Wallach D (Nature 1997) 2 3 4 23 56
  2. Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation. (PMID: 20501937) Razani B … Cheng G (Science signaling 2010) 3 4 23 56
  3. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. (PMID: 15084608) Liao G … Sun SC (The Journal of biological chemistry 2004) 3 4 23 56
  4. NIK is a component of the EGF/heregulin receptor signaling complexes. (PMID: 12853971) Chen D … Shu HB (Oncogene 2003) 3 4 23 56
  5. Structure of the nuclear factor κB-inducing kinase (NIK) kinase domain reveals a constitutively active conformation. (PMID: 22718757) Liu J … Wang Z (The Journal of biological chemistry 2012) 3 4 56

Products for MAP3K14 Gene

Sources for MAP3K14 Gene