UniProtKB - Q99558 (M3K14_HUMAN)
Mitogen-activated protein kinase kinase kinase 14
MAP3K14
Functioni
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.
1 PublicationCatalytic activityi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 429 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 515 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 406 – 414 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- MAP kinase kinase kinase activity Source: UniProtKB-EC
- NF-kappaB-inducing kinase activity Source: UniProtKB
- protein kinase activity Source: MGI
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: Reactome
- protein serine kinase activity Source: RHEA
GO - Biological processi
- cellular response to mechanical stimulus Source: UniProtKB
- defense response to virus Source: UniProtKB
- I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- immune response Source: UniProtKB
- NIK/NF-kappaB signaling Source: Reactome
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q99558 |
Reactomei | R-HSA-389357, CD28 dependent PI3K/Akt signaling R-HSA-5607761, Dectin-1 mediated noncanonical NF-kB signaling R-HSA-5668541, TNFR2 non-canonical NF-kB pathway R-HSA-5676590, NIK-->noncanonical NF-kB signaling R-HSA-5676594, TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway |
SignaLinki | Q99558 |
SIGNORi | Q99558 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase kinase kinase 14 (EC:2.7.11.25)Alternative name(s): NF-kappa-beta-inducing kinase Short name: HsNIK Serine/threonine-protein kinase NIK |
Gene namesi | Name:MAP3K14 Synonyms:NIK |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6853, MAP3K14 |
MIMi | 604655, gene |
neXtProti | NX_Q99558 |
VEuPathDBi | HostDB:ENSG00000006062 |
Subcellular locationi
Cytoplasm and Cytosol
Cytosol
- cytosol Source: HPA
Nucleus
- fibrillar center Source: HPA
- nucleoplasm Source: HPA
Other locations
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 429 – 430 | KK → AA: Loss of autophosphorylation and 'Lys-63'-linked ubiquitination. 2 Publications | 2 | |
Mutagenesisi | 559 | T → A: Abolishes 'Lys-63'-linked ubiquitination. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9020 |
MalaCardsi | MAP3K14 |
OpenTargetsi | ENSG00000006062 |
Orphaneti | 447731, NIK deficiency |
PharmGKBi | PA30597 |
Miscellaneous databases
Pharosi | Q99558, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5888 |
GuidetoPHARMACOLOGYi | 2074 |
Genetic variation databases
BioMutai | MAP3K14 |
DMDMi | 92090612 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086266 | 1 – 947 | Mitogen-activated protein kinase kinase kinase 14Add BLAST | 947 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 559 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
MassIVEi | Q99558 |
PeptideAtlasi | Q99558 |
PRIDEi | Q99558 |
ProteomicsDBi | 78326 |
PTM databases
iPTMneti | Q99558 |
PhosphoSitePlusi | Q99558 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000006062, Expressed in esophagogastric junction muscularis propria and 161 other tissues |
ExpressionAtlasi | Q99558, baseline and differential |
Genevisiblei | Q99558, HS |
Organism-specific databases
HPAi | ENSG00000006062, Low tissue specificity |
Interactioni
Subunit structurei
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. Directly interacts with DDX3X (PubMed:30341167).
By similarity8 PublicationsBinary interactionsi
Q99558
Protein-protein interaction databases
BioGRIDi | 114487, 141 interactors |
CORUMi | Q99558 |
DIPi | DIP-27522N |
IntActi | Q99558, 129 interactors |
MINTi | Q99558 |
STRINGi | 9606.ENSP00000482657 |
Chemistry databases
BindingDBi | Q99558 |
Miscellaneous databases
RNActi | Q99558, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q99558 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 400 – 655 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 256 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 37 | DisorderedSequence analysisAdd BLAST | 37 | |
Regioni | 135 – 171 | DisorderedSequence analysisAdd BLAST | 37 | |
Regioni | 401 – 653 | Interaction with ZFP911 PublicationAdd BLAST | 253 | |
Regioni | 662 – 766 | DisorderedSequence analysisAdd BLAST | 105 | |
Regioni | 805 – 830 | DisorderedSequence analysisAdd BLAST | 26 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 135 – 153 | Basic residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 712 – 728 | Pro residuesSequence analysisAdd BLAST | 17 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0198, Eukaryota |
GeneTreei | ENSGT00940000156497 |
HOGENOMi | CLU_010641_1_0_1 |
InParanoidi | Q99558 |
OMAi | LNWGKEE |
OrthoDBi | 162528at2759 |
PhylomeDBi | Q99558 |
Family and domain databases
CDDi | cd13991, STKc_NIK, 1 hit |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR042787, M3K14_STKc IPR017425, MAPKKK14 IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
PANTHERi | PTHR48016:SF9, PTHR48016:SF9, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF038175, MAPKKK14, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MAVMEMACPG APGSAVGQQK ELPKAKEKTP PLGKKQSSVY KLEAVEKSPV
60 70 80 90 100
FCGKWEILND VITKGTAKEG SEAGPAAISI IAQAECENSQ EFSPTFSERI
110 120 130 140 150
FIAGSKQYSQ SESLDQIPNN VAHATEGKMA RVCWKGKRRS KARKKRKKKS
160 170 180 190 200
SKSLAHAGVA LAKPLPRTPE QESCTIPVQE DESPLGAPYV RNTPQFTKPL
210 220 230 240 250
KEPGLGQLCF KQLGEGLRPA LPRSELHKLI SPLQCLNHVW KLHHPQDGGP
260 270 280 290 300
LPLPTHPFPY SRLPHPFPFH PLQPWKPHPL ESFLGKLACV DSQKPLPDPH
310 320 330 340 350
LSKLACVDSP KPLPGPHLEP SCLSRGAHEK FSVEEYLVHA LQGSVSSGQA
360 370 380 390 400
HSLTSLAKTW AARGSRSREP SPKTEDNEGV LLTEKLKPVD YEYREEVHWA
410 420 430 440 450
THQLRLGRGS FGEVHRMEDK QTGFQCAVKK VRLEVFRAEE LMACAGLTSP
460 470 480 490 500
RIVPLYGAVR EGPWVNIFME LLEGGSLGQL VKEQGCLPED RALYYLGQAL
510 520 530 540 550
EGLEYLHSRR ILHGDVKADN VLLSSDGSHA ALCDFGHAVC LQPDGLGKSL
560 570 580 590 600
LTGDYIPGTE THMAPEVVLG RSCDAKVDVW SSCCMMLHML NGCHPWTQFF
610 620 630 640 650
RGPLCLKIAS EPPPVREIPP SCAPLTAQAI QEGLRKEPIH RVSAAELGGK
660 670 680 690 700
VNRALQQVGG LKSPWRGEYK EPRHPPPNQA NYHQTLHAQP RELSPRAPGP
710 720 730 740 750
RPAEETTGRA PKLQPPLPPE PPEPNKSPPL TLSKEESGMW EPLPLSSLEP
760 770 780 790 800
APARNPSSPE RKATVPEQEL QQLEIELFLN SLSQPFSLEE QEQILSCLSI
810 820 830 840 850
DSLSLSDDSE KNPSKASQSS RDTLSSGVHS WSSQAEARSS SWNMVLARGR
860 870 880 890 900
PTDTPSYFNG VKVQIQSLNG EHLHIREFHR VKVGDIATGI SSQIPAAAFS
910 920 930 940
LVTKDGQPVR YDMEVPDSGI DLQCTLAPDG SFAWSWRVKH GQLENRP
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A7P0Z419 | A0A7P0Z419_HUMAN | Mitogen-activated protein kinase ki... | MAP3K14 | 266 | Annotation score: | ||
A0A087WXF1 | A0A087WXF1_HUMAN | Mitogen-activated protein kinase ki... | MAP3K14 | 98 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 25 | A → P in CAA71306 (PubMed:9020361).Curated | 1 | |
Sequence conflicti | 348 | G → S in CAA71306 (PubMed:9020361).Curated | 1 | |
Sequence conflicti | 880 | R → G in BAF82892 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040711 | 140 | S → N1 PublicationCorresponds to variant dbSNP:rs11574819EnsemblClinVar. | 1 | |
Natural variantiVAR_051641 | 255 | T → M. Corresponds to variant dbSNP:rs11574820EnsemblClinVar. | 1 | |
Natural variantiVAR_040712 | 514 | G → K in a lung neuroendocrine carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. 1 Publication | 1 | |
Natural variantiVAR_051642 | 674 | H → Y. Corresponds to variant dbSNP:rs11867907EnsemblClinVar. | 1 | |
Natural variantiVAR_040713 | 764 | T → A1 PublicationCorresponds to variant dbSNP:rs56302559EnsemblClinVar. | 1 | |
Natural variantiVAR_040714 | 852 | T → I in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040715 | 928 | P → H1 PublicationCorresponds to variant dbSNP:rs56036201EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y10256 mRNA Translation: CAA71306.1 AK290203 mRNA Translation: BAF82892.1 DQ314874 Genomic DNA Translation: ABC40733.1 CH471178 Genomic DNA Translation: EAW51529.1 CH471178 Genomic DNA Translation: EAW51530.1 BC035576 mRNA Translation: AAH35576.1 |
CCDSi | CCDS74079.1 |
RefSeqi | NP_003945.2, NM_003954.4 XP_011523743.1, XM_011525441.2 |
Genome annotation databases
Ensembli | ENST00000344686; ENSP00000478552; ENSG00000006062 ENST00000376926; ENSP00000482657; ENSG00000006062 ENST00000617331; ENSP00000480974; ENSG00000006062 |
GeneIDi | 9020 |
KEGGi | hsa:9020 |
MANE-Selecti | ENST00000344686.8; ENSP00000478552.1; NM_003954.5; NP_003945.2 |
UCSCi | uc032fjy.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y10256 mRNA Translation: CAA71306.1 AK290203 mRNA Translation: BAF82892.1 DQ314874 Genomic DNA Translation: ABC40733.1 CH471178 Genomic DNA Translation: EAW51529.1 CH471178 Genomic DNA Translation: EAW51530.1 BC035576 mRNA Translation: AAH35576.1 |
CCDSi | CCDS74079.1 |
RefSeqi | NP_003945.2, NM_003954.4 XP_011523743.1, XM_011525441.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4DN5 | X-ray | 2.50 | A/B | 330-680 | [»] | |
4G3D | X-ray | 2.90 | A/B/D/E | 308-673 | [»] | |
4IDT | X-ray | 2.40 | A/B | 330-680 | [»] | |
4IDV | X-ray | 2.90 | A/B/C/D | 330-680 | [»] | |
6WPP | X-ray | 2.55 | A/B | 343-686 | [»] | |
6Z1Q | X-ray | 2.42 | AAA/BBB | 330-680 | [»] | |
6Z1T | X-ray | 2.31 | AAA/BBB | 330-680 | [»] | |
SMRi | Q99558 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114487, 141 interactors |
CORUMi | Q99558 |
DIPi | DIP-27522N |
IntActi | Q99558, 129 interactors |
MINTi | Q99558 |
STRINGi | 9606.ENSP00000482657 |
Chemistry databases
BindingDBi | Q99558 |
ChEMBLi | CHEMBL5888 |
GuidetoPHARMACOLOGYi | 2074 |
PTM databases
iPTMneti | Q99558 |
PhosphoSitePlusi | Q99558 |
Genetic variation databases
BioMutai | MAP3K14 |
DMDMi | 92090612 |
Proteomic databases
MassIVEi | Q99558 |
PeptideAtlasi | Q99558 |
PRIDEi | Q99558 |
ProteomicsDBi | 78326 |
Protocols and materials databases
Antibodypediai | 3862, 350 antibodies from 39 providers |
DNASUi | 9020 |
Genome annotation databases
Ensembli | ENST00000344686; ENSP00000478552; ENSG00000006062 ENST00000376926; ENSP00000482657; ENSG00000006062 ENST00000617331; ENSP00000480974; ENSG00000006062 |
GeneIDi | 9020 |
KEGGi | hsa:9020 |
MANE-Selecti | ENST00000344686.8; ENSP00000478552.1; NM_003954.5; NP_003945.2 |
UCSCi | uc032fjy.2, human |
Organism-specific databases
CTDi | 9020 |
DisGeNETi | 9020 |
GeneCardsi | MAP3K14 |
HGNCi | HGNC:6853, MAP3K14 |
HPAi | ENSG00000006062, Low tissue specificity |
MalaCardsi | MAP3K14 |
MIMi | 604655, gene |
neXtProti | NX_Q99558 |
OpenTargetsi | ENSG00000006062 |
Orphaneti | 447731, NIK deficiency |
PharmGKBi | PA30597 |
VEuPathDBi | HostDB:ENSG00000006062 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0198, Eukaryota |
GeneTreei | ENSGT00940000156497 |
HOGENOMi | CLU_010641_1_0_1 |
InParanoidi | Q99558 |
OMAi | LNWGKEE |
OrthoDBi | 162528at2759 |
PhylomeDBi | Q99558 |
Enzyme and pathway databases
PathwayCommonsi | Q99558 |
Reactomei | R-HSA-389357, CD28 dependent PI3K/Akt signaling R-HSA-5607761, Dectin-1 mediated noncanonical NF-kB signaling R-HSA-5668541, TNFR2 non-canonical NF-kB pathway R-HSA-5676590, NIK-->noncanonical NF-kB signaling R-HSA-5676594, TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway |
SignaLinki | Q99558 |
SIGNORi | Q99558 |
Miscellaneous databases
BioGRID-ORCSi | 9020, 3 hits in 208 CRISPR screens |
ChiTaRSi | MAP3K14, human |
GeneWikii | MAP3K14 |
GenomeRNAii | 9020 |
Pharosi | Q99558, Tchem |
PROi | PR:Q99558 |
RNActi | Q99558, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000006062, Expressed in esophagogastric junction muscularis propria and 161 other tissues |
ExpressionAtlasi | Q99558, baseline and differential |
Genevisiblei | Q99558, HS |
Family and domain databases
CDDi | cd13991, STKc_NIK, 1 hit |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR042787, M3K14_STKc IPR017425, MAPKKK14 IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
PANTHERi | PTHR48016:SF9, PTHR48016:SF9, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF038175, MAPKKK14, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | M3K14_HUMAN | |
Accessioni | Q99558Primary (citable) accession number: Q99558 Secondary accession number(s): A8K2D8, D3DX67, Q8IYN1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 2001 |
Last sequence update: | April 4, 2006 | |
Last modified: | February 23, 2022 | |
This is version 207 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families