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Protein

Mitogen-activated protein kinase kinase kinase 14

Gene

MAP3K14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei429ATPPROSITE-ProRule annotation1
Active sitei515Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi406 – 414ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00162-MONOMER.
ReactomeiR-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.
SignaLinkiQ99558.
SIGNORiQ99558.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:6853. MAP3K14.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi429 – 430KK → AA: Loss of autophosphorylation and 'Lys-63'-linked ubiquitination. 2 Publications2
Mutagenesisi559T → A: Abolishes 'Lys-63'-linked ubiquitination. 1 Publication1

Organism-specific databases

DisGeNETi9020.
OpenTargetsiENSG00000006062.
PharmGKBiPA30597.

Chemistry databases

ChEMBLiCHEMBL5888.
GuidetoPHARMACOLOGYi2074.

Polymorphism and mutation databases

BioMutaiMAP3K14.
DMDMi92090612.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862661 – 947Mitogen-activated protein kinase kinase kinase 14Add BLAST947

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei559Phosphothreonine1 Publication1

Post-translational modificationi

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.2 Publications
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.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PeptideAtlasiQ99558.
PRIDEiQ99558.

PTM databases

iPTMnetiQ99558.
PhosphoSitePlusiQ99558.

Expressioni

Tissue specificityi

Weakly expressed in testis, small intestine, spleen, thymus, peripheral blood leukocytes, prostate, ovary and colon.1 Publication

Gene expression databases

CleanExiHS_MAP3K14.
ExpressionAtlasiQ99558. baseline and differential.
GenevisibleiQ99558. HS.

Organism-specific databases

HPAiCAB017631.

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.By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ALPLP051864EBI-358011,EBI-1054354
CDC37Q165432EBI-358011,EBI-295634
CHUKO151116EBI-358011,EBI-81249
ChukQ60680-23EBI-358011,EBI-646264From a different organism.
HSP90AB1P082382EBI-358011,EBI-352572
IKBKBO149203EBI-358011,EBI-81266
TRAF2Q129333EBI-358011,EBI-355744
TRAF6Q9Y4K32EBI-358011,EBI-359276

Protein-protein interaction databases

BioGridi114487. 35 interactors.
DIPiDIP-27522N.
IntActiQ99558. 30 interactors.
MINTiMINT-88636.

Chemistry databases

BindingDBiQ99558.

Structurei

Secondary structure

1947
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi335 – 341Combined sources7
Beta strandi345 – 347Combined sources3
Helixi350 – 363Combined sources14
Beta strandi364 – 366Combined sources3
Beta strandi377 – 381Combined sources5
Turni395 – 397Combined sources3
Beta strandi398 – 408Combined sources11
Beta strandi410 – 419Combined sources10
Turni420 – 422Combined sources3
Beta strandi425 – 432Combined sources8
Helixi433 – 435Combined sources3
Helixi439 – 442Combined sources4
Turni443 – 446Combined sources4
Beta strandi455 – 461Combined sources7
Beta strandi464 – 469Combined sources6
Helixi477 – 484Combined sources8
Helixi489 – 507Combined sources19
Turni508 – 510Combined sources3
Helixi518 – 520Combined sources3
Beta strandi521 – 523Combined sources3
Beta strandi530 – 532Combined sources3
Helixi535 – 537Combined sources3
Beta strandi543 – 547Combined sources5
Turni550 – 553Combined sources4
Helixi560 – 562Combined sources3
Helixi565 – 568Combined sources4
Helixi576 – 591Combined sources16
Turni595 – 599Combined sources5
Helixi605 – 610Combined sources6
Helixi614 – 617Combined sources4
Helixi624 – 633Combined sources10
Turni638 – 640Combined sources3
Helixi644 – 658Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DN5X-ray2.50A/B330-680[»]
4G3DX-ray2.90A/B/D/E308-673[»]
4IDTX-ray2.40A/B330-680[»]
4IDVX-ray2.90A/B/C/D330-680[»]
ProteinModelPortaliQ99558.
SMRiQ99558.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini400 – 655Protein kinasePROSITE-ProRule annotationAdd BLAST256

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni401 – 653Interaction with ZFP911 PublicationAdd BLAST253

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

GeneTreeiENSGT00800000124036.
HOGENOMiHOG000113436.
HOVERGENiHBG052384.
InParanoidiQ99558.
KOiK04466.
OMAiHGQLENR.
OrthoDBiEOG091G018K.
PhylomeDBiQ99558.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017425. MAPKKK14.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24361:SF226. PTHR24361:SF226. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF038175. MAPKKK14. 1 hit.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q99558-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:947
Mass (Da):104,042
Last modified:April 4, 2006 - v2
Checksum:iC9D10F67FF7F48AC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25A → P in CAA71306 (PubMed:9020361).Curated1
Sequence conflicti348G → S in CAA71306 (PubMed:9020361).Curated1
Sequence conflicti880R → G in BAF82892 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040711140S → N.1 PublicationCorresponds to variant rs11574819dbSNPEnsembl.1
Natural variantiVAR_051641255T → M.Corresponds to variant rs11574820dbSNPEnsembl.1
Natural variantiVAR_040712514G → K in a lung neuroendocrine carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_051642674H → Y.Corresponds to variant rs11867907dbSNPEnsembl.1
Natural variantiVAR_040713764T → A.1 PublicationCorresponds to variant rs56302559dbSNPEnsembl.1
Natural variantiVAR_040714852T → I in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040715928P → H.1 PublicationCorresponds to variant rs56036201dbSNPEnsembl.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.
CCDSiCCDS74079.1.
RefSeqiNP_003945.2. NM_003954.4.
XP_011523743.1. XM_011525441.2.
UniGeneiHs.404183.
Hs.668927.
Hs.735695.

Genome annotation databases

EnsembliENST00000344686; ENSP00000478552; ENSG00000006062.
ENST00000376926; ENSP00000482657; ENSG00000006062.
GeneIDi9020.
KEGGihsa:9020.
UCSCiuc032fjy.2. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS74079.1.
RefSeqiNP_003945.2. NM_003954.4.
XP_011523743.1. XM_011525441.2.
UniGeneiHs.404183.
Hs.668927.
Hs.735695.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DN5X-ray2.50A/B330-680[»]
4G3DX-ray2.90A/B/D/E308-673[»]
4IDTX-ray2.40A/B330-680[»]
4IDVX-ray2.90A/B/C/D330-680[»]
ProteinModelPortaliQ99558.
SMRiQ99558.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114487. 35 interactors.
DIPiDIP-27522N.
IntActiQ99558. 30 interactors.
MINTiMINT-88636.

Chemistry databases

BindingDBiQ99558.
ChEMBLiCHEMBL5888.
GuidetoPHARMACOLOGYi2074.

PTM databases

iPTMnetiQ99558.
PhosphoSitePlusiQ99558.

Polymorphism and mutation databases

BioMutaiMAP3K14.
DMDMi92090612.

Proteomic databases

PeptideAtlasiQ99558.
PRIDEiQ99558.

Protocols and materials databases

DNASUi9020.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344686; ENSP00000478552; ENSG00000006062.
ENST00000376926; ENSP00000482657; ENSG00000006062.
GeneIDi9020.
KEGGihsa:9020.
UCSCiuc032fjy.2. human.

Organism-specific databases

CTDi9020.
DisGeNETi9020.
GeneCardsiMAP3K14.
HGNCiHGNC:6853. MAP3K14.
HPAiCAB017631.
MIMi604655. gene.
neXtProtiNX_Q99558.
OpenTargetsiENSG00000006062.
PharmGKBiPA30597.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00800000124036.
HOGENOMiHOG000113436.
HOVERGENiHBG052384.
InParanoidiQ99558.
KOiK04466.
OMAiHGQLENR.
OrthoDBiEOG091G018K.
PhylomeDBiQ99558.

Enzyme and pathway databases

BioCyciZFISH:HS00162-MONOMER.
ReactomeiR-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.
SignaLinkiQ99558.
SIGNORiQ99558.

Miscellaneous databases

ChiTaRSiMAP3K14. human.
GeneWikiiMAP3K14.
GenomeRNAii9020.
PROiQ99558.
SOURCEiSearch...

Gene expression databases

CleanExiHS_MAP3K14.
ExpressionAtlasiQ99558. baseline and differential.
GenevisibleiQ99558. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017425. MAPKKK14.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24361:SF226. PTHR24361:SF226. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF038175. MAPKKK14. 1 hit.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K14_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 170 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.