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UniProtKB - Q99558 (M3K14_HUMAN)

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Protein

Mitogen-activated protein kinase kinase kinase 14

Gene

MAP3K14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000006062.13
HGNCiHGNC:6853 MAP3K14
MIMi604655 gene
neXtProtiNX_Q99558

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
MalaCardsiMAP3K14
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
ProteomicsDBi78326

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

BgeeiENSG00000006062
CleanExiHS_MAP3K14
ExpressionAtlasiQ99558 baseline and differential
GenevisibleiQ99558 HS

Organism-specific databases

HPAiHPA027269
HPA027270

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

Show more details

Protein-protein interaction databases

BioGridi114487, 35 interactors
CORUMiQ99558
DIPiDIP-27522N
IntActiQ99558, 122 interactors
MINTiQ99558

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

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

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.Curated

Phylogenomic databases

GeneTreeiENSGT00800000124036
HOGENOMiHOG000113436
HOVERGENiHBG052384
InParanoidiQ99558
KOiK04466
OMAiYDMEVPD
OrthoDBiEOG091G018K
PhylomeDBiQ99558

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017425 MAPKKK14
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PANTHERiPTHR24361:SF226 PTHR24361:SF226, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF038175 MAPKKK14, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

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 → N1 PublicationCorresponds to variant dbSNP:rs11574819EnsemblClinVar.1
Natural variantiVAR_051641255T → M. Corresponds to variant dbSNP:rs11574820EnsemblClinVar.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 dbSNP:rs11867907EnsemblClinVar.1
Natural variantiVAR_040713764T → A1 PublicationCorresponds to variant dbSNP:rs56302559EnsemblClinVar.1
Natural variantiVAR_040714852T → I in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040715928P → H1 PublicationCorresponds to variant dbSNP:rs56036201Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiM3K14_HUMAN
AccessioniPrimary (citable) accession number: Q99558
Secondary accession number(s): A8K2D8, D3DX67, Q8IYN1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: April 4, 2006
Last modified: July 18, 2018
This is version 184 of the entry and version 2 of the sequence. See 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

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