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Protein

Mitogen-activated protein kinase kinase kinase 14

Gene

Map3k14

Organism
Mus musculus (Mouse)
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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei431 – 4311ATPPROSITE-ProRule annotation
Active sitei517 – 5171Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi408 – 4169ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • cellular response to mechanical stimulus Source: Ensembl
  • I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • immune response Source: UniProtKB
  • NIK/NF-kappaB signaling Source: GOC
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-389357. CD28 dependent PI3K/Akt signaling.
R-MMU-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-MMU-5668541. TNFR2 non-canonical NF-kB pathway.
R-MMU-5676590. NIK-->noncanonical NF-kB signaling.
R-MMU-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.

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
Serine/threonine-protein kinase NIK
Gene namesi
Name:Map3k14
Synonyms:Nik
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1858204. Map3k14.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice display the alymphoplasia phenotype (aly), which is characterized by systemic absence of lymph nodes and Peyer patches and disorganized splenic and thymic structures with immunodeficiency.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi855 – 8551G → R in ALY; no binding to IKKA. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 942942Mitogen-activated protein kinase kinase kinase 14PRO_0000086267Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei561 – 5611PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylation at Thr-561 is required to activates its kinase activity and 'Lys-63'-linked polyubiquitination. Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization (By similarity). Autophosphorylated.By similarity
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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9WUL6.
PRIDEiQ9WUL6.

PTM databases

iPTMnetiQ9WUL6.
PhosphoSiteiQ9WUL6.

Expressioni

Gene expression databases

BgeeiQ9WUL6.
CleanExiMM_MAP3K14.
ExpressionAtlasiQ9WUL6. baseline and differential.
GenevisibleiQ9WUL6. MM.

Interactioni

Subunit structurei

Interacts with TRAF2, TRAF3, TRAF5, TRAF6, IKKA and NF-kappa-B2/P100. Interacts with PELI3. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with ZFP91 (By similarity).By similarity

Protein-protein interaction databases

BioGridi207493. 1 interaction.
IntActiQ9WUL6. 2 interactions.
STRINGi10090.ENSMUSP00000021324.

Structurei

Secondary structure

1
942
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi335 – 3439Combined sources
Beta strandi346 – 3494Combined sources
Helixi352 – 3598Combined sources
Turni360 – 3623Combined sources
Beta strandi379 – 3835Combined sources
Turni397 – 3993Combined sources
Beta strandi400 – 41112Combined sources
Beta strandi414 – 4218Combined sources
Turni422 – 4243Combined sources
Beta strandi427 – 4348Combined sources
Turni435 – 4373Combined sources
Helixi441 – 4444Combined sources
Turni445 – 4484Combined sources
Beta strandi457 – 4637Combined sources
Beta strandi466 – 4716Combined sources
Helixi479 – 4868Combined sources
Helixi491 – 50919Combined sources
Turni510 – 5123Combined sources
Helixi520 – 5223Combined sources
Beta strandi523 – 5253Combined sources
Beta strandi532 – 5343Combined sources
Helixi562 – 5643Combined sources
Helixi567 – 5704Combined sources
Helixi578 – 59316Combined sources
Turni599 – 6013Combined sources
Helixi607 – 6126Combined sources
Helixi616 – 6194Combined sources
Helixi626 – 63510Combined sources
Helixi640 – 6423Combined sources
Helixi646 – 65914Combined sources
Beta strandi667 – 6704Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4G3CX-ray2.15A/B329-675[»]
4G3EX-ray2.50A/B329-675[»]
4G3FX-ray1.64A345-675[»]
4G3GX-ray2.50A345-675[»]
ProteinModelPortaliQ9WUL6.
SMRiQ9WUL6. Positions 334-745.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini402 – 657256Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni403 – 655253Interaction with ZFP91By similarityAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0198. Eukaryota.
ENOG410XQGS. LUCA.
GeneTreeiENSGT00800000124036.
HOGENOMiHOG000113436.
HOVERGENiHBG052384.
InParanoidiQ9WUL6.
KOiK04466.
OMAiHGQLENR.
OrthoDBiEOG780RKZ.
PhylomeDBiQ9WUL6.
TreeFamiTF105120.

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. 2 hits.
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.

Q9WUL6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVMEVACPG TPGSAVGQQK ELAKAKEKTQ SLGKKQSCIF KLEAVEKSPV
60 70 80 90 100
FCGKWEILND VITKGTAKDG SEGGPPAISI IAQAECENSQ EFSPTFSERI
110 120 130 140 150
FIAGSQQYSQ SESLDQIPNN VAHATEGKMA RVCRRGKRHG KARKKRRKKR
160 170 180 190 200
SKSLAQAGVA LAKPLPRTPE QESCTIPVQE DESPLGNLYA RNVSQFTKPL
210 220 230 240 250
GGPGLGHLCF KKQDEGLRPV LPRPELHKLI SPLQCLNHVW KLHHPQATGP
260 270 280 290 300
RPHPTHPFPY SGMPHPFPFY PLEPWKPYML DSAVLDKLAG VSGQRPLPGP
310 320 330 340 350
PHLSQLAHGD SQKPLPGPHL ESSCPSRGAL EKVPVEEYLV HALQGSVSSG
360 370 380 390 400
QAHSLASLAK TWSSGSAKLQ RLGPETEDNE GVLLTEKLKP VDYEYREEVH
410 420 430 440 450
WMTHQPRVGR GSFGEVHRMK DKQTGFQCAV KKVRLEVFRV EELVACAGLS
460 470 480 490 500
SPRIVPLYGA VREGPWVNIF MELLEGGSLG QLIKQMGCLP EDRALYYLGQ
510 520 530 540 550
ALEGLEYLHT RRILHGDVKA DNVLLSSDGS RAALCDFGHA LCLQPDGLGK
560 570 580 590 600
SLLTGDYIPG TETHMAPEVV MGKPCDAKVD IWSSCCMMLH MLNGCHPWTQ
610 620 630 640 650
YFRGPLCLKI ASEPPPIREI PPSCAPLTAQ AIQEGLRKEP VHRASAMELR
660 670 680 690 700
RKVGKALQEV GGLKSPWKGE YKEPRPPPQD QATCHQTLPT PPRENPPAKA
710 720 730 740 750
NTDGAPEPQP PLPPEPPEPS KAPALNLSKE ESGTWEPLPL SSLDPATAKG
760 770 780 790 800
PSFPDRRATL PELELQQLEI ELFLNSLSQP FSLEEQEQIL SCLSIDSLSL
810 820 830 840 850
SDDSEKNPSK ASQSSRDTLS SGVHSWNSQA EARTCSCSTA LARGRPTDIP
860 870 880 890 900
SYFNGVKVQI QSLNGEHLHI REFHRVKVGD IATGISSQIP ATAFSLVTKD
910 920 930 940
GQPVCYDMEV PDSGIDLQCT LAPDGSFAWT WRVKHGQLEN RP
Length:942
Mass (Da):103,080
Last modified:November 1, 1999 - v1
Checksum:i3BE4E4BA2D25C200
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF143094 mRNA. Translation: AAD31512.1.
CCDSiCCDS25516.1.
RefSeqiNP_058592.1. NM_016896.3.
UniGeneiMm.158981.

Genome annotation databases

EnsembliENSMUST00000021324; ENSMUSP00000021324; ENSMUSG00000020941.
GeneIDi53859.
KEGGimmu:53859.
UCSCiuc007lua.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF143094 mRNA. Translation: AAD31512.1.
CCDSiCCDS25516.1.
RefSeqiNP_058592.1. NM_016896.3.
UniGeneiMm.158981.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4G3CX-ray2.15A/B329-675[»]
4G3EX-ray2.50A/B329-675[»]
4G3FX-ray1.64A345-675[»]
4G3GX-ray2.50A345-675[»]
ProteinModelPortaliQ9WUL6.
SMRiQ9WUL6. Positions 334-745.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207493. 1 interaction.
IntActiQ9WUL6. 2 interactions.
STRINGi10090.ENSMUSP00000021324.

PTM databases

iPTMnetiQ9WUL6.
PhosphoSiteiQ9WUL6.

Proteomic databases

PaxDbiQ9WUL6.
PRIDEiQ9WUL6.

Protocols and materials databases

DNASUi53859.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021324; ENSMUSP00000021324; ENSMUSG00000020941.
GeneIDi53859.
KEGGimmu:53859.
UCSCiuc007lua.1. mouse.

Organism-specific databases

CTDi9020.
MGIiMGI:1858204. Map3k14.

Phylogenomic databases

eggNOGiKOG0198. Eukaryota.
ENOG410XQGS. LUCA.
GeneTreeiENSGT00800000124036.
HOGENOMiHOG000113436.
HOVERGENiHBG052384.
InParanoidiQ9WUL6.
KOiK04466.
OMAiHGQLENR.
OrthoDBiEOG780RKZ.
PhylomeDBiQ9WUL6.
TreeFamiTF105120.

Enzyme and pathway databases

ReactomeiR-MMU-389357. CD28 dependent PI3K/Akt signaling.
R-MMU-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-MMU-5668541. TNFR2 non-canonical NF-kB pathway.
R-MMU-5676590. NIK-->noncanonical NF-kB signaling.
R-MMU-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.

Miscellaneous databases

PROiQ9WUL6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WUL6.
CleanExiMM_MAP3K14.
ExpressionAtlasiQ9WUL6. baseline and differential.
GenevisibleiQ9WUL6. MM.

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. 2 hits.
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...

Publicationsi

  1. "Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase."
    Shinkura R., Kitada K., Matsuda F., Tashiro K., Ikuta K., Suzuki M., Kogishi K., Serikawa T., Honjo T.
    Nat. Genet. 22:74-77(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, MUTAGENESIS OF GLY-855.
    Strain: C57BL/6J.
    Tissue: Spleen.
  2. "NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100."
    Xiao G., Harhaj E.W., Sun S.-C.
    Mol. Cell 7:401-409(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, AUTOPHOSPHORYLATION.

Entry informationi

Entry nameiM3K14_MOUSE
AccessioniPrimary (citable) accession number: Q9WUL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: November 1, 1999
Last modified: June 8, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. 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.