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Database: UniProt/SWISS-PROT
Entry: M3K14_MOUSE
LinkDB: M3K14_MOUSE
Original site: M3K14_MOUSE 
ID   M3K14_MOUSE             Reviewed;         942 AA.
AC   Q9WUL6;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   16-JAN-2019, entry version 160.
DE   RecName: Full=Mitogen-activated protein kinase kinase kinase 14;
DE            EC=2.7.11.25;
DE   AltName: Full=NF-kappa-beta-inducing kinase;
DE   AltName: Full=Serine/threonine-protein kinase NIK;
GN   Name=Map3k14; Synonyms=Nik;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP   GLY-855.
RC   STRAIN=C57BL/6J; TISSUE=Spleen;
RX   PubMed=10319865; DOI=10.1038/8780;
RA   Shinkura R., Kitada K., Matsuda F., Tashiro K., Ikuta K., Suzuki M.,
RA   Kogishi K., Serikawa T., Honjo T.;
RT   "Alymphoplasia is caused by a point mutation in the mouse gene
RT   encoding Nf-kappa b-inducing kinase.";
RL   Nat. Genet. 22:74-77(1999).
RN   [2]
RP   FUNCTION, AND AUTOPHOSPHORYLATION.
RX   PubMed=11239468; DOI=10.1016/S1097-2765(01)00187-3;
RA   Xiao G., Harhaj E.W., Sun S.-C.;
RT   "NF-kappaB-inducing kinase regulates the processing of NF-kappaB2
RT   p100.";
RL   Mol. Cell 7:401-409(2001).
CC   -!- FUNCTION: Lymphotoxin beta-activated kinase which seems to be
CC       exclusively involved in the activation of NF-kappa-B and its
CC       transcriptional activity. Promotes proteolytic processing of
CC       NFKB2/P100, which leads to activation of NF-kappa-B via the non-
CC       canonical pathway. Could act in a receptor-selective manner.
CC       {ECO:0000269|PubMed:11239468}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC         EC=2.7.11.25;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.25;
CC   -!- SUBUNIT: Interacts with TRAF2, TRAF3, TRAF5, TRAF6, IKKA and NF-
CC       kappa-B2/P100. Interacts with PELI3. Interacts with NIBP; the
CC       interaction is direct. Interacts with ARRB1 and ARRB2. Interacts
CC       with GRB10. Interacts with ZFP91 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- PTM: Phosphorylation at Thr-561 is required to activates its
CC       kinase activity and 'Lys-63'-linked polyubiquitination.
CC       Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization (By
CC       similarity). Autophosphorylated. {ECO:0000250}.
CC   -!- PTM: Ubiquitinated. Undergoes both 'Lys-48'- and 'Lys-63'-linked
CC       polyubiquitination. 'Lys-48'-linked polyubiquitination leads to
CC       its degradation by the proteasome, while 'Lys-63'-linked
CC       polyubiquitination stabilizes and activates it (By similarity).
CC       {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Mice display the alymphoplasia phenotype
CC       (aly), which is characterized by systemic absence of lymph nodes
CC       and Peyer patches and disorganized splenic and thymic structures
CC       with immunodeficiency. {ECO:0000269|PubMed:10319865}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC       protein kinase family. MAP kinase kinase kinase subfamily.
CC       {ECO:0000305}.
DR   EMBL; AF143094; AAD31512.1; -; mRNA.
DR   CCDS; CCDS25516.1; -.
DR   RefSeq; NP_058592.1; NM_016896.3.
DR   UniGene; Mm.158981; -.
DR   PDB; 4G3C; X-ray; 2.15 A; A/B=329-675.
DR   PDB; 4G3E; X-ray; 2.50 A; A/B=329-675.
DR   PDB; 4G3F; X-ray; 1.64 A; A=345-675.
DR   PDB; 4G3G; X-ray; 2.50 A; A=345-675.
DR   PDB; 5T8O; X-ray; 2.41 A; A/B=329-675.
DR   PDB; 5T8P; X-ray; 2.32 A; A/B=329-675.
DR   PDB; 5T8Q; X-ray; 2.63 A; A/B=329-675.
DR   PDB; 6G4Y; X-ray; 2.65 A; A/B=329-675.
DR   PDB; 6G4Z; X-ray; 2.84 A; A/B=329-675.
DR   PDBsum; 4G3C; -.
DR   PDBsum; 4G3E; -.
DR   PDBsum; 4G3F; -.
DR   PDBsum; 4G3G; -.
DR   PDBsum; 5T8O; -.
DR   PDBsum; 5T8P; -.
DR   PDBsum; 5T8Q; -.
DR   PDBsum; 6G4Y; -.
DR   PDBsum; 6G4Z; -.
DR   ProteinModelPortal; Q9WUL6; -.
DR   SMR; Q9WUL6; -.
DR   BioGrid; 207493; 3.
DR   IntAct; Q9WUL6; 2.
DR   STRING; 10090.ENSMUSP00000021324; -.
DR   GuidetoPHARMACOLOGY; 2074; -.
DR   iPTMnet; Q9WUL6; -.
DR   PhosphoSitePlus; Q9WUL6; -.
DR   PaxDb; Q9WUL6; -.
DR   PRIDE; Q9WUL6; -.
DR   DNASU; 53859; -.
DR   Ensembl; ENSMUST00000021324; ENSMUSP00000021324; ENSMUSG00000020941.
DR   GeneID; 53859; -.
DR   KEGG; mmu:53859; -.
DR   UCSC; uc007lua.1; mouse.
DR   CTD; 9020; -.
DR   MGI; MGI:1858204; Map3k14.
DR   eggNOG; KOG0198; Eukaryota.
DR   eggNOG; ENOG410XQGS; LUCA.
DR   GeneTree; ENSGT00940000156497; -.
DR   HOGENOM; HOG000113436; -.
DR   HOVERGEN; HBG052384; -.
DR   InParanoid; Q9WUL6; -.
DR   KO; K04466; -.
DR   OMA; EQESCTV; -.
DR   OrthoDB; 162528at2759; -.
DR   PhylomeDB; Q9WUL6; -.
DR   TreeFam; TF105120; -.
DR   Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR   Reactome; R-MMU-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR   Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway.
DR   Reactome; R-MMU-5676590; NIK-->noncanonical NF-kB signaling.
DR   Reactome; R-MMU-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR   PRO; PR:Q9WUL6; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   Bgee; ENSMUSG00000020941; Expressed in 144 organ(s), highest expression level in lymph node.
DR   CleanEx; MM_MAP3K14; -.
DR   ExpressionAtlas; Q9WUL6; baseline and differential.
DR   Genevisible; Q9WUL6; MM.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004709; F:MAP kinase kinase kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004704; F:NF-kappaB-inducing kinase activity; IDA:UniProtKB.
DR   GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR   GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR   GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR   GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR   GO; GO:0006955; P:immune response; IDA:UniProtKB.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR   GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR   GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
DR   GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IBA:GO_Central.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR017425; MAPKKK14.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24361:SF226; PTHR24361:SF226; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   PIRSF; PIRSF038175; MAPKKK14; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Complete proteome; Cytoplasm; Kinase;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT   CHAIN         1    942       Mitogen-activated protein kinase kinase
FT                                kinase 14.
FT                                /FTId=PRO_0000086267.
FT   DOMAIN      402    657       Protein kinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   NP_BIND     408    416       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   REGION      403    655       Interaction with ZFP91. {ECO:0000250}.
FT   ACT_SITE    517    517       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159, ECO:0000255|PROSITE-
FT                                ProRule:PRU10027}.
FT   BINDING     431    431       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOD_RES     561    561       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q99558}.
FT   MUTAGEN     855    855       G->R: In ALY; no binding to IKKA.
FT                                {ECO:0000269|PubMed:10319865}.
FT   HELIX       335    343       {ECO:0000244|PDB:4G3C}.
FT   STRAND      346    349       {ECO:0000244|PDB:4G3F}.
FT   HELIX       352    359       {ECO:0000244|PDB:4G3F}.
FT   TURN        360    362       {ECO:0000244|PDB:4G3F}.
FT   STRAND      379    383       {ECO:0000244|PDB:4G3F}.
FT   TURN        397    399       {ECO:0000244|PDB:4G3F}.
FT   STRAND      400    411       {ECO:0000244|PDB:4G3F}.
FT   STRAND      414    421       {ECO:0000244|PDB:4G3F}.
FT   TURN        422    424       {ECO:0000244|PDB:4G3F}.
FT   STRAND      427    434       {ECO:0000244|PDB:4G3F}.
FT   TURN        435    437       {ECO:0000244|PDB:4G3F}.
FT   HELIX       441    444       {ECO:0000244|PDB:4G3F}.
FT   TURN        445    448       {ECO:0000244|PDB:4G3F}.
FT   STRAND      457    463       {ECO:0000244|PDB:4G3F}.
FT   STRAND      466    471       {ECO:0000244|PDB:4G3F}.
FT   HELIX       479    486       {ECO:0000244|PDB:4G3F}.
FT   HELIX       491    509       {ECO:0000244|PDB:4G3F}.
FT   TURN        510    512       {ECO:0000244|PDB:4G3F}.
FT   HELIX       520    522       {ECO:0000244|PDB:4G3F}.
FT   STRAND      523    525       {ECO:0000244|PDB:4G3F}.
FT   STRAND      527    530       {ECO:0000244|PDB:6G4Z}.
FT   STRAND      532    534       {ECO:0000244|PDB:4G3F}.
FT   TURN        545    547       {ECO:0000244|PDB:5T8O}.
FT   STRAND      550    552       {ECO:0000244|PDB:5T8O}.
FT   STRAND      553    556       {ECO:0000244|PDB:5T8Q}.
FT   HELIX       562    564       {ECO:0000244|PDB:4G3F}.
FT   HELIX       567    570       {ECO:0000244|PDB:4G3F}.
FT   HELIX       578    593       {ECO:0000244|PDB:4G3F}.
FT   TURN        599    601       {ECO:0000244|PDB:4G3F}.
FT   HELIX       607    612       {ECO:0000244|PDB:4G3F}.
FT   HELIX       616    619       {ECO:0000244|PDB:4G3F}.
FT   HELIX       626    635       {ECO:0000244|PDB:4G3F}.
FT   HELIX       640    642       {ECO:0000244|PDB:4G3F}.
FT   HELIX       646    659       {ECO:0000244|PDB:4G3F}.
FT   STRAND      667    670       {ECO:0000244|PDB:4G3F}.
SQ   SEQUENCE   942 AA;  103080 MW;  3BE4E4BA2D25C200 CRC64;
     MAVMEVACPG TPGSAVGQQK ELAKAKEKTQ SLGKKQSCIF KLEAVEKSPV FCGKWEILND
     VITKGTAKDG SEGGPPAISI IAQAECENSQ EFSPTFSERI FIAGSQQYSQ SESLDQIPNN
     VAHATEGKMA RVCRRGKRHG KARKKRRKKR SKSLAQAGVA LAKPLPRTPE QESCTIPVQE
     DESPLGNLYA RNVSQFTKPL GGPGLGHLCF KKQDEGLRPV LPRPELHKLI SPLQCLNHVW
     KLHHPQATGP RPHPTHPFPY SGMPHPFPFY PLEPWKPYML DSAVLDKLAG VSGQRPLPGP
     PHLSQLAHGD SQKPLPGPHL ESSCPSRGAL EKVPVEEYLV HALQGSVSSG QAHSLASLAK
     TWSSGSAKLQ RLGPETEDNE GVLLTEKLKP VDYEYREEVH WMTHQPRVGR GSFGEVHRMK
     DKQTGFQCAV KKVRLEVFRV EELVACAGLS SPRIVPLYGA VREGPWVNIF MELLEGGSLG
     QLIKQMGCLP EDRALYYLGQ ALEGLEYLHT RRILHGDVKA DNVLLSSDGS RAALCDFGHA
     LCLQPDGLGK SLLTGDYIPG TETHMAPEVV MGKPCDAKVD IWSSCCMMLH MLNGCHPWTQ
     YFRGPLCLKI ASEPPPIREI PPSCAPLTAQ AIQEGLRKEP VHRASAMELR RKVGKALQEV
     GGLKSPWKGE YKEPRPPPQD QATCHQTLPT PPRENPPAKA NTDGAPEPQP PLPPEPPEPS
     KAPALNLSKE ESGTWEPLPL SSLDPATAKG PSFPDRRATL PELELQQLEI ELFLNSLSQP
     FSLEEQEQIL SCLSIDSLSL SDDSEKNPSK ASQSSRDTLS SGVHSWNSQA EARTCSCSTA
     LARGRPTDIP SYFNGVKVQI QSLNGEHLHI REFHRVKVGD IATGISSQIP ATAFSLVTKD
     GQPVCYDMEV PDSGIDLQCT LAPDGSFAWT WRVKHGQLEN RP
//
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