位置:首页 > 蛋白库 > M3K14_MOUSE
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   03-AUG-2022, entry version 180.
DE   RecName: Full=Mitogen-activated protein kinase kinase kinase 14 {ECO:0000312|MGI:MGI:1858204};
DE            EC=2.7.11.25;
DE   AltName: Full=NF-kappa-beta-inducing kinase {ECO:0000303|PubMed:26029823};
DE   AltName: Full=Serine/threonine-protein kinase NIK {ECO:0000250|UniProtKB:Q99558};
GN   Name=Map3k14 {ECO:0000312|MGI:MGI:1858204};
GN   Synonyms=Nik {ECO:0000303|PubMed:26029823};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   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 encoding Nf-
RT   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 p100.";
RL   Mol. Cell 7:401-409(2001).
RN   [3]
RP   INTERACTION WITH PPP3CA AND PPP3CB.
RX   PubMed=26029823; DOI=10.1038/srep10758;
RA   Shinzawa M., Konno H., Qin J., Akiyama N., Miyauchi M., Ohashi H.,
RA   Miyamoto-Sato E., Yanagawa H., Akiyama T., Inoue J.;
RT   "Catalytic subunits of the phosphatase calcineurin interact with NF-kappaB-
RT   inducing kinase (NIK) and attenuate NIK-dependent gene expression.";
RL   Sci. Rep. 5:10758-10758(2015).
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, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; 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-kappa-
CC       B2/P100. Interacts with PELI3. Interacts with NIBP; the interaction is
CC       direct. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts
CC       with ZFP91 (By similarity). Interacts with NLRP12; this interaction
CC       promotes proteasomal degradation of MAP3K14. Directly interacts with
CC       DDX3X (By similarity). Interacts (via C-terminus and kinase domain)
CC       with PPPC3A (via N-terminus) and PPP3CB (PubMed:26029823).
CC       {ECO:0000250|UniProtKB:Q99558, ECO:0000269|PubMed:26029823}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- PTM: Phosphorylation at Thr-561 is required to activates its kinase
CC       activity and 'Lys-63'-linked polyubiquitination. Phosphorylated by
CC       CHUK/IKKA leading to MAP3K14 destabilization (By similarity).
CC       Autophosphorylated. {ECO:0000250}.
CC   -!- PTM: Ubiquitinated. Undergoes both 'Lys-48'- and 'Lys-63'-linked
CC       polyubiquitination. 'Lys-48'-linked polyubiquitination leads to its
CC       degradation by the proteasome, while 'Lys-63'-linked polyubiquitination
CC       stabilizes and activates it (By similarity). {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Mice display the alymphoplasia phenotype (aly),
CC       which is characterized by systemic absence of lymph nodes and Peyer
CC       patches and disorganized splenic and thymic structures with
CC       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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF143094; AAD31512.1; -; mRNA.
DR   CCDS; CCDS25516.1; -.
DR   RefSeq; NP_058592.1; NM_016896.3.
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   PDB; 6MYN; X-ray; 2.74 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   PDBsum; 6MYN; -.
DR   AlphaFoldDB; Q9WUL6; -.
DR   SMR; Q9WUL6; -.
DR   BioGRID; 207493; 3.
DR   IntAct; Q9WUL6; 2.
DR   STRING; 10090.ENSMUSP00000021324; -.
DR   ChEMBL; CHEMBL4523500; -.
DR   GuidetoPHARMACOLOGY; 2074; -.
DR   iPTMnet; Q9WUL6; -.
DR   PhosphoSitePlus; Q9WUL6; -.
DR   PaxDb; Q9WUL6; -.
DR   PRIDE; Q9WUL6; -.
DR   Antibodypedia; 3862; 354 antibodies from 41 providers.
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   VEuPathDB; HostDB:ENSMUSG00000020941; -.
DR   eggNOG; KOG0198; Eukaryota.
DR   GeneTree; ENSGT00940000156497; -.
DR   HOGENOM; CLU_010641_1_0_1; -.
DR   InParanoid; Q9WUL6; -.
DR   OMA; HRMKDKQ; -.
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   BioGRID-ORCS; 53859; 4 hits in 72 CRISPR screens.
DR   PRO; PR:Q9WUL6; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q9WUL6; protein.
DR   Bgee; ENSMUSG00000020941; Expressed in granulocyte and 117 other tissues.
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:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004709; F:MAP kinase kinase kinase activity; IBA:GO_Central.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
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:0000165; P:MAPK cascade; IBA:GO_Central.
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   CDD; cd13991; STKc_NIK; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR042787; M3K14_STKc.
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; PTHR48016:SF9; PTHR48016:SF9; 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; Cytoplasm; Kinase; Nucleotide-binding;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase; Ubl conjugation.
FT   CHAIN           1..942
FT                   /note="Mitogen-activated protein kinase kinase kinase 14"
FT                   /id="PRO_0000086267"
FT   DOMAIN          402..657
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          136..156
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          291..326
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          403..655
FT                   /note="Interaction with ZFP91"
FT                   /evidence="ECO:0000250"
FT   REGION          660..756
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          801..823
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        136..153
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        703..721
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        517
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         408..416
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         431
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         561
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99558"
FT   MUTAGEN         855
FT                   /note="G->R: In ALY; no binding to IKKA."
FT                   /evidence="ECO:0000269|PubMed:10319865"
FT   HELIX           335..343
FT                   /evidence="ECO:0007829|PDB:4G3C"
FT   STRAND          346..349
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           352..359
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            360..362
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          379..383
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            397..399
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          400..411
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          414..421
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            422..424
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          427..434
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            435..437
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           441..444
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            445..448
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          457..463
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          466..471
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           479..486
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           491..509
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            510..512
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           520..522
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          523..525
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          527..530
FT                   /evidence="ECO:0007829|PDB:6G4Z"
FT   STRAND          532..534
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            545..547
FT                   /evidence="ECO:0007829|PDB:5T8O"
FT   STRAND          550..552
FT                   /evidence="ECO:0007829|PDB:5T8O"
FT   STRAND          553..556
FT                   /evidence="ECO:0007829|PDB:5T8Q"
FT   HELIX           562..564
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           567..570
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           578..593
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   TURN            599..601
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           607..612
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           616..619
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           626..635
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           640..642
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   HELIX           646..659
FT                   /evidence="ECO:0007829|PDB:4G3F"
FT   STRAND          667..670
FT                   /evidence="ECO:0007829|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
 
 
维奥蛋白资源库 - 中文蛋白资源 CopyRight © 2010-2024