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Database: UniProt
Entry: Q99558
LinkDB: Q99558
Original site: Q99558 
ID   M3K14_HUMAN             Reviewed;         947 AA.
AC   Q99558; A8K2D8; D3DX67; Q8IYN1;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   04-APR-2006, sequence version 2.
DT   02-JUN-2021, entry version 205.
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            Short=HsNIK;
DE   AltName: Full=Serine/threonine-protein kinase NIK;
GN   Name=MAP3K14; Synonyms=NIK;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF 429-LYS-LYS-430, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=9020361; DOI=10.1038/385540a0;
RA   Malinin N.L., Boldin M.P., Kovalenko A.V., Wallach D.;
RT   "MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-
RT   1.";
RL   Nature 385:540-544(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   NHLBI resequencing and genotyping service (RS&G);
RL   Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lymph;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   INTERACTION WITH PELI3.
RX   PubMed=12874243; DOI=10.4049/jimmunol.171.3.1500;
RA   Jensen L.E., Whitehead A.S.;
RT   "Pellino3, a novel member of the Pellino protein family, promotes
RT   activation of c-Jun and Elk-1 and may act as a scaffolding protein.";
RL   J. Immunol. 171:1500-1506(2003).
RN   [7]
RP   INTERACTION WITH GRB10.
RX   PubMed=12853971; DOI=10.1038/sj.onc.1206532;
RA   Chen D., Xu L.G., Chen L., Li L., Zhai Z., Shu H.B.;
RT   "NIK is a component of the EGF/heregulin receptor signaling complexes.";
RL   Oncogene 22:4348-4355(2003).
RN   [8]
RP   FUNCTION, UBIQUITINATION, AND INTERACTION WITH TRAF3.
RX   PubMed=15084608; DOI=10.1074/jbc.m403286200;
RA   Liao G., Zhang M., Harhaj E.W., Sun S.C.;
RT   "Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor
RT   receptor-associated factor 3-induced degradation.";
RL   J. Biol. Chem. 279:26243-26250(2004).
RN   [9]
RP   INTERACTION WITH ARRB1 AND ARRB2.
RX   PubMed=15173580; DOI=10.1073/pnas.0402851101;
RA   Witherow D.S., Garrison T.R., Miller W.E., Lefkowitz R.J.;
RT   "beta-Arrestin inhibits NF-kappaB activity by means of its interaction with
RT   the NF-kappaB inhibitor IkappaBalpha.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:8603-8607(2004).
RN   [10]
RP   INTERACTION WITH NIBP.
RX   PubMed=15951441; DOI=10.1074/jbc.m501670200;
RA   Hu W.-H., Pendergast J.S., Mo X.-M., Brambilla R., Bracchi-Ricard V.,
RA   Li F., Walters W.M., Blits B., He L., Schaal S.M., Bethea J.R.;
RT   "NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B
RT   activation.";
RL   J. Biol. Chem. 280:29233-29241(2005).
RN   [11]
RP   INTERACTION WITH NLRP12.
RX   PubMed=17237370; DOI=10.4049/jimmunol.178.3.1256;
RA   Lich J.D., Williams K.L., Moore C.B., Arthur J.C., Davis B.K., Taxman D.J.,
RA   Ting J.P.;
RT   "Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent
RT   chemokine expression in monocytes.";
RL   J. Immunol. 178:1256-1260(2007).
RN   [12]
RP   PHOSPHORYLATION BY CHUK/IKKA.
RX   PubMed=20501937; DOI=10.1126/scisignal.2000778;
RA   Razani B., Zarnegar B., Ytterberg A.J., Shiba T., Dempsey P.W., Ware C.F.,
RA   Loo J.A., Cheng G.;
RT   "Negative feedback in noncanonical NF-kappaB signaling modulates NIK
RT   stability through IKKalpha-mediated phosphorylation.";
RL   Sci. Signal. 3:RA41-RA41(2010).
RN   [13]
RP   INTERACTION WITH DDX3X.
RX   PubMed=30341167; DOI=10.1042/bcj20180163;
RA   Fullam A., Gu L., Hoehn Y., Schroeder M.;
RT   "DDX3 directly facilitates IKKalpha activation and regulates downstream
RT   signalling pathways.";
RL   Biochem. J. 475:3595-3607(2018).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 330-680.
RX   PubMed=22718757; DOI=10.1074/jbc.m112.366658;
RA   Liu J., Sudom A., Min X., Cao Z., Gao X., Ayres M., Lee F., Cao P.,
RA   Johnstone S., Plotnikova O., Walker N., Chen G., Wang Z.;
RT   "Structure of the nuclear factor kappaB-inducing kinase (NIK) kinase domain
RT   reveals a constitutively active conformation.";
RL   J. Biol. Chem. 287:27326-27334(2012).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 308-673.
RX   PubMed=22921830; DOI=10.1016/j.str.2012.07.013;
RA   de Leon-Boenig G., Bowman K.K., Feng J.A., Crawford T., Everett C.,
RA   Franke Y., Oh A., Stanley M., Staben S.T., Starovasnik M.A.,
RA   Wallweber H.J., Wu J., Wu L.C., Johnson A.R., Hymowitz S.G.;
RT   "The crystal structure of the catalytic domain of the NF-kappaB inducing
RT   kinase reveals a narrow but flexible active site.";
RL   Structure 20:1704-1714(2012).
RN   [16]
RP   VARIANTS [LARGE SCALE ANALYSIS] ASN-140; LYS-514; ALA-764; ILE-852 AND
RP   HIS-928.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
RN   [17]
RP   PHOSPHORYLATION AT THR-559, UBIQUITINATION, INTERACTION WITH ZFP91, AND
RP   MUTAGENESIS OF 429-LYS-LYS-430 AND THR-559.
RX   PubMed=20682767; DOI=10.1074/jbc.m110.129551;
RA   Jin X., Jin H.R., Jung H.S., Lee S.J., Lee J.H., Lee J.J.;
RT   "An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-
RT   kappaB-inducing kinase via Lys63-linked ubiquitination.";
RL   J. Biol. Chem. 285:30539-30547(2010).
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:15084608}.
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, TRAF5, TRAF6, IKKA and NFKB2/P100 (By
CC       similarity). Interacts with TRAF3 and PELI3. Interacts with NIBP; the
CC       interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with
CC       GRB10. Interacts with ZFP91. Interacts with NLRP12; this interaction
CC       promotes proteasomal degradation of MAP3K14. Directly interacts with
CC       DDX3X (PubMed:30341167). {ECO:0000250, ECO:0000269|PubMed:12853971,
CC       ECO:0000269|PubMed:12874243, ECO:0000269|PubMed:15084608,
CC       ECO:0000269|PubMed:15173580, ECO:0000269|PubMed:15951441,
CC       ECO:0000269|PubMed:17237370, ECO:0000269|PubMed:20682767,
CC       ECO:0000269|PubMed:30341167}.
CC   -!- INTERACTION:
CC       Q99558; P05186: ALPL; NbExp=4; IntAct=EBI-358011, EBI-1054354;
CC       Q99558; Q16543: CDC37; NbExp=5; IntAct=EBI-358011, EBI-295634;
CC       Q99558; O15111: CHUK; NbExp=11; IntAct=EBI-358011, EBI-81249;
CC       Q99558; P01112: HRAS; NbExp=3; IntAct=EBI-358011, EBI-350145;
CC       Q99558; P07900: HSP90AA1; NbExp=4; IntAct=EBI-358011, EBI-296047;
CC       Q99558; P08238: HSP90AB1; NbExp=4; IntAct=EBI-358011, EBI-352572;
CC       Q99558; O14920: IKBKB; NbExp=5; IntAct=EBI-358011, EBI-81266;
CC       Q99558; Q9Y6K9: IKBKG; NbExp=3; IntAct=EBI-358011, EBI-81279;
CC       Q99558; Q14974: KPNB1; NbExp=2; IntAct=EBI-358011, EBI-286758;
CC       Q99558; P36578: RPL4; NbExp=3; IntAct=EBI-358011, EBI-348313;
CC       Q99558; Q02878: RPL6; NbExp=3; IntAct=EBI-358011, EBI-359655;
CC       Q99558; P62917: RPL8; NbExp=3; IntAct=EBI-358011, EBI-438527;
CC       Q99558; P62280: RPS11; NbExp=3; IntAct=EBI-358011, EBI-1047710;
CC       Q99558; P62277: RPS13; NbExp=3; IntAct=EBI-358011, EBI-351850;
CC       Q99558; Q12933: TRAF2; NbExp=9; IntAct=EBI-358011, EBI-355744;
CC       Q99558; Q13114: TRAF3; NbExp=7; IntAct=EBI-358011, EBI-357631;
CC       Q99558; Q60680-2: Chuk; Xeno; NbExp=3; IntAct=EBI-358011, EBI-646264;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- TISSUE SPECIFICITY: Weakly expressed in testis, small intestine,
CC       spleen, thymus, peripheral blood leukocytes, prostate, ovary and colon.
CC       {ECO:0000269|PubMed:9020361}.
CC   -!- PTM: Autophosphorylated. Phosphorylation at Thr-559 is required to
CC       activates its kinase activity and 'Lys-63'-linked polyubiquitination.
CC       Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization.
CC       {ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:20682767}.
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.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC       protein kinase family. MAP kinase kinase kinase subfamily.
CC       {ECO:0000305}.
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DR   EMBL; Y10256; CAA71306.1; -; mRNA.
DR   EMBL; AK290203; BAF82892.1; -; mRNA.
DR   EMBL; DQ314874; ABC40733.1; -; Genomic_DNA.
DR   EMBL; CH471178; EAW51529.1; -; Genomic_DNA.
DR   EMBL; CH471178; EAW51530.1; -; Genomic_DNA.
DR   EMBL; BC035576; AAH35576.1; -; mRNA.
DR   CCDS; CCDS74079.1; -.
DR   RefSeq; NP_003945.2; NM_003954.4.
DR   RefSeq; XP_011523743.1; XM_011525441.2.
DR   PDB; 4DN5; X-ray; 2.50 A; A/B=330-680.
DR   PDB; 4G3D; X-ray; 2.90 A; A/B/D/E=308-673.
DR   PDB; 4IDT; X-ray; 2.40 A; A/B=330-680.
DR   PDB; 4IDV; X-ray; 2.90 A; A/B/C/D=330-680.
DR   PDB; 6WPP; X-ray; 2.55 A; A/B=343-686.
DR   PDB; 6Z1Q; X-ray; 2.42 A; AAA/BBB=330-680.
DR   PDB; 6Z1T; X-ray; 2.31 A; AAA/BBB=330-680.
DR   PDBsum; 4DN5; -.
DR   PDBsum; 4G3D; -.
DR   PDBsum; 4IDT; -.
DR   PDBsum; 4IDV; -.
DR   PDBsum; 6WPP; -.
DR   PDBsum; 6Z1Q; -.
DR   PDBsum; 6Z1T; -.
DR   SMR; Q99558; -.
DR   BioGRID; 114487; 140.
DR   CORUM; Q99558; -.
DR   DIP; DIP-27522N; -.
DR   IntAct; Q99558; 129.
DR   MINT; Q99558; -.
DR   STRING; 9606.ENSP00000482657; -.
DR   BindingDB; Q99558; -.
DR   ChEMBL; CHEMBL5888; -.
DR   GuidetoPHARMACOLOGY; 2074; -.
DR   iPTMnet; Q99558; -.
DR   PhosphoSitePlus; Q99558; -.
DR   BioMuta; MAP3K14; -.
DR   DMDM; 92090612; -.
DR   MassIVE; Q99558; -.
DR   PeptideAtlas; Q99558; -.
DR   PRIDE; Q99558; -.
DR   ProteomicsDB; 78326; -.
DR   Antibodypedia; 3862; 344 antibodies.
DR   DNASU; 9020; -.
DR   Ensembl; ENST00000344686; ENSP00000478552; ENSG00000006062.
DR   Ensembl; ENST00000376926; ENSP00000482657; ENSG00000006062.
DR   Ensembl; ENST00000617331; ENSP00000480974; ENSG00000006062.
DR   GeneID; 9020; -.
DR   KEGG; hsa:9020; -.
DR   UCSC; uc032fjy.2; human.
DR   CTD; 9020; -.
DR   DisGeNET; 9020; -.
DR   GeneCards; MAP3K14; -.
DR   HGNC; HGNC:6853; MAP3K14.
DR   HPA; ENSG00000006062; Low tissue specificity.
DR   MalaCards; MAP3K14; -.
DR   MIM; 604655; gene.
DR   neXtProt; NX_Q99558; -.
DR   OpenTargets; ENSG00000006062; -.
DR   Orphanet; 447731; NIK deficiency.
DR   PharmGKB; PA30597; -.
DR   VEuPathDB; HostDB:ENSG00000006062.13; -.
DR   eggNOG; KOG0198; Eukaryota.
DR   GeneTree; ENSGT00940000156497; -.
DR   HOGENOM; CLU_010641_1_0_1; -.
DR   InParanoid; Q99558; -.
DR   OMA; WNSQTDG; -.
DR   OrthoDB; 162528at2759; -.
DR   PhylomeDB; Q99558; -.
DR   PathwayCommons; Q99558; -.
DR   Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR   Reactome; R-HSA-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR   Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway.
DR   Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB signaling.
DR   Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR   SignaLink; Q99558; -.
DR   SIGNOR; Q99558; -.
DR   BioGRID-ORCS; 9020; 3 hits in 162 CRISPR screens.
DR   ChiTaRS; MAP3K14; human.
DR   GeneWiki; MAP3K14; -.
DR   GenomeRNAi; 9020; -.
DR   Pharos; Q99558; Tchem.
DR   PRO; PR:Q99558; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q99558; protein.
DR   Bgee; ENSG00000006062; Expressed in esophagogastric junction muscularis propria and 161 other tissues.
DR   ExpressionAtlas; Q99558; baseline and differential.
DR   Genevisible; Q99558; HS.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; ISS:UniProtKB.
DR   GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; EXP:Reactome.
DR   GO; GO:0106311; F:protein threonine kinase activity; IEA:RHEA.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR   GO; GO:0006955; P:immune response; ISS:UniProtKB.
DR   GO; GO:0038061; P:NIK/NF-kappaB signaling; TAS:Reactome.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR   GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; TAS:Reactome.
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..947
FT                   /note="Mitogen-activated protein kinase kinase kinase 14"
FT                   /id="PRO_0000086266"
FT   DOMAIN          400..655
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   NP_BIND         406..414
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          135..171
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          401..653
FT                   /note="Interaction with ZFP91"
FT                   /evidence="ECO:0000269|PubMed:20682767"
FT   REGION          662..766
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          805..830
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        135..153
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        712..728
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        515
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         429
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         559
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:20682767"
FT   VARIANT         140
FT                   /note="S -> N (in dbSNP:rs11574819)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040711"
FT   VARIANT         255
FT                   /note="T -> M (in dbSNP:rs11574820)"
FT                   /id="VAR_051641"
FT   VARIANT         514
FT                   /note="G -> K (in a lung neuroendocrine carcinoma sample;
FT                   somatic mutation; requires 2 nucleotide substitutions)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040712"
FT   VARIANT         674
FT                   /note="H -> Y (in dbSNP:rs11867907)"
FT                   /id="VAR_051642"
FT   VARIANT         764
FT                   /note="T -> A (in dbSNP:rs56302559)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040713"
FT   VARIANT         852
FT                   /note="T -> I (in an ovarian mucinous carcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040714"
FT   VARIANT         928
FT                   /note="P -> H (in dbSNP:rs56036201)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040715"
FT   MUTAGEN         429..430
FT                   /note="KK->AA: Loss of autophosphorylation and 'Lys-63'-
FT                   linked ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:20682767,
FT                   ECO:0000269|PubMed:9020361"
FT   MUTAGEN         559
FT                   /note="T->A: Abolishes 'Lys-63'-linked ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:20682767"
FT   CONFLICT        25
FT                   /note="A -> P (in Ref. 1; CAA71306)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        348
FT                   /note="G -> S (in Ref. 1; CAA71306)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        880
FT                   /note="R -> G (in Ref. 2; BAF82892)"
FT                   /evidence="ECO:0000305"
FT   HELIX           335..341
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          345..347
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           350..363
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          364..366
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          377..381
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   TURN            395..397
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          398..408
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          410..419
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   TURN            420..422
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          425..432
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           433..435
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           439..442
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   TURN            443..446
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          455..461
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          464..469
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           477..484
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           489..507
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   TURN            508..510
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           518..520
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          521..523
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   STRAND          530..532
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           535..537
FT                   /evidence="ECO:0007829|PDB:4IDV"
FT   STRAND          543..547
FT                   /evidence="ECO:0007829|PDB:4G3D"
FT   TURN            550..553
FT                   /evidence="ECO:0007829|PDB:4G3D"
FT   HELIX           560..562
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           565..568
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           576..591
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   TURN            595..599
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           605..610
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           614..617
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           624..633
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   TURN            638..640
FT                   /evidence="ECO:0007829|PDB:4IDT"
FT   HELIX           644..658
FT                   /evidence="ECO:0007829|PDB:4IDT"
SQ   SEQUENCE   947 AA;  104042 MW;  C9D10F67FF7F48AC CRC64;
     MAVMEMACPG APGSAVGQQK ELPKAKEKTP PLGKKQSSVY KLEAVEKSPV FCGKWEILND
     VITKGTAKEG SEAGPAAISI IAQAECENSQ EFSPTFSERI FIAGSKQYSQ SESLDQIPNN
     VAHATEGKMA RVCWKGKRRS KARKKRKKKS SKSLAHAGVA LAKPLPRTPE QESCTIPVQE
     DESPLGAPYV RNTPQFTKPL KEPGLGQLCF KQLGEGLRPA LPRSELHKLI SPLQCLNHVW
     KLHHPQDGGP LPLPTHPFPY SRLPHPFPFH PLQPWKPHPL ESFLGKLACV DSQKPLPDPH
     LSKLACVDSP KPLPGPHLEP SCLSRGAHEK FSVEEYLVHA LQGSVSSGQA HSLTSLAKTW
     AARGSRSREP SPKTEDNEGV LLTEKLKPVD YEYREEVHWA THQLRLGRGS FGEVHRMEDK
     QTGFQCAVKK VRLEVFRAEE LMACAGLTSP RIVPLYGAVR EGPWVNIFME LLEGGSLGQL
     VKEQGCLPED RALYYLGQAL EGLEYLHSRR ILHGDVKADN VLLSSDGSHA ALCDFGHAVC
     LQPDGLGKSL LTGDYIPGTE THMAPEVVLG RSCDAKVDVW SSCCMMLHML NGCHPWTQFF
     RGPLCLKIAS EPPPVREIPP SCAPLTAQAI QEGLRKEPIH RVSAAELGGK VNRALQQVGG
     LKSPWRGEYK EPRHPPPNQA NYHQTLHAQP RELSPRAPGP RPAEETTGRA PKLQPPLPPE
     PPEPNKSPPL TLSKEESGMW EPLPLSSLEP APARNPSSPE RKATVPEQEL QQLEIELFLN
     SLSQPFSLEE QEQILSCLSI DSLSLSDDSE KNPSKASQSS RDTLSSGVHS WSSQAEARSS
     SWNMVLARGR PTDTPSYFNG VKVQIQSLNG EHLHIREFHR VKVGDIATGI SSQIPAAAFS
     LVTKDGQPVR YDMEVPDSGI DLQCTLAPDG SFAWSWRVKH GQLENRP
//
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