M3K14_HUMAN
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 03-AUG-2022, entry version 209.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 14 {ECO:0000312|HGNC:HGNC:6853};
DE EC=2.7.11.25;
DE AltName: Full=NF-kappa-beta-inducing kinase {ECO:0000303|PubMed:12853971};
DE Short=HsNIK {ECO:0000312|HGNC:HGNC:6853};
DE AltName: Full=Serine/threonine-protein kinase NIK {ECO:0000303|PubMed:15951441};
GN Name=MAP3K14 {ECO:0000312|HGNC:HGNC:6853};
GN Synonyms=NIK {ECO:0000303|PubMed:12853971};
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). Interacts (via C-terminus and kinase domain)
CC with PPPC3A (via N-terminus) and PPP3CB (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9WUL6, 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=6; IntAct=EBI-358011, EBI-295634;
CC Q99558; O15111: CHUK; NbExp=12; IntAct=EBI-358011, EBI-81249;
CC Q99558; P01112: HRAS; NbExp=3; IntAct=EBI-358011, EBI-350145;
CC Q99558; P07900: HSP90AA1; NbExp=5; IntAct=EBI-358011, EBI-296047;
CC Q99558; P08238: HSP90AB1; NbExp=5; IntAct=EBI-358011, EBI-352572;
CC Q99558; O14920: IKBKB; NbExp=6; IntAct=EBI-358011, EBI-81266;
CC Q99558; Q9Y6K9: IKBKG; NbExp=4; 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=8; 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 AlphaFoldDB; Q99558; -.
DR SMR; Q99558; -.
DR BioGRID; 114487; 152.
DR CORUM; Q99558; -.
DR DIP; DIP-27522N; -.
DR IntAct; Q99558; 150.
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; 354 antibodies from 41 providers.
DR DNASU; 9020; -.
DR Ensembl; ENST00000344686.8; ENSP00000478552.1; ENSG00000006062.18.
DR Ensembl; ENST00000376926.8; ENSP00000482657.1; ENSG00000006062.18.
DR Ensembl; ENST00000617331.3; ENSP00000480974.3; ENSG00000006062.18.
DR GeneID; 9020; -.
DR KEGG; hsa:9020; -.
DR MANE-Select; ENST00000344686.8; ENSP00000478552.1; NM_003954.5; NP_003945.2.
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; -.
DR eggNOG; KOG0198; Eukaryota.
DR GeneTree; ENSGT00940000156497; -.
DR HOGENOM; CLU_010641_1_0_1; -.
DR InParanoid; Q99558; -.
DR OMA; HRMKDKQ; -.
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; 7 hits in 246 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 granulocyte and 108 other tissues.
DR ExpressionAtlas; Q99558; baseline and differential.
DR Genevisible; Q99558; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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; IBA:GO_Central.
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: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:0000165; P:MAPK cascade; IBA:GO_Central.
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:0006468; P:protein phosphorylation; IBA:GO_Central.
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 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 406..414
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 429
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
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
