M3K13_HUMAN
ID M3K13_HUMAN Reviewed; 966 AA.
AC O43283; B2R6U2; B4DLE3; B4DMV2; B4DZJ4; D3DNU1; Q05BY6; Q15450; Q2NKN3;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 13;
DE EC=2.7.11.25;
DE AltName: Full=Leucine zipper-bearing kinase;
DE AltName: Full=Mixed lineage kinase;
DE Short=MLK;
GN Name=MAP3K13 {ECO:0000312|HGNC:HGNC:6852};
GN Synonyms=LZK {ECO:0000312|EMBL:BAA24817.1};
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] {ECO:0000305, ECO:0000312|EMBL:BAA24817.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP AUTOPHOSPHORYLATION.
RC TISSUE=Cerebellum {ECO:0000269|PubMed:9353328};
RX PubMed=9353328; DOI=10.1074/jbc.272.45.28622;
RA Sakuma H., Ikeda A., Oka S., Kozutsumi Y., Zanetta J., Kawasaki T.;
RT "Molecular cloning and functional expression of a cDNA encoding a new
RT member of mixed lineage protein kinase from human brain.";
RL J. Biol. Chem. 272:28622-28629(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Brain, Testis, and Tongue;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
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] (ISOFORMS 2 AND 5).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 230-340 (ISOFORM 1).
RX PubMed=8274451;
RA Schultz S.J., Nigg E.A.;
RT "Identification of 21 novel human protein kinases, including 3 members of a
RT family related to the cell cycle regulator nimA of Aspergillus nidulans.";
RL Cell Growth Differ. 4:821-830(1993).
RN [7] {ECO:0000305}
RP HOMODIMERIZATION.
RX PubMed=11163770; DOI=10.1016/s0014-5793(00)02432-7;
RA Ikeda A., Masaki M., Kozutsumi Y., Oka S., Kawasaki T.;
RT "Identification and characterization of functional domains in a mixed
RT lineage kinase LZK.";
RL FEBS Lett. 488:190-195(2001).
RN [8] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH MAPK8IP1.
RX PubMed=11726277; DOI=10.1093/oxfordjournals.jbchem.a003048;
RA Ikeda A., Hasegawa K., Masaki M., Moriguchi T., Nishida E., Kozutsumi Y.,
RA Oka S., Kawasaki T.;
RT "Mixed lineage kinase LZK forms a functional signaling complex with JIP-1,
RT a scaffold protein of the c-Jun NH(2)-terminal kinase pathway.";
RL J. Biochem. 130:773-781(2001).
RN [9] {ECO:0000305}
RP FUNCTION, INTERACTION WITH PRDX3, AND MUTAGENESIS OF LYS-195.
RX PubMed=12492477; DOI=10.1046/j.1432-1033.2003.03363.x;
RA Masaki M., Ikeda A., Shiraki E., Oka S., Kawasaki T.;
RT "Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB
RT synergistically.";
RL Eur. J. Biochem. 270:76-83(2003).
RN [10]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-517; LYS-712 AND LEU-746.
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).
CC -!- FUNCTION: Activates the JUN N-terminal pathway through activation of
CC the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to
CC regulate the activation of NF-kappa-B in the cytosol. This activation
CC is kinase-dependent and involves activating the IKK complex, the IKBKB-
CC containing complex that phosphorylates inhibitors of NF-kappa-B.
CC {ECO:0000269|PubMed:11726277, ECO:0000269|PubMed:12492477,
CC ECO:0000269|PubMed:9353328}.
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 Evidence={ECO:0000269|PubMed:9353328};
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; Evidence={ECO:0000269|PubMed:9353328};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q60700};
CC -!- ACTIVITY REGULATION: Activated by autophosphorylation and
CC homodimerization. {ECO:0000269|PubMed:11163770,
CC ECO:0000269|PubMed:9353328}.
CC -!- SUBUNIT: Homodimer; forms dimers through the leucine-zipper motif.
CC Interacts with the C-terminus of MAPK8IP1 through the kinase catalytic
CC domain. Binds PRDX3. Associates with the IKK complex through the kinase
CC domain. {ECO:0000269|PubMed:11163770, ECO:0000269|PubMed:11726277,
CC ECO:0000269|PubMed:12492477}.
CC -!- INTERACTION:
CC O43283; O43283: MAP3K13; NbExp=2; IntAct=EBI-1168480, EBI-1168480;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9353328}. Membrane
CC {ECO:0000269|PubMed:9353328}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9353328}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O43283-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43283-3; Sequence=VSP_036567, VSP_036568;
CC Name=3;
CC IsoId=O43283-4; Sequence=VSP_036563, VSP_036566;
CC Name=4;
CC IsoId=O43283-5; Sequence=VSP_036562, VSP_036569;
CC Name=5;
CC IsoId=O43283-6; Sequence=VSP_036564, VSP_036565;
CC -!- TISSUE SPECIFICITY: Expressed in the adult brain, liver, placenta and
CC pancreas, with expression strongest in the pancreas.
CC {ECO:0000269|PubMed:9353328}.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC {ECO:0000269|PubMed:9353328}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI11727.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=BAG59505.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB001872; BAA24817.1; -; mRNA.
DR EMBL; AK296961; BAG59505.1; ALT_SEQ; mRNA.
DR EMBL; AK297646; BAG60014.1; -; mRNA.
DR EMBL; AK302951; BAG64106.1; -; mRNA.
DR EMBL; AK312714; BAG35589.1; -; mRNA.
DR EMBL; AC099661; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC128680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78224.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78225.1; -; Genomic_DNA.
DR EMBL; BC031677; AAH31677.1; -; mRNA.
DR EMBL; BC111726; AAI11727.1; ALT_SEQ; mRNA.
DR EMBL; Z25428; CAA80915.1; -; mRNA.
DR CCDS; CCDS3270.1; -. [O43283-1]
DR CCDS; CCDS56298.1; -. [O43283-5]
DR PIR; I38218; I38218.
DR RefSeq; NP_001229243.1; NM_001242314.1. [O43283-1]
DR RefSeq; NP_001229246.1; NM_001242317.1. [O43283-5]
DR RefSeq; NP_004712.1; NM_004721.4. [O43283-1]
DR RefSeq; XP_011511612.1; XM_011513310.2. [O43283-1]
DR RefSeq; XP_016862945.1; XM_017007456.1. [O43283-1]
DR AlphaFoldDB; O43283; -.
DR SMR; O43283; -.
DR BioGRID; 114614; 20.
DR IntAct; O43283; 27.
DR STRING; 9606.ENSP00000265026; -.
DR BindingDB; O43283; -.
DR ChEMBL; CHEMBL1163124; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O43283; -.
DR GuidetoPHARMACOLOGY; 2073; -.
DR GlyGen; O43283; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43283; -.
DR PhosphoSitePlus; O43283; -.
DR BioMuta; MAP3K13; -.
DR jPOST; O43283; -.
DR MassIVE; O43283; -.
DR PaxDb; O43283; -.
DR PeptideAtlas; O43283; -.
DR PRIDE; O43283; -.
DR ProteomicsDB; 48852; -. [O43283-1]
DR ProteomicsDB; 48853; -. [O43283-3]
DR ProteomicsDB; 48854; -. [O43283-4]
DR ProteomicsDB; 48855; -. [O43283-5]
DR ProteomicsDB; 48856; -. [O43283-6]
DR Antibodypedia; 33834; 306 antibodies from 27 providers.
DR DNASU; 9175; -.
DR Ensembl; ENST00000265026.8; ENSP00000265026.3; ENSG00000073803.14. [O43283-1]
DR Ensembl; ENST00000424227.5; ENSP00000399910.1; ENSG00000073803.14. [O43283-1]
DR Ensembl; ENST00000433092.5; ENSP00000389798.1; ENSG00000073803.14. [O43283-6]
DR Ensembl; ENST00000438053.5; ENSP00000403561.1; ENSG00000073803.14. [O43283-3]
DR Ensembl; ENST00000443863.5; ENSP00000409325.1; ENSG00000073803.14. [O43283-4]
DR Ensembl; ENST00000446828.5; ENSP00000411483.1; ENSG00000073803.14. [O43283-5]
DR GeneID; 9175; -.
DR KEGG; hsa:9175; -.
DR MANE-Select; ENST00000265026.8; ENSP00000265026.3; NM_004721.5; NP_004712.1.
DR UCSC; uc003fph.5; human. [O43283-1]
DR CTD; 9175; -.
DR DisGeNET; 9175; -.
DR GeneCards; MAP3K13; -.
DR HGNC; HGNC:6852; MAP3K13.
DR HPA; ENSG00000073803; Low tissue specificity.
DR MIM; 604915; gene.
DR neXtProt; NX_O43283; -.
DR OpenTargets; ENSG00000073803; -.
DR PharmGKB; PA30596; -.
DR VEuPathDB; HostDB:ENSG00000073803; -.
DR eggNOG; KOG4721; Eukaryota.
DR GeneTree; ENSGT00940000158216; -.
DR HOGENOM; CLU_1869795_0_0_1; -.
DR InParanoid; O43283; -.
DR OMA; KYPGTCK; -.
DR OrthoDB; 938929at2759; -.
DR PhylomeDB; O43283; -.
DR TreeFam; TF105119; -.
DR PathwayCommons; O43283; -.
DR SignaLink; O43283; -.
DR SIGNOR; O43283; -.
DR BioGRID-ORCS; 9175; 14 hits in 1106 CRISPR screens.
DR ChiTaRS; MAP3K13; human.
DR GeneWiki; MAP3K13; -.
DR GenomeRNAi; 9175; -.
DR Pharos; O43283; Tchem.
DR PRO; PR:O43283; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O43283; protein.
DR Bgee; ENSG00000073803; Expressed in corpus epididymis and 199 other tissues.
DR ExpressionAtlas; O43283; baseline and differential.
DR Genevisible; O43283; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0106137; F:IkappaB kinase complex binding; IDA:UniProtKB.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:ARUK-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0045773; P:positive regulation of axon extension; ISS:ARUK-UCL.
DR GO; GO:1905492; P:positive regulation of branching morphogenesis of a nerve; ISS:ARUK-UCL.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:ARUK-UCL.
DR GO; GO:0014042; P:positive regulation of neuron maturation; ISS:ARUK-UCL.
DR GO; GO:0150012; P:positive regulation of neuron projection arborization; ISS:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017419; MAP3K12_MAP3K13.
DR InterPro; IPR027258; MAPKKK13.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF038165; MAPKKK12_MAPKKK13; 1.
DR PIRSF; PIRSF500742; MAPKKK13; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..966
FT /note="Mitogen-activated protein kinase kinase kinase 13"
FT /id="PRO_0000086264"
FT DOMAIN 168..409
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 30..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 433..454
FT /note="Leucine-zipper 1"
FT REGION 486..507
FT /note="Leucine-zipper 2"
FT REGION 534..599
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 611..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 744..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 815..828
FT /note="Acidic"
FT /evidence="ECO:0000305"
FT REGION 846..908
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 560..582
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 846..863
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 864..887
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 279
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q12852,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 174..182
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q12852,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 195
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q60700,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..207
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036562"
FT VAR_SEQ 1..144
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036563"
FT VAR_SEQ 122..128
FT /note="RSGSGSG -> RYLGSAI (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036564"
FT VAR_SEQ 129..966
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036565"
FT VAR_SEQ 145..159
FT /note="IGKAYSTDYKLQQQD -> MSYVECKCLQLENKN (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036566"
FT VAR_SEQ 159..160
FT /note="DT -> VF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036567"
FT VAR_SEQ 161..966
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036568"
FT VAR_SEQ 208..220
FT /note="LRKLKHPNIIAFK -> MYCGIQILALWER (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036569"
FT VARIANT 44
FT /note="E -> K (in dbSNP:rs35266179)"
FT /id="VAR_051640"
FT VARIANT 517
FT /note="R -> G (in dbSNP:rs56408536)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040708"
FT VARIANT 712
FT /note="E -> K (in dbSNP:rs56309231)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040709"
FT VARIANT 746
FT /note="P -> L (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040710"
FT VARIANT 915
FT /note="R -> H (in dbSNP:rs3732576)"
FT /id="VAR_030577"
FT MUTAGEN 195
FT /note="K->A: Kinase inactive. Fails to activate NF-kappa-
FT B."
FT /evidence="ECO:0000269|PubMed:12492477"
FT CONFLICT 106
FT /note="D -> G (in Ref. 2; BAG59505)"
FT /evidence="ECO:0000305"
FT CONFLICT 230..232
FT /note="CII -> YLY (in Ref. 6; CAA80915)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="N -> D (in Ref. 2; BAG59505)"
FT /evidence="ECO:0000305"
FT CONFLICT 339..340
FT /note="FG -> MV (in Ref. 6; CAA80915)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="E -> G (in Ref. 2; BAG64106)"
FT /evidence="ECO:0000305"
FT CONFLICT 821
FT /note="G -> R (in Ref. 2; BAG60014)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 966 AA; 108296 MW; 9687F38C8AB20AB1 CRC64;
MANFQEHLSC SSSPHLPFSE SKTFNGLQDE LTAMGNHPSP KLLEDQQEKG MVRTELIESV
HSPVTTTVLT SVSEDSRDQF ENSVLQLREH DESETAVSQG NSNTVDGEST SGTEDIKIQF
SRSGSGSGGF LEGLFGCLRP VWNIIGKAYS TDYKLQQQDT WEVPFEEISE LQWLGSGAQG
AVFLGKFRAE EVAIKKVREQ NETDIKHLRK LKHPNIIAFK GVCTQAPCYC IIMEYCAHGQ
LYEVLRAGRK ITPRLLVDWS TGIASGMNYL HLHKIIHRDL KSPNVLVTHT DAVKISDFGT
SKELSDKSTK MSFAGTVAWM APEVIRNEPV SEKVDIWSFG VVLWELLTGE IPYKDVDSSA
IIWGVGSNSL HLPVPSTCPD GFKILMKQTW QSKPRNRPSF RQTLMHLDIA SADVLATPQE
TYFKSQAEWR EEVKKHFEKI KSEGTCIHRL DEELIRRRRE ELRHALDIRE HYERKLERAN
NLYMELSAIM LQLEMREKEL IKREQAVEKK YPGTYKRHPV RPIIHPNAME KLMKRKGVPH
KSGMQTKRPD LLRSEGIPTT EVAPTASPLS GSPKMSTSSS KSRYRSKPRH RRGNSRGSHS
DFAAILKNQP AQENSPHPTY LHQAQSQYPS LHHHNSLQQQ YQQPPPAMSQ SHHPRLNMHG
QDIATCANNL RYFGPAAALR SPLSNHAQRQ LPGSSPDLIS TAMAADCWRS SEPDKGQAGP
WGCCQADAYD PCLQCRPEQY GSLDIPSAEP VGRSPDLSKS PAHNPLLENA QSSEKTEENE
FSGCRSESSL GTSHLGTPPA LPRKTRPLQK SGDDSSEEEE GEVDSEVEFP RRQRPHRCIS
SCQSYSTFSS ENFSVSDGEE GNTSDHSNSP DELADKLEDR LAEKLDDLLS QTPEIPIDIS
SHSDGLSDKE CAVRRVKTQM SLGKLCVEER GYENPMQFEE SDCDSSDGEC SDATVRTNKH
YSSATW
