ID MP2K7_HUMAN Reviewed; 419 AA. AC O14733; B2R9S5; D6W659; O14648; O14816; O60452; O60453; Q1PG43; Q8IY10; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 28-JAN-2026, entry version 226. DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 7; DE Short=MAP kinase kinase 7; DE Short=MAPKK 7; DE EC=2.7.12.2; DE AltName: Full=JNK-activating kinase 2; DE AltName: Full=MAPK/ERK kinase 7; DE Short=MEK 7; DE AltName: Full=Stress-activated protein kinase kinase 4; DE Short=SAPK kinase 4; DE Short=SAPKK-4; DE Short=SAPKK4; DE AltName: Full=c-Jun N-terminal kinase kinase 2; DE Short=JNK kinase 2; DE Short=JNKK 2; GN Name=MAP2K7; Synonyms=JNKK2, MEK7, MKK7, PRKMK7, SKK4; 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] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Heart, and Skeletal muscle; RX PubMed=9372971; DOI=10.1128/mcb.17.12.7407; RA Wu Z., Wu J., Jacinto E., Karin M.; RT "Molecular cloning and characterization of human JNKK2, a novel jun NH2- RT terminal kinase-specific kinase."; RL Mol. Cell. Biol. 17:7407-7416(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND ACTIVITY REGULATION. RX PubMed=9312068; DOI=10.1074/jbc.272.40.24751; RA Lu X., Nemoto S., Lin A.; RT "Identification of c-Jun NH2-terminal protein kinase (JNK)-activating RT kinase 2 as an activator of JNK but not p38."; RL J. Biol. Chem. 272:24751-24754(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE RP SPECIFICITY, AND VARIANT PHE-259. RC TISSUE=Fetal kidney; RX PubMed=9535930; DOI=10.1074/jbc.273.15.9344; RA Foltz I.N., Gerl R.E., Wieler J.S., Luckach M., Salmon R.A., Schrader J.W.; RT "Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly RT conserved c-Jun N-terminal kinase/stress-activated protein kinase RT (JNK/SAPK) activated by environmental stresses and physiological stimuli."; RL J. Biol. Chem. 273:9344-9351(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ACTIVITY REGULATION, AND TISSUE RP SPECIFICITY. RX PubMed=16442502; DOI=10.1016/j.bbrc.2005.12.223; RA Michael L., Swantek J., Robinson M.J.; RT "Cloning and expression of human mitogen-activated protein kinase kinase RT 7gamma1."; RL Biochem. Biophys. Res. Commun. 341:679-683(2006). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION IN PHOSPHORYLATION OF RP MAPK8/JNK1 AND MAPK9/JNK2. RA Yang J., New L., Yong J., Han J., Su B.; RT "Molecular cloning of human JNKK2 reveals a novel kinase module for c-Jun RT N-terminal kinase activation."; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Testis; 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-260 (ISOFORMS 1/4). RX PubMed=9207092; DOI=10.1073/pnas.94.14.7337; RA Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J.; RT "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun RT NH2-terminal kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 94:7337-7342(1997). RN [10] RP INTERACTION WITH MAPK8IP1/JIP1 AND MAPK8IP2/JIP2. RX PubMed=10490659; DOI=10.1128/mcb.19.10.7245; RA Yasuda J., Whitmarsh A.J., Cavanagh J., Sharma M., Davis R.J.; RT "The JIP group of mitogen-activated protein kinase scaffold proteins."; RL Mol. Cell. Biol. 19:7245-7254(1999). RN [11] RP CLEAVAGE BY ANTHRAX LETHAL FACTOR. RX PubMed=11104681; DOI=10.1042/bj3520739; RA Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.; RT "Susceptibility of mitogen-activated protein kinase kinase family members RT to proteolysis by anthrax lethal factor."; RL Biochem. J. 352:739-745(2000). RN [12] RP INTERACTION WITH MAPK8IP3/JIP3. RX PubMed=12189133; DOI=10.1074/jbc.m202004200; RA Matsuura H., Nishitoh H., Takeda K., Matsuzawa A., Amagasa T., Ito M., RA Yoshioka K., Ichijo H.; RT "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK RT signaling pathway. A new mode of regulation of the MAP kinase cascade."; RL J. Biol. Chem. 277:40703-40709(2002). RN [13] RP DOMAIN. RX PubMed=15866172; DOI=10.1016/j.molcel.2005.04.001; RA Takekawa M., Tatebayashi K., Saito H.; RT "Conserved docking site is essential for activation of mammalian MAP kinase RT kinases by specific MAP kinase kinase kinases."; RL Mol. Cell 18:295-306(2005). RN [14] RP INTERACTION WITH VRK2. RX PubMed=18286207; DOI=10.1371/journal.pone.0001660; RA Blanco S., Sanz-Garcia M., Santos C.R., Lazo P.A.; RT "Modulation of interleukin-1 transcriptional response by the interaction RT between VRK2 and the JIP1 scaffold protein."; RL PLoS ONE 3:E1660-E1660(2008). RN [15] RP REVIEW ON ACTIVITY REGULATION. RX PubMed=17496909; DOI=10.1038/sj.onc.1210392; RA Raman M., Chen W., Cobb M.H.; RT "Differential regulation and properties of MAPKs."; RL Oncogene 26:3100-3112(2007). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [17] RP REVIEW ON FUNCTION. RX PubMed=20801953; DOI=10.1093/jb/mvq098; RA Asaoka Y., Nishina H.; RT "Diverse physiological functions of MKK4 and MKK7 during early RT embryogenesis."; RL J. Biochem. 148:393-401(2010). RN [18] RP INTERACTION WITH RASSF7. RX PubMed=21278800; DOI=10.1038/cdd.2010.137; RA Takahashi S., Ebihara A., Kajiho H., Kontani K., Nishina H., Katada T.; RT "RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the RT activity of phosphorylated-MKK7."; RL Cell Death Differ. 18:645-655(2011). RN [19] RP REVIEW ON REGULATION, AND REVIEW ON FUNCTION. RX PubMed=21333379; DOI=10.1016/j.ejcb.2010.11.008; RA Haeusgen W., Herdegen T., Waetzig V.; RT "The bottleneck of JNK signaling: molecular and functional characteristics RT of MKK4 and MKK7."; RL Eur. J. Cell Biol. 90:536-544(2011). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [22] RP FUNCTION. RX PubMed=28111074; DOI=10.1016/j.cell.2016.12.044; RA Huang Y.A., Zhou B., Wernig M., Suedhof T.C.; RT "ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and RT Abeta Secretion."; RL Cell 168:427-441(2017). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 101-405. RG RIKEN structural genomics initiative (RSGI); RT "Crystal structure of human mitogen-activated protein kinase kinase 7 RT activated mutant (s287d, t291d)."; RL Submitted (FEB-2009) to the PDB data bank. RN [24] RP VARIANTS [LARGE SCALE ANALYSIS] SER-118; CYS-138; CYS-162; HIS-162 AND RP THR-195. 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: Dual specificity protein kinase which acts as an essential CC component of the MAP kinase signal transduction pathway. Essential CC component of the stress-activated protein kinase/c-Jun N-terminal CC kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the CC only known kinase to directly activate the stress-activated protein CC kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. CC MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, CC but they differ in their preference for the phosphorylation site in the CC Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of CC the Tyr residue and MAP2K7/MKK7 for the Thr residue. The CC monophosphorylation of JNKs on the Thr residue is sufficient to CC increase JNK activity indicating that MAP2K7/MKK7 is important to CC trigger JNK activity, while the additional phosphorylation of the Tyr CC residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific CC role in JNK signal transduction pathway activated by pro-inflammatory CC cytokines. The MKK/JNK signaling pathway is also involved in CC mitochondrial death signaling pathway, including the release cytochrome CC c, leading to apoptosis. Part of a non-canonical MAPK signaling CC pathway, composed of the upstream MAP3K12 kinase and downstream MAP CC kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated CC transcription of APP in response to APOE (PubMed:28111074). CC {ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:9312068, CC ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930, CC ECO:0000269|Ref.5}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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=2.7.12.2; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.2; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.12.2; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- ACTIVITY REGULATION: Activated by phosphorylation by specific MAP CC kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 CC and MAP3K12/DLK. {ECO:0000269|PubMed:16442502, CC ECO:0000269|PubMed:9312068}. CC -!- SUBUNIT: Interacts with isoform 1 of VRK2. Interacts (via its D domain) CC with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 (By CC similarity). Interacts (via its DVD domain) with MAP3Ks activators like CC MAP3K5/ASK1 and MAP3K1/MEKK1 (By similarity). Interacts with CC MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. CC Interacts with RASSF7, the interaction promotes phosphorylation. Found CC in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAPK8IP1/JIP1 and CC MAPK8/JNK1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, CC MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (By similarity). CC {ECO:0000250|UniProtKB:Q8CE90, ECO:0000269|PubMed:10490659, CC ECO:0000269|PubMed:12189133, ECO:0000269|PubMed:18286207, CC ECO:0000269|PubMed:21278800}. CC -!- INTERACTION: CC O14733; O15519-1: CFLAR; NbExp=2; IntAct=EBI-492605, EBI-4567563; CC O14733; O75293: GADD45B; NbExp=8; IntAct=EBI-492605, EBI-448187; CC O14733; P08238: HSP90AB1; NbExp=2; IntAct=EBI-492605, EBI-352572; CC O14733; Q5S007: LRRK2; NbExp=3; IntAct=EBI-492605, EBI-5323863; CC O14733; O43318: MAP3K7; NbExp=3; IntAct=EBI-492605, EBI-358684; CC O14733; Q9UQF2: MAPK8IP1; NbExp=5; IntAct=EBI-492605, EBI-78404; CC O14733; P62258: YWHAE; NbExp=2; IntAct=EBI-492605, EBI-356498; CC O14733-2; P45983: MAPK8; NbExp=3; IntAct=EBI-492627, EBI-286483; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=A; CC IsoId=O14733-1; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=O14733-2; Sequence=VSP_004883; CC Name=3; Synonyms=gamma1; CC IsoId=O14733-3; Sequence=VSP_022309; CC Name=4; CC IsoId=O14733-4; Sequence=VSP_022310; CC -!- TISSUE SPECIFICITY: Ubiquitous; with highest level of expression in CC skeletal muscle. Isoform 3 is found at low levels in placenta, fetal CC liver, and skeletal muscle. {ECO:0000269|PubMed:16442502, CC ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930}. CC -!- DOMAIN: The DVD domain (residues 377-400) contains a conserved docking CC site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD CC sites bind to their specific upstream MAP kinase kinase kinases CC (MAP3Ks) and are essential for activation. CC {ECO:0000269|PubMed:15866172}. CC -!- DOMAIN: The D domain (residues 37-57) contains a conserved docking site CC and is required for the binding to MAPK substrates. CC {ECO:0000269|PubMed:15866172}. CC -!- PTM: Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase CC kinase kinases (MAP3Ks). {ECO:0000250}. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB97813.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAB97813.1; Type=Frameshift; Evidence={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; AF014401; AAB88048.1; -; mRNA. DR EMBL; AF006689; AAB97813.1; ALT_SEQ; mRNA. DR EMBL; AF013588; AAC16272.1; -; mRNA. DR EMBL; AF013589; AAC16273.1; -; mRNA. DR EMBL; DQ445915; ABE03013.1; -; mRNA. DR EMBL; AF022805; AAC26142.1; -; mRNA. DR EMBL; AK313899; BAG36622.1; -; mRNA. DR EMBL; CH471139; EAW68964.1; -; Genomic_DNA. DR EMBL; CH471139; EAW68968.1; -; Genomic_DNA. DR EMBL; BC038295; AAH38295.1; -; mRNA. DR EMBL; AF003199; AAB63374.1; -; mRNA. DR CCDS; CCDS42491.1; -. [O14733-1] DR CCDS; CCDS74277.1; -. [O14733-3] DR CCDS; CCDS74278.1; -. [O14733-4] DR RefSeq; NP_001284484.1; NM_001297555.2. [O14733-3] DR RefSeq; NP_001284485.1; NM_001297556.2. [O14733-4] DR RefSeq; NP_660186.1; NM_145185.4. [O14733-1] DR PDB; 2DYL; X-ray; 2.45 A; A=101-405. DR PDB; 3WZU; X-ray; 3.01 A; A=103-419. DR PDB; 4UX9; X-ray; 2.34 A; F/G/H/I=37-48. DR PDB; 5B2K; X-ray; 2.75 A; A=103-419. DR PDB; 5B2L; X-ray; 2.10 A; A=103-419. DR PDB; 5B2M; X-ray; 3.06 A; A=103-419. DR PDB; 5Y8U; X-ray; 2.92 A; A=103-419. DR PDB; 5Y90; X-ray; 1.30 A; A=103-419. DR PDB; 5Z1D; X-ray; 2.28 A; A=102-419. DR PDB; 5Z1E; X-ray; 2.30 A; A=102-419. DR PDB; 6IB0; X-ray; 2.60 A; A=101-408. DR PDB; 6IB2; X-ray; 2.10 A; A=101-408. DR PDB; 6QFL; X-ray; 2.20 A; A=101-408. DR PDB; 6QFR; X-ray; 2.30 A; A=101-408. DR PDB; 6QFT; X-ray; 2.70 A; A=101-408. DR PDB; 6QG4; X-ray; 2.30 A; A=111-408. DR PDB; 6QG7; X-ray; 2.10 A; A=101-408. DR PDB; 6QHO; X-ray; 2.70 A; A=111-408. DR PDB; 6QHR; X-ray; 2.52 A; A=111-408. DR PDB; 6YFZ; X-ray; 1.90 A; A=100-405. DR PDB; 6YG0; X-ray; 2.00 A; A=100-405. DR PDB; 6YG1; X-ray; 2.22 A; A/B/C=60-405. DR PDB; 6YG2; X-ray; 2.00 A; A=100-405. DR PDB; 6YG3; X-ray; 2.05 A; A=100-405. DR PDB; 6YG4; X-ray; 2.30 A; A=100-405. DR PDB; 6YG5; X-ray; 2.40 A; A=100-405. DR PDB; 6YG6; X-ray; 2.15 A; A/B=100-405. DR PDB; 6YG7; X-ray; 2.20 A; A/B=100-405. DR PDB; 6YZ4; X-ray; 1.70 A; A=100-405. DR PDB; 7CBX; X-ray; 2.06 A; A=103-419. DR PDB; 7OVI; X-ray; 1.95 A; A=101-408. DR PDB; 7OVJ; X-ray; 2.35 A; A=101-408. DR PDB; 7OVK; X-ray; 2.05 A; A=101-408. DR PDB; 7OVL; X-ray; 2.90 A; A=101-408. DR PDB; 7OVM; X-ray; 2.90 A; A=101-408. DR PDB; 7OVN; X-ray; 2.90 A; A=101-408. DR PDB; 9HZ0; X-ray; 2.25 A; A=101-408. DR PDBsum; 2DYL; -. DR PDBsum; 3WZU; -. DR PDBsum; 4UX9; -. DR PDBsum; 5B2K; -. DR PDBsum; 5B2L; -. DR PDBsum; 5B2M; -. DR PDBsum; 5Y8U; -. DR PDBsum; 5Y90; -. DR PDBsum; 5Z1D; -. DR PDBsum; 5Z1E; -. DR PDBsum; 6IB0; -. DR PDBsum; 6IB2; -. DR PDBsum; 6QFL; -. DR PDBsum; 6QFR; -. DR PDBsum; 6QFT; -. DR PDBsum; 6QG4; -. DR PDBsum; 6QG7; -. DR PDBsum; 6QHO; -. DR PDBsum; 6QHR; -. DR PDBsum; 6YFZ; -. DR PDBsum; 6YG0; -. DR PDBsum; 6YG1; -. DR PDBsum; 6YG2; -. DR PDBsum; 6YG3; -. DR PDBsum; 6YG4; -. DR PDBsum; 6YG5; -. DR PDBsum; 6YG6; -. DR PDBsum; 6YG7; -. DR PDBsum; 6YZ4; -. DR PDBsum; 7CBX; -. DR PDBsum; 7OVI; -. DR PDBsum; 7OVJ; -. DR PDBsum; 7OVK; -. DR PDBsum; 7OVL; -. DR PDBsum; 7OVM; -. DR PDBsum; 7OVN; -. DR PDBsum; 9HZ0; -. DR AlphaFoldDB; O14733; -. DR SMR; O14733; -. DR BioGRID; 111595; 203. DR FunCoup; O14733; 4166. DR IntAct; O14733; 149. DR MINT; O14733; -. DR STRING; 9606.ENSP00000381070; -. DR BindingDB; O14733; -. DR ChEMBL; CHEMBL3530; -. DR DrugBank; DB14904; Pimasertib. DR DrugCentral; O14733; -. DR GuidetoPHARMACOLOGY; 2068; -. DR iPTMnet; O14733; -. DR MetOSite; O14733; -. DR PhosphoSitePlus; O14733; -. DR BioMuta; MAP2K7; -. DR CPTAC; CPTAC-3079; -. DR CPTAC; CPTAC-3080; -. DR CPTAC; CPTAC-822; -. DR CPTAC; CPTAC-823; -. DR jPOST; O14733; -. DR MassIVE; O14733; -. DR PaxDb; 9606-ENSP00000381070; -. DR PeptideAtlas; O14733; -. DR ProteomicsDB; 48192; -. [O14733-1] DR ProteomicsDB; 48193; -. [O14733-2] DR ProteomicsDB; 48194; -. [O14733-3] DR ProteomicsDB; 48195; -. [O14733-4] DR Pumba; O14733; -. DR Antibodypedia; 1176; 769 antibodies from 43 providers. DR DNASU; 5609; -. DR Ensembl; ENST00000397979.4; ENSP00000381066.3; ENSG00000076984.19. [O14733-1] DR Ensembl; ENST00000397981.7; ENSP00000381068.3; ENSG00000076984.19. [O14733-4] DR Ensembl; ENST00000397983.7; ENSP00000381070.2; ENSG00000076984.19. [O14733-3] DR GeneID; 5609; -. DR KEGG; hsa:5609; -. DR MANE-Select; ENST00000397979.4; ENSP00000381066.3; NM_145185.4; NP_660186.1. DR UCSC; uc002mit.4; human. [O14733-1] DR AGR; HGNC:6847; -. DR CIViC; 5609; 1 evidence item across 1 molecular profile. DR ClinPGx; PA284; -. DR CTD; 5609; -. DR DisGeNET; 5609; -. DR GeneCards; MAP2K7; -. DR HGNC; HGNC:6847; MAP2K7. DR HPA; ENSG00000076984; Low tissue specificity. DR MIM; 603014; gene. DR OpenTargets; ENSG00000076984; -. DR VEuPathDB; HostDB:ENSG00000076984; -. DR eggNOG; KOG0983; Eukaryota. DR GeneTree; ENSGT00940000158914; -. DR HOGENOM; CLU_000288_63_23_1; -. DR InParanoid; O14733; -. DR OMA; NVWICME; -. DR OrthoDB; 10252354at2759; -. DR PAN-GO; O14733; 2 GO annotations based on evolutionary models. DR PhylomeDB; O14733; -. DR BRENDA; 2.7.12.2; 2681. DR PathwayCommons; O14733; -. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins. DR SignaLink; O14733; -. DR SIGNOR; O14733; -. DR Agora; ENSG00000076984; -. DR BioGRID-ORCS; 5609; 92 hits in 1195 CRISPR screens. DR ChiTaRS; MAP2K7; human. DR EvolutionaryTrace; O14733; -. DR GeneWiki; MAP2K7; -. DR GenomeRNAi; 5609; -. DR Pharos; O14733; Tchem. DR PRO; PR:O14733; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O14733; protein. DR Bgee; ENSG00000076984; Expressed in buccal mucosa cell and 189 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0008545; F:JUN kinase kinase activity; ISS:ARUK-UCL. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0004707; F:MAP kinase activity; IEA:Ensembl. DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:UniProtKB. DR GO; GO:0140677; F:molecular function activator activity; EXP:DisProt. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; ISS:BHF-UCL. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0090398; P:cellular senescence; TAS:Reactome. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0007254; P:JNK cascade; ISS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0032206; P:positive regulation of telomere maintenance; IMP:BHF-UCL. DR GO; GO:2000671; P:regulation of motor neuron apoptotic process; IEA:Ensembl. DR GO; GO:0009408; P:response to heat; IDA:UniProtKB. DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:UniProtKB. DR GO; GO:0009411; P:response to UV; IDA:UniProtKB. DR GO; GO:0009611; P:response to wounding; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB. DR CDD; cd06618; PKc_MKK7; 1. DR DisProt; DP00841; -. DR FunFam; 3.30.200.20:FF:000040; Dual specificity mitogen-activated protein kinase kinase; 1. DR FunFam; 1.10.510.10:FF:000214; Dual specificity mitogen-activated protein kinase kinase 7; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR052468; Dual_spec_MAPK_kinase. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR47238:SF2; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE HEMIPTEROUS; 1. DR PANTHER; PTHR47238; MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; KW Coiled coil; Cytoplasm; Kinase; Magnesium; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; KW Reference proteome; Serine/threonine-protein kinase; Stress response; KW Transferase; Tyrosine-protein kinase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..419 FT /note="Dual specificity mitogen-activated protein kinase FT kinase 7" FT /id="PRO_0000086388" FT DOMAIN 120..380 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 18..76 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 37..57 FT /note="D domain" FT /evidence="ECO:0000250" FT REGION 377..400 FT /note="DVD domain" FT COILED 2..30 FT /evidence="ECO:0000255" FT COMPBIAS 18..30 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 36..63 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 243 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 126..134 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 149 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 44..45 FT /note="Cleavage; by anthrax lethal factor" FT SITE 76..77 FT /note="Cleavage; by anthrax lethal factor" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT MOD_RES 271 FT /note="Phosphoserine; by MAP3K" FT /evidence="ECO:0000250" FT MOD_RES 275 FT /note="Phosphothreonine; by MAP3K" FT /evidence="ECO:0000250" FT MOD_RES 411 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 42 FT /note="T -> IIVITLSPAPAPSQRAA (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16442502" FT /id="VSP_022309" FT VAR_SEQ 111 FT /note="Q -> QVPPSLWRGEGGGPARLDPSWERQWGAGGGGRAPGTLQPSLSSQ FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9535930" FT /id="VSP_004883" FT VAR_SEQ 312 FT /note="L -> LPCPSPSQ (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_022310" FT VARIANT 118 FT /note="N -> S (in dbSNP:rs56316660)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040825" FT VARIANT 138 FT /note="R -> C (in dbSNP:rs56106612)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040826" FT VARIANT 162 FT /note="R -> C (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs1982759144)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040827" FT VARIANT 162 FT /note="R -> H (in a colorectal adenocarcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040828" FT VARIANT 195 FT /note="A -> T (in dbSNP:rs55800262)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040829" FT VARIANT 259 FT /note="L -> F (in dbSNP:rs1053566)" FT /evidence="ECO:0000269|PubMed:9535930" FT /id="VAR_029890" FT CONFLICT 94 FT /note="Q -> H (in Ref. 2; AAB97813)" FT /evidence="ECO:0000305" FT CONFLICT 106 FT /note="L -> P (in Ref. 4; ABE03013)" FT /evidence="ECO:0000305" FT CONFLICT 133 FT /note="Q -> P (in Ref. 2; AAB97813)" FT /evidence="ECO:0000305" FT CONFLICT 142 FT /note="T -> N (in Ref. 1; AAB88048)" FT /evidence="ECO:0000305" FT CONFLICT 407 FT /note="S -> N (in Ref. 2; AAB97813)" FT /evidence="ECO:0000305" FT CONFLICT 415 FT /note="L -> LG (in Ref. 2; AAB97813)" FT /evidence="ECO:0000305" FT HELIX 87..100 FT /evidence="ECO:0007829|PDB:6YG1" FT STRAND 104..108 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 111..115 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 117..119 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 120..126 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 129..138 FT /evidence="ECO:0007829|PDB:5Y90" FT TURN 140..142 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 145..152 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 157..171 FT /evidence="ECO:0007829|PDB:5Y90" FT TURN 172..175 FT /evidence="ECO:0007829|PDB:6YFZ" FT STRAND 182..187 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 189..196 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 200..202 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 203..210 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 216..237 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 246..248 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 257..259 FT /evidence="ECO:0007829|PDB:5Y90" FT TURN 262..265 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 281..283 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 286..289 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:6YZ4" FT HELIX 302..317 FT /evidence="ECO:0007829|PDB:5Y90" FT TURN 321..324 FT /evidence="ECO:0007829|PDB:6YZ4" FT HELIX 328..337 FT /evidence="ECO:0007829|PDB:5Y90" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 351..360 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 365..367 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 371..374 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 378..385 FT /evidence="ECO:0007829|PDB:5Y90" FT HELIX 390..401 FT /evidence="ECO:0007829|PDB:5Y90" SQ SEQUENCE 419 AA; 47485 MW; F1B22E050F54299A CRC64; MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES SPQHPTPPAR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QRYQAEINDL ENLGEMGSGT CGQVWKMRFR KTGHVIAVKQ MRRSGNKEEN KRILMDLDVV LKSHDCPYIV QCFGTFITNT DVFIAMELMG TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI HRDVKPSNIL LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD IRADVWSLGI SLVELATGQF PYKNCKTDFE VLTKVLQEEP PLLPGHMGFS GDFQSFVKDC LTKDHRKRPK YNKLLEHSFI KRYETLEVDV ASWFKDVMAK TESPRTSGVL SQPHLPFFR //