MP2K7_HUMAN
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 03-AUG-2022, entry version 209.
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=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=2.7.12.2;
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=2.7.12.2;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, 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 O14733-2; 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};
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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_001297555.1. [O14733-3]
DR RefSeq; NP_001284485.1; NM_001297556.1. [O14733-4]
DR RefSeq; NP_660186.1; NM_145185.3. [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 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 AlphaFoldDB; O14733; -.
DR SMR; O14733; -.
DR BioGRID; 111595; 113.
DR IntAct; O14733; 111.
DR MINT; O14733; -.
DR STRING; 9606.ENSP00000381070; -.
DR BindingDB; O14733; -.
DR ChEMBL; CHEMBL3530; -.
DR DrugCentral; O14733; -.
DR GuidetoPHARMACOLOGY; 2068; -.
DR iPTMnet; O14733; -.
DR MetOSite; O14733; -.
DR PhosphoSitePlus; O14733; -.
DR BioMuta; MAP2K7; -.
DR CPTAC; CPTAC-822; -.
DR CPTAC; CPTAC-823; -.
DR EPD; O14733; -.
DR jPOST; O14733; -.
DR MassIVE; O14733; -.
DR MaxQB; O14733; -.
DR PaxDb; O14733; -.
DR PeptideAtlas; O14733; -.
DR PRIDE; O14733; -.
DR ProteomicsDB; 48192; -. [O14733-1]
DR ProteomicsDB; 48193; -. [O14733-2]
DR ProteomicsDB; 48194; -. [O14733-3]
DR ProteomicsDB; 48195; -. [O14733-4]
DR Antibodypedia; 1176; 773 antibodies from 42 providers.
DR DNASU; 5609; -.
DR Ensembl; ENST00000397979.4; ENSP00000381066.3; ENSG00000076984.18. [O14733-1]
DR Ensembl; ENST00000397981.7; ENSP00000381068.3; ENSG00000076984.18. [O14733-4]
DR Ensembl; ENST00000397983.7; ENSP00000381070.2; ENSG00000076984.18. [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 CTD; 5609; -.
DR DisGeNET; 5609; -.
DR GeneCards; MAP2K7; -.
DR HGNC; HGNC:6847; MAP2K7.
DR HPA; ENSG00000076984; Low tissue specificity.
DR MIM; 603014; gene.
DR neXtProt; NX_O14733; -.
DR OpenTargets; ENSG00000076984; -.
DR PharmGKB; PA284; -.
DR VEuPathDB; HostDB:ENSG00000076984; -.
DR eggNOG; KOG0983; Eukaryota.
DR GeneTree; ENSGT00940000158914; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; O14733; -.
DR OMA; CFGYFIT; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; O14733; -.
DR TreeFam; TF350701; -.
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 BioGRID-ORCS; 5609; 78 hits in 1116 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 187 other tissues.
DR Genevisible; O14733; HS.
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:0031435; F:mitogen-activated protein kinase kinase kinase binding; IEA:Ensembl.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
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:0072709; P:cellular response to sorbitol; 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:0000165; P:MAPK cascade; IBA:GO_Central.
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:0043507; P:positive regulation of JUN kinase activity; ISS:BHF-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL.
DR GO; GO:1904355; P:positive regulation of telomere capping; IMP:BHF-UCL.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
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 DisProt; DP00841; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
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 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Coiled coil; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW 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..33
FT /note="Basic and acidic residues"
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)"
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
