ID MP2K5_HUMAN Reviewed; 448 AA. AC Q13163; B4DE43; Q92961; Q92962; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2006, sequence version 2. DT 27-MAR-2024, entry version 220. DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 5; DE Short=MAP kinase kinase 5; DE Short=MAPKK 5; DE EC=2.7.12.2; DE AltName: Full=MAPK/ERK kinase 5; DE Short=MEK 5; GN Name=MAP2K5; Synonyms=MEK5, MKK5, PRKMK5; 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 A), FUNCTION, INTERACTION WITH ERK5 AND RP MAPK7, MUTAGENESIS OF LYS-195; SER-311 AND THR-315, AND PHOSPHORYLATION AT RP SER-311 AND THR-315. RC TISSUE=Fetal brain; RX PubMed=7759517; DOI=10.1074/jbc.270.21.12665; RA Zhou G., Bao Z.Q., Dixon J.E.; RT "Components of a new human protein kinase signal transduction pathway."; RL J. Biol. Chem. 270:12665-12669(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), AND FUNCTION. RC TISSUE=Placenta; RX PubMed=9384584; DOI=10.1093/emboj/16.23.7054; RA Kato Y., Kravchenko V.V., Tapping R.I., Han J., Ulevitch R.J., Lee J.-D.; RT "BMK1/ERK5 regulates serum-induced early gene expression through RT transcription factor MEF2C."; RL EMBO J. 16:7054-7066(1997). RN [3] RP SEQUENCE REVISION TO C-TERMINUS OF ISOFORM C. RA Lee J.D.; RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Cerebellum; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). 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 [9] RP INTERACTION WITH YOPJ (MICROBIAL INFECTION), AND ACETYLATION. RX PubMed=16728640; DOI=10.1126/science.1126867; RA Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., RA Orth K.; RT "Yersinia YopJ acetylates and inhibits kinase activation by blocking RT phosphorylation."; RL Science 312:1211-1214(2006). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 4-108 IN COMPLEX WITH MAP3K2. RG Structural genomics consortium (SGC); RT "Crystal structure of the complex of human mitogen activated protein kinase RT kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated protein RT kinase kinase kinase 3 (MAP3K2B-Phox)."; RL Submitted (NOV-2006) to the PDB data bank. RN [13] RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 4-108 IN COMPLEX WITH MAP3K3. RG Structural genomics consortium (SGC); RT "Crystal structure of the complex of human mitogen activated protein kinase RT kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated protein RT kinase kinase kinase 3 (MAP3K3B-Phox)."; RL Submitted (NOV-2006) to the PDB data bank. RN [14] RP VARIANTS [LARGE SCALE ANALYSIS] ARG-118; VAL-427 AND THR-428. 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: Acts as a scaffold for the formation of a ternary CC MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this CC pathway appears to play a critical role in protecting cells from CC stress-induced apoptosis, neuronal survival and cardiac development and CC angiogenesis. As part of the MAPK/ERK signaling pathway, acts as a CC negative regulator of apoptosis in cardiomyocytes via promotion of CC STUB1/CHIP-mediated ubiquitination and degradation of ICER-type CC isoforms of CREM (By similarity). {ECO:0000250|UniProtKB:Q62862, CC ECO:0000269|PubMed:7759517, ECO:0000269|PubMed:9384584}. 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 -!- SUBUNIT: Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with CC SQSTM1 and PRKCZ or PRKCI (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:7759517, ECO:0000269|Ref.12, ECO:0000269|Ref.13}. CC -!- SUBUNIT: (Microbial infection) Interacts with Yersinia YopJ. CC {ECO:0000269|PubMed:16728640}. CC -!- INTERACTION: CC Q13163; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-307294, EBI-18036948; CC Q13163; Q9H596: DUSP21; NbExp=3; IntAct=EBI-307294, EBI-7357329; CC Q13163; P62993: GRB2; NbExp=2; IntAct=EBI-307294, EBI-401755; CC Q13163; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-307294, EBI-11978177; CC Q13163; P08238: HSP90AB1; NbExp=4; IntAct=EBI-307294, EBI-352572; CC Q13163; Q8N448: LNX2; NbExp=3; IntAct=EBI-307294, EBI-2340947; CC Q13163; Q9Y2U5: MAP3K2; NbExp=6; IntAct=EBI-307294, EBI-357393; CC Q13163; Q99759: MAP3K3; NbExp=4; IntAct=EBI-307294, EBI-307281; CC Q13163; Q13164: MAPK7; NbExp=7; IntAct=EBI-307294, EBI-1213983; CC Q13163; Q99471: PFDN5; NbExp=3; IntAct=EBI-307294, EBI-357275; CC Q13163; Q13501: SQSTM1; NbExp=5; IntAct=EBI-307294, EBI-307104; CC Q13163; Q9BUY5: ZNF426; NbExp=3; IntAct=EBI-307294, EBI-743265; CC Q13163; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-307294, EBI-4395669; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=B; CC IsoId=Q13163-1; Sequence=Displayed; CC Name=A; CC IsoId=Q13163-2; Sequence=VSP_021825; CC Name=C; CC IsoId=Q13163-3; Sequence=VSP_021825, VSP_021826; CC Name=4; CC IsoId=Q13163-4; Sequence=VSP_043333; CC -!- TISSUE SPECIFICITY: Expressed in many adult tissues. Abundant in heart CC and skeletal muscle. CC -!- DOMAIN: Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of CC the PB1 domain. This domain also mediates interactions with SQSTM1 and CC PARD6A (By similarity). {ECO:0000250}. CC -!- PTM: Activated by phosphorylation on Ser/Thr by MAP kinase kinase CC kinases. {ECO:0000250}. CC -!- PTM: (Microbial infection) Yersinia YopJ may acetylate Ser/Thr CC residues, preventing phosphorylation and activation, thus blocking the CC MAPK signaling pathway. {ECO:0000269|PubMed:16728640, CC ECO:0000269|PubMed:7759517}. CC -!- MISCELLANEOUS: [Isoform C]: Incomplete sequence. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr CC protein kinase family. MAP kinase kinase subfamily. {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; U25265; AAA96146.1; -; mRNA. DR EMBL; U71087; AAB16851.1; -; mRNA. DR EMBL; U71088; AAB16852.2; -; mRNA. DR EMBL; BT006780; AAP35426.1; -; mRNA. DR EMBL; AK293459; BAG56954.1; -; mRNA. DR EMBL; CR542229; CAG47025.1; -; mRNA. DR EMBL; AC009292; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC016355; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC103753; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008838; AAH08838.1; -; mRNA. DR CCDS; CCDS10224.1; -. [Q13163-1] DR CCDS; CCDS42051.1; -. [Q13163-2] DR CCDS; CCDS55970.1; -. [Q13163-4] DR RefSeq; NP_001193733.1; NM_001206804.1. [Q13163-4] DR RefSeq; NP_002748.1; NM_002757.3. [Q13163-2] DR RefSeq; NP_660143.1; NM_145160.2. [Q13163-1] DR PDB; 2NPT; X-ray; 1.75 A; A/C=5-108. DR PDB; 2O2V; X-ray; 1.83 A; A=5-108. DR PDB; 4IC7; X-ray; 2.60 A; B/E=16-130. DR PDBsum; 2NPT; -. DR PDBsum; 2O2V; -. DR PDBsum; 4IC7; -. DR AlphaFoldDB; Q13163; -. DR SMR; Q13163; -. DR BioGRID; 111593; 119. DR CORUM; Q13163; -. DR DIP; DIP-27558N; -. DR IntAct; Q13163; 65. DR MINT; Q13163; -. DR STRING; 9606.ENSP00000178640; -. DR BindingDB; Q13163; -. DR ChEMBL; CHEMBL4948; -. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB14904; Pimasertib. DR DrugCentral; Q13163; -. DR GuidetoPHARMACOLOGY; 2066; -. DR iPTMnet; Q13163; -. DR PhosphoSitePlus; Q13163; -. DR BioMuta; MAP2K5; -. DR DMDM; 118572669; -. DR CPTAC; CPTAC-818; -. DR CPTAC; CPTAC-819; -. DR EPD; Q13163; -. DR jPOST; Q13163; -. DR MassIVE; Q13163; -. DR MaxQB; Q13163; -. DR PaxDb; 9606-ENSP00000178640; -. DR PeptideAtlas; Q13163; -. DR ProteomicsDB; 59199; -. [Q13163-1] DR ProteomicsDB; 59200; -. [Q13163-2] DR ProteomicsDB; 59201; -. [Q13163-3] DR ProteomicsDB; 59202; -. [Q13163-4] DR Pumba; Q13163; -. DR Antibodypedia; 26267; 710 antibodies from 37 providers. DR DNASU; 5607; -. DR Ensembl; ENST00000178640.10; ENSP00000178640.5; ENSG00000137764.20. [Q13163-1] DR Ensembl; ENST00000354498.9; ENSP00000346493.5; ENSG00000137764.20. [Q13163-4] DR Ensembl; ENST00000395476.6; ENSP00000378859.2; ENSG00000137764.20. [Q13163-2] DR GeneID; 5607; -. DR KEGG; hsa:5607; -. DR MANE-Select; ENST00000178640.10; ENSP00000178640.5; NM_145160.3; NP_660143.1. DR UCSC; uc002aqu.4; human. [Q13163-1] DR AGR; HGNC:6845; -. DR CTD; 5607; -. DR DisGeNET; 5607; -. DR GeneCards; MAP2K5; -. DR HGNC; HGNC:6845; MAP2K5. DR HPA; ENSG00000137764; Low tissue specificity. DR MIM; 602520; gene. DR neXtProt; NX_Q13163; -. DR OpenTargets; ENSG00000137764; -. DR PharmGKB; PA30590; -. DR VEuPathDB; HostDB:ENSG00000137764; -. DR eggNOG; KOG0581; Eukaryota. DR GeneTree; ENSGT00940000157505; -. DR HOGENOM; CLU_000288_2_0_1; -. DR InParanoid; Q13163; -. DR OMA; ANDCTQV; -. DR OrthoDB; 2900742at2759; -. DR PhylomeDB; Q13163; -. DR TreeFam; TF106468; -. DR BRENDA; 2.7.12.2; 2681. DR PathwayCommons; Q13163; -. DR Reactome; R-HSA-198765; Signalling to ERK5. DR SignaLink; Q13163; -. DR SIGNOR; Q13163; -. DR BioGRID-ORCS; 5607; 24 hits in 1192 CRISPR screens. DR ChiTaRS; MAP2K5; human. DR EvolutionaryTrace; Q13163; -. DR GeneWiki; MAP2K5; -. DR GenomeRNAi; 5607; -. DR Pharos; Q13163; Tchem. DR PRO; PR:Q13163; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q13163; Protein. DR Bgee; ENSG00000137764; Expressed in right testis and 204 other cell types or tissues. DR ExpressionAtlas; Q13163; baseline and differential. DR GO; GO:0005819; C:spindle; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004708; F:MAP kinase kinase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:BHF-UCL. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; TAS:BHF-UCL. DR GO; GO:0070375; P:ERK5 cascade; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISS:BHF-UCL. DR GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; ISS:BHF-UCL. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:BHF-UCL. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISS:BHF-UCL. DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; ISS:BHF-UCL. DR GO; GO:0032717; P:negative regulation of interleukin-8 production; ISS:BHF-UCL. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:BHF-UCL. DR GO; GO:0060761; P:negative regulation of response to cytokine stimulus; ISS:BHF-UCL. DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:BHF-UCL. DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd06395; PB1_Map2k5; 1. DR CDD; cd06619; PKc_MKK5; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000270; PB1_dom. DR InterPro; IPR034851; PB1_MAP2K5. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR48013:SF26; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5; 1. DR PANTHER; PTHR48013; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5-RELATED; 1. DR Pfam; PF00564; PB1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00666; PB1; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF54277; CAD & PB1 domains; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51745; PB1; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q13163; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Kinase; KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Tyrosine-protein kinase. FT CHAIN 1..448 FT /note="Dual specificity mitogen-activated protein kinase FT kinase 5" FT /id="PRO_0000086383" FT DOMAIN 18..109 FT /note="PB1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081" FT DOMAIN 166..409 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 18..25 FT /note="Interaction with MAPK7" FT /evidence="ECO:0000250" FT REGION 64..68 FT /note="Interaction with MAP3K2/MAP3K3" FT /evidence="ECO:0000250" FT REGION 116..144 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 117..131 FT /note="Interaction with MAPK7" FT /evidence="ECO:0000250" FT COMPBIAS 123..144 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 283 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 172..180 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 195 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT MOD_RES 311 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:7759517, FT ECO:0007744|PubMed:19369195" FT MOD_RES 315 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:7759517" FT VAR_SEQ 1..45 FT /note="MLWLALGPFPAMENQVLVIRIKIPNSGAVDWTVHSGPQLLFRDVL -> MME FT GHFPQS (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043333" FT VAR_SEQ 349..358 FT /note="Missing (in isoform A and isoform C)" FT /evidence="ECO:0000303|PubMed:7759517, FT ECO:0000303|PubMed:9384584" FT /id="VSP_021825" FT VAR_SEQ 444..448 FT /note="QQGPP -> LASLPSPSPSV (in isoform C)" FT /evidence="ECO:0000303|PubMed:9384584" FT /id="VSP_021826" FT VARIANT 118 FT /note="H -> R (in dbSNP:rs56241934)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040823" FT VARIANT 427 FT /note="A -> V (in dbSNP:rs1226964455)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040824" FT VARIANT 428 FT /note="A -> T (in dbSNP:rs55811347)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_046070" FT MUTAGEN 195 FT /note="K->M: Inactivation." FT /evidence="ECO:0000269|PubMed:7759517" FT MUTAGEN 311 FT /note="S->A: Inactivation." FT /evidence="ECO:0000269|PubMed:7759517" FT MUTAGEN 315 FT /note="T->A: Inactivation." FT /evidence="ECO:0000269|PubMed:7759517" FT STRAND 17..23 FT /evidence="ECO:0007829|PDB:2NPT" FT TURN 24..26 FT /evidence="ECO:0007829|PDB:2NPT" FT STRAND 27..33 FT /evidence="ECO:0007829|PDB:2NPT" FT HELIX 41..51 FT /evidence="ECO:0007829|PDB:2NPT" FT STRAND 58..63 FT /evidence="ECO:0007829|PDB:2NPT" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:4IC7" FT STRAND 69..72 FT /evidence="ECO:0007829|PDB:2NPT" FT HELIX 75..93 FT /evidence="ECO:0007829|PDB:2NPT" FT TURN 94..96 FT /evidence="ECO:0007829|PDB:2NPT" FT STRAND 102..107 FT /evidence="ECO:0007829|PDB:2NPT" SQ SEQUENCE 448 AA; 50112 MW; F23BB327E2A9C7DC CRC64; MLWLALGPFP AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ VLPEATTTAF EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE PLQIFPRACK PPGERNIHGL KVNTRAGPSQ HSSPAVSDSL PSNSLKKSSA ELKKILANGQ MNEQDIRYRD TLGHGNGGTV YKAYHVPSGK ILAVKVILLD ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC TEFMDGGSLD VYRKMPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTRGQVKLC DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMELA LGRFPYPQIQ KNQGSLMPLQ LLQCIVDEDS PVLPVGEFSE PFVHFITQCM RKQPKERPAP EELMGHPFIV QFNDGNAAVV SMWVCRALEE RRSQQGPP //