MP2K5_HUMAN
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 03-AUG-2022, entry version 211.
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. {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}.
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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; 99.
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 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; Q13163; -.
DR PeptideAtlas; Q13163; -.
DR PRIDE; Q13163; -.
DR ProteomicsDB; 59199; -. [Q13163-1]
DR ProteomicsDB; 59200; -. [Q13163-2]
DR ProteomicsDB; 59201; -. [Q13163-3]
DR ProteomicsDB; 59202; -. [Q13163-4]
DR Antibodypedia; 26267; 609 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 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; ILANGQX; -.
DR OrthoDB; 81952at2759; -.
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; 19 hits in 1114 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 202 other tissues.
DR ExpressionAtlas; Q13163; baseline and differential.
DR Genevisible; Q13163; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
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:0000165; P:MAPK cascade; IBA:GO_Central.
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:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
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 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 Pfam; PF00564; PB1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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
