Full text data of MAP2K5
MAP2K5
(MEK5, MKK5, PRKMK5)
[Confidence: low (only semi-automatic identification from reviews)]
Dual specificity mitogen-activated protein kinase kinase 5; MAP kinase kinase 5; MAPKK 5; 2.7.12.2 (MAPK/ERK kinase 5; MEK 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Dual specificity mitogen-activated protein kinase kinase 5; MAP kinase kinase 5; MAPKK 5; 2.7.12.2 (MAPK/ERK kinase 5; MEK 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q13163
ID MP2K5_HUMAN Reviewed; 448 AA.
AC Q13163; B4DE43; Q92961; Q92962;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 28-NOV-2006, sequence version 2.
DT 22-JAN-2014, entry version 141.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH
RP ERK5 AND MAPK7, MUTAGENESIS OF LYS-195; SER-311 AND THR-315, AND
RP PHOSPHORYLATION AT SER-311 AND THR-315.
RC TISSUE=Fetal brain;
RX PubMed=7759517;
RA Zhou G., Bao Z.Q., Dixon J.E.;
RT "Components of a new human protein kinase signal transduction
RT 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.,
RA 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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., 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.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH YOPJ, 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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311, AND MASS
RP SPECTROMETRY.
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 IDENTIFICATION BY MASS SPECTROMETRY [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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 4-108 IN COMPLEX WITH
RP MAP3K2.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the complex of human mitogen activated protein
RT kinase kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated
RT protein kinase kinase kinase 3 (MAP3K2B-Phox).";
RL Submitted (NOV-2006) to the PDB data bank.
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 4-108 IN COMPLEX WITH
RP MAP3K3.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the complex of human mitogen activated protein
RT kinase kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated
RT protein kinase kinase kinase 3 (MAP3K3B-Phox).";
RL Submitted (NOV-2006) to the PDB data bank.
RN [15]
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.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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
CC development and angiogenesis.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- SUBUNIT: Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex
CC with SQSTM1 and PRKCZ or PRKCI (By similarity). Interacts with
CC Yersinia yopJ.
CC -!- INTERACTION:
CC P62993:GRB2; NbExp=2; IntAct=EBI-307294, EBI-401755;
CC Q13164:MAPK7; NbExp=2; IntAct=EBI-307294, EBI-1213983;
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 Note=Incomplete sequence;
CC Name=4;
CC IsoId=Q13163-4; Sequence=VSP_043333;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in many adult tissues. Abundant in
CC heart and skeletal muscle.
CC -!- DOMAIN: Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues
CC of the OPR domain. This domain also mediates interactions with
CC SQSTM1 and PARD6A (By similarity).
CC -!- PTM: Activated by phosphorylation on Ser/Thr by MAP kinase kinase
CC kinases (By similarity).
CC -!- PTM: Yersinia yopJ may acetylate Ser/Thr residues, preventing
CC phosphorylation and activation, thus blocking the MAPK signaling
CC pathway.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily.
CC -!- SIMILARITY: Contains 1 OPR domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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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 RefSeq; NP_001193733.1; NM_001206804.1.
DR RefSeq; NP_002748.1; NM_002757.3.
DR RefSeq; NP_660143.1; NM_145160.2.
DR UniGene; Hs.114198; -.
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 ProteinModelPortal; Q13163; -.
DR SMR; Q13163; 16-130, 160-445.
DR DIP; DIP-27558N; -.
DR IntAct; Q13163; 12.
DR MINT; MINT-1155433; -.
DR STRING; 9606.ENSP00000178640; -.
DR BindingDB; Q13163; -.
DR ChEMBL; CHEMBL4948; -.
DR GuidetoPHARMACOLOGY; 2066; -.
DR PhosphoSite; Q13163; -.
DR DMDM; 118572669; -.
DR PaxDb; Q13163; -.
DR PRIDE; Q13163; -.
DR DNASU; 5607; -.
DR Ensembl; ENST00000178640; ENSP00000178640; ENSG00000137764.
DR Ensembl; ENST00000354498; ENSP00000346493; ENSG00000137764.
DR Ensembl; ENST00000395476; ENSP00000378859; ENSG00000137764.
DR GeneID; 5607; -.
DR KEGG; hsa:5607; -.
DR UCSC; uc002aqu.3; human.
DR CTD; 5607; -.
DR GeneCards; GC15P067835; -.
DR HGNC; HGNC:6845; MAP2K5.
DR HPA; CAB022094; -.
DR HPA; HPA027347; -.
DR HPA; HPA027755; -.
DR MIM; 602520; gene.
DR neXtProt; NX_Q13163; -.
DR PharmGKB; PA30590; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000234206; -.
DR HOVERGEN; HBG108518; -.
DR InParanoid; Q13163; -.
DR KO; K04463; -.
DR OMA; EVVSMWV; -.
DR OrthoDB; EOG7HF1KZ; -.
DR BRENDA; 2.7.12.2; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; Q13163; -.
DR ChiTaRS; MAP2K5; human.
DR EvolutionaryTrace; Q13163; -.
DR GeneWiki; MAP2K5; -.
DR GenomeRNAi; 5607; -.
DR NextBio; 21792; -.
DR PRO; PR:Q13163; -.
DR ArrayExpress; Q13163; -.
DR Bgee; Q13163; -.
DR CleanEx; HS_MAP2K5; -.
DR Genevestigator; Q13163; -.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
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:0000187; P:activation of MAPK activity; 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:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
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:0045415; P:negative regulation of interleukin-8 biosynthetic process; 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 from RNA polymerase II promoter; ISS:BHF-UCL.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:GOC.
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:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000270; OPR_PB1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
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; 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;
KW Complete proteome; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1 448 Dual specificity mitogen-activated
FT protein kinase kinase 5.
FT /FTId=PRO_0000086383.
FT DOMAIN 18 97 OPR.
FT DOMAIN 166 409 Protein kinase.
FT NP_BIND 172 180 ATP (By similarity).
FT REGION 18 25 Interaction with MAPK7 (By similarity).
FT REGION 64 68 Interaction with MAP3K2/MAP3K3 (By
FT similarity).
FT REGION 117 131 Interaction with MAPK7 (By similarity).
FT ACT_SITE 283 283 Proton acceptor (By similarity).
FT BINDING 195 195 ATP.
FT MOD_RES 311 311 Phosphoserine.
FT MOD_RES 315 315 Phosphothreonine.
FT VAR_SEQ 1 45 MLWLALGPFPAMENQVLVIRIKIPNSGAVDWTVHSGPQLLF
FT RDVL -> MMEGHFPQS (in isoform 4).
FT /FTId=VSP_043333.
FT VAR_SEQ 349 358 Missing (in isoform A and isoform C).
FT /FTId=VSP_021825.
FT VAR_SEQ 444 448 QQGPP -> LASLPSPSPSV (in isoform C).
FT /FTId=VSP_021826.
FT VARIANT 118 118 H -> R (in dbSNP:rs56241934).
FT /FTId=VAR_040823.
FT VARIANT 427 427 A -> V.
FT /FTId=VAR_040824.
FT VARIANT 428 428 A -> T (in dbSNP:rs55811347).
FT /FTId=VAR_046070.
FT MUTAGEN 195 195 K->M: Inactivation.
FT MUTAGEN 311 311 S->A: Inactivation.
FT MUTAGEN 315 315 T->A: Inactivation.
FT STRAND 17 23
FT TURN 24 26
FT STRAND 27 33
FT HELIX 41 51
FT STRAND 58 63
FT STRAND 65 67
FT STRAND 69 72
FT HELIX 75 93
FT TURN 94 96
FT STRAND 102 107
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
//
ID MP2K5_HUMAN Reviewed; 448 AA.
AC Q13163; B4DE43; Q92961; Q92962;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 28-NOV-2006, sequence version 2.
DT 22-JAN-2014, entry version 141.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH
RP ERK5 AND MAPK7, MUTAGENESIS OF LYS-195; SER-311 AND THR-315, AND
RP PHOSPHORYLATION AT SER-311 AND THR-315.
RC TISSUE=Fetal brain;
RX PubMed=7759517;
RA Zhou G., Bao Z.Q., Dixon J.E.;
RT "Components of a new human protein kinase signal transduction
RT 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.,
RA 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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., 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.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH YOPJ, 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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311, AND MASS
RP SPECTROMETRY.
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 IDENTIFICATION BY MASS SPECTROMETRY [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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 4-108 IN COMPLEX WITH
RP MAP3K2.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the complex of human mitogen activated protein
RT kinase kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated
RT protein kinase kinase kinase 3 (MAP3K2B-Phox).";
RL Submitted (NOV-2006) to the PDB data bank.
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 4-108 IN COMPLEX WITH
RP MAP3K3.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the complex of human mitogen activated protein
RT kinase kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated
RT protein kinase kinase kinase 3 (MAP3K3B-Phox).";
RL Submitted (NOV-2006) to the PDB data bank.
RN [15]
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.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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
CC development and angiogenesis.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- SUBUNIT: Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex
CC with SQSTM1 and PRKCZ or PRKCI (By similarity). Interacts with
CC Yersinia yopJ.
CC -!- INTERACTION:
CC P62993:GRB2; NbExp=2; IntAct=EBI-307294, EBI-401755;
CC Q13164:MAPK7; NbExp=2; IntAct=EBI-307294, EBI-1213983;
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 Note=Incomplete sequence;
CC Name=4;
CC IsoId=Q13163-4; Sequence=VSP_043333;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in many adult tissues. Abundant in
CC heart and skeletal muscle.
CC -!- DOMAIN: Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues
CC of the OPR domain. This domain also mediates interactions with
CC SQSTM1 and PARD6A (By similarity).
CC -!- PTM: Activated by phosphorylation on Ser/Thr by MAP kinase kinase
CC kinases (By similarity).
CC -!- PTM: Yersinia yopJ may acetylate Ser/Thr residues, preventing
CC phosphorylation and activation, thus blocking the MAPK signaling
CC pathway.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily.
CC -!- SIMILARITY: Contains 1 OPR domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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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 RefSeq; NP_001193733.1; NM_001206804.1.
DR RefSeq; NP_002748.1; NM_002757.3.
DR RefSeq; NP_660143.1; NM_145160.2.
DR UniGene; Hs.114198; -.
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 ProteinModelPortal; Q13163; -.
DR SMR; Q13163; 16-130, 160-445.
DR DIP; DIP-27558N; -.
DR IntAct; Q13163; 12.
DR MINT; MINT-1155433; -.
DR STRING; 9606.ENSP00000178640; -.
DR BindingDB; Q13163; -.
DR ChEMBL; CHEMBL4948; -.
DR GuidetoPHARMACOLOGY; 2066; -.
DR PhosphoSite; Q13163; -.
DR DMDM; 118572669; -.
DR PaxDb; Q13163; -.
DR PRIDE; Q13163; -.
DR DNASU; 5607; -.
DR Ensembl; ENST00000178640; ENSP00000178640; ENSG00000137764.
DR Ensembl; ENST00000354498; ENSP00000346493; ENSG00000137764.
DR Ensembl; ENST00000395476; ENSP00000378859; ENSG00000137764.
DR GeneID; 5607; -.
DR KEGG; hsa:5607; -.
DR UCSC; uc002aqu.3; human.
DR CTD; 5607; -.
DR GeneCards; GC15P067835; -.
DR HGNC; HGNC:6845; MAP2K5.
DR HPA; CAB022094; -.
DR HPA; HPA027347; -.
DR HPA; HPA027755; -.
DR MIM; 602520; gene.
DR neXtProt; NX_Q13163; -.
DR PharmGKB; PA30590; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000234206; -.
DR HOVERGEN; HBG108518; -.
DR InParanoid; Q13163; -.
DR KO; K04463; -.
DR OMA; EVVSMWV; -.
DR OrthoDB; EOG7HF1KZ; -.
DR BRENDA; 2.7.12.2; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; Q13163; -.
DR ChiTaRS; MAP2K5; human.
DR EvolutionaryTrace; Q13163; -.
DR GeneWiki; MAP2K5; -.
DR GenomeRNAi; 5607; -.
DR NextBio; 21792; -.
DR PRO; PR:Q13163; -.
DR ArrayExpress; Q13163; -.
DR Bgee; Q13163; -.
DR CleanEx; HS_MAP2K5; -.
DR Genevestigator; Q13163; -.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
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:0000187; P:activation of MAPK activity; 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:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
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:0045415; P:negative regulation of interleukin-8 biosynthetic process; 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 from RNA polymerase II promoter; ISS:BHF-UCL.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:GOC.
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:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000270; OPR_PB1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
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; 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;
KW Complete proteome; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1 448 Dual specificity mitogen-activated
FT protein kinase kinase 5.
FT /FTId=PRO_0000086383.
FT DOMAIN 18 97 OPR.
FT DOMAIN 166 409 Protein kinase.
FT NP_BIND 172 180 ATP (By similarity).
FT REGION 18 25 Interaction with MAPK7 (By similarity).
FT REGION 64 68 Interaction with MAP3K2/MAP3K3 (By
FT similarity).
FT REGION 117 131 Interaction with MAPK7 (By similarity).
FT ACT_SITE 283 283 Proton acceptor (By similarity).
FT BINDING 195 195 ATP.
FT MOD_RES 311 311 Phosphoserine.
FT MOD_RES 315 315 Phosphothreonine.
FT VAR_SEQ 1 45 MLWLALGPFPAMENQVLVIRIKIPNSGAVDWTVHSGPQLLF
FT RDVL -> MMEGHFPQS (in isoform 4).
FT /FTId=VSP_043333.
FT VAR_SEQ 349 358 Missing (in isoform A and isoform C).
FT /FTId=VSP_021825.
FT VAR_SEQ 444 448 QQGPP -> LASLPSPSPSV (in isoform C).
FT /FTId=VSP_021826.
FT VARIANT 118 118 H -> R (in dbSNP:rs56241934).
FT /FTId=VAR_040823.
FT VARIANT 427 427 A -> V.
FT /FTId=VAR_040824.
FT VARIANT 428 428 A -> T (in dbSNP:rs55811347).
FT /FTId=VAR_046070.
FT MUTAGEN 195 195 K->M: Inactivation.
FT MUTAGEN 311 311 S->A: Inactivation.
FT MUTAGEN 315 315 T->A: Inactivation.
FT STRAND 17 23
FT TURN 24 26
FT STRAND 27 33
FT HELIX 41 51
FT STRAND 58 63
FT STRAND 65 67
FT STRAND 69 72
FT HELIX 75 93
FT TURN 94 96
FT STRAND 102 107
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
//
MIM
602520
*RECORD*
*FIELD* NO
602520
*FIELD* TI
*602520 MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5; MAP2K5
;;PROTEIN KINASE, MITOGEN-ACTIVATED, KINASE 5; PRKMK5;;
read moreMAPK/ERK KINASE 5; MEK5;;
MAPKK5
*FIELD* TX
CLONING
Some cell surface receptors respond to extracellular stimuli via a
sequential protein kinase cascade. The kinase signaling cascades involve
multiple protein kinases, including the mitogen-activated protein kinase
kinases (MAP2KS, also called MAPKKs or PRKMKs) and the mitogen-activated
protein kinases (MAPKs, or PRKMs). Specific MAP2Ks have been shown to
phosphorylate specific MAPKs in a given pathway. By degenerate PCR and
screening of a human fetal brain cDNA library, Zhou et al. (1995) cloned
a cDNA encoding MAP2K5, called MEK5 by them. The 444-amino acid protein
is approximately 40% identical to other MAP2Ks and contains all 11
conserved kinase subdomains. MAP2K5 differs from other MAP2Ks by having
a long N-terminal sequence. The authors suggested that this region may
be important in coupling GTPases to the MAP2K5 protein kinase cascade.
Zhou et al. (1995) demonstrated that MAP2K5 interacts specifically with
MAPK7 (602521) in vitro. Since these proteins did not interact with
kinases in the MAP2K1 (176872)/MAPK3 (601795) pathway, the authors
proposed that the MAP2K5/MAPK7 protein cascade is a novel signaling
pathway. Northern blot analysis detected a 2.7-kb MAP2K5 transcript in
many human tissues, with the highest levels in heart and skeletal
muscle.
*FIELD* RF
1. Zhou, G.; Bao, Z. Q.; Dixon, J. E.: Components of a new human
protein kinase signal transduction pathway. J. Biol. Chem. 270:
12665-12669, 1995.
*FIELD* CD
Patti M. Sherman: 4/14/1998
*FIELD* ED
alopez: 05/03/2010
mgross: 9/14/1999
psherman: 4/21/1998
dholmes: 4/14/1998
*RECORD*
*FIELD* NO
602520
*FIELD* TI
*602520 MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5; MAP2K5
;;PROTEIN KINASE, MITOGEN-ACTIVATED, KINASE 5; PRKMK5;;
read moreMAPK/ERK KINASE 5; MEK5;;
MAPKK5
*FIELD* TX
CLONING
Some cell surface receptors respond to extracellular stimuli via a
sequential protein kinase cascade. The kinase signaling cascades involve
multiple protein kinases, including the mitogen-activated protein kinase
kinases (MAP2KS, also called MAPKKs or PRKMKs) and the mitogen-activated
protein kinases (MAPKs, or PRKMs). Specific MAP2Ks have been shown to
phosphorylate specific MAPKs in a given pathway. By degenerate PCR and
screening of a human fetal brain cDNA library, Zhou et al. (1995) cloned
a cDNA encoding MAP2K5, called MEK5 by them. The 444-amino acid protein
is approximately 40% identical to other MAP2Ks and contains all 11
conserved kinase subdomains. MAP2K5 differs from other MAP2Ks by having
a long N-terminal sequence. The authors suggested that this region may
be important in coupling GTPases to the MAP2K5 protein kinase cascade.
Zhou et al. (1995) demonstrated that MAP2K5 interacts specifically with
MAPK7 (602521) in vitro. Since these proteins did not interact with
kinases in the MAP2K1 (176872)/MAPK3 (601795) pathway, the authors
proposed that the MAP2K5/MAPK7 protein cascade is a novel signaling
pathway. Northern blot analysis detected a 2.7-kb MAP2K5 transcript in
many human tissues, with the highest levels in heart and skeletal
muscle.
*FIELD* RF
1. Zhou, G.; Bao, Z. Q.; Dixon, J. E.: Components of a new human
protein kinase signal transduction pathway. J. Biol. Chem. 270:
12665-12669, 1995.
*FIELD* CD
Patti M. Sherman: 4/14/1998
*FIELD* ED
alopez: 05/03/2010
mgross: 9/14/1999
psherman: 4/21/1998
dholmes: 4/14/1998