MP2K5_RAT
ID MP2K5_RAT Reviewed; 448 AA.
AC Q62862; Q62863; Q62864;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 173.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1; ALPHA-2 AND BETA), FUNCTION,
RP AND MUTAGENESIS.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7499418; DOI=10.1074/jbc.270.48.28897;
RA English J.M., Vanderbilt C.A., Xu S., Marcus S., Cobb M.H.;
RT "Isolation of MEK5 and differential expression of alternatively spliced
RT forms.";
RL J. Biol. Chem. 270:28897-28902(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
RC TISSUE=Lung;
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).
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 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:7499418}.
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 -!- SUBCELLULAR LOCATION: [Isoform Beta]: Cytoplasm, cytosol.
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha-1]: Membrane. Note=The
CC alternatively spliced exon in alpha isoform resemble conserved
CC sequences that mediate interactions with the cytoskeleton, thereby
CC explaining the differential localization.
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha-2]: Membrane. Note=The
CC alternatively spliced exon in alpha isoform resemble conserved
CC sequences that mediate interactions with the cytoskeleton, thereby
CC explaining the differential localization.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Alpha-1;
CC IsoId=Q62862-1; Sequence=Displayed;
CC Name=Alpha-2;
CC IsoId=Q62862-2; Sequence=VSP_004881;
CC Name=Beta;
CC IsoId=Q62862-3; Sequence=VSP_004880;
CC -!- TISSUE SPECIFICITY: MEK5 beta is ubiquitously distributed with highest
CC levels in the liver, whereas MEK5 alpha is expressed only in liver and
CC brain.
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 -!- 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; U37462; AAC52320.1; -; mRNA.
DR EMBL; U37463; AAC52321.1; -; mRNA.
DR EMBL; U37464; AAC52322.1; -; mRNA.
DR EMBL; BC078860; AAH78860.1; -; mRNA.
DR RefSeq; NP_001029159.1; NM_001033987.1. [Q62862-1]
DR RefSeq; NP_058942.1; NM_017246.2. [Q62862-2]
DR RefSeq; XP_017450991.1; XM_017595502.1. [Q62862-3]
DR AlphaFoldDB; Q62862; -.
DR SMR; Q62862; -.
DR IntAct; Q62862; 1.
DR STRING; 10116.ENSRNOP00000050528; -.
DR iPTMnet; Q62862; -.
DR PhosphoSitePlus; Q62862; -.
DR PaxDb; Q62862; -.
DR PRIDE; Q62862; -.
DR Ensembl; ENSRNOT00000010991; ENSRNOP00000010991; ENSRNOG00000007926. [Q62862-2]
DR Ensembl; ENSRNOT00000051558; ENSRNOP00000050528; ENSRNOG00000007926. [Q62862-1]
DR GeneID; 29568; -.
DR KEGG; rno:29568; -.
DR UCSC; RGD:61890; rat. [Q62862-1]
DR CTD; 5607; -.
DR RGD; 61890; Map2k5.
DR eggNOG; KOG0581; Eukaryota.
DR GeneTree; ENSGT00940000157505; -.
DR InParanoid; Q62862; -.
DR OMA; ILANGQX; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; Q62862; -.
DR BRENDA; 2.7.12.2; 5301.
DR PRO; PR:Q62862; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000007926; Expressed in skeletal muscle tissue and 20 other tissues.
DR Genevisible; Q62862; RN.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005819; C:spindle; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0004707; F:MAP kinase activity; TAS:Reactome.
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; IDA:RGD.
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:0071363; P:cellular response to growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0070375; P:ERK5 cascade; IMP:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; IMP:BHF-UCL.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IMP:BHF-UCL.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IMP:BHF-UCL.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0060761; P:negative regulation of response to cytokine stimulus; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
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 Alternative splicing; ATP-binding; Cytoplasm; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..448
FT /note="Dual specificity mitogen-activated protein kinase
FT kinase 5"
FT /id="PRO_0000086385"
FT DOMAIN 18..109
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 166..419
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13163"
FT MOD_RES 315
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13163"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:7499418"
FT /id="VSP_004880"
FT VAR_SEQ 349..358
FT /note="Missing (in isoform Alpha-2)"
FT /evidence="ECO:0000303|PubMed:7499418"
FT /id="VSP_004881"
FT MUTAGEN 311
FT /note="S->D: No change in activity."
FT /evidence="ECO:0000269|PubMed:7499418"
FT MUTAGEN 315
FT /note="T->D: No change in activity."
FT /evidence="ECO:0000269|PubMed:7499418"
SQ SEQUENCE 448 AA; 50198 MW; 1B1CC8B05789B90D CRC64;
MLWLALGPFR AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ VLPEATTTAF
EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE PLQIFPRACK PPGERNIHGL
KVNTRAGPSQ HTSPVVSDSL PSNSLKKSSA ELRKILANGQ MNEQDIRYRD TLGHGNGGTV
YKAYHVPSGK ILAVKVILLD ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC
TEFMDGGSLD VYRKIPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTSGQVKLC
DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMELA LGRFPYPQIQ
KNQGSLMPLQ LLQCIVDEDS PVLPLGEFSE PFVHFITQCM RKQPKERPAP EELMGHPFIV
QFNDGNATVV SMWVCRALEE RRSQQGPP
