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Dual specificity mitogen-activated protein kinase kinase 5 (MAP kinase kinase 5) (MAPKK 5) (EC 2.7.12.2) (MAPK/ERK kinase 5) (MEK 5)

 MP2K5_RAT               Reviewed;         448 AA.
Q62862; Q62863; Q62864;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
01-NOV-1997, sequence version 1.
23-MAY-2018, entry version 154.
RecName: Full=Dual specificity mitogen-activated protein kinase kinase 5;
Short=MAP kinase kinase 5;
Short=MAPKK 5;
EC=2.7.12.2;
AltName: Full=MAPK/ERK kinase 5;
Short=MEK 5;
Name=Map2k5; Synonyms=Mek5, Mkk5, Prkmk5;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1; ALPHA-2 AND BETA),
FUNCTION, AND MUTAGENESIS.
STRAIN=Sprague-Dawley; TISSUE=Brain;
PubMed=7499418; DOI=10.1074/jbc.270.48.28897;
English J.M., Vanderbilt C.A., Xu S., Marcus S., Cobb M.H.;
"Isolation of MEK5 and differential expression of alternatively
spliced forms.";
J. Biol. Chem. 270:28897-28902(1995).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
-!- FUNCTION: Acts as a scaffold for the formation of a ternary
MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this
pathway appears to play a critical role in protecting cells from
stress-induced apoptosis, neuronal survival and cardiac
development and angiogenesis (By similarity). {ECO:0000250,
ECO:0000269|PubMed:7499418}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
-!- SUBUNIT: Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex
with SQSTM1 and PRKCZ or PRKCI (By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Isoform Beta: Cytoplasm, cytosol.
-!- SUBCELLULAR LOCATION: Isoform Alpha-1: Membrane. Note=The
alternatively spliced exon in alpha isoform resemble conserved
sequences that mediate interactions with the cytoskeleton, thereby
explaining the differential localization.
-!- SUBCELLULAR LOCATION: Isoform Alpha-2: Membrane. Note=The
alternatively spliced exon in alpha isoform resemble conserved
sequences that mediate interactions with the cytoskeleton, thereby
explaining the differential localization.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=Alpha-1;
IsoId=Q62862-1; Sequence=Displayed;
Name=Alpha-2;
IsoId=Q62862-2; Sequence=VSP_004881;
Name=Beta;
IsoId=Q62862-3; Sequence=VSP_004880;
-!- TISSUE SPECIFICITY: MEK5 beta is ubiquitously distributed with
highest levels in the liver, whereas MEK5 alpha is expressed only
in liver and brain.
-!- DOMAIN: Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues
of the PB1 domain. This domain also mediates interactions with
SQSTM1 and PARD6A (By similarity). {ECO:0000250}.
-!- PTM: Activated by phosphorylation on Ser/Thr by MAP kinase kinase
kinases. {ECO:0000250}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; U37462; AAC52320.1; -; mRNA.
EMBL; U37463; AAC52321.1; -; mRNA.
EMBL; U37464; AAC52322.1; -; mRNA.
EMBL; BC078860; AAH78860.1; -; mRNA.
RefSeq; NP_001029159.1; NM_001033987.1. [Q62862-1]
RefSeq; NP_058942.1; NM_017246.2. [Q62862-2]
RefSeq; XP_017450991.1; XM_017595502.1. [Q62862-3]
UniGene; Rn.11054; -.
ProteinModelPortal; Q62862; -.
SMR; Q62862; -.
IntAct; Q62862; 1.
STRING; 10116.ENSRNOP00000050528; -.
iPTMnet; Q62862; -.
PhosphoSitePlus; Q62862; -.
PaxDb; Q62862; -.
Ensembl; ENSRNOT00000010991; ENSRNOP00000010991; ENSRNOG00000007926. [Q62862-2]
Ensembl; ENSRNOT00000051558; ENSRNOP00000050528; ENSRNOG00000007926. [Q62862-1]
Ensembl; ENSRNOT00000079122; ENSRNOP00000070803; ENSRNOG00000007926. [Q62862-3]
GeneID; 29568; -.
KEGG; rno:29568; -.
UCSC; RGD:61890; rat. [Q62862-1]
CTD; 5607; -.
RGD; 61890; Map2k5.
eggNOG; KOG0581; Eukaryota.
eggNOG; ENOG410XQ5A; LUCA.
GeneTree; ENSGT00760000119199; -.
HOGENOM; HOG000234206; -.
HOVERGEN; HBG108518; -.
InParanoid; Q62862; -.
KO; K04463; -.
OMA; EDLMGHP; -.
OrthoDB; EOG091G06I7; -.
PhylomeDB; Q62862; -.
BRENDA; 2.7.12.2; 5301.
PRO; PR:Q62862; -.
Proteomes; UP000002494; Chromosome 8.
Bgee; ENSRNOG00000007926; -.
Genevisible; Q62862; RN.
GO; GO:0005829; C:cytosol; IDA:RGD.
GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0005819; C:spindle; IEA:Ensembl.
GO; GO:0005524; F:ATP binding; IDA:RGD.
GO; GO:0004707; F:MAP kinase activity; TAS:Reactome.
GO; GO:0004708; F:MAP kinase kinase activity; IC:RGD.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0004672; F:protein kinase activity; IDA:RGD.
GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
GO; GO:0000187; P:activation of MAPK activity; IMP:BHF-UCL.
GO; GO:0071363; P:cellular response to growth factor stimulus; IMP:BHF-UCL.
GO; GO:0070375; P:ERK5 cascade; IMP:RGD.
GO; GO:0007507; P:heart development; IEA:Ensembl.
GO; GO:0000165; P:MAPK cascade; IC:RGD.
GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; IMP:BHF-UCL.
GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IMP:BHF-UCL.
GO; GO:0045415; P:negative regulation of interleukin-8 biosynthetic process; IMP:BHF-UCL.
GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:BHF-UCL.
GO; GO:0060761; P:negative regulation of response to cytokine stimulus; IMP:BHF-UCL.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
GO; GO:0030307; P:positive regulation of cell growth; IMP:RGD.
GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:RGD.
GO; GO:0051247; P:positive regulation of protein metabolic process; IMP:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central.
GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IBA:GO_Central.
CDD; cd06395; PB1_Map2k5; 1.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000270; PB1_dom.
InterPro; IPR034851; PB1_MAP2K5.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00564; PB1; 1.
Pfam; PF00069; Pkinase; 1.
SMART; SM00666; PB1; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS51745; PB1; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
Alternative splicing; ATP-binding; Complete proteome; Cytoplasm;
Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
Transferase; Tyrosine-protein kinase.
CHAIN 1 448 Dual specificity mitogen-activated
protein kinase kinase 5.
/FTId=PRO_0000086385.
DOMAIN 18 109 PB1. {ECO:0000255|PROSITE-
ProRule:PRU01081}.
DOMAIN 166 419 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 172 180 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REGION 18 25 Interaction with MAPK7. {ECO:0000250}.
REGION 64 68 Interaction with MAP3K2/MAP3K3.
{ECO:0000250}.
REGION 117 131 Interaction with MAPK7. {ECO:0000250}.
ACT_SITE 283 283 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 195 195 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 311 311 Phosphoserine.
{ECO:0000250|UniProtKB:Q13163}.
MOD_RES 315 315 Phosphothreonine.
{ECO:0000250|UniProtKB:Q13163}.
VAR_SEQ 1 89 Missing (in isoform Beta).
{ECO:0000303|PubMed:7499418}.
/FTId=VSP_004880.
VAR_SEQ 349 358 Missing (in isoform Alpha-2).
{ECO:0000303|PubMed:7499418}.
/FTId=VSP_004881.
MUTAGEN 311 311 S->D: No change in activity.
{ECO:0000269|PubMed:7499418}.
MUTAGEN 315 315 T->D: No change in activity.
{ECO:0000269|PubMed:7499418}.
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


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