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Protein

Dual specificity mitogen-activated protein kinase kinase 5

Gene

Map2k5

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei195 – 1951ATPPROSITE-ProRule annotation
Active sitei283 – 2831Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi172 – 1809ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: RGD
  • MAP kinase kinase activity Source: RGD
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: RGD
  • protein serine/threonine kinase activity Source: UniProtKB-KW
  • protein tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

  • activation of MAPK activity Source: BHF-UCL
  • cellular response to growth factor stimulus Source: BHF-UCL
  • ERK5 cascade Source: RGD
  • heart development Source: Ensembl
  • MAPK cascade Source: RGD
  • negative regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
  • negative regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  • negative regulation of heterotypic cell-cell adhesion Source: BHF-UCL
  • negative regulation of interleukin-8 biosynthetic process Source: BHF-UCL
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • negative regulation of response to cytokine stimulus Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of cell growth Source: RGD
  • positive regulation of epithelial cell proliferation Source: RGD
  • positive regulation of protein metabolic process Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • protein phosphorylation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 5 (EC:2.7.12.2)
Short name:
MAP kinase kinase 5
Short name:
MAPKK 5
Alternative name(s):
MAPK/ERK kinase 5
Short name:
MEK 5
Gene namesi
Name:Map2k5
Synonyms:Mek5, Mkk5, Prkmk5
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi61890. Map2k5.

Subcellular locationi

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.
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.

GO - Cellular componenti

  • cytosol Source: RGD
  • membrane Source: UniProtKB-SubCell
  • nucleus Source: RGD
  • spindle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi311 – 3111S → D: No change in activity. 1 Publication
Mutagenesisi315 – 3151T → D: No change in activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 448448Dual specificity mitogen-activated protein kinase kinase 5PRO_0000086385Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei311 – 3111PhosphoserineBy similarity
Modified residuei315 – 3151PhosphothreonineBy similarity

Post-translational modificationi

Activated by phosphorylation on Ser/Thr by MAP kinase kinase kinases.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ62862.

PTM databases

PhosphoSiteiQ62862.

Expressioni

Tissue specificityi

MEK5 beta is ubiquitously distributed with highest levels in the liver, whereas MEK5 alpha is expressed only in liver and brain.

Gene expression databases

GenevisibleiQ62862. RN.

Interactioni

Subunit structurei

Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI (By similarity).By similarity

Protein-protein interaction databases

IntActiQ62862. 1 interaction.
STRINGi10116.ENSRNOP00000050528.

Structurei

3D structure databases

ProteinModelPortaliQ62862.
SMRiQ62862. Positions 7-113.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 10992PB1PROSITE-ProRule annotationAdd
BLAST
Domaini166 – 419254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni18 – 258Interaction with MAPK7By similarity
Regioni64 – 685Interaction with MAP3K2/MAP3K3By similarity
Regioni117 – 13115Interaction with MAPK7By similarityAdd
BLAST

Domaini

Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the PB1 domain. This domain also mediates interactions with SQSTM1 and PARD6A (By similarity).By similarity

Sequence similaritiesi

Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ62862.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ62862.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-1 (identifier: Q62862-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLWLALGPFR AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ
60 70 80 90 100
VLPEATTTAF EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE
110 120 130 140 150
PLQIFPRACK PPGERNIHGL KVNTRAGPSQ HTSPVVSDSL PSNSLKKSSA
160 170 180 190 200
ELRKILANGQ MNEQDIRYRD TLGHGNGGTV YKAYHVPSGK ILAVKVILLD
210 220 230 240 250
ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC TEFMDGGSLD
260 270 280 290 300
VYRKIPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTSGQVKLC
310 320 330 340 350
DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMELA
360 370 380 390 400
LGRFPYPQIQ KNQGSLMPLQ LLQCIVDEDS PVLPLGEFSE PFVHFITQCM
410 420 430 440
RKQPKERPAP EELMGHPFIV QFNDGNATVV SMWVCRALEE RRSQQGPP
Length:448
Mass (Da):50,198
Last modified:November 1, 1997 - v1
Checksum:i1B1CC8B05789B90D
GO
Isoform Alpha-2 (identifier: Q62862-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     349-358: Missing.

Show »
Length:438
Mass (Da):49,054
Checksum:iE48EA719AAFB4A2D
GO
Isoform Beta (identifier: Q62862-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: Missing.

Show »
Length:359
Mass (Da):40,091
Checksum:i583D96CC477AD92A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8989Missing in isoform Beta. 1 PublicationVSP_004880Add
BLAST
Alternative sequencei349 – 35810Missing in isoform Alpha-2. 1 PublicationVSP_004881

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37462 mRNA. Translation: AAC52320.1.
U37463 mRNA. Translation: AAC52321.1.
U37464 mRNA. Translation: AAC52322.1.
BC078860 mRNA. Translation: AAH78860.1.
RefSeqiNP_001029159.1. NM_001033987.1. [Q62862-1]
NP_058942.1. NM_017246.2. [Q62862-2]
XP_008764443.1. XM_008766221.1. [Q62862-3]
UniGeneiRn.11054.

Genome annotation databases

EnsembliENSRNOT00000010991; ENSRNOP00000010991; ENSRNOG00000007926. [Q62862-2]
ENSRNOT00000051558; ENSRNOP00000050528; ENSRNOG00000007926. [Q62862-1]
ENSRNOT00000079122; ENSRNOP00000070803; ENSRNOG00000007926. [Q62862-3]
GeneIDi29568.
KEGGirno:29568.
UCSCiRGD:61890. rat. [Q62862-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37462 mRNA. Translation: AAC52320.1.
U37463 mRNA. Translation: AAC52321.1.
U37464 mRNA. Translation: AAC52322.1.
BC078860 mRNA. Translation: AAH78860.1.
RefSeqiNP_001029159.1. NM_001033987.1. [Q62862-1]
NP_058942.1. NM_017246.2. [Q62862-2]
XP_008764443.1. XM_008766221.1. [Q62862-3]
UniGeneiRn.11054.

3D structure databases

ProteinModelPortaliQ62862.
SMRiQ62862. Positions 7-113.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ62862. 1 interaction.
STRINGi10116.ENSRNOP00000050528.

PTM databases

PhosphoSiteiQ62862.

Proteomic databases

PaxDbiQ62862.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000010991; ENSRNOP00000010991; ENSRNOG00000007926. [Q62862-2]
ENSRNOT00000051558; ENSRNOP00000050528; ENSRNOG00000007926. [Q62862-1]
ENSRNOT00000079122; ENSRNOP00000070803; ENSRNOG00000007926. [Q62862-3]
GeneIDi29568.
KEGGirno:29568.
UCSCiRGD:61890. rat. [Q62862-1]

Organism-specific databases

CTDi5607.
RGDi61890. Map2k5.

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ62862.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ62862.

Enzyme and pathway databases

BRENDAi2.7.12.2. 5301.

Miscellaneous databases

NextBioi609644.
PROiQ62862.

Gene expression databases

GenevisibleiQ62862. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation of MEK5 and differential expression of alternatively spliced forms."
    English J.M., Vanderbilt C.A., Xu S., Marcus S., Cobb M.H.
    J. Biol. Chem. 270:28897-28902(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1; ALPHA-2 AND BETA), FUNCTION, MUTAGENESIS.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
    Tissue: Lung.

Entry informationi

Entry nameiMP2K5_RAT
AccessioniPrimary (citable) accession number: Q62862
Secondary accession number(s): Q62863, Q62864
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: May 11, 2016
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.