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Protein

Dual specificity mitogen-activated protein kinase kinase 5

Gene

Map2k5

Organism
Mus musculus (Mouse)
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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei195ATPPROSITE-ProRule annotation1
Active sitei283Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi172 – 180ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Ligandi

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

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1346345. Map2k5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • cytosol Source: Ensembl
  • nucleus Source: Ensembl
  • spindle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20R → A: Loss of MAPK7 binding; when associated with A-21. 1 Publication1
Mutagenesisi21I → A: Loss of MAPK7 binding; when associated with A-20. 1 Publication1
Mutagenesisi64D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-65. 1 Publication1
Mutagenesisi65E → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-64. 1 Publication1
Mutagenesisi67G → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-68. 1 Publication1
Mutagenesisi68D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-67. 1 Publication1
Mutagenesisi311S → A: Dominant negative form; when associated with V-315. 1 Publication1
Mutagenesisi311S → D: Dominant active form; when associated with D-315. 1 Publication1
Mutagenesisi315T → D: Dominant active form; when associated with D-311. 1 Publication1
Mutagenesisi315T → V: Dominant negative form; when associated with A-311. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863841 – 448Dual specificity mitogen-activated protein kinase kinase 5Add BLAST448

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei311PhosphoserineBy similarity1
Modified residuei315PhosphothreonineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9WVS7.
PRIDEiQ9WVS7.

PTM databases

iPTMnetiQ9WVS7.
PhosphoSitePlusiQ9WVS7.

Expressioni

Gene expression databases

BgeeiENSMUSG00000058444.
CleanExiMM_MAP2K5.
GenevisibleiQ9WVS7. MM.

Interactioni

Subunit structurei

Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Map3k2Q610834EBI-446144,EBI-446134
Map3k3Q6108415EBI-446144,EBI-446250
Nap1l1P2865620EBI-446144,EBI-645055
Sqstm1Q643373EBI-446144,EBI-645025

Protein-protein interaction databases

IntActiQ9WVS7. 11 interactors.
MINTiMINT-1728345.
STRINGi10090.ENSMUSP00000034920.

Structurei

Secondary structure

1448
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi17 – 22Combined sources6
Beta strandi28 – 34Combined sources7
Beta strandi36 – 38Combined sources3
Helixi41 – 51Combined sources11
Beta strandi60 – 62Combined sources3
Beta strandi70 – 74Combined sources5
Helixi75 – 95Combined sources21
Beta strandi102 – 106Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WI0NMR-A8-107[»]
ProteinModelPortaliQ9WVS7.
SMRiQ9WVS7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9WVS7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 109PB1PROSITE-ProRule annotationAdd BLAST92
Domaini166 – 419Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni18 – 25Interaction with MAPK71 Publication8
Regioni64 – 68Interaction with MAP3K2/MAP3K32 Publications5
Regioni117 – 131Interaction with MAPK71 PublicationAdd BLAST15

Domaini

Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the PB1 domain. This domain also mediates interactions with SQSTM1 and PARD6A.2 Publications

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.
InParanoidiQ9WVS7.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG091G06I7.
PhylomeDBiQ9WVS7.
TreeFamiTF106468.

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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9WVS7-1) [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
MLWLALGPFC 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 YKAHHVPSGK ILAVKVILLD
210 220 230 240 250
ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC TEFMDGGSLD
260 270 280 290 300
VYRKIPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTGGQVKLC
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 QFNDGNSTVV SMWVCRALEE RRSQQGPP
Length:448
Mass (Da):50,105
Last modified:November 1, 1999 - v1
Checksum:i50C50E8F0F712BE7
GO
Isoform 2 (identifier: Q9WVS7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-367: Missing.

Show »
Length:439
Mass (Da):49,105
Checksum:iABAFCC35482F0EF6
GO
Isoform 3 (identifier: Q9WVS7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     183-186: AHHV → LLHI
     187-448: Missing.

Show »
Length:186
Mass (Da):20,737
Checksum:i9978D2D647198D15
GO
Isoform 4 (identifier: Q9WVS7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     108-118: ACKPPGERNIH → GYRRGSRLREY
     119-448: Missing.

Show »
Length:118
Mass (Da):13,589
Checksum:iCACEC8FE6518544A
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015836108 – 118ACKPPGERNIH → GYRRGSRLREY in isoform 4. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_015837119 – 448Missing in isoform 4. 1 PublicationAdd BLAST330
Alternative sequenceiVSP_015838183 – 186AHHV → LLHI in isoform 3. 1 Publication4
Alternative sequenceiVSP_015839187 – 448Missing in isoform 3. 1 PublicationAdd BLAST262
Alternative sequenceiVSP_015840359 – 367Missing in isoform 2. 1 Publication9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB019374 mRNA. Translation: BAA82040.1.
AK020716 mRNA. Translation: BAB32187.1.
BC013697 mRNA. Translation: AAH13697.1.
BC028260 mRNA. Translation: AAH28260.1.
CCDSiCCDS23269.1. [Q9WVS7-1]
RefSeqiNP_035970.1. NM_011840.2. [Q9WVS7-1]
XP_006511208.1. XM_006511145.2. [Q9WVS7-2]
UniGeneiMm.325746.

Genome annotation databases

EnsembliENSMUST00000034920; ENSMUSP00000034920; ENSMUSG00000058444. [Q9WVS7-1]
GeneIDi23938.
KEGGimmu:23938.
UCSCiuc009qaw.1. mouse. [Q9WVS7-1]
uc009qaz.1. mouse. [Q9WVS7-4]
uc012guv.1. mouse. [Q9WVS7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB019374 mRNA. Translation: BAA82040.1.
AK020716 mRNA. Translation: BAB32187.1.
BC013697 mRNA. Translation: AAH13697.1.
BC028260 mRNA. Translation: AAH28260.1.
CCDSiCCDS23269.1. [Q9WVS7-1]
RefSeqiNP_035970.1. NM_011840.2. [Q9WVS7-1]
XP_006511208.1. XM_006511145.2. [Q9WVS7-2]
UniGeneiMm.325746.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WI0NMR-A8-107[»]
ProteinModelPortaliQ9WVS7.
SMRiQ9WVS7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9WVS7. 11 interactors.
MINTiMINT-1728345.
STRINGi10090.ENSMUSP00000034920.

PTM databases

iPTMnetiQ9WVS7.
PhosphoSitePlusiQ9WVS7.

Proteomic databases

PaxDbiQ9WVS7.
PRIDEiQ9WVS7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034920; ENSMUSP00000034920; ENSMUSG00000058444. [Q9WVS7-1]
GeneIDi23938.
KEGGimmu:23938.
UCSCiuc009qaw.1. mouse. [Q9WVS7-1]
uc009qaz.1. mouse. [Q9WVS7-4]
uc012guv.1. mouse. [Q9WVS7-2]

Organism-specific databases

CTDi5607.
MGIiMGI:1346345. Map2k5.

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ9WVS7.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG091G06I7.
PhylomeDBiQ9WVS7.
TreeFamiTF106468.

Miscellaneous databases

EvolutionaryTraceiQ9WVS7.
PROiQ9WVS7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000058444.
CleanExiMM_MAP2K5.
GenevisibleiQ9WVS7. MM.

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...

Entry informationi

Entry nameiMP2K5_MOUSE
AccessioniPrimary (citable) accession number: Q9WVS7
Secondary accession number(s): Q8CFM3, Q8K360, Q9D222
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: November 1, 1999
Last modified: November 2, 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. 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.