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Q9WVS7 (MP2K5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity mitogen-activated protein kinase kinase 5

Short name=MAP kinase kinase 5
Short name=MAPKK 5
EC=2.7.12.2
Alternative name(s):
MAPK/ERK kinase 5
Short name=MEK 5
Gene names
Name:Map2k5
Synonyms:Mek5, Mkk5, Prkmk5
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length448 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Subunit structure

Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI. Ref.4 Ref.5

Subcellular location

Cytoplasm By similarity.

Domain

Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the OPR domain. This domain also mediates interactions with SQSTM1 and PARD6A. Ref.4 Ref.5

Post-translational modification

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

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.

Contains 1 OPR domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processERK5 cascade

Inferred from electronic annotation. Source: Ensembl

MAPK cascade

Inferred from mutant phenotype PubMed 15601854. Source: MGI

activation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

cellular response to growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from mutant phenotype PubMed 15601854. Source: MGI

negative regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell migration involved in sprouting angiogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of chemokine (C-X-C motif) ligand 2 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

negative regulation of heterotypic cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-8 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of response to cytokine stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

spindle

Inferred from direct assay PubMed 15509711. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 12912994PubMed 15102471. Source: IntAct

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9WVS7-1)

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.
Isoform 2 (identifier: Q9WVS7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     359-367: Missing.
Isoform 3 (identifier: Q9WVS7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     183-186: AHHV → LLHI
     187-448: Missing.
Isoform 4 (identifier: Q9WVS7-4)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 448448Dual specificity mitogen-activated protein kinase kinase 5
PRO_0000086384

Regions

Domain18 – 9780OPR
Domain166 – 419254Protein kinase
Nucleotide binding172 – 1809ATP By similarity
Region18 – 258Interaction with MAPK7
Region64 – 685Interaction with MAP3K2/MAP3K3
Region117 – 13115Interaction with MAPK7

Sites

Active site2831Proton acceptor By similarity
Binding site1951ATP By similarity

Amino acid modifications

Modified residue3111Phosphoserine By similarity
Modified residue3151Phosphothreonine By similarity

Natural variations

Alternative sequence108 – 11811ACKPPGERNIH → GYRRGSRLREY in isoform 4.
VSP_015836
Alternative sequence119 – 448330Missing in isoform 4.
VSP_015837
Alternative sequence183 – 1864AHHV → LLHI in isoform 3.
VSP_015838
Alternative sequence187 – 448262Missing in isoform 3.
VSP_015839
Alternative sequence359 – 3679Missing in isoform 2.
VSP_015840

Experimental info

Mutagenesis201R → A: Loss of MAPK7 binding; when associated with A-21. Ref.5
Mutagenesis211I → A: Loss of MAPK7 binding; when associated with A-20. Ref.5
Mutagenesis641D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-65. Ref.5
Mutagenesis651E → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-64. Ref.5
Mutagenesis671G → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-68. Ref.5
Mutagenesis681D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-67. Ref.5
Mutagenesis3111S → A: Dominant negative form; when associated with V-315. Ref.1
Mutagenesis3111S → D: Dominant active form; when associated with D-315. Ref.1
Mutagenesis3151T → D: Dominant active form; when associated with D-311. Ref.1
Mutagenesis3151T → V: Dominant negative form; when associated with A-311. Ref.1

Secondary structure

................ 448
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 50C50E8F0F712BE7

FASTA44850,105
        10         20         30         40         50         60 
MLWLALGPFC AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ VLPEATTTAF 

        70         80         90        100        110        120 
EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE PLQIFPRACK PPGERNIHGL 

       130        140        150        160        170        180 
KVNTRAGPSQ HTSPVVSDSL PSNSLKKSSA ELRKILANGQ MNEQDIRYRD TLGHGNGGTV 

       190        200        210        220        230        240 
YKAHHVPSGK ILAVKVILLD ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC 

       250        260        270        280        290        300 
TEFMDGGSLD VYRKIPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTGGQVKLC 

       310        320        330        340        350        360 
DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMELA LGRFPYPQIQ 

       370        380        390        400        410        420 
KNQGSLMPLQ LLQCIVDEDS PVLPLGEFSE PFVHFITQCM RKQPKERPAP EELMGHPFIV 

       430        440 
QFNDGNSTVV SMWVCRALEE RRSQQGPP 

« Hide

Isoform 2 [UniParc].

Checksum: ABAFCC35482F0EF6
Show »

FASTA43949,105
Isoform 3 [UniParc].

Checksum: 9978D2D647198D15
Show »

FASTA18620,737
Isoform 4 [UniParc].

Checksum: CACEC8FE6518544A
Show »

FASTA11813,589

References

« Hide 'large scale' references
[1]"Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus."
Kamakura S., Moriguchi T., Nishida E.
J. Biol. Chem. 274:26563-26571(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF SER-311 AND THR-315.
Tissue: Brain.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Strain: C57BL/6J.
Tissue: Head and Hypothalamus.
[3]"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] (ISOFORMS 2 AND 3).
Strain: Czech II.
Tissue: Mammary gland.
[4]"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins."
Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T.
J. Biol. Chem. 278:34568-34581(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SQSTM1; PRKCZ; PRKCI; PARD6A AND MAP3K3, DOMAIN.
[5]"PB1 domain-dependent signaling complex is required for extracellular signal-regulated kinase 5 activation."
Nakamura K., Uhlik M.T., Johnson N.L., Hahn K.M., Johnson G.L.
Mol. Cell. Biol. 26:2065-2079(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN, INTERACTION WITH MAP3K2 AND MAPK7, MUTAGENESIS OF ARG-20; ILE-21; ASP-64; GLU-65; GLY-67 AND ASP-68.
[6]"Solution structure of the PB1 domain of mouse mitogen activated protein kinase kinase 5 (MAP2K5)."
RIKEN structural genomics initiative (RSGI)
Submitted (JAN-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 7-107.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB019374 mRNA. Translation: BAA82040.1.
AK020716 mRNA. Translation: BAB32187.1.
BC013697 mRNA. Translation: AAH13697.1.
BC028260 mRNA. Translation: AAH28260.1.
CCDSCCDS23269.1. [Q9WVS7-1]
RefSeqNP_035970.1. NM_011840.2. [Q9WVS7-1]
XP_006511208.1. XM_006511145.1. [Q9WVS7-2]
UniGeneMm.325746.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WI0NMR-A8-107[»]
ProteinModelPortalQ9WVS7.
SMRQ9WVS7. Positions 16-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9WVS7. 10 interactions.
MINTMINT-1728345.

PTM databases

PhosphoSiteQ9WVS7.

Proteomic databases

PaxDbQ9WVS7.
PRIDEQ9WVS7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034920; ENSMUSP00000034920; ENSMUSG00000058444. [Q9WVS7-1]
GeneID23938.
KEGGmmu:23938.
UCSCuc009qaw.1. mouse. [Q9WVS7-1]
uc009qaz.1. mouse. [Q9WVS7-4]
uc012guv.1. mouse. [Q9WVS7-2]

Organism-specific databases

CTD5607.
MGIMGI:1346345. Map2k5.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00690000101918.
HOGENOMHOG000234206.
HOVERGENHBG108518.
InParanoidQ9WVS7.
KOK04463.
OMAEVVSMWV.
OrthoDBEOG7HF1KZ.
PhylomeDBQ9WVS7.
TreeFamTF106468.

Gene expression databases

BgeeQ9WVS7.
CleanExMM_MAP2K5.
GenevestigatorQ9WVS7.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAP2K5. mouse.
EvolutionaryTraceQ9WVS7.
NextBio303741.
PROQ9WVS7.
SOURCESearch...

Entry information

Entry nameMP2K5_MOUSE
AccessionPrimary (citable) accession number: Q9WVS7
Secondary accession number(s): Q8CFM3, Q8K360, Q9D222
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot