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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)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

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

Enzyme and pathway databases

ReactomeiREACT_272924. Signalling to ERK5.

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
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1346345. Map2k5.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi20 – 201R → A: Loss of MAPK7 binding; when associated with A-21. 1 Publication
Mutagenesisi21 – 211I → A: Loss of MAPK7 binding; when associated with A-20. 1 Publication
Mutagenesisi64 – 641D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-65. 1 Publication
Mutagenesisi65 – 651E → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-64. 1 Publication
Mutagenesisi67 – 671G → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-68. 1 Publication
Mutagenesisi68 – 681D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-67. 1 Publication
Mutagenesisi311 – 3111S → A: Dominant negative form; when associated with V-315. 1 Publication
Mutagenesisi311 – 3111S → D: Dominant active form; when associated with D-315. 1 Publication
Mutagenesisi315 – 3151T → D: Dominant active form; when associated with D-311. 1 Publication
Mutagenesisi315 – 3151T → V: Dominant negative form; when associated with A-311. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 448448Dual specificity mitogen-activated protein kinase kinase 5PRO_0000086384Add
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

MaxQBiQ9WVS7.
PaxDbiQ9WVS7.
PRIDEiQ9WVS7.

PTM databases

PhosphoSiteiQ9WVS7.

Expressioni

Gene expression databases

BgeeiQ9WVS7.
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. 10 interactions.
MINTiMINT-1728345.
STRINGi10090.ENSMUSP00000034920.

Structurei

Secondary structure

1
448
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi17 – 226Combined sources
Beta strandi28 – 347Combined sources
Beta strandi36 – 383Combined sources
Helixi41 – 5111Combined sources
Beta strandi60 – 623Combined sources
Beta strandi70 – 745Combined sources
Helixi75 – 9521Combined sources
Beta strandi102 – 1065Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WI0NMR-A8-107[»]
ProteinModelPortaliQ9WVS7.
SMRiQ9WVS7. Positions 16-438.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9WVS7.

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 MAPK7
Regioni64 – 685Interaction with MAP3K2/MAP3K3
Regioni117 – 13115Interaction with MAPK7Add
BLAST

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

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ9WVS7.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ9WVS7.
TreeFamiTF106468.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei108 – 11811ACKPPGERNIH → GYRRGSRLREY in isoform 4. 1 PublicationVSP_015836Add
BLAST
Alternative sequencei119 – 448330Missing in isoform 4. 1 PublicationVSP_015837Add
BLAST
Alternative sequencei183 – 1864AHHV → LLHI in isoform 3. 1 PublicationVSP_015838
Alternative sequencei187 – 448262Missing in isoform 3. 1 PublicationVSP_015839Add
BLAST
Alternative sequencei359 – 3679Missing in isoform 2. 1 PublicationVSP_015840

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_006511145.1. [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_006511145.1. [Q9WVS7-2]
UniGeneiMm.325746.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WI0NMR-A8-107[»]
ProteinModelPortaliQ9WVS7.
SMRiQ9WVS7. Positions 16-438.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9WVS7. 10 interactions.
MINTiMINT-1728345.
STRINGi10090.ENSMUSP00000034920.

PTM databases

PhosphoSiteiQ9WVS7.

Proteomic databases

MaxQBiQ9WVS7.
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

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ9WVS7.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ9WVS7.
TreeFamiTF106468.

Enzyme and pathway databases

ReactomeiREACT_272924. Signalling to ERK5.

Miscellaneous databases

EvolutionaryTraceiQ9WVS7.
NextBioi303741.
PROiQ9WVS7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WVS7.
CleanExiMM_MAP2K5.
GenevisibleiQ9WVS7. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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. "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.
    , 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.

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: June 24, 2015
This is version 127 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

External Data

Dasty 3

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 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.