Q9WVS7 (MP2K5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	448 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ERK5 cascade Inferred from electronic annotation. Source: Compara MAPK cascade Inferred from mutant phenotype PubMed 15601854. Source: MGI activation of MAPK activity Inferred from electronic annotation. Source: Compara cellular response to growth factor stimulus Inferred from electronic annotation. Source: Compara heart development Inferred from mutant phenotype PubMed 15601854. Source: MGI negative regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cell migration involved in sprouting angiogenesis Inferred from electronic annotation. Source: Compara negative regulation of chemokine (C-X-C motif) ligand 2 production Inferred from electronic annotation. Source: Compara negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of heterotypic cell-cell adhesion Inferred from electronic annotation. Source: Compara negative regulation of interleukin-8 biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of response to cytokine stimulus Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara spindle Inferred from direct assay PubMed 15509711. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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

With	Entry	#Exp.	IntAct	Notes
Map3k2	Q61083	4	EBI-446144,EBI-446134
Map3k3	Q61084	15	EBI-446144,EBI-446250
Nap1l1	P28656	20	EBI-446144,EBI-645055
Sqstm1	Q64337	3	EBI-446144,EBI-645025

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 448

448

Dual specificity mitogen-activated protein kinase kinase 5

PRO_0000086384

Regions

Domain

18 – 97

80

OPR

Domain

166 – 419

254

Protein kinase

Nucleotide binding

172 – 180

9

ATP By similarity

Region

18 – 25

8

Interaction with MAPK7

Region

64 – 68

5

Interaction with MAP3K2/MAP3K3

Region

117 – 131

15

Interaction with MAPK7

Sites

Active site

283

1

Proton acceptor By similarity

Binding site

195

1

ATP By similarity

Amino acid modifications

Modified residue

311

1

Phosphoserine By similarity

Modified residue

315

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

108 – 118

11

ACKPPGERNIH → GYRRGSRLREY in isoform 4.

VSP_015836

Alternative sequence

119 – 448

330

Missing in isoform 4.

VSP_015837

Alternative sequence

183 – 186

4

AHHV → LLHI in isoform 3.

VSP_015838

Alternative sequence

187 – 448

262

Missing in isoform 3.

VSP_015839

Alternative sequence

359 – 367

9

Missing in isoform 2.

VSP_015840

Experimental info

Mutagenesis

20

1

R → A: Loss of MAPK7 binding; when associated with A-21. Ref.5

Mutagenesis

21

1

I → A: Loss of MAPK7 binding; when associated with A-20. Ref.5

Mutagenesis

64

1

D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-65. Ref.5

Mutagenesis

65

1

E → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-64. Ref.5

Mutagenesis

67

1

G → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-68. Ref.5

Mutagenesis

68

1

D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-67. Ref.5

Mutagenesis

311

1

S → A: Dominant negative form; when associated with V-315. Ref.1

Mutagenesis

311

1

S → D: Dominant active form; when associated with D-315. Ref.1

Mutagenesis

315

1

T → D: Dominant active form; when associated with D-311. Ref.1

Mutagenesis

315

1

T → V: Dominant negative form; when associated with A-311. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

448

Helix Strand Turn

Details...

Beta strand

17 – 22

6

Beta strand

28 – 34

7

Beta strand

36 – 38

3

Helix

41 – 51

11

Beta strand

60 – 62

3

Beta strand

70 – 74

5

Helix

75 – 95

21

Beta strand

102 – 106

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 50C50E8F0F712BE7	FASTA	448	50,105
	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
	Isoform 2 [UniParc]. Checksum: ABAFCC35482F0EF6	FASTA	439	49,105
	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 LGRFPYPQPL 370 380 390 400 410 420 QLLQCIVDED SPVLPLGEFS EPFVHFITQC MRKQPKERPA PEELMGHPFI VQFNDGNSTV 430 VSMWVCRALE ERRSQQGPP
	Isoform 3 [UniParc]. Checksum: 9978D2D647198D15	FASTA	186	20,737
	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 YKLLHI
	Isoform 4 [UniParc]. Checksum: CACEC8FE6518544A	FASTA	118	13,589
	10 20 30 40 50 60 MLWLALGPFC AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ VLPEATTTAF 70 80 90 100 110 EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE PLQIFPRGYR RGSRLREY

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00126447.
IPI00134154.
IPI00653118.
IPI00653587.

RefSeq

NP_035970.1. NM_011840.2.

UniGene

Mm.325746.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WI0	NMR	-	A	8-107	[»]

ProteinModelPortal

Q9WVS7.

SMR

Q9WVS7. Positions 16-419.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9WVS7. 10 interactions.

PTM databases

PhosphoSite

Q9WVS7.

Proteomic databases

PaxDb

Q9WVS7.

PRIDE

Q9WVS7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000034920; ENSMUSP00000034920; ENSMUSG00000058444.

GeneID

23938.

KEGG

mmu:23938.

UCSC

uc009qaw.1. mouse.
uc012guv.1. mouse.

Organism-specific databases

CTD

5607.

MGI

MGI:1346345. Map2k5.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00690000101918.

HOGENOM

HOG000234206.

HOVERGEN

HBG108518.

InParanoid

Q9WVS7.

KO

K04463.

OMA

FNDGNAT.

OrthoDB

EOG49GKGK.

Gene expression databases

Bgee

Q9WVS7.

CleanEx

MM_MAP2K5.

Genevestigator

Q9WVS7.

GermOnline

ENSMUSG00000058444. Mus musculus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

MAP2K5. mouse.

EvolutionaryTrace

Q9WVS7.

NextBio

303741.

SOURCE

Search...

Entry information

Entry name

MP2K5_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program