Dual specificity mitogen-activated protein kinase kinase 5

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Reviewed, UniProtKB/Swiss-Prot Q62862 (MP2K5_RAT)

Last modified October 13, 2009. Version 85. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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

Gene names

Name:	Map2k5
Synonyms:	Mek5, Mkk5, Prkmk5

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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Protein attributes

Sequence length	448 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appear to play a critical role in protecting cells from stress-induced apopotosis, neuronal survival and cardiac development and angiogenesis By similarity.
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 By similarity.
Subcellular location	Isoform Beta: Cytoplasm › cytosol. 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.
Tissue specificity	MEK5 beta is ubiquitously distributed with highest levels in the liver, whereas MEK5 alpha is expressed only in liver and brain.
Domain	Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the OPR domain. This domain also mediates interactions with SQSTM1 and PARD6A By similarity.
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.

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Ontologies

Keywords
Cellular component	Cytoplasm Membrane
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
Gene Ontology (GO)
Biological process	MAPKKK cascade Ref.1 Inferred by curator. Source: RGD positive regulation of cell growth Inferred from mutant phenotype. Source: RGD positive regulation of epithelial cell proliferation Inferred from direct assay. Source: RGD protein amino acid phosphorylation Ref.1 Inferred from direct assay. Source: RGD
Cellular component	cytosol Ref.1 Inferred from direct assay. Source: RGD membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: RGD
Molecular function	ATP binding Ref.1 Inferred from direct assay. Source: RGD MAP kinase activity Inferred from Experiment. Source: Reactome MAP kinase kinase activity Ref.1 Inferred by curator. Source: RGD magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha-1 (identifier: Q62862-1) 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.
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 (identifier: Q62862-2) The sequence of this isoform differs from the canonical sequence as follows: 349-358: Missing.
Note: The alternatively spliced exon in alpha isoform resemble conserved sequences that mediate interactions with the cytoskeleton, thereby explaining the differential localization.

Isoform Beta (identifier: Q62862-3) The sequence of this isoform differs from the canonical sequence as follows: 1-89: Missing.

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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_0000086385

Regions

Domain

18 – 97

OPR

Domain

166 – 419

254

Protein kinase

Nucleotide binding

172 – 180

ATP By similarity

Region

18 – 25

Interaction with MAPK7 By similarity

Region

64 – 68

Interaction with MAP3K2/MAP3K3 By similarity

Region

117 – 131

Interaction with MAPK7 By similarity

Sites

Active site

283

Proton acceptor By similarity

Binding site

195

ATP By similarity

Amino acid modifications

Modified residue

133

Phosphoserine By similarity

Modified residue

311

Phosphoserine By similarity

Modified residue

315

Phosphothreonine By similarity

Natural variations

Alternative sequence

1 – 89

Missing in isoform Beta.

VSP_004880

Alternative sequence

349 – 358

Missing in isoform Alpha-2.

VSP_004881

Experimental info

Mutagenesis

311

S → D: No change in activity.

Mutagenesis

315

T → D: No change in activity.

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Sequences

Sequence		Length	Mass (Da)
Isoform Alpha-1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 1B1CC8B05789B90D Show »	FASTA	448	50,198
10 20 30 40 50 60 MLWLALGPFR 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 YKAYHVPSGK ILAVKVILLD ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC 250 260 270 280 290 300 TEFMDGGSLD VYRKIPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTSGQVKLC 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 QFNDGNATVV SMWVCRALEE RRSQQGPP « Hide
Isoform Alpha-2. Checksum: E48EA719AAFB4A2D Show »	FASTA	438	49,054
10 20 30 40 50 60 MLWLALGPFR 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 YKAYHVPSGK ILAVKVILLD ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC 250 260 270 280 290 300 TEFMDGGSLD VYRKIPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTSGQVKLC 310 320 330 340 350 360 DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMEIQ KNQGSLMPLQ 370 380 390 400 410 420 LLQCIVDEDS PVLPLGEFSE PFVHFITQCM RKQPKERPAP EELMGHPFIV QFNDGNATVV 430 SMWVCRALEE RRSQQGPP « Hide
Isoform Beta. Checksum: 583D96CC477AD92A Show »	FASTA	359	40,091
10 20 30 40 50 60 MEQQVNGQLI EPLQIFPRAC KPPGERNIHG LKVNTRAGPS QHTSPVVSDS LPSNSLKKSS 70 80 90 100 110 120 AELRKILANG QMNEQDIRYR DTLGHGNGGT VYKAYHVPSG KILAVKVILL DITLELQKQI 130 140 150 160 170 180 MSELEILYKC DSSYIIGFYG AFFVENRISI CTEFMDGGSL DVYRKIPEHV LGRIAVAVVK 190 200 210 220 230 240 GLTYLWSLKI LHRDVKPSNM LVNTSGQVKL CDFGVSTQLV NSIAKTYVGT NAYMAPERIS 250 260 270 280 290 300 GEQYGIHSDV WSLGISFMEL ALGRFPYPQI QKNQGSLMPL QLLQCIVDED SPVLPLGEFS 310 320 330 340 350 EPFVHFITQC MRKQPKERPA PEELMGHPFI VQFNDGNATV VSMWVCRALE ERRSQQGPP « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 7499418] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1). Tissue: Lung.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	U37462 mRNA. Translation: AAC52320.1. U37463 mRNA. Translation: AAC52321.1. U37464 mRNA. Translation: AAC52322.1. BC078860 mRNA. Translation: AAH78860.1.
IPI	IPI00209255. IPI00230846. IPI00230847.
RefSeq	NP_001029159.1. NP_058942.1.
UniGene	Rn.11054
3D structure databases
HSSP	HSSP built from PDB template 1F3M based on UniProtKB Q13153.
SMR	Q62862. Positions 4-108.
ModBase	Search...
Protein-protein interaction databases
STRING	Q62862.
PTM databases
PhosphoSite	Q62862.
Genome annotation databases
Ensembl	ENSRNOT00000010991; ENSRNOP00000010991; ENSRNOG00000007926; Rattus norvegicus. [Genome view] ENSRNOT00000051558; ENSRNOP00000050528; ENSRNOG00000007926; Rattus norvegicus. [Genome view]
GeneID	29568.
KEGG	rno:29568.
UCSC	U37462. rat.
Organism-specific databases
CTD	29568.
RGD	61890. Map2k5.
Phylogenomic databases
HOVERGEN	Q62862.
Enzyme and pathway databases
BRENDA	2.7.12.2. 248.
Gene expression databases
ArrayExpress	Q62862.
Genevestigator	Q62862.
GermOnline	ENSRNOG00000007926. Rattus norvegicus.
Family and domain databases
InterPro	IPR000270. OPR_PB1. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00564. PB1. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00666. PB1. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	609644.

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Entry information

Entry name

MP2K5_RAT

Accession

Primary (citable) accession number: Q62862
Secondary accession number(s): Q62863, Q62864

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	October 13, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents