Dual specificity mitogen-activated protein kinase kinase 3

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Preferred order of sections

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Contribute

Send feedback

Read comments (?) or add your own

O09110 (MP2K3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 121. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Protein names

Recommended name:
Dual specificity mitogen-activated protein kinase kinase 3
Short name=MAP kinase kinase 3
Short name=MAPKK 3
EC=2.7.12.2

Alternative name(s):
MAPK/ERK kinase 3
Short name=MEK 3

Gene names

Name:	Map2k3
Synonyms:	Mkk3, Prkmk3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Sequence length	347 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

Function	Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by dual phosphorylation on Ser-218 and Thr-222 By similarity.
Subunit structure	Binds to DYRK1B/MIRK and increases its kinase activity By similarity. Part of a complex with MAP3K3, RAC1 and CCM2. Interacts with ARRB1 By similarity. Ref.5
Post-translational modification	Phosphorylation on Ser-218 and Thr-222 by MAP kinase kinase kinases regulates positively the kinase activity. Phosphorylated by TAOK2 By similarity. Autophosphorylated.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain.

Keywords
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle contraction Inferred from mutant phenotype PubMed 11593045. Source: MGI inflammatory response Inferred from mutant phenotype PubMed 10097111 PubMed 10202148. Source: MGI positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara regulation of cytokine biosynthetic process Inferred from mutant phenotype PubMed 10097111. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase activity Inferred from direct assay PubMed 10202148 Ref.2. Source: MGI 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...

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 347

347

Dual specificity mitogen-activated protein kinase kinase 3

PRO_0000086379

Domain

64 – 325

262

Protein kinase

Nucleotide binding

70 – 78

ATP By similarity

Active site

190

Proton acceptor By similarity

Binding site

ATP By similarity

Modified residue

N-acetylmethionine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

218

Phosphoserine By similarity

Modified residue

222

Phosphothreonine By similarity

Alternative sequence

1 – 37

MESPA…PPVSN → MSKP in isoform 1.

VSP_004879

Sequence conflict

T → A Ref.1

Sequence conflict

E → K in CAA63649. Ref.1

Sequence conflict

173 – 347

175

IVRAL…LGEDS → M Ref.4

Sequence conflict

216

V → E in CAA63649. Ref.1

Sequence conflict

292

D → Y in CAA63649. Ref.1

Sequence		Length	Mass (Da)
Isoform 2 (3b) [UniParc]. Last modified November 1, 2002. Version 2. Checksum: 4A2A420EDCA8A2BC Show »	FASTA	347	39,296
10 20 30 40 50 60 MESPAASPPA SLPQTKGKSK RKKDLRISCV SKPPVSNPTP PRNLDSRTFI TIGDRNFEVE 70 80 90 100 110 120 ADDLVTISEL GRGAYGVVEK VRHAQSGTIM AVKRIRATVN TQEQKRLLMD LDINMRTVDC 130 140 150 160 170 180 FYTVTFYGAL FREGDVWICM ELMDTSLDKF YRKVLEKNMK IPEDILGEIA VSIVRALEHL 190 200 210 220 230 240 HSKLSVIHRD VKPSNVLINK EGHVKMCDFG ISGYLVDSVA KTMDAGCKPY MAPERINPEL 250 260 270 280 290 300 NQKGYNVKSD VWSLGITMIE MAILRFPYES WGTPFQQLKQ VVEEPSPQLP ADQFSPEFVD 310 320 330 340 FTSQCLRKNP AERMSYLELM EHPFFTLHKT KKTDIAAFVK EILGEDS « Hide
Isoform 1 [UniParc]. Checksum: 3F85122E7F272D5B Show »	FASTA	314	35,836
10 20 30 40 50 60 MSKPPTPPRN LDSRTFITIG DRNFEVEADD LVTISELGRG AYGVVEKVRH AQSGTIMAVK 70 80 90 100 110 120 RIRATVNTQE QKRLLMDLDI NMRTVDCFYT VTFYGALFRE GDVWICMELM DTSLDKFYRK 130 140 150 160 170 180 VLEKNMKIPE DILGEIAVSI VRALEHLHSK LSVIHRDVKP SNVLINKEGH VKMCDFGISG 190 200 210 220 230 240 YLVDSVAKTM DAGCKPYMAP ERINPELNQK GYNVKSDVWS LGITMIEMAI LRFPYESWGT 250 260 270 280 290 300 PFQQLKQVVE EPSPQLPADQ FSPEFVDFTS QCLRKNPAER MSYLELMEHP FFTLHKTKKT 310 DIAAFVKEIL GEDS « Hide

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Neininger A., Gaestel M. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Purification and identification of a major activator for p38 from osmotically shocked cells: activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2." Moriguchi T., Toyoshima F., Gotoh Y., Iwamatsu A., Irie K., Mori E., Kuroyanagi N., Hagiwara M., Matsumoto K., Nishida E. J. Biol. Chem. 271:26981-26988(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"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. Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Embryonic liver and Small intestine.
[4]	"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] (ISOFORM 1). Tissue: Mammary gland.
[5]	"Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock." Uhlik M.T., Abell A.N., Johnson N.L., Sun W., Cuevas B.D., Lobel-Rice K.E., Horne E.A., Dell'Acqua M.L., Johnson G.L. Nat. Cell Biol. 5:1104-1110(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP3K3; RAC1 AND CCM2.
+	Additional computationally mapped references.

EMBL
GenBank
DDBJ

X93150 mRNA. Translation: CAA63649.1.
D87115 mRNA. Translation: BAA13247.1.
AK011002 mRNA. Translation: BAB27321.1.
AK008141 mRNA. Translation: BAB25489.1.
BC007467 mRNA. Translation: AAH07467.1.

IPI

IPI00114245.
IPI00230052.

RefSeq

NP_032954.1. NM_008928.4.

UniGene

Mm.18494.

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LEZ	X-ray	2.30	B	16-32	[»]

ProteinModelPortal

O09110.

SMR

O09110. Positions 16-345.

ModBase

Search...

IntAct

O09110. 2 interactions.

PhosphoSite

O09110.

PaxDb

O09110.

PRIDE

O09110.

StructuralBiologyKnowledgebase

Search...

Ensembl

ENSMUST00000019076; ENSMUSP00000019076; ENSMUSG00000018932.
ENSMUST00000130269; ENSMUSP00000114430; ENSMUSG00000018932.

GeneID

26397.

KEGG

mmu:26397.

CTD

5606.

MGI

MGI:1346868. Map2k3.

eggNOG

COG0515.

GeneTree

ENSGT00690000102058.

HOGENOM

HOG000234206.

HOVERGEN

HBG108518.

InParanoid

O09110.

K04432.

OMA

LRISCVS.

OrthoDB

EOG4P2Q2M.

BRENDA

2.7.12.2. 3474.

ArrayExpress

O09110.

Bgee

O09110.

CleanEx

MM_MAP2K3.

Genevestigator

O09110.

GermOnline

ENSMUSG00000018932. Mus musculus.

InterPro

IPR011009. Kinase-like_dom.
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

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

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...

NextBio

304347.

SOURCE

Search...

Entry name

MP2K3_MOUSE

Accession

Primary (citable) accession number: O09110
Secondary accession number(s): P97293, Q91VX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 2002
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: O09110-1)

Also known as: 3b;

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 1 (identifier: O09110-2)

The sequence of this isoform differs from the canonical sequence as follows:
1-37: MESPAASPPASLPQTKGKSKRKKDLRISCVSKPPVSN → MSKP