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Protein

Dual specificity mitogen-activated protein kinase kinase 3

Gene

Map2k3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by dual phosphorylation on Ser-218 and Thr-222.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei93 – 931ATPPROSITE-ProRule annotation
Active sitei190 – 1901Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi70 – 789ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase kinase activity Source: MGI
  3. protein kinase binding Source: UniProtKB
  4. protein tyrosine kinase activity Source: UniProtKB-KW
  5. receptor signaling protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

  1. activation of MAPK activity Source: MGI
  2. cardiac muscle contraction Source: MGI
  3. inflammatory response Source: MGI
  4. MAPK cascade Source: MGI
  5. positive regulation of protein kinase activity Source: MGI
  6. positive regulation of transcription, DNA-templated Source: MGI
  7. regulation of cytokine biosynthetic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiREACT_188970. Oxidative Stress Induced Senescence.
REACT_237946. activated TAK1 mediates p38 MAPK activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 3 (EC:2.7.12.2)
Short name:
MAP kinase kinase 3
Short name:
MAPKK 3
Alternative name(s):
MAPK/ERK kinase 3
Short name:
MEK 3
Gene namesi
Name:Map2k3
Synonyms:Mkk3, Prkmk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:1346868. Map2k3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. membrane Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 347347Dual specificity mitogen-activated protein kinase kinase 3PRO_0000086379Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei3 – 31PhosphoserineBy similarity
Modified residuei218 – 2181PhosphoserineBy similarity
Modified residuei222 – 2221PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylation on Ser-218 and Thr-222 by MAP kinase kinase kinases regulates positively the kinase activity. Phosphorylated by TAOK2 (By similarity). Autophosphorylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO09110.
PaxDbiO09110.
PRIDEiO09110.

PTM databases

PhosphoSiteiO09110.

Expressioni

Gene expression databases

BgeeiO09110.
CleanExiMM_MAP2K3.
ExpressionAtlasiO09110. baseline and differential.
GenevestigatoriO09110.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi204951. 8 interactions.
IntActiO09110. 3 interactions.
MINTiMINT-4102274.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LEZX-ray2.30B16-32[»]
ProteinModelPortaliO09110.
SMRiO09110. Positions 16-345.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini64 – 325262Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiO09110.
KOiK04432.
OMAiNYLELME.
OrthoDBiEOG7J9VPW.
PhylomeDBiO09110.
TreeFamiTF350701.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: O09110-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MESPAASPPA SLPQTKGKSK RKKDLRISCV SKPPVSNPTP PRNLDSRTFI
60 70 80 90 100
TIGDRNFEVE ADDLVTISEL GRGAYGVVEK VRHAQSGTIM AVKRIRATVN
110 120 130 140 150
TQEQKRLLMD LDINMRTVDC FYTVTFYGAL FREGDVWICM ELMDTSLDKF
160 170 180 190 200
YRKVLEKNMK IPEDILGEIA VSIVRALEHL HSKLSVIHRD VKPSNVLINK
210 220 230 240 250
EGHVKMCDFG ISGYLVDSVA KTMDAGCKPY MAPERINPEL NQKGYNVKSD
260 270 280 290 300
VWSLGITMIE MAILRFPYES WGTPFQQLKQ VVEEPSPQLP ADQFSPEFVD
310 320 330 340
FTSQCLRKNP AERMSYLELM EHPFFTLHKT KKTDIAAFVK EILGEDS
Length:347
Mass (Da):39,296
Last modified:November 1, 2002 - v2
Checksum:i4A2A420EDCA8A2BC
GO
Isoform 1 (identifier: O09110-2) [UniParc]FASTAAdd to basket

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

Show »
Length:314
Mass (Da):35,836
Checksum:i3F85122E7F272D5B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti39 – 391T → A (Ref. 1) Curated
Sequence conflicti60 – 601E → K in CAA63649 (Ref. 1) Curated
Sequence conflicti173 – 347175IVRAL…LGEDS → M (PubMed:15489334).CuratedAdd
BLAST
Sequence conflicti216 – 2161V → E in CAA63649 (Ref. 1) Curated
Sequence conflicti292 – 2921D → Y in CAA63649 (Ref. 1) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3737MESPA…PPVSN → MSKP in isoform 1. 2 PublicationsVSP_004879Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24804.1. [O09110-1]
RefSeqiNP_032954.1. NM_008928.4. [O09110-1]
UniGeneiMm.18494.

Genome annotation databases

EnsembliENSMUST00000019076; ENSMUSP00000019076; ENSMUSG00000018932. [O09110-1]
GeneIDi26397.
KEGGimmu:26397.
UCSCiuc007jgw.1. mouse. [O09110-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24804.1. [O09110-1]
RefSeqiNP_032954.1. NM_008928.4. [O09110-1]
UniGeneiMm.18494.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LEZX-ray2.30B16-32[»]
ProteinModelPortaliO09110.
SMRiO09110. Positions 16-345.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204951. 8 interactions.
IntActiO09110. 3 interactions.
MINTiMINT-4102274.

PTM databases

PhosphoSiteiO09110.

Proteomic databases

MaxQBiO09110.
PaxDbiO09110.
PRIDEiO09110.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019076; ENSMUSP00000019076; ENSMUSG00000018932. [O09110-1]
GeneIDi26397.
KEGGimmu:26397.
UCSCiuc007jgw.1. mouse. [O09110-1]

Organism-specific databases

CTDi5606.
MGIiMGI:1346868. Map2k3.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiO09110.
KOiK04432.
OMAiNYLELME.
OrthoDBiEOG7J9VPW.
PhylomeDBiO09110.
TreeFamiTF350701.

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiREACT_188970. Oxidative Stress Induced Senescence.
REACT_237946. activated TAK1 mediates p38 MAPK activation.

Miscellaneous databases

NextBioi304347.
PROiO09110.
SOURCEiSearch...

Gene expression databases

BgeeiO09110.
CleanExiMM_MAP2K3.
ExpressionAtlasiO09110. baseline and differential.
GenevestigatoriO09110.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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. 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.
    , 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 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. Cited for: INTERACTION WITH MAP3K3; RAC1 AND CCM2.

Entry informationi

Entry nameiMP2K3_MOUSE
AccessioniPrimary (citable) accession number: O09110
Secondary accession number(s): P97293, Q91VX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 2002
Last modified: March 4, 2015
This is version 141 of the entry and version 2 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.