Reviewed, UniProtKB/Swiss-Prot O09110 (MP2K3_MOUSE)

Names and origin

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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

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

General annotation (Comments)

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	Autophosphorylated.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain.

Ontologies

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
Gene Ontology (GO)
Biological process	activation of MAPK activity Inferred from direct assay. Source: MGI cardiac muscle contraction Inferred from mutant phenotype. Source: MGI inflammatory response Inferred from mutant phenotype. Source: MGI regulation of cytokine biosynthetic process Inferred from mutant phenotype. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase activity Ref.2 Inferred from direct assay. 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...

Alternative products

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 347	347	Dual specificity mitogen-activated protein kinase kinase 3		PRO_0000086379
Regions
	Domain	64 – 325	262	Protein kinase
	Nucleotide binding	70 – 78	9	ATP By similarity
Sites
	Active site	190	1	Proton acceptor By similarity
	Binding site	93	1	ATP By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	3	1	Phosphoserine By similarity
	Modified residue	218	1	Phosphoserine By similarity
	Modified residue	222	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	1 – 37	37	MESPA…PPVSN → MSKP in isoform 1.		VSP_004879
Experimental info
	Sequence conflict	39	1	T → A Ref.1
	Sequence conflict	60	1	E → K in CAA63649. Ref.1
	Sequence conflict	173 – 347	175	IVRAL…LGEDS → M Ref.4
	Sequence conflict	216	1	V → E in CAA63649. Ref.1
	Sequence conflict	292	1	D → Y in CAA63649. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (3b) [UniParc]. Last modified November 1, 2002. Version 2. Checksum: 4A2A420EDCA8A2BC	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
	Isoform 1. Checksum: 3F85122E7F272D5B	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

References

	« 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: 8900184] [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: 16141072] [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: 15489334] [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: 14634666] [Abstract] Cited for: INTERACTION WITH MAP3K3; RAC1 AND CCM2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
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.
UniGene	Mm.18494
3D structure databases
SMR	O09110. Positions 21-326.
ModBase	Search...
Protein-protein interaction databases
STRING	O09110.
PTM databases
PhosphoSite	O09110.
Proteomic databases
PRIDE	O09110.
Genome annotation databases
Ensembl	ENSMUST00000019076; ENSMUSP00000019076; ENSMUSG00000018932; Mus musculus. [Genome view]
GeneID	26397.
KEGG	mmu:26397.
UCSC	uc007jgx.1. mouse.
Organism-specific databases
CTD	26397.
MGI	MGI:1346868. Map2k3.
Phylogenomic databases
eggNOG	roNOG15456.
HOGENOM	HBG755340.
HOVERGEN	O09110.
InParanoid	O09110.
OMA	LDKNMTI.
OrthoDB	EOG9Q87GM.
PhylomeDB	O09110.
Enzyme and pathway databases
BRENDA	2.7.12.2. 244.
Gene expression databases
ArrayExpress	O09110.
Bgee	O09110.
CleanEx	MM_MAP2K3.
Genevestigator	O09110.
GermOnline	ENSMUSG00000018932. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	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	304347.
SOURCE	Search...

Entry information

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:	February 9, 2010
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)