Reviewed, UniProtKB/Swiss-Prot P63085 (MK01_MOUSE)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 1
    EC=2.7.11.24
Alternative name(s):
    Extracellular signal-regulated kinase 2
      Short name=ERK-2
    Mitogen-activated protein kinase 2
      Short name=MAP kinase 2
      Short name=MAPK 2
    p42-MAPK
    ERT1

Gene names

Name:	Mapk1
Synonyms:	Erk2, Mapk, Prkm1

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	358 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2) and heat shock factor protein 4 (HSF4) By similarity. Phosphorylates SPZ1.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by phosphorylation on tyrosine and threonine in response to insulin and NGF. Both phosphorylations are required for activity By similarity.
Subunit structure	Interacts with HSF4 and NISCH By similarity. Interacts with MORG1.
Tissue specificity	Widely expressed.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	B cell receptor signaling pathway Inferred from direct assay. Source: MGI MAPKKK cascade Inferred from direct assay. Source: MGI T cell receptor signaling pathway Inferred from direct assay. Source: MGI cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cytosine metabolic process Inferred from direct assay. Source: MGI lipopolysaccharide-mediated signaling pathway Inferred from direct assay. Source: MGI negative regulation of cell differentiation Inferred from genetic interaction. Source: MGI organ morphogenesis Inferred from direct assay. Source: MGI protein amino acid phosphorylation Inferred from direct assay. Source: MGI response to DNA damage stimulus Inferred from direct assay. Source: MGI response to exogenous dsRNA Inferred from direct assay. Source: MGI response to lipopolysaccharide Inferred from direct assay. Source: MGI
Cellular component	cytoplasm Inferred from direct assay. Source: MGI nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro MAP kinase 2 activity Inferred from direct assay. Source: MGI phosphotyrosine binding Inferred from mutant phenotype. Source: MGI transcription factor activity Inferred from Experiment. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2L11	O43521-1	1	EBI-397697,EBI-526416	From a different organism.
ELK1	P19419	1	EBI-397697,EBI-726632	From a different organism.
GSK3B	P49841	1	EBI-397697,EBI-373586	From a different organism.
Hivep1	Q03172	3	EBI-397697,EBI-646850
Mknk1	O08605	2	EBI-397697,EBI-646859
Mknk2	Q8CDB0	3	EBI-397697,EBI-646209
Rps6ka4	Q9Z2B9	2	EBI-397697,EBI-412887

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 358	357	Mitogen-activated protein kinase 1		PRO_0000186248
Regions
	Domain	23 – 311	289	Protein kinase
	Nucleotide binding	29 – 37	9	ATP By similarity
	Motif	183 – 185	3	TXY
	Compositional bias	2 – 7	6	Poly-Ala
Sites
	Active site	147	1	Proton acceptor By similarity
	Binding site	52	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	183	1	Phosphothreonine
	Modified residue	185	1	Phosphotyrosine
	Modified residue	188	1	Phosphothreonine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P63085-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3BBCF22471EDBA0B	FASTA	358	41,276
	10 20 30 40 50 60 MAAAAAAGPE MVRGQVFDVG PRYTNLSYIG EGAYGMVCSA YDNLNKVRVA IKKISPFEHQ 70 80 90 100 110 120 TYCQRTLREI KILLRFRHEN IIGINDIIRA PTIEQMKDVY IVQDLMETDL YKLLKTQHLS 130 140 150 160 170 180 NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP SNLLLNTTCD LKICDFGLAR VADPDHDHTG 190 200 210 220 230 240 FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML SNRPIFPGKH YLDQLNHILG 250 260 270 280 290 300 ILGSPSQEDL NCIINLKARN YLLSLPHKNK VPWNRLFPNA DSKALDLLDK MLTFNPHKRI 310 320 330 340 350 EVEQALAHPY LEQYYDPSDE PIAEAPFKFD MELDDLPKEK LKELIFEETA RFQPGYRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of pp42/MAP kinase, a serine/threonine kinase regulated by tyrosine phosphorylation." Her J.-H., Wu J.-S., Rall T.B., Sturgill T.W., Weber M.J. Nucleic Acids Res. 19:3743-3743(1991) [PubMed: 1649458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Swiss. Tissue: Fibroblast.
[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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Brain, Head, Thymus and Urinary bladder.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[4]	Lubec G., Klug S. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 54-65; 76-89; 137-146 AND 171-189, MASS SPECTROMETRY. Tissue: Hippocampus.
[5]	Lubec G., Kang S.U. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 137-146 AND 193-201, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain.
[6]	"Novel CDC2-related protein kinases produced in murine hematopoietic stem cells." Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V. Gene 124:305-306(1993) [PubMed: 8444355] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 152-190. Strain: CBA. Tissue: Bone marrow.
[7]	"Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase)." Payne D.M., Rossomando A.J., Martino P., Erickson A.K., Her J.-H., Shabanowitz J., Hunt D.F., Weber M.J., Sturgill T.W. EMBO J. 10:885-892(1991) [PubMed: 1849075] [Abstract] Cited for: PHOSPHORYLATION AT THR-183 AND TYR-185, PARTIAL PROTEIN SEQUENCE.
[8]	"Modular construction of a signaling scaffold: MORG1 interacts with components of the ERK cascade and links ERK signaling to specific agonists." Vomastek T., Schaeffer H.-J., Tarcsafalvi A., Smolkin M.E., Bissonette E.A., Weber M.J. Proc. Natl. Acad. Sci. U.S.A. 101:6981-6986(2004) [PubMed: 15118098] [Abstract] Cited for: INTERACTION WITH MORG1.
[9]	"bHLH-zip transcription factor Spz1 mediates mitogen-activated protein kinase cell proliferation, transformation, and tumorigenesis." Hsu S.-H., Hsieh-Li H.-M., Huang H.-Y., Huang P.-H., Li H. Cancer Res. 65:4041-4050(2005) [PubMed: 15899793] [Abstract] Cited for: PHOSPHORYLATION OF SPZ1.
[10]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY. Tissue: Mast cell.
[11]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY.
[12]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY. Tissue: Brain.
[13]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X58712 mRNA. Translation: CAA41548.1. AK035386 mRNA. Translation: BAC29053.1. AK048127 mRNA. Translation: BAC33251.1. AK087925 mRNA. Translation: BAC40044.1. AK132241 mRNA. Translation: BAE21053.1. BC058258 mRNA. Translation: AAH58258.1. D10939 mRNA. Translation: BAA01733.1.
PIR	S16444.
RefSeq	NP_001033752.1. NP_036079.1.
UniGene	Mm.196581
3D structure databases
SMR	P63085. Positions 9-353, 10-354.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63085.
PTM databases
PhosphoSite	P63085.
Genome annotation databases
Ensembl	ENSMUSG00000063358. Mus musculus. [Contig view]
GeneID	26413.
KEGG	mmu:26413.
NMPDR	fig|10090.3.peg.30922.
Organism-specific databases
MGI	MGI:1346858. Mapk1.
Phylogenomic databases
HOGENOM	P63085.
HOVERGEN	P63085.
Gene expression databases
ArrayExpress	P63085.
CleanEx	MM_MAPK1.
GermOnline	ENSMUSG00000063358. Mus musculus.
Family and domain databases
InterPro	IPR008349. Erk_1_2_MAPK. IPR003527. MAP_kin_CS. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01770. ERK1ERK2MAPK.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS01351. MAPK. 1 hit. 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	304409.
SOURCE	Search...

Entry information

Entry name

MK01_MOUSE

Accession

Primary (citable) accession number: P63085
Secondary accession number(s): P27703, Q3V1U6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	January 23, 2007
Last modified:	November 25, 2008
This is version 65 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)