Reviewed, UniProtKB/Swiss-Prot P27361 (MK03_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 3
    EC=2.7.11.24
Alternative name(s):
    Extracellular signal-regulated kinase 1
      Short name=ERK-1
    Insulin-stimulated MAP2 kinase
    MAP kinase 1
      Short name=MAPK 1
    p44-ERK1
    ERT2
    p44-MAPK
    Microtubule-associated protein 2 kinase

Gene names

Name:	MAPK3
Synonyms:	ERK1, PRKM3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	379 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 ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1 By similarity. Phosphorylates heat shock factor protein 4 (HSF4).
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by tyrosine phosphorylation in response to insulin and NGF.
Subunit structure	Interacts with MORG1 By similarity. Binds to HIV-1 Nef. This interaction inhibits its kinase activity. Interacts with HSF4 and NISCH.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14
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 Host-virus interaction
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from Experiment. Source: Reactome cell cycle Inferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoskeleton Inferred from direct assay. Source: HPA cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB MAP kinase activity Ref.1 Non-traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAPK1	P53355	3	EBI-73995,EBI-358616
ELK1	P19419	1	EBI-73995,EBI-726632
PTPRB	P23467	1	EBI-73995,EBI-1265766
PTPRC	P08575	1	EBI-73995,EBI-1341
PTPRG	P23470	1	EBI-73995,EBI-2258115
PTPRJ	Q12913	1	EBI-73995,EBI-2264500
PTPRK	Q15262	1	EBI-73995,EBI-474052
PTPRO	Q16827	1	EBI-73995,EBI-723739
RPS6KA4	O75676	1	EBI-73995,EBI-73933

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.3
	Chain	2 – 379	378	Mitogen-activated protein kinase 3		PRO_0000186251
Regions
	Domain	42 – 330	289	Protein kinase
	Nucleotide binding	48 – 56	9	ATP By similarity
	Motif	202 – 204	3	TXY
Sites
	Active site	166	1	Proton acceptor By similarity
	Binding site	71	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.3
	Modified residue	202	1	Phosphothreonine Ref.9 Ref.12 Ref.13 Ref.14
	Modified residue	204	1	Phosphotyrosine Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14
Natural variations
	Natural variant	323	1	E → K Ref.16		VAR_042253
Experimental info
	Sequence conflict	174	1	I → S in CAA42744. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P27361-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: E6020CE413EC41F7	FASTA	379	43,136
	10 20 30 40 50 60 MAAAAAQGGG GGEPRRTEGV GPGVPGEVEM VKGQPFDVGP RYTQLQYIGE GAYGMVSSAY 70 80 90 100 110 120 DHVRKTRVAI KKISPFEHQT YCQRTLREIQ ILLRFRHENV IGIRDILRAS TLEAMRDVYI 130 140 150 160 170 180 VQDLMETDLY KLLKSQQLSN DHICYFLYQI LRGLKYIHSA NVLHRDLKPS NLLINTTCDL 190 200 210 220 230 240 KICDFGLARI ADPEHDHTGF LTEYVATRWY RAPEIMLNSK GYTKSIDIWS VGCILAEMLS 250 260 270 280 290 300 NRPIFPGKHY LDQLNHILGI LGSPSQEDLN CIINMKARNY LQSLPSKTKV AWAKLFPKSD 310 320 330 340 350 360 SKALDLLDRM LTFNPNKRIT VEEALAHPYL EQYYDPTDEP VAEEPFTFAM ELDDLPKERL 370 KELIFQETAR FQPGVLEAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1." Charest D.L., Jirik F., Harder K., Pelech S.L., Mordret G. Mol. Cell. Biol. 13:4679-4690(1993) [PubMed: 7687743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hepatoma.
[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]. Tissue: Lymph.
[3]	Bienvenut W.V., Dhillon A.S., Kolch W. Submitted (FEB-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-15; 33-41; 88-94; 117-131; 212-220; 279-287; 303-318 AND 360-370, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Hepatoma.
[4]	"Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs." Owaki H., Makar R., Boulton T.G., Cobb M.H., Geppert T.D. Biochem. Biophys. Res. Commun. 182:1416-1422(1992) [PubMed: 1540184] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-379.
[5]	"Heterogeneous expression of four MAP kinase isoforms in human tissues." Gonzalez F.A., Raden D.L., Rigby M.R., Davis R.J. FEBS Lett. 304:170-178(1992) [PubMed: 1319925] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-379.
[6]	"Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen-activated protein kinase, inhibiting kinase activity." Greenway A.L., Azad A., Mills J., McPhee D.A. J. Virol. 70:6701-6708(1996) [PubMed: 8794306] [Abstract] Cited for: INTERACTION WITH HIV-1 NEF.
[7]	"Insulin receptor substrate 4 associates with the protein IRAS." Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E. J. Biol. Chem. 277:19439-19447(2002) [PubMed: 11912194] [Abstract] Cited for: INTERACTION WITH NISCH.
[8]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-204, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26." Hu Y., Mivechi N.F. Mol. Cell. Biol. 26:3282-3294(2006) [PubMed: 16581800] [Abstract] Cited for: FUNCTION, INTERACTION WITH HSF4.
[11]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-204, MASS SPECTROMETRY.
[12]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, MASS SPECTROMETRY.
[13]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, MASS SPECTROMETRY.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, MASS SPECTROMETRY.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-323.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X60188 mRNA. Translation: CAA42744.1.
BC013992 mRNA. Translation: AAH13992.1.
M84490 mRNA. Translation: AAA36142.1.
Z11696 mRNA. Translation: CAA77754.1.

IPI

IPI00018195.

PIR

A48082.

RefSeq

NP_002737.2.

UniGene

Hs.861

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZOQ	X-ray	2.39	A/B	1-379	[»]

SMR

P27361. Positions 28-372, 29-373.

ModBase

Search...

Protein-protein interaction databases

IntAct

P27361. 25 interactions.

PTM databases

PhosphoSite

P27361.

Proteomic databases

PRIDE

P27361.

Genome annotation databases

Ensembl

ENSG00000102882. Homo sapiens. [Contig view]

GeneID

5595.

NMPDR

fig|9606.3.peg.12045.

Organism-specific databases

GeneCards

GC16M030032.

H-InvDB

HIX0012930.

HGNC

HGNC:6877. MAPK3.

HPA

CAB002683.
HPA003995.
HPA005700.

MIM

601795. gene.

PharmGKB

PA30622.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P27361.

HOVERGEN

P27361.

OMA

P27361. HFRHENI.

Enzyme and pathway databases

BRENDA

2.7.11.24. 247.

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
arf6downstreampathway. Arf6 downstream pathway.
bcr_5pathway. BCR signaling pathway.
anthraxpathway. Cellular roles of Anthrax toxin.
ceramidepathway. Ceramide signaling pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
ephbfwdpathway. EPHB forward signaling.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
ifngpathway. IFN-gamma pathway.
il2_1pathway. IL2-mediated signaling events.
avb3_integrin_pathway. Integrins in angiogenesis.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
avb3_opn_pathway. Osteopontin-mediated events.
ps1pathway. Presenilin action in Notch and Wnt signaling.
tcrraspathway. Ras signaling in the CD4+ TCR pathway.
smad2_3pathway. Regulation of cytoplasmic and nuclear SMAD2/3 signaling.
telomerasepathway. Regulation of Telomerase.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
s1p_s1p1_pathway. S1P1 pathway.
s1p_s1p2_pathway. S1P2 pathway.
s1p_s1p3_pathway. S1P3 pathway.
s1p_s1p4_pathway. S1P4 pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
prlsignalingeventspathway. Signaling events mediated by PRL.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
syndecan_1_pathway. Syndecan-1-mediated signaling events.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
trail_pathway. TRAIL signaling pathway.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
vegfr1_pathway. VEGFR1 specific signals.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_11061. Signalling by NGF.
REACT_1788. Transcription.
REACT_498. Signaling by Insulin receptor.
REACT_508. Signal attenuation.

Gene expression databases

ArrayExpress

P27361.

Bgee

P27361.

CleanEx

HS_MAPK3.

GermOnline

ENSG00000102882. Homo sapiens.

Family and domain databases

InterPro

IPR008349. Erk_1_2_MAPK.
IPR003527. MAP_kinase_CS.
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

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

DrugBank

DB01169. Arsenic trioxide.
DB01064. Isoproterenol.
DB00641. Simvastatin.
DB00605. Sulindac.

NextBio

21714.

SOURCE

Search...

Entry information

Entry name

MK03_HUMAN

Accession

Primary (citable) accession number: P27361

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 111 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)