Reviewed, UniProtKB/Swiss-Prot P28482 (MK01_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 1
      Short name=MAP kinase 1
      Short name=MAPK 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
    MAP kinase isoform p42
      Short name=p42-MAPK
    ERT1

Gene names

Name:	MAPK1
Synonyms:	ERK2, PRKM1, PRKM2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	360 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). Phosphorylates SPZ1 By similarity. Phosphorylates heat shock factor protein 4 (HSF4) and ARHGEF2. Ref.13
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 MORG1 By similarity. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with its substrates HSF4 and ARHGEF2. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation By similarity. Interacts with NISCH. Interacts with ARRB2. Ref.13 Ref.5 Ref.6 Ref.8 Ref.15
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.20 Ref.22
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
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome 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 chemotaxis Traceable author statement. Source: ProtInc induction of apoptosis Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW synaptic transmission Traceable author statement. Source: ProtInc
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 Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DUSP1	P28562	2	EBI-959949,EBI-975493
ELK1	P19419	1	EBI-959949,EBI-726632
MBP	P02687	1	EBI-959949,EBI-908215	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4

Chain

2 – 360

359

Mitogen-activated protein kinase 1

PRO_0000186247

Regions

Domain

25 – 313

289

Protein kinase

Nucleotide binding

31 – 39

9

ATP By similarity

Motif

185 – 187

3

TXY

Compositional bias

2 – 9

8

Poly-Ala

Sites

Active site

149

1

Proton acceptor By similarity

Binding site

54

1

ATP By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.4 Ref.19

Modified residue

63

1

Phosphothreonine

Modified residue

181

1

Phosphothreonine

Modified residue

185

1

Phosphothreonine Ref.12 Ref.14 Ref.16 Ref.17 Ref.22

Modified residue

187

1

Phosphotyrosine Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.20 Ref.22

Modified residue

190

1

Phosphothreonine By similarity

Modified residue

202

1

Phosphoserine Ref.16

Modified residue

284

1

Phosphoserine

Experimental info

Sequence conflict

91

1

R → Q in CAA77752. Ref.2

Secondary structure

1

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360

Helix Strand Turn

Details...

Beta strand

25 – 30

6

Beta strand

39 – 44

6

Turn

45 – 47

3

Beta strand

49 – 56

8

Helix

62 – 77

16

Beta strand

88 – 90

3

Turn

95 – 97

3

Beta strand

101 – 106

6

Helix

112 – 118

7

Helix

123 – 142

20

Helix

152 – 154

3

Beta strand

155 – 157

3

Beta strand

163 – 165

3

Helix

176 – 178

3

Helix

191 – 193

3

Helix

196 – 198

3

Turn

199 – 201

3

Helix

208 – 223

16

Helix

233 – 244

12

Helix

249 – 253

5

Helix

258 – 265

8

Helix

275 – 278

4

Helix

284 – 293

10

Turn

298 – 300

3

Helix

304 – 308

5

Helix

311 – 313

3

Turn

314 – 316

3

Helix

319 – 321

3

Helix

340 – 350

11

Helix

352 – 354

3

Turn

356 – 358

3

Sequences

	Sequence		Length	Mass (Da)
	P28482-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E85D0B2A5D2D724E	FASTA	360	41,390
	10 20 30 40 50 60 MAAAAAAGAG PEMVRGQVFD VGPRYTNLSY IGEGAYGMVC SAYDNVNKVR VAIKKISPFE 70 80 90 100 110 120 HQTYCQRTLR EIKILLRFRH ENIIGINDII RAPTIEQMKD VYIVQDLMET DLYKLLKTQH 130 140 150 160 170 180 LSNDHICYFL YQILRGLKYI HSANVLHRDL KPSNLLLNTT CDLKICDFGL ARVADPDHDH 190 200 210 220 230 240 TGFLTEYVAT RWYRAPEIML NSKGYTKSID IWSVGCILAE MLSNRPIFPG KHYLDQLNHI 250 260 270 280 290 300 LGILGSPSQE DLNCIINLKA RNYLLSLPHK NKVPWNRLFP NADSKALDLL DKMLTFNPHK 310 320 330 340 350 360 RIEVEQALAH PYLEQYYDPS DEPIAEAPFK FDMELDDLPK EKLKELIFEE TARFQPGYRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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].
[2]	"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].
[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: Lung.
[4]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-15, ACETYLATION AT ALA-2. Tissue: Platelet.
[5]	"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.
[6]	"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.
[7]	"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-187, MASS SPECTROMETRY.
[8]	"ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA." Fujishiro S.H., Tanimura S., Mure S., Kashimoto Y., Watanabe K., Kohno M. Biochem. Biophys. Res. Commun. 368:162-167(2008) [PubMed: 18211802] [Abstract] Cited for: INTERACTION WITH ARHGEF2.
[9]	"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-187, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"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-185 AND TYR-187, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"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.
[14]	"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-185 AND TYR-187, MASS SPECTROMETRY.
[15]	"Mutations of beta-arrestin 2 that limit self-association also interfere with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs: implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs." Xu T.-R., Baillie G.S., Bhari N., Houslay T.M., Pitt A.M., Adams D.R., Kolch W., Houslay M.D., Milligan G. Biochem. J. 413:51-60(2008) [PubMed: 18435604] [Abstract] Cited for: INTERACTION WITH ARRB2.
[16]	"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-185; TYR-187 AND SER-202, MASS SPECTROMETRY.
[17]	"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-185 AND TYR-187, MASS SPECTROMETRY.
[18]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[19]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
[20]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[21]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-63; THR-181; THR-185; TYR-187; SER-202 AND SER-284, MASS SPECTROMETRY.
[22]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, MASS SPECTROMETRY. Tissue: T-cell.
+	Additional computationally mapped references.

Web resources

Wikipedia

Extracellular signal-regulated kinase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M84489 mRNA. Translation: AAA58459.1.
Z11694 mRNA. Translation: CAA77752.1.
Z11695 mRNA. Translation: CAA77753.1. Different initiation.
BC017832 mRNA. Translation: AAH17832.1.

IPI

IPI00003479.

PIR

JQ1400.

RefSeq

NP_002736.3.
NP_620407.1.

UniGene

Hs.431850

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PME	X-ray	2.00	A	1-360	[»]
1TVO	X-ray	2.50	A	1-360	[»]
1WZY	X-ray	2.50	A	1-360	[»]
2E14	X-ray	3.00	A	1-360	[»]
2OJG	X-ray	2.00	A	2-359	[»]
2OJI	X-ray	2.60	A	2-359	[»]
2OJJ	X-ray	2.40	A	2-359	[»]
3D42	X-ray	2.46	B	184-191	[»]
3D44	X-ray	1.90	B	186-191	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-519N.

IntAct

P28482. 21 interactions.

STRING

P28482.

PTM databases

PhosphoSite

P28482.

2-D gel databases

OGP

P28482.

Proteomic databases

PeptideAtlas

P28482.

PRIDE

P28482.

Genome annotation databases

Ensembl

ENST00000215832; ENSP00000215832; ENSG00000100030; Homo sapiens. [Genome view]
ENST00000398822; ENSP00000381803; ENSG00000100030; Homo sapiens. [Genome view]

GeneID

5594.

KEGG

hsa:5594.

UCSC

uc002zvn.1. human.

Organism-specific databases

CTD

5594.

GeneCards

GC22M020441.

H-InvDB

HIX0016281.

HGNC

HGNC:6871. MAPK1.

HPA

CAB004229.
HPA003995.
HPA005700.

MIM

176948. gene.

Orphanet

567. Monosomy 22q11.

PharmGKB

PA30616.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10833.

HOGENOM

HBG755340.

HOVERGEN

P28482.

InParanoid

P28482.

OMA

QAFDVGP.

OrthoDB

EOG9TTK32.

PhylomeDB

P28482.

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.
bmppathway. BMP receptor signaling.
anthraxpathway. Cellular roles of Anthrax toxin.
ceramidepathway. Ceramide signaling pathway.
pi3kcibpathway. Class IB PI3K non-lipid kinase events.
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.
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.
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_13685. Synaptic Transmission.
REACT_16888. Signaling by PDGF.
REACT_18266. Axon guidance.
REACT_498. Signaling by Insulin receptor.
REACT_6900. Signaling in Immune system.
REACT_9417. Signaling by EGFR.

Gene expression databases

CleanEx

HS_MAPK1.

Genevestigator

P28482.

GermOnline

ENSG00000100030. Homo sapiens.

Family and domain databases

InterPro

IPR008349. Erk_1_2_MAPK.
IPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
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]

PRINTS

PR01770. ERK1ERK2MAPK.

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.

NextBio

21708.

SOURCE

Search...

Entry information

Entry name

MK01_HUMAN

Accession

Primary (citable) accession number: P28482

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 121 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.