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Reviewed, UniProtKB/Swiss-Prot P28482 (MK01_HUMAN)

Last modified February 9, 2010. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length360 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DUSP1P285622EBI-959949,EBI-975493
ELK1P194191EBI-959949,EBI-726632
MBPP026871EBI-959949,EBI-908215From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4
Chain2 – 360359Mitogen-activated protein kinase 1
PRO_0000186247

Regions

Domain25 – 313289Protein kinase
Nucleotide binding31 – 399ATP By similarity
Motif185 – 1873TXY
Compositional bias2 – 98Poly-Ala

Sites

Active site1491Proton acceptor By similarity
Binding site541ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.4 Ref.19
Modified residue631Phosphothreonine
Modified residue1811Phosphothreonine
Modified residue1851Phosphothreonine Ref.12 Ref.14 Ref.16 Ref.17 Ref.22
Modified residue1871Phosphotyrosine Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.20 Ref.22
Modified residue1901Phosphothreonine By similarity
Modified residue2021Phosphoserine Ref.16
Modified residue2841Phosphoserine

Experimental info

Sequence conflict911R → Q in CAA77752. Ref.2

Secondary structure

........................................................... 360
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P28482-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E85D0B2A5D2D724E

FASTA36041,390
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
IPIIPI00003479.
PIRJQ1400.
RefSeqNP_002736.3.
NP_620407.1.
UniGeneHs.431850

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PMEX-ray2.00A1-360[»]
1TVOX-ray2.50A1-360[»]
1WZYX-ray2.50A1-360[»]
2E14X-ray3.00A1-360[»]
2OJGX-ray2.00A2-359[»]
2OJIX-ray2.60A2-359[»]
2OJJX-ray2.40A2-359[»]
3D42X-ray2.46B184-191[»]
3D44X-ray1.90B186-191[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-519N.
IntActP28482. 21 interactions.
STRINGP28482.

PTM databases

PhosphoSiteP28482.

2-D gel databases

OGPP28482.

Proteomic databases

PeptideAtlasP28482.
PRIDEP28482.

Genome annotation databases

EnsemblENST00000215832; ENSP00000215832; ENSG00000100030; Homo sapiens. [Genome view]
ENST00000398822; ENSP00000381803; ENSG00000100030; Homo sapiens. [Genome view]
GeneID5594.
KEGGhsa:5594.
UCSCuc002zvn.1. human.

Organism-specific databases

CTD5594.
GeneCardsGC22M020441.
H-InvDBHIX0016281.
HGNCHGNC:6871. MAPK1.
HPACAB004229.
HPA003995.
HPA005700.
MIM176948. gene.
Orphanet567. Monosomy 22q11.
PharmGKBPA30616.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG10833.
HOGENOMHBG755340.
HOVERGENP28482.
InParanoidP28482.
OMAQAFDVGP.
OrthoDBEOG9TTK32.
PhylomeDBP28482.

Enzyme and pathway databases

BRENDA2.7.11.24. 247.
Pathway_Interaction_DBalphasynuclein_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.
ReactomeREACT_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

CleanExHS_MAPK1.
GenevestigatorP28482.
GermOnlineENSG00000100030. Homo sapiens.

Family and domain databases

InterProIPR008349. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01770. ERK1ERK2MAPK.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01169. Arsenic trioxide.
NextBio21708.
SOURCESearch...

Entry information

Entry nameMK01_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

Relevant documents

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents