Reviewed,
UniProtKB/Swiss-Prot P27361 (MK03_HUMAN)
Last modified
June 16, 2009.
Version 111.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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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 |
| ||||
| 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
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
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References
| « Hide '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. 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. 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 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | |||||||||||||
| |||||||||||||
| 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 |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 16 Human chromosome 16: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| 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 |

Clusters with


