| UniProt ID | MK01_HUMAN | |
|---|---|---|
| UniProt AC | P28482 | |
| Protein Name | Mitogen-activated protein kinase 1 | |
| Gene Name | MAPK1 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 360 | |
| Subcellular Localization | Cytoplasm, cytoskeleton, spindle. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm. Membrane, caveola . Associated with the spindle during prometaphase and metaphase (By similarity). PEA15-binding and phosphoryla | |
| Protein Description | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).; Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.. | |
| Protein Sequence | MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 2 | Acetylation | ------MAAAAAAGA ------CHHHHHCCC | 13.05 | 19413330 | |
| 13 | Sulfoxidation | AAGAGPEMVRGQVFD HCCCCHHHHCCCEEE | 2.54 | 28465586 | |
| 25 | Phosphorylation | VFDVGPRYTNLSYIG EEECCCCCCCCEEEC | 11.78 | 24927040 | |
| 29 | Phosphorylation | GPRYTNLSYIGEGAY CCCCCCCEEECCCCC | 19.44 | 19447520 | |
| 36 | Phosphorylation | SYIGEGAYGMVCSAY EEECCCCCEEEECCC | 19.33 | - | |
| 41 | Phosphorylation | GAYGMVCSAYDNVNK CCCEEEECCCCCCCE | 20.60 | 1378617 | |
| 43 | Phosphorylation | YGMVCSAYDNVNKVR CEEEECCCCCCCEEE | 7.55 | - | |
| 55 | Ubiquitination | KVRVAIKKISPFEHQ EEEEEEEECCCCCCH | 42.16 | - | |
| 55 | Ubiquitination | KVRVAIKKISPFEHQ EEEEEEEECCCCCCH | 42.16 | - | |
| 63 | Phosphorylation | ISPFEHQTYCQRTLR CCCCCCHHHHHHHHH | 28.33 | 28152594 | |
| 64 | Phosphorylation | SPFEHQTYCQRTLRE CCCCCHHHHHHHHHH | 4.68 | 28152594 | |
| 65 | S-nitrosylation | PFEHQTYCQRTLREI CCCCHHHHHHHHHHH | 2.21 | 19483679 | |
| 65 | S-nitrosocysteine | PFEHQTYCQRTLREI CCCCHHHHHHHHHHH | 2.21 | - | |
| 99 | Ubiquitination | APTIEQMKDVYIVQD CCCHHHHCCEEEEEC | 43.68 | - | |
| 99 | Ubiquitination | APTIEQMKDVYIVQD CCCHHHHCCEEEEEC | 43.68 | 21890473 | |
| 113 | Phosphorylation | DLMETDLYKLLKTQH CHHHCCHHHHHHHCC | 11.47 | - | |
| 138 | Ubiquitination | YQILRGLKYIHSANV HHHHHHCHHHHHCCC | 45.01 | - | |
| 142 | Phosphorylation | RGLKYIHSANVLHRD HHCHHHHHCCCCCCC | 16.39 | - | |
| 151 | Ubiquitination | NVLHRDLKPSNLLLN CCCCCCCCHHHEECC | 51.17 | - | |
| 151 | Ubiquitination | NVLHRDLKPSNLLLN CCCCCCCCHHHEECC | 51.17 | - | |
| 164 | Ubiquitination | LNTTCDLKICDFGLA CCCCCCEEECCCCCE | 28.21 | - | |
| 164 | Ubiquitination | LNTTCDLKICDFGLA CCCCCCEEECCCCCE | 28.21 | - | |
| 166 | S-nitrosylation | TTCDLKICDFGLARV CCCCEEECCCCCEEE | 3.20 | 19483679 | |
| 166 | S-nitrosocysteine | TTCDLKICDFGLARV CCCCEEECCCCCEEE | 3.20 | - | |
| 181 | Phosphorylation | ADPDHDHTGFLTEYV CCCCCCCCCHHHHHH | 35.37 | 22322096 | |
| 185 | Phosphorylation | HDHTGFLTEYVATRW CCCCCHHHHHHHHCC | 24.02 | 17591920 | |
| 186 | Phosphorylation | DHTGFLTEYVATRWY CCCCHHHHHHHHCCC | 39.91 | 17016520 | |
| 187 | Dephosphorylation | HTGFLTEYVATRWYR CCCHHHHHHHHCCCC | 7.08 | 12082107 | |
| 187 | Phosphorylation | HTGFLTEYVATRWYR CCCHHHHHHHHCCCC | 7.08 | 17591920 | |
| 190 | Phosphorylation | FLTEYVATRWYRAPE HHHHHHHHCCCCCCE | 16.22 | 29255136 | |
| 193 | Phosphorylation | EYVATRWYRAPEIML HHHHHCCCCCCEEHH | 8.13 | 25884760 | |
| 194 | Methylation | YVATRWYRAPEIMLN HHHHCCCCCCEEHHC | 36.38 | - | |
| 202 | Phosphorylation | APEIMLNSKGYTKSI CCEEHHCCCCCCCCH | 24.40 | 17192257 | |
| 203 | Malonylation | PEIMLNSKGYTKSID CEEHHCCCCCCCCHH | 55.66 | 26320211 | |
| 203 | Ubiquitination | PEIMLNSKGYTKSID CEEHHCCCCCCCCHH | 55.66 | 21890473 | |
| 203 | Ubiquitination | PEIMLNSKGYTKSID CEEHHCCCCCCCCHH | 55.66 | 21890473 | |
| 205 | Phosphorylation | IMLNSKGYTKSIDIW EHHCCCCCCCCHHHH | 18.09 | 9124279 | |
| 206 | Phosphorylation | MLNSKGYTKSIDIWS HHCCCCCCCCHHHHH | 27.30 | - | |
| 246 | Phosphorylation | HILGILGSPSQEDLN HHHHHCCCCCHHHHH | 20.24 | 25159151 | |
| 248 | Phosphorylation | LGILGSPSQEDLNCI HHHCCCCCHHHHHHH | 48.15 | 21730285 | |
| 248 | Ubiquitination | LGILGSPSQEDLNCI HHHCCCCCHHHHHHH | 48.15 | - | |
| 259 | Ubiquitination | LNCIINLKARNYLLS HHHHHHHHHHHHHHH | 40.59 | - | |
| 263 | Phosphorylation | INLKARNYLLSLPHK HHHHHHHHHHHCCCC | 11.94 | 20393185 | |
| 270 | Ubiquitination | YLLSLPHKNKVPWNR HHHHCCCCCCCCHHH | 57.43 | - | |
| 272 | Ubiquitination | LSLPHKNKVPWNRLF HHCCCCCCCCHHHCC | 55.25 | - | |
| 284 | Phosphorylation | RLFPNADSKALDLLD HCCCCCCHHHHHHHH | 19.88 | 18794356 | |
| 285 | Ubiquitination | LFPNADSKALDLLDK CCCCCCHHHHHHHHH | 54.22 | - | |
| 292 | Ubiquitination | KALDLLDKMLTFNPH HHHHHHHHHHHCCHH | 35.46 | 21890473 | |
| 295 | Phosphorylation | DLLDKMLTFNPHKRI HHHHHHHHCCHHHCC | 20.19 | 20071362 | |
| 300 | Ubiquitination | MLTFNPHKRIEVEQA HHHCCHHHCCCHHHH | 57.22 | - | |
| 300 | Ubiquitination | MLTFNPHKRIEVEQA HHHCCHHHCCCHHHH | 57.22 | - | |
| 330 | Ubiquitination | PIAEAPFKFDMELDD CCCCCCCCCCCCHHH | 39.12 | - | |
| 340 | Ubiquitination | MELDDLPKEKLKELI CCHHHCCHHHHHHHH | 74.83 | - | |
| 344 | Ubiquitination | DLPKEKLKELIFEET HCCHHHHHHHHHHHH | 62.64 | 21890473 | |
| 358 | Phosphorylation | TARFQPGYRS----- HHCCCCCCCC----- | 17.86 | 28102081 | |
| 360 | Phosphorylation | RFQPGYRS------- CCCCCCCC------- | 35.77 | 21712546 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 29 | S | Phosphorylation | Kinase | SGK1 | O00141 | Uniprot |
| 185 | T | Phosphorylation | Kinase | MEK1 | Q02750 | PSP |
| 185 | T | Phosphorylation | Kinase | MAP2K2 | P36507 | Uniprot |
| 185 | T | Phosphorylation | Kinase | MAP2K-FAMILY | - | GPS |
| 185 | T | Phosphorylation | Kinase | MAP2K_GROUP | - | PhosphoELM |
| 187 | Y | Phosphorylation | Kinase | JAK2 | O60674 | PSP |
| 187 | Y | Phosphorylation | Kinase | MP2K1 | Q02750 | PhosphoELM |
| 187 | Y | Phosphorylation | Kinase | MAP2K2 | P36507 | Uniprot |
| 187 | Y | Phosphorylation | Kinase | RET | P07949 | PSP |
| 190 | T | Phosphorylation | Kinase | MAPK1 | P28482 | GPS |
| 246 | S | Phosphorylation | Kinase | CSNK2A1 | P68400 | GPS |
| 246 | S | Phosphorylation | Kinase | MAPK1 | P28482 | GPS |
| 248 | S | Phosphorylation | Kinase | CSNK2A1 | P68400 | GPS |
| - | K | Ubiquitination | E3 ubiquitin ligase | MAP3K1 | Q13233 | PMID:12049732 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of MK01_HUMAN !! | ||||||
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| Acetylation | |
| Reference | PubMed |
| "Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY. | |
| "Exploring proteomes and analyzing protein processing by massspectrometric 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). Cited for: PROTEIN SEQUENCE OF 2-15, AND ACETYLATION AT ALA-2. | |
| Phosphorylation | |
| Reference | PubMed |
| "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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-63; THR-181; THR-185;TYR-187; SER-202 AND SER-284, AND MASS SPECTROMETRY. | |
| "Protein kinase SGK1 enhances MEK/ERK complex formation through thephosphorylation of ERK2: implication for the positive regulatory roleof SGK1 on the ERK function during liver regeneration."; Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J.,Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M.,Hur G.M.; J. Hepatol. 51:67-76(2009). Cited for: PHOSPHORYLATION AT SER-29 BY SGK1, AND INTERACTION WITH SGK1. | |
| "Identification and characterization of a general nucleartranslocation signal in signaling proteins."; Chuderland D., Konson A., Seger R.; Mol. Cell 31:850-861(2008). Cited for: PHOSPHORYLATION AT SER-246 AND SER-248, INTERACTION WITH IPO7, ANDSUBCELLULAR LOCATION. | |
| "Kinase-selective enrichment enables quantitative phosphoproteomics ofthe 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185; TYR-187 ANDSER-202, AND MASS SPECTROMETRY. | |
| "Quantitative phosphoproteomic analysis of T cell receptor signalingreveals 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, ANDMASS SPECTROMETRY. | |
| "A new type of ERK1/2 autophosphorylation causes cardiachypertrophy."; Lorenz K., Schmitt J.P., Schmitteckert E.M., Lohse M.J.; Nat. Med. 15:75-83(2009). Cited for: AUTOPHOSPHORYLATION AT THR-190, ENZYME REGULATION, SUBUNIT, ANDSUBCELLULAR LOCATION. | |
| "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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, ANDMASS SPECTROMETRY. | |
| "Proteomics analysis of protein kinases by target class-selectiveprefractionation 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, ANDMASS SPECTROMETRY. | |
| "Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, ANDMASS SPECTROMETRY. | |
| "Multiple reaction monitoring for robust quantitative proteomicanalysis 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, ANDMASS SPECTROMETRY. | |
| "Structural basis of substrate recognition by hematopoietic tyrosinephosphatase."; Critton D.A., Tortajada A., Stetson G., Peti W., Page R.; Biochemistry 47:13336-13345(2008). Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 186-191, AND PHOSPHORYLATIONAT TYR-187. | |
| "An extensive survey of tyrosine phosphorylation revealing new sitesin 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, AND MASSSPECTROMETRY. | |
| "Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits theRAS pathway by direct dephosphorylation of ERK1/2 kinases."; Sacco F., Tinti M., Palma A., Ferrari E., Nardozza A.P.,Hooft van Huijsduijnen R., Takahashi T., Castagnoli L., Cesareni G.; J. Biol. Chem. 284:22048-22058(2009). Cited for: PHOSPHORYLATION AT TYR-187, DEPHOSPHORYLATION BY PTPRJ AT TYR-187, ANDMUTAGENESIS OF ASP-318. | |
| "Quantitative phosphoproteome analysis using a dendrimer conjugationchemistry 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, AND MASSSPECTROMETRY. | |
| "Immunoaffinity profiling of tyrosine phosphorylation in cancercells."; 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, AND MASSSPECTROMETRY. | |
| "Time-resolved mass spectrometry of tyrosine phosphorylation sites inthe epidermal growth factor receptor signaling network reveals dynamicmodules."; 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, AND MASSSPECTROMETRY. | |
| "Global survey of phosphotyrosine signaling identifies oncogenickinases 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-187, AND MASSSPECTROMETRY. | |
