Protein: P28482

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P28482 (Uniprot) MK01_HUMAN MAPK1 Mitogen-activated protein kinase 1 human No
Uniprot: 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. more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0006139 nucleobase-containing compound metabolic process 27 GO:0007165 signal transduction 355 1.10e-111 5.07e-25
GO:0007165 signal transduction 355 GO:0006725 cellular aromatic compound metabolic process 736 5.44e-126 5.27e-27
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
3 GO:0022607 cellular component assembly
3 GO:0060255 regulation of macromolecule metabolic process
27 GO:0090304 nucleic acid metabolic process
27 GO:0060255 regulation of macromolecule metabolic process
29 GO:0060255 regulation of macromolecule metabolic process
29 GO:0007165 signal transduction
77 GO:0007165 signal transduction
238 GO:0060255 regulation of macromolecule metabolic process
355 GO:0007166 cell surface receptor signaling pathway
355 GO:0006464 cellular protein modification process
355 GO:0035556 intracellular signal transduction
355 GO:0016310 phosphorylation
355 GO:0010647 positive regulation of cell communication
355 GO:0048584 positive regulation of response to stimulus
355 GO:0023056 positive regulation of signaling
355 GO:0060255 regulation of macromolecule metabolic process
355 GO:0009966 regulation of signal transduction
412 GO:0019538 protein metabolic process
412 GO:0060255 regulation of macromolecule metabolic process
483 GO:0006464 cellular protein modification process
483 GO:0010467 gene expression
483 GO:0009059 macromolecule biosynthetic process
483 GO:0090304 nucleic acid metabolic process
483 GO:0060255 regulation of macromolecule metabolic process
483 GO:0007165 signal transduction
549 GO:0008219 cell death
549 GO:0070887 cellular response to chemical stimulus
549 GO:0033554 cellular response to stress
549 GO:0035556 intracellular signal transduction
549 GO:0031325 positive regulation of cellular metabolic process
549 GO:0010604 positive regulation of macromolecule metabolic process
549 GO:0051173 positive regulation of nitrogen compound metabolic process
549 GO:0048584 positive regulation of response to stimulus
549 GO:0006468 protein phosphorylation
549 GO:0051252 regulation of RNA metabolic process
549 GO:2000112 regulation of cellular macromolecule biosynthetic process
549 GO:0032268 regulation of cellular protein metabolic process
549 GO:0010468 regulation of gene expression
549 GO:0009966 regulation of signal transduction
549 GO:0006351 transcription, DNA-templated
577 GO:0006464 cellular protein modification process
577 GO:0033554 cellular response to stress
577 GO:0006796 phosphate-containing compound metabolic process
577 GO:0031326 regulation of cellular biosynthetic process
577 GO:0010556 regulation of macromolecule biosynthetic process
577 GO:0009966 regulation of signal transduction
610 GO:0008219 cell death
610 GO:0007166 cell surface receptor signaling pathway
610 GO:0006464 cellular protein modification process
610 GO:0031324 negative regulation of cellular metabolic process
610 GO:0051172 negative regulation of nitrogen compound metabolic process
610 GO:0016310 phosphorylation
610 GO:0010604 positive regulation of macromolecule metabolic process
610 GO:0051173 positive regulation of nitrogen compound metabolic process
610 GO:0008104 protein localization
610 GO:0051128 regulation of cellular component organization
610 GO:0032268 regulation of cellular protein metabolic process
610 GO:0009966 regulation of signal transduction
610 GO:0006355 regulation of transcription, DNA-templated
736 GO:0006139 nucleobase-containing compound metabolic process
736 GO:0060255 regulation of macromolecule metabolic process
837 GO:0009887 animal organ morphogenesis
837 GO:0006915 apoptotic process
837 GO:0007166 cell surface receptor signaling pathway
837 GO:0033554 cellular response to stress
837 GO:0018193 peptidyl-amino acid modification
837 GO:0051130 positive regulation of cellular component organization
837 GO:1902533 positive regulation of intracellular signal transduction
837 GO:0001934 positive regulation of protein phosphorylation
837 GO:0045893 positive regulation of transcription, DNA-templated
837 GO:0006357 regulation of transcription from RNA polymerase II promoter
837 GO:0051338 regulation of transferase activity
837 GO:0009628 response to abiotic stimulus
837 GO:0001501 skeletal system development
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
3 GO:0044430 cytoskeletal part
3 GO:0005829 cytosol
3 GO:0005634 nucleus
27 GO:0031981 nuclear lumen
29 GO:0005634 nucleus
77 GO:0070013 intracellular organelle lumen
77 GO:0005634 nucleus
238 GO:0005829 cytosol
238 GO:0005634 nucleus
317 GO:0005829 cytosol
328 GO:0005829 cytosol
328 GO:0043232 intracellular non-membrane-bounded organelle
328 GO:0005654 nucleoplasm
355 GO:0044459 plasma membrane part
412 GO:0005829 cytosol
412 GO:0005634 nucleus
483 GO:0005829 cytosol
483 GO:0031981 nuclear lumen
549 GO:0005829 cytosol
549 GO:0005634 nucleus
577 GO:0005829 cytosol
577 GO:0043232 intracellular non-membrane-bounded organelle
577 GO:0070013 intracellular organelle lumen
577 GO:0044428 nuclear part
577 GO:0031982 vesicle
610 GO:0031981 nuclear lumen
736 GO:0005829 cytosol
736 GO:0070013 intracellular organelle lumen
736 GO:0044428 nuclear part
812 GO:0005634 nucleus
837 GO:0005829 cytosol
837 GO:0005654 nucleoplasm
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000165 MAPK cascade TAS
GO:0000187 activation of MAPK activity TAS
GO:0006351 transcription, DNA-templated IEA
GO:0006468 protein phosphorylation IDA
GO:0006915 apoptotic process IEA
GO:0006935 chemotaxis TAS
GO:0006950 response to stress TAS
GO:0006974 cellular response to DNA damage stimulus IEA
GO:0007049 cell cycle IEA
GO:0007165 signal transduction TAS
GO:0007268 chemical synaptic transmission TAS
GO:0007411 axon guidance TAS
GO:0007611 learning or memory NAS
GO:0008284 positive regulation of cell proliferation IEA
GO:0008543 fibroblast growth factor receptor signaling pathway TAS
GO:0009636 response to toxic substance IEA
GO:0010628 positive regulation of gene expression IMP
GO:0010800 positive regulation of peptidyl-threonine phosphorylation IDA
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling TAS
GO:0015966 diadenosine tetraphosphate biosynthetic process IEA
GO:0016032 viral process IEA
GO:0018105 peptidyl-serine phosphorylation IDA
GO:0018107 peptidyl-threonine phosphorylation ISS
GO:0019233 sensory perception of pain IEA
GO:0019858 cytosine metabolic process IEA
GO:0030168 platelet activation TAS
GO:0030278 regulation of ossification IEA
GO:0030335 positive regulation of cell migration IEA
GO:0030641 regulation of cellular pH IEA
GO:0030878 thyroid gland development IEA
GO:0031647 regulation of protein stability ISS
GO:0031663 lipopolysaccharide-mediated signaling pathway IEA
GO:0032212 positive regulation of telomere maintenance via telomerase IMP
GO:0032872 regulation of stress-activated MAPK cascade TAS
GO:0033160 positive regulation of protein import into nucleus, translocation IEA
GO:0033598 mammary gland epithelial cell proliferation IEA
GO:0034198 cellular response to amino acid starvation IDA
GO:0034614 cellular response to reactive oxygen species IMP
GO:0035094 response to nicotine ISS
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0038127 ERBB signaling pathway IDA
GO:0042473 outer ear morphogenesis IEA
GO:0043312 neutrophil degranulation TAS
GO:0043330 response to exogenous dsRNA IEA
GO:0043627 response to estrogen IEA
GO:0045596 negative regulation of cell differentiation IEA
GO:0045727 positive regulation of translation IEA
GO:0045893 positive regulation of transcription, DNA-templated IEA
GO:0048538 thymus development IEA
GO:0050852 T cell receptor signaling pathway IEA
GO:0050853 B cell receptor signaling pathway IEA
GO:0051090 regulation of DNA binding transcription factor activity TAS
GO:0051403 stress-activated MAPK cascade IDA
GO:0051493 regulation of cytoskeleton organization TAS
GO:0051973 positive regulation of telomerase activity IMP
GO:0060020 Bergmann glial cell differentiation IEA
GO:0060291 long-term synaptic potentiation IEA
GO:0060324 face development IEA
GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway TAS
GO:0060425 lung morphogenesis IEA
GO:0060440 trachea formation IEA
GO:0060716 labyrinthine layer blood vessel development IEA
GO:0061308 cardiac neural crest cell development involved in heart development IEA
GO:0070371 ERK1 and ERK2 cascade TAS
GO:0070849 response to epidermal growth factor IDA
GO:0071276 cellular response to cadmium ion IMP
GO:0072584 caveolin-mediated endocytosis TAS
GO:0090170 regulation of Golgi inheritance TAS
GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus IEA
GO:1900034 regulation of cellular response to heat TAS
GO:1903351 cellular response to dopamine IMP
GO:1904355 positive regulation of telomere capping IMP
GO:2000641 regulation of early endosome to late endosome transport TAS
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005576 extracellular region TAS
GO:0005634 nucleus TAS
GO:0005654 nucleoplasm TAS
GO:0005737 cytoplasm IDA
GO:0005739 mitochondrion TAS
GO:0005769 early endosome TAS
GO:0005770 late endosome TAS
GO:0005794 Golgi apparatus TAS
GO:0005815 microtubule organizing center IEA
GO:0005829 cytosol TAS
GO:0005856 cytoskeleton TAS
GO:0005886 plasma membrane ISS
GO:0005901 caveola TAS
GO:0005925 focal adhesion TAS
GO:0030424 axon IEA
GO:0031143 pseudopodium IEA
GO:0032839 dendrite cytoplasm IEA
GO:0035578 azurophil granule lumen TAS
GO:0043204 perikaryon IEA
GO:0043234 protein complex IEA
GO:0070062 extracellular exosome IDA
GO:0072686 mitotic spindle ISS
GO:1904813 ficolin-1-rich granule lumen TAS
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005576 extracellular region GO:0005634 nucleus 4.48e-91 1.28e-107
GO:0005576 extracellular region GO:0005654 nucleoplasm 6.62e-72 7.68e-98
GO:0005576 extracellular region GO:0005815 microtubule organizing center 4.23e-04 2.20e-25
GO:0005634 nucleus GO:0005770 late endosome 4.75e-02 1.57e-04
GO:0005634 nucleus GO:0005794 Golgi apparatus 4.39e-25 2.14e-64
GO:0005634 nucleus GO:0005886 plasma membrane 5.35e-300 7.52e-165
GO:0005634 nucleus GO:0070062 extracellular exosome 6.30e-13 4.54e-26
GO:0005654 nucleoplasm GO:0005769 early endosome 5.29e-05 1.04e-19
GO:0005654 nucleoplasm GO:0005794 Golgi apparatus 1.14e-11 3.23e-62
GO:0005654 nucleoplasm GO:0005886 plasma membrane 9.14e-199 6.17e-196
GO:0005654 nucleoplasm GO:0030424 axon 9.82e-03 1.17e-43
GO:0005654 nucleoplasm GO:0070062 extracellular exosome 3.37e-20 1.23e-35
GO:0005815 microtubule organizing center GO:0005886 plasma membrane 3.20e-06 1.55e-21
PMID Article Title
1319925 Heterogeneous expression of four MAP kinase isoforms in human tissues.
1540184 Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs.
7588608 ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation.
8622688 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region.
8794306 Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen-activated protein kinase, inhibiting kinase activity.
9480836 MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated protein kinase, is a substrate of the extracellular-regulated kinase (ERK) and p38 kinase.
9596579 Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase.
9649500 Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor.
9687510 Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB.
9827991 A single amino acid substitution makes ERK2 susceptible to pyridinyl imidazole inhibitors of p38 MAP kinase.
10224087 Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway.
10591208 The DNA sequence of human chromosome 22.
10617468 Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation.
10637505 ERK activation induces phosphorylation of Elk-1 at multiple S/T-P motifs to high stoichiometry.
11154262 The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells.
11912194 Insulin receptor substrate 4 associates with the protein IRAS.
12110590 Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38.
12356731 IEX-1: a new ERK substrate involved in both ERK survival activity and ERK activation.
12665801 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.
12792650 Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.
12794087 Activation of ERK induces phosphorylation of MAPK phosphatase-7, a JNK specific phosphatase, at Ser-446.
12974390 EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2.
15184391 Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin.
15241487 MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol.
15358203 Nek2A specifies the centrosomal localization of Erk2.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15526160 Signal transduction via the stem cell factor receptor/c-Kit.
15616583 Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK.
15664191 Regulation of Raf-1 by direct feedback phosphorylation.
15788397 Phosphorylation of serine 147 of tis21/BTG2/pc3 by p-Erk1/2 induces Pin-1 binding in cytoplasm and cell death.
15952796 Phosphorylation of Grb10 by mitogen-activated protein kinase: identification of Ser150 and Ser476 of human Grb10zeta as major phosphorylation sites.
16139248 Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex.
16242327 Crystal structure of human ERK2 complexed with a pyrazolo[3,4-c]pyridazine derivative.
16393692 The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions.
16581800 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.
17081983 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
17194451 Role of a cysteine residue in the active site of ERK and the MAPKK family.
17274988 ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation.
17300186 Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.
18211802 ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA.
18296648 Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma.
18435604 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.
18669648 A quantitative atlas of mitotic phosphorylation.
18691976 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18760948 Identification and characterization of a general nuclear translocation signal in signaling proteins.
18794356 Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction.
19053285 Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.
19060905 A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy.
19265199 The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction.
19369195 Large-scale proteomics analysis of the human kinome.
19413330 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19447520 Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration.
19494114 Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases.
19565474 The ERK signaling cascade--views from different subcellular compartments.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19827834 Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control.
19879846 Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling.
20068231 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
21269460 Initial characterization of the human central proteome.
21406692 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21779493 The ERK cascade: distinct functions within various subcellular organelles.
22033920 Mitogen-activated protein kinase extracellular signal-regulated kinase 2 phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia protein turnover.
22223895 Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.
22814378 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23847209 Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
No results found.
Domain Name Domain ID Source
Prot_kinase_dom IPR000719 InterPro
MAP_kinase_CS IPR003527 InterPro
Ser/Thr_kinase_AS IPR008271 InterPro
MAPK_ERK1/2 IPR008349 InterPro
Kinase-like_dom_sf IPR011009 InterPro
Protein_kinase_ATP_BS IPR017441 InterPro
JQ1400 JQ1400 PIR
Pkinase PF00069 Pfam
ERK1ERK2MAPK PR01770 PRINTS
PROTEIN_KINASE_ATP PS00107 PROSITE
PROTEIN_KINASE_ST PS00108 PROSITE
MAPK PS01351 PROSITE
PROTEIN_KINASE_DOM PS50011 PROSITE
S_TKc SM00220 SMART
SSF56112 SSF56112 SUPFAM