Protein: P27361

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P27361 (Uniprot) MK03_HUMAN MAPK3 Mitogen-activated protein kinase 3 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, 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. 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:0007165 signal transduction 355 GO:0006139 nucleobase-containing compound metabolic process 572 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
29 GO:0060255 regulation of macromolecule metabolic process
29 GO:0007165 signal transduction
45 GO:0071495 cellular response to endogenous stimulus
45 GO:0071310 cellular response to organic substance
45 GO:0032270 positive regulation of cellular protein metabolic process
45 GO:0006468 protein phosphorylation
45 GO:0042325 regulation of phosphorylation
45 GO:0009966 regulation of signal transduction
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
401 GO:0034645 cellular macromolecule biosynthetic process
401 GO:0060255 regulation of macromolecule metabolic process
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
572 GO:0090304 nucleic acid metabolic process
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
724 GO:0016070 RNA metabolic process
724 GO:0035556 intracellular signal transduction
724 GO:0009892 negative regulation of metabolic process
724 GO:0034654 nucleobase-containing compound biosynthetic process
724 GO:0006468 protein phosphorylation
724 GO:2000112 regulation of cellular macromolecule biosynthetic process
724 GO:0032268 regulation of cellular protein metabolic process
724 GO:0010468 regulation of gene expression
724 GO:0019219 regulation of nucleobase-containing compound metabolic process
736 GO:0006139 nucleobase-containing compound metabolic process
736 GO:0060255 regulation of macromolecule metabolic process
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
3 GO:0044430 cytoskeletal part
3 GO:0005829 cytosol
3 GO:0005634 nucleus
29 GO:0005634 nucleus
45 GO:0005829 cytosol
45 GO:0031981 nuclear lumen
45 GO:0005886 plasma membrane
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
401 GO:0005634 nucleus
549 GO:0005829 cytosol
549 GO:0005634 nucleus
572 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
724 GO:0005829 cytosol
724 GO:0070013 intracellular organelle lumen
724 GO:0005634 nucleus
736 GO:0005829 cytosol
736 GO:0070013 intracellular organelle lumen
736 GO:0044428 nuclear part
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000165 MAPK cascade TAS
GO:0000187 activation of MAPK activity TAS
GO:0001934 positive regulation of protein phosphorylation IMP
GO:0002741 positive regulation of cytokine secretion involved in immune response IEA
GO:0006361 transcription initiation from RNA polymerase I promoter TAS
GO:0006461 protein complex assembly IEA
GO:0006468 protein phosphorylation IDA
GO:0006915 apoptotic process IEA
GO:0006975 DNA damage induced protein phosphorylation IDA
GO:0007049 cell cycle IEA
GO:0007411 axon guidance TAS
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:0010759 positive regulation of macrophage chemotaxis IEA
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling TAS
GO:0016032 viral process IEA
GO:0016310 phosphorylation IDA
GO:0018105 peptidyl-serine phosphorylation IEA
GO:0019233 sensory perception of pain IEA
GO:0019369 arachidonic acid metabolic process IEA
GO:0030168 platelet activation TAS
GO:0030278 regulation of ossification IEA
GO:0030509 BMP signaling pathway IMP
GO:0030641 regulation of cellular pH IEA
GO:0030878 thyroid gland development IEA
GO:0031281 positive regulation of cyclase activity IMP
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:0033129 positive regulation of histone phosphorylation IMP
GO:0034198 cellular response to amino acid starvation IDA
GO:0034614 cellular response to reactive oxygen species IMP
GO:0035066 positive regulation of histone acetylation IMP
GO:0038083 peptidyl-tyrosine autophosphorylation IDA
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0042473 outer ear morphogenesis IEA
GO:0043330 response to exogenous dsRNA IEA
GO:0045727 positive regulation of translation IEA
GO:0045944 positive regulation of transcription from RNA polymerase II promoter IMP
GO:0048538 thymus development IEA
GO:0051090 regulation of DNA binding transcription factor activity TAS
GO:0051216 cartilage development IEA
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: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:0061308 cardiac neural crest cell development involved in heart development IEA
GO:0070371 ERK1 and ERK2 cascade IEA
GO:0070374 positive regulation of ERK1 and ERK2 cascade IMP
GO:0070498 interleukin-1-mediated signaling pathway IMP
GO:0070849 response to epidermal growth factor IDA
GO:0071260 cellular response to mechanical stimulus IEP
GO:0071276 cellular response to cadmium ion IMP
GO:0072584 caveolin-mediated endocytosis TAS
GO:0090170 regulation of Golgi inheritance TAS
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:1904417 positive regulation of xenophagy IEA
GO:1905050 positive regulation of metallopeptidase activity IEA
GO:2000641 regulation of early endosome to late endosome transport TAS
GO:2000657 negative regulation of apolipoprotein binding IEA
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005634 nucleus TAS
GO:0005635 nuclear envelope IDA
GO:0005654 nucleoplasm TAS
GO:0005737 cytoplasm ISS
GO:0005739 mitochondrion TAS
GO:0005769 early endosome TAS
GO:0005770 late endosome TAS
GO:0005794 Golgi apparatus TAS
GO:0005829 cytosol TAS
GO:0005856 cytoskeleton TAS
GO:0005886 plasma membrane ISS
GO:0005901 caveola TAS
GO:0005925 focal adhesion TAS
GO:0031143 pseudopodium IEA
GO:0043234 protein complex IEA
GO:0070062 extracellular exosome IDA
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
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:0070062 extracellular exosome 3.37e-20 1.23e-35
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.
7687743 Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1.
8325880 Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase.
8794306 Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen-activated protein kinase, inhibiting kinase activity.
9155018 MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates.
9480836 MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated protein kinase, is a substrate of the extracellular-regulated kinase (ERK) and p38 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.
10393181 Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes.
10521408 Identification of a cytoplasmic-retention sequence in ERK2.
10617468 Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation.
10747973 c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock factor-1 suppress its transcriptional activity.
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.
12974390 EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2.
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.
15616553 The sequence and analysis of duplication-rich human chromosome 16.
15616583 Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK.
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.
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.
17274988 ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation.
17344846 Patterns of somatic mutation in human cancer genomes.
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.
18794356 Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction.
18983981 Crystal structure of human mono-phosphorylated ERK1 at Tyr204.
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.
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.
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.
24825908 Collaborator of ARF (CARF) regulates proliferative fate of human cells by dose-dependent regulation of DNA damage signaling.
No results found.
Domain Name Domain ID Source
A48082 A48082 PIR
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
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