Gene: MAPK3

Basic information

Tag Content
Uniprot ID P27361; A8CZ58; B0LPG3; Q8NHX1;
Entrez ID 5595
Genbank protein ID CAA42744.1; ABD60302.1; EAW79912.1; EAW79915.1; CAA77754.1; AAK52329.1; AAH13992.1; ABY87542.1; AAA36142.1;
Genbank nucleotide ID NM_002746.2; NM_001109891.1; NM_001040056.2;
Ensembl protein ID ENSP00000378625; ENSP00000263025; ENSP00000327293; ENSP00000378628;
Ensembl nucleotide ID ENSG00000102882
Gene name Mitogen-activated protein kinase 3
Gene symbol MAPK3
Organism Homo sapiens
NCBI taxa ID 9606
Cleft type
Developmental stage
Data sources Homology search
Reference
Functional 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, 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.
Sequence
MAAAAAQGGG GGEPRRTEGV GPGVPGEVEM VKGQPFDVGP RYTQLQYIGE GAYGMVSSAY 60
DHVRKTRVAI KKISPFEHQT YCQRTLREIQ ILLRFRHENV IGIRDILRAS TLEAMRDVYI 120
VQDLMETDLY KLLKSQQLSN DHICYFLYQI LRGLKYIHSA NVLHRDLKPS NLLINTTCDL 180
KICDFGLARI ADPEHDHTGF LTEYVATRWY RAPEIMLNSK GYTKSIDIWS VGCILAEMLS 240
NRPIFPGKHY LDQLNHILGI LGSPSQEDLN CIINMKARNY LQSLPSKTKV AWAKLFPKSD 300
SKALDLLDRM LTFNPNKRIT VEEALAHPYL EQYYDPTDEP VAEEPFTFAM ELDDLPKERL 360
KELIFQETAR FQPGVLEAP 379

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

  

Gene expression in different tissues (ENCODE)

  

Protein structural annotations

3D structure in PDB database


loading...

Protein disorder information

Orthologous information

Relation Gene symbol Entrez ID UniProt ID Cleft type Developmental stage Species Evidence Details
1:1 orthologMAPK3531391A0A3Q1MNN7Bos taurusPredictionMore>>
1:1 orthologMAPK3A0A452ETI1Capra hircusPredictionMore>>
1:1 orthologMAPK35595P27361Homo sapiensPredictionMore>>
1:1 orthologMapk326417Q63844CPOE13.5, E14.5, E15.5, E16.5Mus musculusPublicationMore>>
1:1 orthologMAPK3454037H2RA86Pan troglodytesPredictionMore>>
1:1 orthologA0A480NH74Sus scrofaPredictionMore>>
1:1 orthologMapk350689P21708Rattus norvegicusPredictionMore>>
1:1 orthologmapk3399480Q7ZVK8Danio rerioPredictionMore>>

Other genetic variants/mutations

loading...

Disease or phenotype associated information

loading...

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID GO Term Evidence
GO:0001784 phosphotyrosine residue bindingIEA
GO:0004707 MAP kinase activityIBA
GO:0004707 MAP kinase activityNAS
GO:0004707 MAP kinase activityIDA
GO:0004708 MAP kinase kinase activityIEA
GO:0005515 protein bindingIPI
GO:0005524 ATP bindingIEA
GO:0019902 phosphatase bindingIPI
GO:0042802 identical protein bindingIPI
GO:0097110 scaffold protein bindingIEA

GO:Biological Process

GO ID GO Term Evidence
GO:0000165 MAPK cascadeNAS
GO:0000165 MAPK cascadeTAS
GO:0000186 activation of MAPKK activityTAS
GO:0000187 activation of MAPK activityTAS
GO:0001934 positive regulation of protein phosphorylationIMP
GO:0002741 positive regulation of cytokine secretion involved in immune responseIEA
GO:0006361 transcription initiation from RNA polymerase I promoterTAS
GO:0006468 protein phosphorylationIDA
GO:0006915 apoptotic processIEA
GO:0006975 DNA damage induced protein phosphorylationIDA
GO:0007049 cell cycleIEA
GO:0007166 cell surface receptor signaling pathwayIBA
GO:0007411 axon guidanceTAS
GO:0007568 agingIEA
GO:0008543 fibroblast growth factor receptor signaling pathwayTAS
GO:0009636 response to toxic substanceIEA
GO:0010468 regulation of gene expressionIBA
GO:0010628 positive regulation of gene expressionIMP
GO:0010759 positive regulation of macrophage chemotaxisIEA
GO:0014066 regulation of phosphatidylinositol 3-kinase signalingTAS
GO:0016032 viral processIEA
GO:0016310 phosphorylationIDA
GO:0018105 peptidyl-serine phosphorylationIEA
GO:0019233 sensory perception of painIEA
GO:0019369 arachidonic acid metabolic processIEA
GO:0030168 platelet activationTAS
GO:0030278 regulation of ossificationIEA
GO:0030509 BMP signaling pathwayIMP
GO:0030641 regulation of cellular pHIEA
GO:0030878 thyroid gland developmentIEA
GO:0031281 positive regulation of cyclase activityIMP
GO:0031663 lipopolysaccharide-mediated signaling pathwayIEA
GO:0032212 positive regulation of telomere maintenance via telomeraseIMP
GO:0032872 regulation of stress-activated MAPK cascadeTAS
GO:0033129 positive regulation of histone phosphorylationIMP
GO:0034198 cellular response to amino acid starvationIDA
GO:0034614 cellular response to reactive oxygen speciesIMP
GO:0035066 positive regulation of histone acetylationIMP
GO:0035556 intracellular signal transductionIBA
GO:0038083 peptidyl-tyrosine autophosphorylationIDA
GO:0038095 Fc-epsilon receptor signaling pathwayTAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosisTAS
GO:0042473 outer ear morphogenesisIEA
GO:0043330 response to exogenous dsRNAIEA
GO:0045727 positive regulation of translationIEA
GO:0045944 positive regulation of transcription by RNA polymerase IIIMP
GO:0046697 decidualizationIEA
GO:0048538 thymus developmentIEA
GO:0051090 regulation of DNA-binding transcription factor activityTAS
GO:0051216 cartilage developmentIEA
GO:0051403 stress-activated MAPK cascadeIDA
GO:0051493 regulation of cytoskeleton organizationTAS
GO:0051973 positive regulation of telomerase activityIMP
GO:0060020 Bergmann glial cell differentiationIEA
GO:0060324 face developmentIEA
GO:0060425 lung morphogenesisIEA
GO:0060440 trachea formationIEA
GO:0061308 cardiac neural crest cell development involved in heart developmentIEA
GO:0065003 protein-containing complex assemblyIEA
GO:0070371 ERK1 and ERK2 cascadeIEA
GO:0070374 positive regulation of ERK1 and ERK2 cascadeIMP
GO:0070498 interleukin-1-mediated signaling pathwayIMP
GO:0070849 response to epidermal growth factorIDA
GO:0071260 cellular response to mechanical stimulusIEP
GO:0071276 cellular response to cadmium ionIMP
GO:0071310 cellular response to organic substanceIBA
GO:0071356 cellular response to tumor necrosis factorIEA
GO:0072584 caveolin-mediated endocytosisTAS
GO:0090170 regulation of Golgi inheritanceTAS
GO:1900034 regulation of cellular response to heatTAS
GO:1903351 cellular response to dopamineIMP
GO:1904355 positive regulation of telomere cappingIMP
GO:1904417 positive regulation of xenophagyIEA
GO:1905050 positive regulation of metallopeptidase activityIEA
GO:2000641 regulation of early endosome to late endosome transportTAS
GO:2000657 negative regulation of apolipoprotein bindingIEA

GO:Cellular Component

GO ID GO Term Evidence
GO:0005623 cellIEA
GO:0005634 nucleusTAS
GO:0005634 nucleusIBA
GO:0005635 nuclear envelopeIDA
GO:0005654 nucleoplasmTAS
GO:0005737 cytoplasmISS
GO:0005737 cytoplasmIBA
GO:0005739 mitochondrionTAS
GO:0005769 early endosomeTAS
GO:0005770 late endosomeTAS
GO:0005794 Golgi apparatusTAS
GO:0005829 cytosolTAS
GO:0005856 cytoskeletonTAS
GO:0005886 plasma membraneISS
GO:0005901 caveolaISS
GO:0005901 caveolaTAS
GO:0005925 focal adhesionTAS
GO:0031143 pseudopodiumIEA
GO:0032991 protein-containing complexIEA

Reactome Pathway

Reactome ID Reactome Term Evidence
R-HSA-109581 ApoptosisTAS
R-HSA-109582 HemostasisTAS
R-HSA-109606 Intrinsic Pathway for ApoptosisTAS
R-HSA-110056 MAPK3 (ERK1) activationTAS
R-HSA-111458 Formation of apoptosomeTAS
R-HSA-111461 Cytochrome c-mediated apoptotic responseTAS
R-HSA-111471 Apoptotic factor-mediated responseTAS
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmissionIEA
R-HSA-112315 Transmission across Chemical SynapsesIEA
R-HSA-112316 Neuronal SystemIEA
R-HSA-112409 RAF-independent MAPK1/3 activationTAS
R-HSA-1169408 ISG15 antiviral mechanismTAS
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genesTAS
R-HSA-1257604 PIP3 activates AKT signalingTAS
R-HSA-1266738 Developmental BiologyTAS
R-HSA-1280215 Cytokine Signaling in Immune systemTAS
R-HSA-1280215 Cytokine Signaling in Immune systemIEA
R-HSA-1295596 Spry regulation of FGF signalingTAS
R-HSA-162582 Signal TransductionTAS
R-HSA-162582 Signal TransductionIEA
R-HSA-162658 Golgi Cisternae Pericentriolar Stack ReorganizationTAS
R-HSA-1640170 Cell CycleTAS
R-HSA-1643685 DiseaseTAS
R-HSA-166016 Toll Like Receptor 4 (TLR4) CascadeTAS
R-HSA-166016 Toll Like Receptor 4 (TLR4) CascadeIEA
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membraneTAS
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membraneIEA
R-HSA-166166 MyD88-independent TLR4 cascade TAS
R-HSA-166166 MyD88-independent TLR4 cascade IEA
R-HSA-166520 Signaling by NTRKsTAS
R-HSA-166520 Signaling by NTRKsIEA
R-HSA-168138 Toll Like Receptor 9 (TLR9) CascadeTAS
R-HSA-168138 Toll Like Receptor 9 (TLR9) CascadeIEA
R-HSA-168142 Toll Like Receptor 10 (TLR10) CascadeTAS
R-HSA-168142 Toll Like Receptor 10 (TLR10) CascadeIEA
R-HSA-168164 Toll Like Receptor 3 (TLR3) CascadeTAS
R-HSA-168164 Toll Like Receptor 3 (TLR3) CascadeIEA
R-HSA-168176 Toll Like Receptor 5 (TLR5) CascadeTAS
R-HSA-168176 Toll Like Receptor 5 (TLR5) CascadeIEA
R-HSA-168179 Toll Like Receptor TLR1:TLR2 CascadeTAS
R-HSA-168179 Toll Like Receptor TLR1:TLR2 CascadeIEA
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) CascadeTAS
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) CascadeIEA
R-HSA-168188 Toll Like Receptor TLR6:TLR2 CascadeTAS
R-HSA-168188 Toll Like Receptor TLR6:TLR2 CascadeIEA
R-HSA-168249 Innate Immune SystemTAS
R-HSA-168249 Innate Immune SystemIEA
R-HSA-168256 Immune SystemTAS
R-HSA-168256 Immune SystemIEA
R-HSA-168898 Toll-like Receptor CascadesTAS
R-HSA-168898 Toll-like Receptor CascadesIEA
R-HSA-169893 Prolonged ERK activation eventsTAS
R-HSA-170968 Frs2-mediated activationTAS
R-HSA-181438 Toll Like Receptor 2 (TLR2) CascadeTAS
R-HSA-181438 Toll Like Receptor 2 (TLR2) CascadeIEA
R-HSA-187037 Signaling by NTRK1 (TRKA)TAS
R-HSA-187037 Signaling by NTRK1 (TRKA)IEA
R-HSA-187687 Signalling to ERKsTAS
R-HSA-190236 Signaling by FGFRTAS
R-HSA-194315 Signaling by Rho GTPasesTAS
R-HSA-195258 RHO GTPase EffectorsTAS
R-HSA-198725 Nuclear Events (kinase and transcription factor activation)TAS
R-HSA-198725 Nuclear Events (kinase and transcription factor activation)IEA
R-HSA-198753 ERK/MAPK targetsTAS
R-HSA-198753 ERK/MAPK targetsIEA
R-HSA-199418 Negative regulation of the PI3K/AKT networkTAS
R-HSA-202670 ERKs are inactivatedTAS
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosisTAS
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formationTAS
R-HSA-212436 Generic Transcription PathwayIEA
R-HSA-2262752 Cellular responses to stressTAS
R-HSA-2262752 Cellular responses to stressIEA
R-HSA-2454202 Fc epsilon receptor (FCERI) signalingTAS
R-HSA-2559580 Oxidative Stress Induced SenescenceTAS
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)TAS
R-HSA-2559583 Cellular SenescenceTAS
R-HSA-2559583 Cellular SenescenceIEA
R-HSA-2559585 Oncogene Induced SenescenceTAS
R-HSA-2559585 Oncogene Induced SenescenceIEA
R-HSA-2871796 FCERI mediated MAPK activationTAS
R-HSA-3371453 Regulation of HSF1-mediated heat shock responseTAS
R-HSA-3371556 Cellular response to heat stressTAS
R-HSA-372790 Signaling by GPCRTAS
R-HSA-373760 L1CAM interactionsTAS
R-HSA-375165 NCAM signaling for neurite out-growthTAS
R-HSA-388396 GPCR downstream signallingTAS
R-HSA-416476 G alpha (q) signalling eventsTAS
R-HSA-422475 Axon guidanceTAS
R-HSA-438064 Post NMDA receptor activation eventsIEA
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signalingIEA
R-HSA-442755 Activation of NMDA receptors and postsynaptic eventsIEA
R-HSA-444257 RSK activationIEA
R-HSA-445144 Signal transduction by L1TAS
R-HSA-448424 Interleukin-17 signalingTAS
R-HSA-448424 Interleukin-17 signalingIEA
R-HSA-449147 Signaling by InterleukinsTAS
R-HSA-449147 Signaling by InterleukinsIEA
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinasesTAS
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinasesIEA
R-HSA-450294 MAP kinase activationTAS
R-HSA-450294 MAP kinase activationIEA
R-HSA-450341 Activation of the AP-1 family of transcription factorsTAS
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs)TAS
R-HSA-5357801 Programmed Cell DeathTAS
R-HSA-5654726 Negative regulation of FGFR1 signalingTAS
R-HSA-5654727 Negative regulation of FGFR2 signalingTAS
R-HSA-5654732 Negative regulation of FGFR3 signalingTAS
R-HSA-5654733 Negative regulation of FGFR4 signalingTAS
R-HSA-5654736 Signaling by FGFR1TAS
R-HSA-5654738 Signaling by FGFR2TAS
R-HSA-5654741 Signaling by FGFR3TAS
R-HSA-5654743 Signaling by FGFR4TAS
R-HSA-5663202 Diseases of signal transductionTAS
R-HSA-5663205 Infectious diseaseTAS
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEsTAS
R-HSA-5668599 RHO GTPases Activate NADPH OxidasesTAS
R-HSA-5673001 RAF/MAP kinase cascadeTAS
R-HSA-5674135 MAP2K and MAPK activationTAS
R-HSA-5674499 Negative feedback regulation of MAPK pathwayTAS
R-HSA-5675221 Negative regulation of MAPK pathwayTAS
R-HSA-5683057 MAPK family signaling cascadesTAS
R-HSA-5684996 MAPK1/MAPK3 signalingTAS
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutantsTAS
R-HSA-6802948 Signaling by high-kinase activity BRAF mutantsTAS
R-HSA-6802949 Signaling by RAS mutantsTAS
R-HSA-6802952 Signaling by BRAF and RAF fusionsTAS
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAFTAS
R-HSA-6802957 Oncogenic MAPK signalingTAS
R-HSA-6807070 PTEN RegulationTAS
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingTAS
R-HSA-68875 Mitotic ProphaseTAS
R-HSA-68886 M PhaseTAS
R-HSA-69278 Cell Cycle, MitoticTAS
R-HSA-73728 RNA Polymerase I Promoter OpeningTAS
R-HSA-73854 RNA Polymerase I Promoter ClearanceTAS
R-HSA-73857 RNA Polymerase II TranscriptionIEA
R-HSA-73864 RNA Polymerase I TranscriptionTAS
R-HSA-74160 Gene expression (Transcription)IEA
R-HSA-74160 Gene expression (Transcription)TAS
R-HSA-74749 Signal attenuationTAS
R-HSA-74751 Insulin receptor signalling cascadeTAS
R-HSA-74752 Signaling by Insulin receptorTAS
R-HSA-76002 Platelet activation, signaling and aggregationTAS
R-HSA-879415 Advanced glycosylation endproduct receptor signalingIEA
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPKTAS
R-HSA-8878166 Transcriptional regulation by RUNX2IEA
R-HSA-8939211 ESR-mediated signalingIEA
R-HSA-8939211 ESR-mediated signalingTAS
R-HSA-8940973 RUNX2 regulates osteoblast differentiationIEA
R-HSA-8941326 RUNX2 regulates bone developmentIEA
R-HSA-8943724 Regulation of PTEN gene transcriptionTAS
R-HSA-8953897 Cellular responses to external stimuliTAS
R-HSA-8953897 Cellular responses to external stimuliIEA
R-HSA-9006925 Intracellular signaling by second messengersTAS
R-HSA-9006931 Signaling by Nuclear ReceptorsIEA
R-HSA-9006931 Signaling by Nuclear ReceptorsTAS
R-HSA-9006934 Signaling by Receptor Tyrosine KinasesTAS
R-HSA-9006934 Signaling by Receptor Tyrosine KinasesIEA
R-HSA-9009391 Extra-nuclear estrogen signalingIEA
R-HSA-913531 Interferon SignalingTAS
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling TAS
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling IEA
R-HSA-9607240 FLT3 SignalingTAS
R-HSA-9627069 Regulation of the apoptosome activityTAS
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signalingIEA
R-HSA-9635465 Suppression of apoptosisTAS
R-HSA-9635486 Infection with Mycobacterium tuberculosisTAS
R-HSA-9637690 Response of Mtb to phagocytosisTAS
R-HSA-9649948 Signaling downstream of RAS mutantsTAS
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationTAS
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationIEA
R-HSA-975155 MyD88 dependent cascade initiated on endosomeTAS
R-HSA-975155 MyD88 dependent cascade initiated on endosomeIEA
R-HSA-975871 MyD88 cascade initiated on plasma membraneTAS
R-HSA-975871 MyD88 cascade initiated on plasma membraneIEA
R-HSA-982772 Growth hormone receptor signalingTAS

Drugs and compounds information

loading...

Functional annotations

Keywords

Keyword ID Keyword Term
KW-0002 3D-structure
KW-0007 Acetylation
KW-0025 Alternative splicing
KW-0053 Apoptosis
KW-0067 ATP-binding
KW-0131 Cell cycle
KW-0963 Cytoplasm
KW-0903 Direct protein sequencing
KW-0945 Host-virus interaction
KW-0418 Kinase
KW-0472 Membrane
KW-0547 Nucleotide-binding
KW-0539 Nucleus
KW-0597 Phosphoprotein
KW-0621 Polymorphism
KW-1185 Reference proteome
KW-0723 Serine/threonine-protein kinase
KW-0808 Transferase

Interpro

InterPro ID InterPro Term
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008349 MAPK_ERK1/2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS

PROSITE

PROSITE ID PROSITE Term
PS01351 MAPK
PS00107 PROTEIN_KINASE_ATP
PS50011 PROTEIN_KINASE_DOM
PS00108 PROTEIN_KINASE_ST

Pfam

Pfam ID Pfam Term
PF00069 Pkinase

Protein-protein interaction

Protein-miRNA interaction