MAPK3 (mitogen-activated protein kinase 3)

Gene

• Entrez ID: 5595
• Gene name: Mitogen-activated protein kinase 3
• Gene symbol: MAPK3
• Synonyms: ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1, P44MAPK, PRKM3, p44-ERK1, p44-MAPK
• Chromosome: 16
• Chromosome location: 16p11.2
• Summary: The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006217	hsa-miR-483-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	22465663
MIRT006217	hsa-miR-483-5p	Luciferase reporter assay, qRT-PCR, Western blot	25622783
MIRT036229	hsa-miR-320b	CLASH	23622248
MIRT042561	hsa-miR-423-3p	CLASH	23622248
MIRT047369	hsa-miR-34a-5p	CLASH	23622248
MIRT732137	hsa-miR-550a-3p	Immunohistochemistry, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	27462780
MIRT732886	hsa-miR-9-3p	Western blot	28413458
MIRT734094	hsa-miR-375	Western blot	28186962

Transcription factors

Transcription factor	Regulation	Reference
TWIST1	Activation	23222305

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	NAS	20018936
GO:0000165	Process	MAPK cascade	TAS
GO:0000186	Process	Activation of MAPKK activity	TAS
GO:0000187	Process	Activation of MAPK activity	TAS
GO:0001784	Function	Phosphotyrosine residue binding	IEA
GO:0001934	Process	Positive regulation of protein phosphorylation	IMP	19664780
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	18391015
GO:0004707	Function	MAP kinase activity	IBA	21873635
GO:0004707	Function	MAP kinase activity	IDA	8388392
GO:0004707	Function	MAP kinase activity	NAS	7687743
GO:0004708	Function	MAP kinase kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	10066421, 10419510, 10617468, 10747973, 11238443, 12840032, 15616583, 15950189, 16291755, 18794356, 19167335, 19197339, 19494114, 19564905, 20347885, 20622900, 21900206, 22307056, 23397142, 23452857, 23602568, 24606918, 24722188, 24825908, 25066297, 25241761, 25852190, 26496610, 319
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	TAS	19565474
GO:0005635	Component	Nuclear envelope	IDA	20455999
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	ISS
GO:0005739	Component	Mitochondrion	TAS	19565474
GO:0005769	Component	Early endosome	TAS	19565474
GO:0005770	Component	Late endosome	TAS	19565474
GO:0005794	Component	Golgi apparatus	TAS	19565474
GO:0005829	Component	Cytosol	TAS	19565474
GO:0005856	Component	Cytoskeleton	TAS	19565474
GO:0005886	Component	Plasma membrane	ISS
GO:0005901	Component	Caveola	ISS
GO:0005901	Component	Caveola	TAS	19565474
GO:0005925	Component	Focal adhesion	TAS	19565474
GO:0006361	Process	Transcription initiation from RNA polymerase I promoter	TAS
GO:0006468	Process	Protein phosphorylation	IDA	7687743
GO:0006915	Process	Apoptotic process	IEA
GO:0006975	Process	DNA damage induced protein phosphorylation	IDA	17560175
GO:0007049	Process	Cell cycle	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IBA	21873635
GO:0007411	Process	Axon guidance	TAS
GO:0007568	Process	Aging	IEA
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	TAS
GO:0009636	Process	Response to toxic substance	IEA
GO:0010628	Process	Positive regulation of gene expression	IMP	24136195
GO:0010759	Process	Positive regulation of macrophage chemotaxis	IGI	26754294
GO:0014066	Process	Regulation of phosphatidylinositol 3-kinase signaling	TAS
GO:0016032	Process	Viral process	IEA
GO:0016310	Process	Phosphorylation	IDA	15950189
GO:0018105	Process	Peptidyl-serine phosphorylation	IEA
GO:0019233	Process	Sensory perception of pain	IEA
GO:0019369	Process	Arachidonic acid metabolic process	IEA
GO:0019902	Function	Phosphatase binding	IPI	19494114
GO:0030168	Process	Platelet activation	TAS
GO:0030278	Process	Regulation of ossification	IEA
GO:0030509	Process	BMP signaling pathway	IMP	19664780
GO:0030641	Process	Regulation of cellular pH	IEA
GO:0030878	Process	Thyroid gland development	IEA
GO:0031143	Component	Pseudopodium	IEA
GO:0031281	Process	Positive regulation of cyclase activity	IMP	22027397
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IEA
GO:0032212	Process	Positive regulation of telomere maintenance via telomerase	IMP	21531765
GO:0032872	Process	Regulation of stress-activated MAPK cascade	TAS	19565474
GO:0032991	Component	Protein-containing complex	IEA
GO:0033129	Process	Positive regulation of histone phosphorylation	IMP	20018936
GO:0034198	Process	Cellular response to amino acid starvation	IDA	11096076
GO:0034614	Process	Cellular response to reactive oxygen species	IMP	26514923
GO:0035066	Process	Positive regulation of histone acetylation	IMP	20018936
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0038083	Process	Peptidyl-tyrosine autophosphorylation	IDA	8388392
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0042473	Process	Outer ear morphogenesis	IEA
GO:0042802	Function	Identical protein binding	IPI	16627622, 22307056
GO:0043330	Process	Response to exogenous dsRNA	IEA
GO:0045727	Process	Positive regulation of translation	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	20018936
GO:0046697	Process	Decidualization	IEA
GO:0048538	Process	Thymus development	IEA
GO:0051090	Process	Regulation of DNA-binding transcription factor activity	TAS
GO:0051216	Process	Cartilage development	IEA
GO:0051403	Process	Stress-activated MAPK cascade	IDA	11096076
GO:0051493	Process	Regulation of cytoskeleton organization	TAS	19565474
GO:0051973	Process	Positive regulation of telomerase activity	IMP	21531765
GO:0060020	Process	Bergmann glial cell differentiation	IEA
GO:0060324	Process	Face development	IEA
GO:0060425	Process	Lung morphogenesis	IEA
GO:0060440	Process	Trachea formation	IEA
GO:0061308	Process	Cardiac neural crest cell development involved in heart development	IEA
GO:0065003	Process	Protein-containing complex assembly	IEA
GO:0070371	Process	ERK1 and ERK2 cascade	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IMP	19664780
GO:0070498	Process	Interleukin-1-mediated signaling pathway	IMP	20018936
GO:0070849	Process	Response to epidermal growth factor	IDA	18794356, 21968647
GO:0071260	Process	Cellular response to mechanical stimulus	IEP	19593445
GO:0071276	Process	Cellular response to cadmium ion	IMP	26514923
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0072584	Process	Caveolin-mediated endocytosis	TAS	19565474
GO:0090170	Process	Regulation of Golgi inheritance	TAS	19565474
GO:0097110	Function	Scaffold protein binding	IEA
GO:0120041	Process	Positive regulation of macrophage proliferation	IGI	26754294
GO:1900034	Process	Regulation of cellular response to heat	TAS
GO:1903351	Process	Cellular response to dopamine	IMP	24136195
GO:1904355	Process	Positive regulation of telomere capping	IMP	21531765
GO:1904417	Process	Positive regulation of xenophagy	IEA
GO:2000641	Process	Regulation of early endosome to late endosome transport	TAS	19565474
GO:2000657	Process	Negative regulation of apolipoprotein binding	IEA

Other IDs

• MIM: 601795
• HGNC: 6877
• e!Ensembl: ENSG00000102882

Protein

• UniProt ID: P27361
• Protein name: Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1)
• Protein function: 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.
• PDB: 2ZOQ, 4QTB, 6GES
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	42 → 330	Protein kinase domain	Domain

• Sequence:

  MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAY
  DHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYI
  VQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL
  KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLS
  NRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSD
  SKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERL
  KELIFQETARFQPGVLEAP

• Sequence length: 379