Tchem MAPK3 Mitogen-activated protein kinase 3

Protein Summary

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. 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]

Uniprot Accession IDs

• P27361
• A8CZ58
• B0LPG3
• Q8NHX1
• MAP kinase 3

Gene Name

• MAPK3

Ensembl ID

• ENST00000263025
• ENSP00000263025
• ENSG00000102882
• ENST00000322266
• ENSP00000327293
• ENST00000395199
• ENSP00000378625
• ENST00000395202
• ENSP00000378628

Symbol

• ERK1
• PRKM3
• ERK1
• ERT2
• ERK-1
• PRKM3
• P44ERK1
• P44MAPK
• HS44KDAP
• HUMKER1A
• p44-ERK1
• p44-MAPK

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
hub protein	1
interacting protein	1

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Mitogen-activated Protein Kinase 3

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Mapk Family / Erk Subfamily / Mitogen-activated Protein Kinase 3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 6106.72   (req: < 5)

Gene RIFs: 967   (req: <= 3)

Antibodies: 1997   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 6106.72   (req: >= 5)

Gene RIFs: 967   (req: > 3)

Antibodies: 1997   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 80

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 40

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (2)

Explore Approved Drugs

1 – 2 of 2

sorafenib

MAPK3Tchem Kinase

INHIBITOR pKd : 7.8

nalfurafine

MAPK3Tchem Kinase

AGONIST pKi : 9.64

Active Ligands (40)

Explore Active Ligands

1 – 10 of 40

CHEMBL4571067

MAPK3Tchem Kinase

pIC50 : 9.03

GDC-0994

MAPK3Tchem Kinase

pKd : 6.33

CHEMBL3577641

MAPK3Tchem Kinase

pIC50 : 7.68

CHEMBL3577643

MAPK3Tchem Kinase

pIC50 : 8.46

CHEMBL3577566

MAPK3Tchem Kinase

pIC50 : 8.49

ERK inhibitor II

MAPK3Tchem Kinase

pKi : 6.39

MK-8353

MAPK3Tchem Kinase

pIC50 : 8.15

SCH772984

MAPK3Tchem Kinase

pKd : 10

ulixertinib

MAPK3Tchem Kinase

pKd : 8

CHEMBL4434915

MAPK3Tchem Kinase

pIC50 : 9.15

Protein-Protein Interactions (1162)

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1 – 10 of 1162

• See Interactions on String-DB

ZDHHC11

Tdark

Family:  Enzyme

Novelty:  0.35249931

p_int:  0.986668658

p_ni:  0.013331342

Score:  0.206

Data Source:  BioPlex,STRINGDB

CPLX4

Tdark

Novelty:  0.1755035

p_int:  0.978478981

p_ni:  0.021521019

Score:  0.229

Data Source:  BioPlex,STRINGDB

SPANXN4

Tdark

Novelty:  1.91062423

p_int:  0.963588317

p_ni:  0.036411683

Data Source:  BioPlex

RNF181

Tbio

Family:  Enzyme

Novelty:  0.27482636

p_int:  0.956767114

p_ni:  0.043232886

Data Source:  BioPlex

UXS1

Tbio

Family:  Enzyme

Novelty:  0.04671281

p_int:  0.950592351

p_ni:  0.049407649

Score:  0.172

Data Source:  BioPlex,STRINGDB

SNRNP27

Tbio

Novelty:  0.0175187

p_int:  0.941105443

p_ni:  0.058894557

Data Source:  BioPlex

NPTX2

Tbio

Novelty:  0.00686292

p_int:  0.936298848

p_ni:  0.063701152

Data Source:  BioPlex

ECM1

Tbio

Novelty:  0.00518679

p_int:  0.916115183

p_ni:  0.083884817

Data Source:  BioPlex

GPS2

Tbio

Novelty:  0.00986158

p_int:  0.903651996

p_ni:  0.096347982

p_wrong:  2.2e-8

Score:  0.255

Data Source:  BioPlex,STRINGDB

CUEDC1

Tbio

Novelty:  0.14401061

p_int:  0.858982958

p_ni:  0.141017042

Data Source:  BioPlex

Nearest Tclin Targets (31)

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Upstream (9)

Downstream (22)

1 – 5 of 9

FGFR1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  14

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: Adherens junction

4: Parathyroid hormone synthesis, secretion and action

more:  10 more common pathways

RAF1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  75

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: Axon guidance

4: EGFR tyrosine kinase inhibitor resistance

more:  71 more common pathways

EGFR

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  40

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: EGFR tyrosine kinase inhibitor resistance

4: Endocrine resistance

more:  36 more common pathways

IGF1R

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  23

1: PI3K-Akt signaling pathway

2: EGFR tyrosine kinase inhibitor resistance

3: Endocrine resistance

4: Focal adhesion

more:  19 more common pathways

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  83

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: EGFR tyrosine kinase inhibitor resistance

4: Endocrine resistance

more:  79 more common pathways

Pathways (459)

Reactome (136)

KEGG (109)

PathwayCommons (126)

WikiPathways (88)

Activation of NMDA receptors and postsynaptic events (R-HSA-442755)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of NMDA receptors and postsynaptic events	74 targets	R-HSA-442755
Reactome	Activation of the AP-1 family of transcription factors	10 targets	R-HSA-450341
Reactome	Advanced glycosylation endproduct receptor signaling	13 targets	R-HSA-879415
Reactome	Antiviral mechanism by IFN-stimulated genes	82 targets	R-HSA-1169410
Reactome	Apoptosis	177 targets	R-HSA-109581

Name	Explore in Pharos	Explore in Source
Activation of NMDA receptors and postsynaptic events	74 targets	R-HSA-442755
Activation of the AP-1 family of transcription factors	10 targets	R-HSA-450341
Advanced glycosylation endproduct receptor signaling	13 targets	R-HSA-879415
Antiviral mechanism by IFN-stimulated genes	82 targets	R-HSA-1169410
Apoptosis	177 targets	R-HSA-109581

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (95)

Functions (9)

Components (15)

Processes (71)

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Items per page:

10

1 – 9 of 9

GO Term	Evidence	Assigned by
MAP kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
phosphatase binding	Inferred from Physical Interaction (IPI)	UniProtKB
kinase activity	Traceable Author Statement (TAS)	Reactome
protein serine/threonine kinase activity	Traceable Author Statement (TAS)	Reactome
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
MAP kinase kinase activity	Inferred from Electronic Annotation (IEA)	Ensembl
phosphotyrosine residue binding	Inferred from Electronic Annotation (IEA)	Ensembl
scaffold protein binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (27)

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5

1 – 5 of 27

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
appendicular lean mass	EFO_0004980	2	3	6		94.7
mean corpuscular volume	EFO_0004526	3	2	3		94
red blood cell density measurement	EFO_0007978	2	1	2		87.3
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		87
eosinophil count	EFO_0004842	3	2	3		86.9

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 27

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
appendicular lean mass	EFO_0004980	6		94.7
mean corpuscular volume	EFO_0004526	3		94
red blood cell density measurement	EFO_0007978	2		87.3
mean corpuscular hemoglobin concentration	EFO_0004528	1		87
eosinophil count	EFO_0004842	3		86.9

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Apoptosis
ATP-binding
Cell cycle
Complete proteome
Cytoplasm
Direct protein sequencing
Host-virus interaction

GWAS Trait Find Similar Targets

No Header	No Header
Agents acting on the renin-angiotensin system use measurement
alcohol consumption measurement
alcohol use disorder measurement
appendicular lean mass
body mass index
diastolic blood pressure
Diuretic use measurement
eosinophil count
eosinophil percentage of granulocytes
eosinophil percentage of leukocytes

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
hematopoietic system phenotype
immune system phenotype
mortality/aging
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	mitogen-activated protein kinase 3	VGNC:8987	454037
Macaque	mitogen-activated protein kinase 3		708938
Mouse	mitogen-activated protein kinase 3	MGI:1346859	26417
Rat	mitogen activated protein kinase 3	RGD:3046	50689
Dog	mitogen-activated protein kinase 3		100855877

Species	Name	OMA	EggNOG	Inparanoid
Chimp	mitogen-activated protein kinase 3
Macaque	mitogen-activated protein kinase 3
Mouse	mitogen-activated protein kinase 3
Rat	mitogen activated protein kinase 3
Dog	mitogen-activated protein kinase 3

Publication Statistics

PubMed Score 6106.72

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PubTator Score 6793.44

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Related Publications

Text Mined References (1102)

GeneRif Annotations (967)

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PMID	Year	Title