InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAPK1

Summary

InnateDB Protein

IDBP-2149.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAPK1

Protein Name

mitogen-activated protein kinase 1

Synonyms

ERK; ERK-2; ERK2; ERT1; MAPK2; p38; p40; p41; p41mapk; p42-MAPK; P42MAPK; PRKM1; PRKM2;

Species

Homo sapiens

Ensembl Protein

ENSP00000215832

InnateDB Gene

IDBG-2147 (MAPK1)

Protein Structure

UniProt Annotation

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, 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.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.

Subcellular Localization

Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm. Note=Associated with the spindle during prometaphase and metaphase (By similarity). PEA15- binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser- 246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 359 experimentally validated interaction(s) in this database.
They are also associated with 48 interaction(s) predicted by orthology.

Experimentally validated
Total	359 [view]
Protein-Protein	356 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	48 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001784	phosphotyrosine binding
GO:0003677	DNA binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004707	MAP kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0008353	RNA polymerase II carboxy-terminal domain kinase activity
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0019902	phosphatase binding
GO:0031435	mitogen-activated protein kinase kinase kinase binding

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0000187	activation of MAPK activity
GO:0000189	MAPK import into nucleus
GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006351	transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006935	chemotaxis
GO:0006950	response to stress
GO:0006974	cellular response to DNA damage stimulus
GO:0007049	cell cycle
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007264	small GTPase mediated signal transduction
GO:0007265	Ras protein signal transduction
GO:0007268	synaptic transmission
GO:0007411	axon guidance
GO:0007596	blood coagulation
GO:0008284	positive regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009636	response to toxic substance
GO:0009887	organ morphogenesis
GO:0010800	positive regulation of peptidyl-threonine phosphorylation
GO:0016032	viral process
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0019233	sensory perception of pain
GO:0019858	cytosine metabolic process
GO:0030168	platelet activation
GO:0030335	positive regulation of cell migration
GO:0031647	regulation of protein stability
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032496	response to lipopolysaccharide
GO:0032872	regulation of stress-activated MAPK cascade
GO:0033598	mammary gland epithelial cell proliferation
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035556	intracellular signal transduction
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0038127	ERBB signaling pathway
GO:0043330	response to exogenous dsRNA
GO:0043627	response to estrogen
GO:0045087	innate immune response (InnateDB)
GO:0045596	negative regulation of cell differentiation
GO:0045727	positive regulation of translation
GO:0045893	positive regulation of transcription, DNA-templated
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050852	T cell receptor signaling pathway
GO:0050853	B cell receptor signaling pathway
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity
GO:0051403	stress-activated MAPK cascade
GO:0051493	regulation of cytoskeleton organization
GO:0060397	JAK-STAT cascade involved in growth hormone signaling pathway
GO:0060716	labyrinthine layer blood vessel development
GO:0070371	ERK1 and ERK2 cascade
GO:0070849	response to epidermal growth factor
GO:0071310	cellular response to organic substance
GO:0072584	caveolin-mediated endocytosis
GO:0090170	regulation of Golgi inheritance
GO:0097011	cellular response to granulocyte macrophage colony-stimulating factor stimulus
GO:2000641	regulation of early endosome to late endosome transport

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005769	early endosome
GO:0005770	late endosome
GO:0005794	Golgi apparatus
GO:0005815	microtubule organizing center
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005901	caveola
GO:0005925	focal adhesion
GO:0015630	microtubule cytoskeleton
GO:0030424	axon
GO:0031143	pseudopodium
GO:0032839	dendrite cytoplasm
GO:0043204	perikaryon
GO:0043234	protein complex
GO:0070062	extracellular vesicular exosome
GO:0072686	mitotic spindle

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR008349 Mitogen-activated protein (MAP) kinase, ERK1/2
IPR008350 Mitogen-activated protein (MAP) kinase, ERK3/4
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109
PR01770
PR01771

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt