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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

MAPK1 Gene

protein-coding GIFtS: 74
GCID: GC22M022108

mitogen-activated protein kinase 1

(Previous symbols: PRKM2, PRKM1)

Explore 259 diseases affiliated with
MAPK1 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Mitogen-Activated Protein Kinase 1¹ ²		MAP Kinase 2² ³
ERK2¹ ² ³ ⁵		MAP Kinase Isoform P42² ³
PRKM1¹ ² ³ ⁵		MAPK 2² ³
PRKM2¹ ² ³		P42-MAPK¹
ERK¹ ²		EC 2.7.11.24³ ⁸
MAPK2¹ ²		P42MAPK²
P41mapk¹		P38¹
Extracellular Signal-Regulated Kinase 2² ³		P40¹
Mitogen-Activated Protein Kinase 2² ³		P41¹
ERK-2² ³		Protein Tyrosine Kinase ERK2²
ERT1² ³		MAPK 1³
MAP Kinase 1² ³		EC 2.7.11⁸

External Ids:	HGNC: 6871¹	Entrez Gene: 5594²	Ensembl: ENSG00000100030⁷	OMIM: 176948⁵	UniProtKB: P28482³

Export aliases for MAPK1 gene to outside databases

Previous GC identifers: GC22M018815 GC22M020441 GC22M005071

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for MAPK1:

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 as an integration point for multiple biochemical signals, and are involved in a

wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development.

The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase

translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively

spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.

(provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: MK01_HUMAN, P28482

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. May play a role in the spindle assembly checkpoint

Function: 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

Gene Wiki entry for MAPK1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000022.10 NC_018933.1 NT_011520.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the MAPK1 gene promoter:
CREB ATF-2 deltaCREB c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 6): MAPK1 promoter sequence

Search SABiosciences Chromatin IP Primers for MAPK1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat MAPK1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 22q11.21 Ensembl cytogenetic band: 22q11.22 HGNC cytogenetic band: 22q11.2

MAPK1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MAPK1 gene location

GeneLoc information about chromosome 22 GeneLoc Exon Structure

GeneLoc location for GC22M022108: view genomic region (about GC identifiers)

Start:	22,108,789 bp from pter	End:	22,221,970 bp from pter
Size:	113,182 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: MK01_HUMAN, P28482 (See protein sequence)

Recommended Name: Mitogen-activated protein kinase 1

Size: 360 amino acids; 41390 Da

Cofactor: Magnesium (By similarity)

Subunit: Binds both upstream activators and downstream substrates in multimolecular complexes. Binds to HIV-1 Nef

through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARHGEF2, ARRB2,

DAPK1 (via death domain), HSF4, IER3, IPO7, DUSP6, NISCH, SGK1, and isoform 1 of NEK2. Interacts (phosphorylated form)

with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1

activation. Interacts with MORG1, PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from

dephosphorylation and inactivation (By similarity). Interacts with DCC (By similarity)

Subcellular location: Cytoplasm, cytoskeleton, spindle (By similarity). Nucleus. Cytoplasm, cytoskeleton, 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

Sequence caution: Sequence=CAA77753.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

6/29 PDB 3D structures from and Proteopedia for MAPK1 (see all 29):

1PME (3D)

1TVO (3D)

1WZY (3D)

2OJG (3D)

2OJI (3D)

2OJJ (3D)

Explore the universe of human proteins at neXtProt for MAPK1: NX_P28482

Post-translational modifications:

Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-185 and Tyr-187, which

activates the enzyme. Undergoes regulatory phosphorylation on additional residues such as Ser-246 and Ser-248 in the

kinase insert domain (KID) These phosphorylations, which are probably mediated by more than one kinase, are important

for binding of MAPK1/ERK2 to importin-7 (IPO7) and its nuclear translocation. In addition, autophosphorylation of

Thr-190 was shown to affect the subcellular localization of MAPK1/ERK2 as well. Ligand-activated ALK induces tyrosine

phosphorylation. Dephosphorylated by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its activation by

enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2

and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P28482

4/33 DME Specific Peptides for MAPK1 (P28482) (see all 33)

LKYIHSA

RVAIKKI

GCILAEM

VLHRDLK

MAPK1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_002736.3 NP_620407.1

ENSEMBL proteins:

ENSP00000215832 ENSP00000381803 ENSP00000440842

Reactome Protein details: P28482
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant MAPK1 Protein
	R&D Systems Recombinant & Natural Proteins for MAPK1 (ERK2)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Proteins (see all 2): MAPK1 OriGene Protein Over-expression Lysate (see all 2): MAPK1 OriGene Custom Protein Services for MAPK1
	GenScript Purified and Recombinant Proteins for MAPK1
	Novus Biologicals MAPK1 Proteins Novus Biologicals MAPK1 Lysates
	Sino Biological Recombinant Protein for MAPK1
	ProSpec Recombinant Protein for MAPK1
	Uscn Proteins for MAPK1

Gene Ontology (GO): 5/22 cellular component terms (GO ID links to tree view) (see all 22): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005625	soluble fraction	--	--
GO:0005626	insoluble fraction	--	--
GO:0005634	nucleus	TAS	19565474
GO:0005654	nucleoplasm	TAS	--
GO:0005730	NOT nucleolus	IDA	--

MAPK1 for ontologies About GeneDecksing

MAPK1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of MAPK1
	R&D Systems Antibodies for MAPK1 (ERK2)
	Cell Signaling Technology (CST) Antibodies for MAPK1 (ERK2)
	OriGene Antibodies (see all 18): MAPK1 OriGene Custom Antibody Services for MAPK1
	GenScript Superior Antibodies for MAPK1
	Novus Biologicals MAPK1 Antibodies
	Abcam antibodies for MAPK1
	Uscn Antibodies for MAPK1
	ThermoFisher Antibody for MAPK1

Assay Products for MAPK1:

	EMD Millipore Kits and Assays for the Analysis of MAPK1
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for MAPK1 (ERK2) (see all)
	GenScript MAPK1-Activity-based Kinase Assay for Compound Screening
	Cell Signaling Technology (CST) Sandwich ELISA Kits for MAPK1 (ERK2)
	Enzo Life Sciences assays for MAPK1
	Uscn ELISAs and CLIAs for MAPK1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

MAPK1 for domains About GeneDecksing

5/7 InterPro domains/families (see all 7):

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR003527 MAP_kinase_CS

Graphical View of Domain Structure for InterPro Entry P28482

ProtoNet protein and cluster: P28482

2 Blocks protein families:

IPB003527 MAP kinase

IPB008349 ERK1/2 MAP kinase signature

UniProtKB/Swiss-Prot: MK01_HUMAN, P28482

Domain: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases

Similarity: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: