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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

MAPK8 Gene

protein-coding GIFtS: 73
GCID: GC10P049514

mitogen-activated protein kinase 8

(Previous symbol: PRKM8)

Explore 191 diseases affiliated with
MAPK8 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 8¹ ²		JNK1A2²
JNK1¹ ² ³ ⁵		JNK21B1/2²
PRKM8¹ ² ³ ⁵		JUN N-Terminal Kinase²
SAPK1¹ ² ³ ⁵		Mitogen-Activated Protein Kinase 8 Isoform JNK1 Alpha1²
JNK¹ ²		Mitogen-Activated Protein Kinase 8 Isoform JNK1 Beta2²
Stress-Activated Protein Kinase 1c² ³		Stress-Activated Protein Kinase 1²
JNK-46² ³		SAPK1C³
SAPK1c² ³		MAPK 8³
C-Jun N-Terminal Kinase 1² ³		Stress-Activated Protein Kinase JNK1³
MAP Kinase 8² ³		EC 2.7.11⁸
EC 2.7.11.24³ ⁸

External Ids:	HGNC: 6881¹	Entrez Gene: 5599²	Ensembl: ENSG00000107643⁷	OMIM: 601158⁵	UniProtKB: P45983³

Export aliases for MAPK8 gene to outside databases

Previous GC identifers: GC10P048468 GC10P049407 GC10P048954 GC10P049279 GC10P043874

(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 MAPK8:

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases 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. This kinase is activated by various cell stimuli, and

targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli.

The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced

apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom

c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key

role in T cell proliferation, apoptosis and differentiation. Four alternatively spliced transcript variants encoding

distinct isoforms have been reported. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: MK08_HUMAN, P45983

Function: Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation,

migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or

physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In

this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn,

MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2

and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the

interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates

the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key

regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for

polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by

phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2

phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence

regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through

its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration

from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the

deacetylase SIRT1, ELK1, or the E3 ligase ITCH

Function: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1,

alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation

between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms

summary for MAPK8:

MAPKs (mitogen-activated protein kinases) are serine-threonine kinases that regulate a wide variety of

cellular functions. Six groups of MAPK have so far been identified: Extracellular signal-regulated kinases

(ERK1, ERK2), c-Jun N-terminal kinases (JNKs), p38 isoforms (MAPK11, MAPK12, MAPK13, MAPK14), ERK5 (MAPK7),

ERK3 (MAPK6) and ERK4 (MAPK4) and ERK7/8 (MAPK15). ERK 1 and ERK 2 transduce signals from growth factors and

are key in regulating differentiation and proliferation in many cell types. Upon activation by MEK, ERK1 and

2 translocate to the nucleus where they phosphorylate transcription factors such as Elk1 and downstream

kinases such as p90 RSK. JNK 1,2 and 3 (sometimes known as SAPKs or stress-activated kinases) and the p38

MAPKs (alpha-, beta-, delta and gamma- isoforms) are activated by UV irradiation, inflammatory cytokines and

hyperosmolarity. The p38 MAPKs are also activated by lipopolysaccharide. Dysregulation of MAPK kinase

pathways has been associated with various diseases including cancer (ERK), neurodegeneration (JNK) and

inflammation (p38).

Gene Wiki entry for MAPK8

(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_000010.10 NC_018921.1 NT_030059.13

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the MAPK8 gene promoter:
AP-1 ATF-2 STAT3
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: MAPK8 promoter sequence

Search SABiosciences Chromatin IP Primers for MAPK8

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat MAPK8

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

Entrez Gene cytogenetic band: 10q11.22 Ensembl cytogenetic band: 10q11.22 HGNC cytogenetic band: 10q11

MAPK8 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MAPK8 gene location

GeneLoc information about chromosome 10 GeneLoc Exon Structure

GeneLoc location for GC10P049514: view genomic region (about GC identifiers)

Start:	49,514,698 bp from pter	End:	49,647,403 bp from pter
Size:	132,706 bases	Orientation:	plus 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: MK08_HUMAN, P45983 (See protein sequence)

Recommended Name: Mitogen-activated protein kinase 8

Size: 427 amino acids; 48296 Da

Cofactor: Magnesium

Subunit: Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and

SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with TP53 and

WWOX. Interacts with JAMP. Forms a complex with MAPK8IP1 and ARHGEF28 (By similarity). Interacts (phosphorylated form)

with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells (By similarity). Interacts with NFATC4.

Interacts with MECOM; regulates JNK signaling. Interacts with PIN1; this interaction mediates MAPK8 conformational

changes leading to the binding of MAPK8 to its substrates

Subcellular location: Cytoplasm. Nucleus

6/13 PDB 3D structures from and Proteopedia for MAPK8 (see all 13):

1UKH (3D)

1UKI (3D)

2G01 (3D)

2GMX (3D)

2H96 (3D)

2NO3 (3D)

Secondary accessions: B5BTZ5 B7ZLV4 D3DX88 D3DX92 Q15709 Q15712 Q15713

Alternative splicing: 4 isoforms: P45983-1 P45983-2 P45983-3 P45983-4 (Contains a phosphoserine at position 377)

Explore the universe of human proteins at neXtProt for MAPK8: NX_P45983

Post-translational modifications:

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Phosphorylated by TAOK2¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P45983

4/27 DME Specific Peptides for MAPK8 (P45983) (see all 27)

KELIYKE

ILDFGLA

LDFGLAR

LLSKMLV

MAPK8 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (4 alternative transcripts):

NP_002741.1 NP_620634.1 NP_620635.1 NP_620637.1

ENSEMBL proteins:

ENSP00000387936 ENSP00000393223 ENSP00000363304 ENSP00000397729 ENSP00000363297

ENSP00000363294 ENSP00000363291 ENSP00000363289 ENSP00000353483 ENSP00000378974

Reactome Protein details: P45983
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant MAPK8 Protein
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for MAPK8
	OriGene Purified Proteins (see all 3): MAPK8 OriGene Protein Over-expression Lysate (see all 5): MAPK8 OriGene Custom Protein Services for MAPK8
	GenScript Custom Purified and Recombinant Proteins Services for MAPK8
	Novus Biologicals MAPK8 Proteins Novus Biologicals MAPK8 Lysates
	Sino Biological Recombinant Protein for MAPK8
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for MAPK8

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

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	--
GO:0005654	nucleoplasm	TAS	--
GO:0005737	cytoplasm	--	--
GO:0005739	mitochondrion	IEA	--
GO:0005829	cytosol	TAS	--

MAPK8 for ontologies About GeneDecksing

MAPK8 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of MAPK8
	R&D Systems Antibodies for MAPK8 (JNK1)
	Cell Signaling Technology (CST) Antibodies for MAPK8 (JNK1)
	OriGene Antibodies (see all 7): MAPK8 OriGene Custom Antibody Services for MAPK8
	GenScript Superior Antibodies for MAPK8
	Novus Biologicals MAPK8 Antibodies
	Abcam antibodies for MAPK8
	Uscn Antibodies for MAPK8
	ThermoFisher Antibody for MAPK8

Assay Products for MAPK8:

	EMD Millipore Kits and Assays for the Analysis of MAPK8
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for MAPK8 (JNK1) (see all)
	GenScript Custom Assay Services for MAPK8
	Cell Signaling Technology (CST) Sandwich ELISA Kits for MAPK8 (JNK1)
	Enzo Life Sciences assays for MAPK8
	Uscn ELISAs and CLIAs for MAPK8

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

MAPK8 for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR008351 MAPK_JNK

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 P45983

ProtoNet protein and cluster: P45983

2 Blocks protein families:

IPB003527 MAP kinase

IPB008351 JNK MAP kinase signature

UniProtKB/Swiss-Prot: MK08_HUMAN, P45983

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: