Reviewed, UniProtKB/Swiss-Prot P49185 (MK08_RAT)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 8
    EC=2.7.11.24
Alternative name(s):
    Stress-activated protein kinase JNK1
    c-Jun N-terminal kinase 1
    SAPK gamma
    p54 gamma

Gene names

Name:	Mapk8
Synonyms:	Jnk1, Prkm8

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. In T-cells, JNK1 and JNK2 are required for polarized differentiation of T-helper cells into Th1 cells. Phosphorylates heat shock factor protein 4 (HSF4) By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.2
Enzyme regulation	Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. Inhibited by dual specificity phosphatases, such as DUSP1 By similarity. Inhibited by IFN-gamma-induced S-nitrosylation.
Subunit structure	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, WWOX and JAMP. Interacts with NFATC4 By similarity. Forms a complex with MAPK8IP1 and RGNEF.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme By similarity. Nitrosylated upon IFN-gamma-induced endogenous NO production, which inhibits the enzyme.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein S-nitrosylation
Gene Ontology (GO)
Biological process	inflammatory response Inferred from direct assay. Source: RGD negative regulation of apoptosis Inferred from direct assay. Source: RGD neuron projection development Inferred from mutant phenotype. Source: RGD positive regulation of DNA replication Inferred from mutant phenotype. Source: RGD positive regulation of cell migration Inferred from direct assay. Source: RGD positive regulation of microtubule polymerization Inferred from mutant phenotype. Source: RGD regulation of transcription, DNA-dependent Inferred from direct assay. Source: RGD response to heat Inferred from direct assay. Source: RGD response to hydrogen peroxide Inferred from direct assay. Source: RGD response to osmotic stress Inferred from direct assay. Source: RGD response to steroid hormone stimulus Inferred from expression pattern. Source: RGD
Cellular component	axon part Inferred from direct assay. Source: RGD cytosol Inferred from Experiment. Source: Reactome dendrite cytoplasm Inferred from direct assay. Source: RGD mitochondrion Inferred from direct assay. Source: RGD nucleus Inferred from direct assay. Source: RGD perikaryon Inferred from direct assay. Source: RGD vesicle Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 411	411	Mitogen-activated protein kinase 8		PRO_0000186264
Regions
	Domain	26 – 321	296	Protein kinase
	Nucleotide binding	32 – 40	9	ATP By similarity
	Motif	183 – 185	3	TXY
Sites
	Active site	151	1	Proton acceptor By similarity
	Binding site	55	1	ATP By similarity
Amino acid modifications
	Modified residue	116	1	S-nitrosocysteine; in inhibited form
	Modified residue	183	1	Phosphothreonine By similarity
	Modified residue	185	1	Phosphotyrosine By similarity
	Modified residue	255	1	Phosphothreonine By similarity
	Modified residue	258	1	Phosphothreonine By similarity
	Modified residue	259	1	Phosphotyrosine By similarity
	Modified residue	308	1	N6-acetyllysine By similarity
	Modified residue	357	1	Phosphotyrosine By similarity
	Modified residue	367	1	Phosphothreonine By similarity
	Modified residue	377	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	116	1	C → S: Abolished inhibitory effect of IFN-gamma on JNK1 activity. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P49185-1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 04E388B4F94633D4	FASTA	411	46,807
	10 20 30 40 50 60 MSRSKRDNNF YSVEIADSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP 70 80 90 100 110 120 FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ 130 140 150 160 170 180 MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF 190 200 210 220 230 240 MMTPYVVTRY YRAPEVILGM GYKENVDLWS VGCIMGEMVC LKILFPGRDY IDQWNKVIEQ 250 260 270 280 290 300 LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 310 320 330 340 350 360 MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV 370 380 390 400 410 MDLEERTKNG VIRGQPSPLG AAVINGSQHP VSSPSVNDMS SMSTDPTLAS D

References

[1]	"The stress-activated protein kinase subfamily of c-Jun kinases." Kyriakis J.M., Banerjee P., Nikolakaki E., Dai T., Rubie E.A., Ahmad M.F., Avruch J., Woodgett J.R. Nature 369:156-160(1994) [PubMed: 8177321] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Stimulation of 'stress-regulated' mitogen-activated protein kinases (stress-activated protein kinases/c-Jun N-terminal kinases and p38-mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses." Clerk A., Fuller S.J., Michael A., Sugden P.H. J. Biol. Chem. 273:7228-7234(1998) [PubMed: 9516415] [Abstract] Cited for: FUNCTION, COFACTOR. Tissue: Heart.
[3]	"Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation." Park H.S., Huh S.H., Kim M.S., Lee S.H., Choi E.J. Proc. Natl. Acad. Sci. U.S.A. 97:14382-14387(2000) [PubMed: 11121042] [Abstract] Cited for: S-NITROSYLATION AT CYS-116, MUTAGENESIS OF CYS-116.
[4]	"Cytoplasmic retention sites in p190RhoGEF confer anti-apoptotic activity to an EGFP-tagged protein." Wu J., Zhai J., Lin H., Nie Z., Ge W.-W., Garcia-Bermejo L., Muschel R.J., Schlaepfer W.W., Canete-Soler R. Brain Res. Mol. Brain Res. 117:27-38(2003) [PubMed: 14499478] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH MAPK8IP1 AND RGNEF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L27129 mRNA. Translation: AAA42111.1.
IPI	IPI00191803.
PIR	S43970.
UniGene	Rn.4090
3D structure databases
HSSP	HSSP built from PDB template 1JNK based on UniProtKB P53779.
SMR	P49185. Positions 8-362.
ModBase	Search...
Protein-protein interaction databases
STRING	P49185.
PTM databases
PhosphoSite	P49185.
Genome annotation databases
Ensembl	ENSRNOT00000027338; ENSRNOP00000027338; ENSRNOG00000020155; Rattus norvegicus. [Genome view]
Organism-specific databases
RGD	621506. Mapk8.
Phylogenomic databases
HOVERGEN	P49185.
Enzyme and pathway databases
BRENDA	2.7.11.24. 248.
Gene expression databases
ArrayExpress	P49185.
Genevestigator	P49185.
GermOnline	ENSRNOG00000020155. Rattus norvegicus.
Family and domain databases
InterPro	IPR008351. JNK_MAPK. IPR003527. MAP_kinase_CS. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01772. JNKMAPKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS01351. MAPK. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

MK08_RAT

Accession

Primary (citable) accession number: P49185

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	October 13, 2009
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)