P49186 (MK09_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase 9
Short name=MAP kinase 9
Short name=MAPK 9
EC=2.7.11.24

Alternative name(s):
SAPK-alpha
Stress-activated protein kinase JNK2
c-Jun N-terminal kinase 2
p54-alpha

Gene names

Name:	Mapk9
Synonyms:	Jnk2, Prkm9

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1 By similarity.
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 NFATC4 and DCLK2. Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN. Interacts with BCL10. Interacts with CTNNB1 and GSK3B By similarity. Interacts with MECOM. Ref.2
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
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 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to UV Inferred from mutant phenotype PubMed 8875991. Source: RGD cellular response to growth factor stimulus Inferred from expression pattern PubMed 17568197. Source: RGD cellular response to interleukin-1 Inferred from expression pattern PubMed 10593906. Source: RGD cellular response to lipopolysaccharide Inferred from expression pattern PubMed 9475517. Source: RGD cellular response to tumor necrosis factor Inferred from expression pattern PubMed 9475517. Source: RGD central nervous system development Inferred from expression pattern PubMed 9748503. Source: RGD neuron projection development Inferred from mutant phenotype PubMed 16006144. Source: RGD positive regulation of apoptotic process Inferred from mutant phenotype PubMed 12029621PubMed 15504737. Source: RGD positive regulation of apoptotic signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of cell morphogenesis involved in differentiation Inferred from mutant phenotype PubMed 16006144. Source: RGD positive regulation of chemokine production Inferred from mutant phenotype PubMed 16942465. Source: RGD positive regulation of macrophage derived foam cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of nitric oxide biosynthetic process Inferred from mutant phenotype PubMed 10593906. Source: RGD positive regulation of nitric-oxide synthase biosynthetic process Inferred from mutant phenotype PubMed 10593906. Source: RGD positive regulation of prostaglandin biosynthetic process Inferred from mutant phenotype PubMed 9786861. Source: RGD positive regulation of prostaglandin secretion Inferred from mutant phenotype PubMed 9786861. Source: RGD positive regulation of protein phosphorylation Inferred from mutant phenotype PubMed 16942465. Source: RGD positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 15504737. Source: RGD protein targeting to mitochondrion Inferred from expression pattern PubMed 15504737. Source: RGD regulation of JNK cascade Inferred from mutant phenotype PubMed 17348686. Source: RGD regulation of protein ubiquitination Inferred from mutant phenotype PubMed 8875991. Source: RGD release of cytochrome c from mitochondria Inferred from mutant phenotype PubMed 15504737. Source: RGD response to amine stimulus Inferred from expression pattern PubMed 18081878. Source: RGD response to cadmium ion Inferred from electronic annotation. Source: Compara response to drug Inferred from mutant phenotype PubMed 14522843. Source: RGD response to mechanical stimulus Inferred from expression pattern PubMed 16041628. Source: RGD response to toxin Inferred from expression pattern PubMed 15504737. Source: RGD
Cellular_component	cytosolic part Inferred from direct assay PubMed 18385140. Source: MGI mitochondrion Inferred from direct assay PubMed 15504737. Source: RGD nucleus Inferred from direct assay PubMed 15504737. Source: RGD
Molecular_function	ATP binding Inferred from direct assay PubMed 10051439. Source: RGD JUN kinase activity Inferred from direct assay PubMed 10051439PubMed 17064355. Source: RGD cysteine-type endopeptidase activator activity involved in apoptotic process Inferred from mutant phenotype PubMed 14522843. Source: RGD transcription factor binding Inferred from direct assay PubMed 9475517. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha-2 (identifier: P49186-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Alpha-1 (identifier: P49186-2)

The sequence of this isoform differs from the canonical sequence as follows:
     216-230: GELVKGCVIFQGTDH → AEMVLHKSCSPGRDY

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 423	423	Mitogen-activated protein kinase 9		PRO_0000186275
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	183	1	Phosphothreonine; by MAP2K7 By similarity
	Modified residue	185	1	Phosphotyrosine; by MAP2K4 By similarity
Natural variations
	Alternative sequence	216 – 230	15	GELVK…QGTDH → AEMVLHKSCSPGRDY in isoform Alpha-1.		VSP_004838

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-2 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: EE549B9F4F12F421	FASTA	423	48,017
	10 20 30 40 50 60 MSDSKSDGQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI NVAVKKLSRP 70 80 90 100 110 120 FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE FQDVYLVMEL MDANLCQVIH 130 140 150 160 170 180 MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTACTNF 190 200 210 220 230 240 MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ 250 260 270 280 290 300 LGTPSAEFMK KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK 310 320 330 340 350 360 MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE EWKELIYKEV 370 380 390 400 410 420 MDWEERSKNG VKDQPSDAAV SSKATPSQSS SINDISSMST EHTLASDTDS SLDASTGPLE GCR
	Isoform Alpha-1 [UniParc]. Checksum: 6419E1052BDC0292	FASTA	423	48,107
	10 20 30 40 50 60 MSDSKSDGQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI NVAVKKLSRP 70 80 90 100 110 120 FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE FQDVYLVMEL MDANLCQVIH 130 140 150 160 170 180 MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTACTNF 190 200 210 220 230 240 MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMAEMVL HKSCSPGRDY IDQWNKVIEQ 250 260 270 280 290 300 LGTPSAEFMK KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK 310 320 330 340 350 360 MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE EWKELIYKEV 370 380 390 400 410 420 MDWEERSKNG VKDQPSDAAV SSKATPSQSS SINDISSMST EHTLASDTDS SLDASTGPLE GCR

References

	« Hide 'large scale' referencesShow 'large scale' 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2), PARTIAL PROTEIN SEQUENCE. Tissue: Brain.
[2]	"The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death." Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., Ogawa S., Moriguchi T., Nishida E., Yazaki Y., Hirai H. EMBO J. 19:2958-2968(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MECOM.
[3]	"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites." Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A. Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY. Tissue: Renal collecting duct.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L27112 mRNA. Translation: AAA42109.1. L27111 mRNA. Translation: AAA42108.1.
IPI	IPI00191806. IPI00231634.
PIR	S43968.
RefSeq	NP_001257473.1. NM_001270544.1. NP_059018.1. NM_017322.2.
UniGene	Rn.177202. Rn.9910.
3D structure databases
ProteinModelPortal	P49186.
SMR	P49186. Positions 7-363.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-5027617.
STRING	10116.ENSRNOP00000003987.
PTM databases
PhosphoSite	P49186.
Proteomic databases
PaxDb	P49186.
PRIDE	P49186.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000003987; ENSRNOP00000003987; ENSRNOG00000002823.
GeneID	50658.
KEGG	rno:50658.
UCSC	RGD:628847. rat.
Organism-specific databases
CTD	5601.
RGD	628847. Mapk9.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00550000074271.
HOGENOM	HOG000233024.
HOVERGEN	HBG014652.
InParanoid	P49186.
KO	K04440.
OMA	DWEERNK.
Enzyme and pathway databases
BRENDA	2.7.11.24. 5301.
Gene expression databases
ArrayExpress	P49186.
Genevestigator	P49186.
GermOnline	ENSRNOG00000002823. Rattus norvegicus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR008351. MAPK_JNK. IPR000719. Prot_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01772. JNKMAPKINASE.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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...
Other
ChEMBL	CHEMBL5231.
NextBio	610470.

Entry information

Entry name

MK09_RAT

Accession

Primary (citable) accession number: P49186

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program