Reviewed, UniProtKB/Swiss-Prot P45984 (MK09_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 9
    EC=2.7.11.24
Alternative name(s):
    Stress-activated protein kinase JNK2
    c-Jun N-terminal kinase 2
    JNK-55

Gene names

Name:	MAPK9
Synonyms:	JNK2, PRKM9

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	424 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 c-Jun 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. JNK2 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to c-Jun, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.7
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.
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. Ref.8 Ref.9
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. Autophosphorylated in vitro. Ref.10 Ref.11
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	JNK cascade Ref.3 Inferred from direct assay. Source: UniProtKB positive regulation of foam cell differentiation Inferred from mutant phenotype. Source: UniProtKB positive regulation of gene expression Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase activity Ref.3 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATF2	P15336	1	EBI-713586,EBI-1170906
Ctnnb1	Q02248	1	EBI-713586,EBI-397872	From a different organism.
JUN	P05412	1	EBI-713586,EBI-852823

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha-2 (identifier: P45984-1)

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: P45984-2)

The sequence of this isoform differs from the canonical sequence as follows:
     378-424: DAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR → AQMQQ

Isoform Beta-1 (identifier: P45984-3)

The sequence of this isoform differs from the canonical sequence as follows:
     216-230: GELVKGCVIFQGTDH → AEMVLHKVLFPGRDY
     378-424: DAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR → AQMQQ

Isoform Beta-2 (identifier: P45984-4)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 424	424	Mitogen-activated protein kinase 9		PRO_0000186273
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 Ref.11
	Modified residue	185	1	Phosphotyrosine Ref.10 Ref.11
Natural variations
	Alternative sequence	216 – 230	15	GELVK…QGTDH → AEMVLHKVLFPGRDY in isoform Beta-1 and isoform Beta-2.		VSP_004834
	Alternative sequence	378 – 424	47	DAAVS…LEGCR → AQMQQ in isoform Alpha-1 and isoform Beta-1.		VSP_004835
	Natural variant	13	1	V → M in a colorectal adenocarcinoma sample; somatic mutation. Ref.12		VAR_042260
	Natural variant	56	1	K → N in a head & Neck squamous cell carcinoma sample; somatic mutation. Ref.12		VAR_042261
	Natural variant	246	1	A → T Ref.12		VAR_042262
	Natural variant	268	1	G → A Ref.5		VAR_025175
	Natural variant	366	1	R → I Ref.12		VAR_042263
Experimental info
	Sequence conflict	51	1	N → S Ref.1
	Sequence conflict	51	1	N → S Ref.3
	Sequence conflict	377	1	S → P in AAA74740. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-2 [UniParc]. Last modified January 24, 2006. Version 2. Checksum: 9C15DA79981290AF	FASTA	424	48,139
	10 20 30 40 50 60 MSDSKCDSQF 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 VVKDQPSDAA VSSNATPSQS SSINDISSMS TEQTLASDTD SSLDASTGPL EGCR
	Isoform Alpha-1. Checksum: A1963C01247BDFF4	FASTA	382	44,051
	10 20 30 40 50 60 MSDSKCDSQF 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 MDWEERSKNG VVKDQPSAQM QQ
	Isoform Beta-1. Checksum: 808ED1F85085CB4E	FASTA	382	44,223
	10 20 30 40 50 60 MSDSKCDSQF 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 HKVLFPGRDY 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 MDWEERSKNG VVKDQPSAQM QQ
	Isoform Beta-2. Checksum: A1B5FB794F373EB9	FASTA	424	48,311
	10 20 30 40 50 60 MSDSKCDSQF 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 HKVLFPGRDY 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 VVKDQPSDAA VSSNATPSQS SSINDISSMS TEQTLASDTD SSLDASTGPL EGCR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Signal transduction by tumor necrosis factor mediated by JNK protein kinases." Sluss H.K., Barrett T., Derijard B., Davis R.J. Mol. Cell. Biol. 14:8376-8384(1994) [PubMed: 7969172] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation." Kallunki T., Su B., Tsigelny I., Sluss H.K., Derijard B., Moore G., Davis R., Karin M. Genes Dev. 8:2996-3007(1994) [PubMed: 8001819] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Selective interaction of JNK protein kinase isoforms with transcription factors." Gupta S., Barrett T., Whitmarsh A.J., Cavanagh J., Sluss H.K., Derijard B., Davis R.J. EMBO J. 15:2760-2770(1996) [PubMed: 8654373] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Brain.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-268.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[7]	"Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7." Fleming Y., Armstrong C.G., Morrice N., Paterson A., Goedert M., Cohen P. Biochem. J. 352:145-154(2000) [PubMed: 11062067] [Abstract] Cited for: REGULATION BY MAP2K4 AND MAP2K7, COFACTOR.
[8]	"Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein." Jagadish N., Rana R., Selvi R., Mishra D., Garg M., Yadav S., Herr J.C., Okumura K., Hasegawa A., Koyama K., Suri A. Biochem. J. 389:73-82(2005) [PubMed: 15693750] [Abstract] Cited for: INTERACTION WITH SPAG9.
[9]	"Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 induced cell transformation." Yao K., Cho Y.-Y., Bergen H.R. III, Madden B.J., Choi B.Y., Ma W.-Y., Bode A.M., Dong Z. Cancer Res. 67:8725-8735(2007) [PubMed: 17875713] [Abstract] Cited for: INTERACTION WITH NFATC4.
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185, MASS SPECTROMETRY.
[11]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY.
[12]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-13; ASN-56; THR-246 AND ILE-366.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

L31951 mRNA. Translation: AAA56831.1.
U09759 mRNA. Translation: AAA74740.1.
U34821 mRNA. Translation: AAC50606.1.
U35002 mRNA. Translation: AAC50608.1.
U35003 mRNA. Translation: AAC50609.1.
CR536580 mRNA. Translation: CAG38817.1.
DQ066599 Genomic DNA. Translation: AAY46156.1.
BC032539 mRNA. Translation: AAH32539.1.

IPI

IPI00024673.
IPI00220382.
IPI00220383.
IPI00303550.

PIR

A55480.
S71102.

RefSeq

NP_002743.3.
NP_620707.1.

UniGene

Hs.654461

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3E7O	X-ray	2.14	A/B	7-362	[»]

SMR

P45984. Positions 7-362.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:270N.
DIP:281N.

IntAct

P45984. 18 interactions.

PTM databases

PhosphoSite

P45984.

2-D gel databases

REPRODUCTION-2DPAGE

P45984.

Proteomic databases

PRIDE

P45984.

Genome annotation databases

Ensembl

ENSG00000050748. Homo sapiens. [Contig view]

GeneID

5601.

Organism-specific databases

GeneCards

GC05M179595.

H-InvDB

HIX0005495.

HGNC

HGNC:6886. MAPK9.

HPA

CAB008910.

MIM

602896. gene.

PharmGKB

PA30630.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P45984.

OMA

P45984. NGVVKDQ.

Enzyme and pathway databases

BRENDA

2.7.11.24. 247.

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
foxopathway. FoxO family signaling.
glypican_3pathway. Glypican 3 network.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il2_1pathway. IL2-mediated signaling events.
p75ntrpathway. p75(NTR)-mediated signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.

Gene expression databases

ArrayExpress

P45984.

Bgee

P45984.

CleanEx

HS_MAPK9.

GermOnline

ENSG00000050748. Homo sapiens.

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. 2 hits.
[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...

Other Resources

NextBio

21752.

SOURCE

Search...

Entry information

Entry name

MK09_HUMAN

Accession

Primary (citable) accession number: P45984
Secondary accession number(s): Q15708 , Q15710, Q15711, Q8N5C5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 24, 2006
Last modified:	June 16, 2009
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)