Reviewed, UniProtKB/Swiss-Prot P49187 (MK10_RAT)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 10
    EC=2.7.11.24
Alternative name(s):
    Stress-activated protein kinase JNK3
    c-Jun N-terminal kinase 3
    SAPK-beta
    p54-beta

Gene names

Name:	Mapk10
Synonyms:	Jnk3, Prkm10

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	464 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript 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. Required for stress-induced neuronal apoptosis and the pathogenesis of glutamate excitotoxicity By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax for the enzyme. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9 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 HDAC9 and MAPKBP1 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-221 and Tyr-223, which activates the enzyme By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAA42110.1 differs from that shown. Reason: Frameshift at position 22.

Ontologies

Keywords
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	JNK cascade Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid phosphorylation Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from direct assay. Source: RGD JUN kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 464	464	Mitogen-activated protein kinase 10		PRO_0000186279
Regions
	Domain	64 – 359	296	Protein kinase
	Nucleotide binding	70 – 78	9	ATP By similarity
	Motif	221 – 223	3	TXY
Sites
	Active site	189	1	Proton acceptor By similarity
	Binding site	93	1	ATP By similarity
Amino acid modifications
	Modified residue	221	1	Phosphothreonine By similarity
	Modified residue	223	1	Phosphotyrosine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P49187-1 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 6D6279D7C3E68AF9	FASTA	464	52,530
	10 20 30 40 50 60 MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSVVKHYNMS KSKVDNQFYS VEVGDSTFTV 70 80 90 100 110 120 LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ NQTHAKRAYR ELVLMKCVNH 130 140 150 160 170 180 KNIISLLNVF TPQKTLEEFQ DVYLVMELMD ANLCQVIQME LDHERMSYLL YQMLSAIKHL 190 200 210 220 230 240 HSAGIIHRDL KPSNIVVKSD CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY 250 260 270 280 290 300 KENVDIWSVG CIMGEMVRHK ILFPGRDYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN 310 320 330 340 350 360 RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPAKRISV DDALQHPYIN 370 380 390 400 410 420 VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN SEEKTKNGVV KGQPSPSGAA 430 440 450 460 VNSSESLPPS SSVNDISSMS TDQTLASDTD SSLEASAGPL GCCR

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]	Hulo-Demole C., Braconi-Quintaje S. Unpublished observations (MAR-1997) Cited for: IDENTIFICATION OF PROBABLE FRAMESHIFT.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L27128 mRNA. Translation: AAA42110.1. Frameshift.
IPI	IPI00191810.
PIR	S43969.
RefSeq	NP_036938.1.
UniGene	Rn.9911
3D structure databases
HSSP	HSSP built from PDB template 1JNK based on UniProtKB P53779.
SMR	P49187. Positions 46-400.
ModBase	Search...
Protein-protein interaction databases
STRING	P49187.
PTM databases
PhosphoSite	P49187.
Genome annotation databases
Ensembl	ENSRNOT00000002855; ENSRNOP00000002855; ENSRNOG00000002079; Rattus norvegicus. [Genome view]
GeneID	25272.
KEGG	rno:25272.
UCSC	NM_012806. rat.
Organism-specific databases
CTD	25272.
RGD	3663. Mapk10.
Phylogenomic databases
HOVERGEN	P49187.
Enzyme and pathway databases
BRENDA	2.7.11.24. 248.
Gene expression databases
ArrayExpress	P49187.
Genevestigator	P49187.
GermOnline	ENSRNOG00000002079. 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...
Other Resources
NextBio	605961.

Entry information

Entry name

MK10_RAT

Accession

Primary (citable) accession number: P49187

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	November 1, 1997
Last modified:	October 13, 2009
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)