Q61831 (MK10_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase 10
Short name=MAP kinase 10
Short name=MAPK 10
EC=2.7.11.24

Alternative name(s):
MAP kinase p49 3F12
Stress-activated protein kinase JNK3
c-Jun N-terminal kinase 3

Gene names

Name:	Mapk10
Synonyms:	Jnk3, Prkm10, Serk2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

Protein attributes

Sequence length	464 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration 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 MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Ref.4 Ref.9 Ref.10
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.4
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 By similarity. Inhibited by HDAC9. Ref.6
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 By similarity. Interacts with HDAC9 and MAPKBP1. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5 By similarity. Interacts with SARM1. Ref.5 Ref.6 Ref.7
Subcellular location	Cytoplasm. Membrane; Lipid-anchor. Nucleus. Mitochondrion. Note: Palmitoylation regulates MAPK10 trafficking to cytoskeleton By similarity. Recruited to the mitochondria in the presence of SARM1. Ref.7
Tissue specificity	Expressed specifically in neurons of the hippocampus, cortex, cerebellum, brainstem, and spinal cord. Seems to be also found in testis, and very weakly in the heart.
Developmental stage	Expression begins in day E11.5 embryos, and is localized in both the rostral spinal cord and rhombencephalon. In day E12.5-13 embryos, it is found throughout the telencephalon. By day 17.5, JNK3 is also expressed in neurons of dorsal root and sensory ganglia and at lower levels in neurons of the myenteric plexus and the developing heart.
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 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro By similarity. Palmitoylation regulates subcellular location and axonal development 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 Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	mitochondrion Inferred from direct assay Ref.7. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform Alpha-2 (identifier: Q61831-1)

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: Q61831-2)

The sequence of this isoform differs from the canonical sequence as follows:
     418-464: GAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLEASAGPLGCCR → AQVQQ

Note: No experimental confirmation available.

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_0000186278
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 MAP2K7 Ref.8
	Modified residue	223	1	Phosphotyrosine; by MAP2K4 Ref.8
	Lipidation	462	1	S-palmitoyl cysteine By similarity
	Lipidation	463	1	S-palmitoyl cysteine By similarity
Natural variations
	Alternative sequence	418 – 464	47	GAAVN…LGCCR → AQVQQ in isoform Alpha-1.		VSP_004840
Experimental info
	Sequence conflict	267	1	S → D in BAA85877. Ref.2
	Sequence conflict	345	1	V → A in BAA85877. Ref.2
	Sequence conflict	412	1	S → G in BAA85877. Ref.2
	Sequence conflict	418 – 423	6	GAAVNS → AQVQQ Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-2 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 4313335AC2E9D2E6	FASTA	464	52,532
	10 20 30 40 50 60 MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSIAKHYNMS 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 YQMLCGIKHL 190 200 210 220 230 240 HSAGIIHRDL KPSNIVVKSD CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY 250 260 270 280 290 300 KENVDIWSVG CIMGEMVRHK ILFPGRSYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN 310 320 330 340 350 360 RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPVKRISV DDALQHPYIN 370 380 390 400 410 420 VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN SEEKTKNGVV KSQPSPSGAA 430 440 450 460 VNSSESLPPS SAVNDISSMS TDQTLASDTD SSLEASAGPL GCCR
	Isoform Alpha-1 [UniParc]. Checksum: BECC560711189590	FASTA	422	48,517
	10 20 30 40 50 60 MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSIAKHYNMS 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 YQMLCGIKHL 190 200 210 220 230 240 HSAGIIHRDL KPSNIVVKSD CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY 250 260 270 280 290 300 KENVDIWSVG CIMGEMVRHK ILFPGRSYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN 310 320 330 340 350 360 RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPVKRISV DDALQHPYIN 370 380 390 400 410 420 VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN SEEKTKNGVV KSQPSPSAQV QQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Developmental expression in the mouse nervous system of the p493F12 SAP kinase." Martin J.H., Mohit A.A., Miller C.A. Brain Res. Mol. Brain Res. 35:47-57(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Brain.
[2]	"JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a scaffold factor in the JNK signaling pathway." Ito M., Yoshioka K., Akechi M., Yamashita S., Takamatsu N., Sugiyama K., Hibi M., Nakabeppu Y., Shiba T., Yamamoto K. Mol. Cell. Biol. 19:7539-7548(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 39-464. Tissue: Brain.
[3]	Hulo-Demole C., Braconi-Quintaje S. Unpublished observations (MAR-1997) Cited for: IDENTIFICATION OF LONG FORM (ALPHA-2).
[4]	"Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene." Yang D.D., Kuan C.-Y., Whitmarsh A.J., Rincon M., Zheng T.S., Davis R.J., Rakic P., Flavell R.A. Nature 389:865-870(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COFACTOR. Tissue: Hippocampus.
[5]	"A novel Jun N-terminal kinase (JNK)-binding protein that enhances the activation of JNK by MEK kinase 1 and TGF-beta-activated kinase 1." Koyano S., Ito M., Takamatsu N., Shiba T., Yamamoto K., Yoshioka K. FEBS Lett. 457:385-388(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAPKBP1.
[6]	"Neuroprotection by histone deacetylase-related protein." Morrison B.E., Majdzadeh N., Zhang X., Lyles A., Bassel-Duby R., Olson E.N., D'Mello S.R. Mol. Cell. Biol. 26:3550-3564(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HDAC9, ENZYME REGULATION.
[7]	"MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival." Kim Y., Zhou P., Qian L., Chuang J.Z., Lee J., Li C., Iadecola C., Nathan C., Ding A. J. Exp. Med. 204:2063-2074(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SARM1.
[8]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-221 AND TYR-223, MASS SPECTROMETRY. Tissue: Brain.
[9]	"JNK3 mediates paraquat- and rotenone-induced dopaminergic neuron death." Choi W.S., Abel G., Klintworth H., Flavell R.A., Xia Z. J. Neuropathol. Exp. Neurol. 69:511-520(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NEURONAL APOPTOSIS.
[10]	"Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons." Atkinson P.J., Cho C.H., Hansen M.R., Green S.H. Hear. Res. 278:77-85(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NEURITE GROWTH.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L35236 mRNA. Translation: AAB37741.1. AB005665 mRNA. Translation: BAA85877.1.
IPI	IPI00623629. IPI00775773.
UniGene	Mm.39253. Mm.472459.
3D structure databases
ProteinModelPortal	Q61831.
SMR	Q61831. Positions 11-400.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q61831. 2 interactions.
MINT	MINT-1487701.
PTM databases
PhosphoSite	Q61831.
Proteomic databases
PaxDb	Q61831.
PRIDE	Q61831.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	uc008yjg.1. mouse.
Organism-specific databases
MGI	MGI:1346863. Mapk10.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233024.
HOVERGEN	HBG014652.
InParanoid	Q61831.
OrthoDB	EOG48SGT3.
Enzyme and pathway databases
BRENDA	2.7.11.24. 3474.
Gene expression databases
CleanEx	MM_MAPK10.
Genevestigator	Q61831.
GermOnline	ENSMUSG00000046709. Mus musculus.
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
ChiTaRS	MAPK10. mouse.
SOURCE	Search...

Entry information

Entry name

MK10_MOUSE

Accession

Primary (citable) accession number: Q61831
Secondary accession number(s): Q9R0U6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 29, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program