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Q61831 (MK10_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length464 AA.
Sequence statusComplete.
Protein existenceEvidence 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.8 Ref.9

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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 464464Mitogen-activated protein kinase 10
PRO_0000186278

Regions

Domain64 – 359296Protein kinase
Nucleotide binding70 – 789ATP By similarity
Motif221 – 2233TXY

Sites

Active site1891Proton acceptor By similarity
Binding site931ATP By similarity

Amino acid modifications

Modified residue1541S-nitrosocysteine By similarity
Modified residue2211Phosphothreonine; by MAP2K7
Modified residue2231Phosphotyrosine; by MAP2K4
Lipidation4621S-palmitoyl cysteine By similarity
Lipidation4631S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence418 – 46447GAAVN…LGCCR → AQVQQ in isoform Alpha-1.
VSP_004840

Experimental info

Sequence conflict2671S → D in BAA85877. Ref.2
Sequence conflict3451V → A in BAA85877. Ref.2
Sequence conflict4121S → G in BAA85877. Ref.2
Sequence conflict418 – 4236GAAVNS → AQVQQ Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha-2 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 4313335AC2E9D2E6

FASTA46452,532
        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 

« Hide

Isoform Alpha-1 [UniParc].

Checksum: BECC560711189590
Show »

FASTA42248,517

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]"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.
[9]"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.
RefSeqXP_006535014.1. XM_006534951.1.
UniGeneMm.39253.
Mm.472459.

3D structure databases

ProteinModelPortalQ61831.
SMRQ61831. Positions 7-400.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ61831. 2 interactions.
MINTMINT-1487701.

PTM databases

PhosphoSiteQ61831.

Proteomic databases

PaxDbQ61831.
PRIDEQ61831.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID26414.
UCSCuc008yjg.1. mouse. [Q61831-1]

Organism-specific databases

MGIMGI:1346863. Mapk10.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ61831.
PhylomeDBQ61831.

Enzyme and pathway databases

BRENDA2.7.11.24. 3474.

Gene expression databases

CleanExMM_MAPK10.
GenevestigatorQ61831.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01772. JNKMAPKINASE.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAPK10. mouse.
PROQ61831.
SOURCESearch...

Entry information

Entry nameMK10_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot