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P49187 (MK10_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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):
SAPK-beta
Stress-activated protein kinase JNK3
c-Jun N-terminal kinase 3
p54-beta
Gene names
Name:Mapk10
Synonyms:Jnk3, Prkm10
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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 By similarity. Ref.4 Ref.5

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. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. Interacts with SARM1 By similarity. Ref.3 Ref.6

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 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 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.

Sequence caution

The sequence AAA42110.1 differs from that shown. Reason: Frameshift at position 22.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Syt4P502322EBI-7155513,EBI-540118

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 464464Mitogen-activated protein kinase 10
PRO_0000186279

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 By similarity
Modified residue2231Phosphotyrosine; by MAP2K4 By similarity
Lipidation4621S-palmitoyl cysteine By similarity
Lipidation4631S-palmitoyl cysteine By similarity

Sequences

Sequence LengthMass (Da)Tools
P49187 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 6D6279D7C3E68AF9

FASTA46452,530
        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 

« Hide

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].
Tissue: Brain.
[2]Hulo-Demole C., Braconi-Quintaje S.
Unpublished observations (MAR-1997)
Cited for: IDENTIFICATION OF PROBABLE FRAMESHIFT.
[3]"Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3."
McDonald P.H., Chow C.W., Miller W.E., Laporte S.A., Field M.E., Lin F.-T., Davis R.J., Lefkowitz R.J.
Science 290:1574-1577(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB2.
[4]"JNK3 contributes to c-jun induction and apoptosis in 4-hydroxynonenal-treated sympathetic neurons."
Bruckner S.R., Estus S.
J. Neurosci. Res. 70:665-670(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation."
Kimberly W.T., Zheng J.B., Town T., Flavell R.A., Selkoe D.J.
J. Neurosci. 25:5533-5543(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF APP.
[6]"The beta-arrestin-2 scaffold protein promotes c-Jun N-terminal kinase-3 activation by binding to its nonconserved N terminus."
Guo C., Whitmarsh A.J.
J. Biol. Chem. 283:15903-15911(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L27128 mRNA. Translation: AAA42110.1. Frameshift.
PIRS43969.
RefSeqNP_036938.2. NM_012806.2.
UniGeneRn.9911.

3D structure databases

ProteinModelPortalP49187.
SMRP49187. Positions 45-400.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP49187. 1 interaction.
MINTMINT-151503.

Chemistry

BindingDBP49187.
ChEMBLCHEMBL4092.

PTM databases

PhosphoSiteP49187.

Proteomic databases

PaxDbP49187.
PRIDEP49187.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25272.
KEGGrno:25272.

Organism-specific databases

CTD5602.
RGD3663. Mapk10.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidP49187.
KOK04440.
PhylomeDBP49187.

Enzyme and pathway databases

BRENDA2.7.11.24. 5301.

Gene expression databases

GenevestigatorP49187.

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

NextBio605961.

Entry information

Entry nameMK10_RAT
AccessionPrimary (citable) accession number: P49187
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: November 1, 1997
Last modified: June 11, 2014
This is version 126 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