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Protein

Mitogen-activated protein kinase 10

Gene

Mapk10

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692).4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+1 Publication

Enzyme regulationi

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.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei93ATPPROSITE-ProRule annotation1
Active sitei189Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi70 – 78ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • JUN kinase activity Source: UniProtKB

GO - Biological processi

  • JNK cascade Source: UniProtKB
  • locomotor rhythm Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of circadian rhythm Source: UniProtKB
  • response to light stimulus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Biological rhythms

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 10 (EC:2.7.11.24)
Short name:
MAP kinase 10
Short name:
MAPK 10
Alternative name(s):
MAP kinase p49 3F12
Stress-activated protein kinase JNK3
c-Jun N-terminal kinase 3
Gene namesi
Name:Mapk10
Synonyms:Jnk3, Prkm10, Serk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1346863. Mapk10.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862781 – 464Mitogen-activated protein kinase 10Add BLAST464

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei221Phosphothreonine; by MAP2K7By similarity1
Modified residuei223Phosphotyrosine; by MAP2K4By similarity1
Lipidationi462S-palmitoyl cysteineBy similarity1
Lipidationi463S-palmitoyl cysteineBy similarity1

Post-translational modificationi

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).By similarity
Palmitoylation regulates subcellular location and axonal development.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ61831.
PeptideAtlasiQ61831.
PRIDEiQ61831.

PTM databases

iPTMnetiQ61831.
PhosphoSitePlusiQ61831.

Expressioni

Tissue specificityi

Brain (at protein level). 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.1 Publication

Developmental stagei

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.

Gene expression databases

CleanExiMM_MAPK10.

Interactioni

Subunit structurei

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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Mapk8ip3Q9ESN9-24EBI-400741,EBI-9549291

Protein-protein interaction databases

BioGridi204967. 3 interactors.
IntActiQ61831. 3 interactors.
MINTiMINT-1487701.
STRINGi10090.ENSMUSP00000108468.

Structurei

3D structure databases

ProteinModelPortaliQ61831.
SMRiQ61831.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini64 – 359Protein kinasePROSITE-ProRule annotationAdd BLAST296

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi221 – 223TXY3

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0665. Eukaryota.
ENOG410XSHI. LUCA.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ61831.
KOiK04440.
PhylomeDBiQ61831.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01772. JNKMAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-2 (identifier: Q61831-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSIAKHYNMS KSKVDNQFYS
60 70 80 90 100
VEVGDSTFTV LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ
110 120 130 140 150
NQTHAKRAYR ELVLMKCVNH KNIISLLNVF TPQKTLEEFQ DVYLVMELMD
160 170 180 190 200
ANLCQVIQME LDHERMSYLL YQMLCGIKHL HSAGIIHRDL KPSNIVVKSD
210 220 230 240 250
CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY KENVDIWSVG
260 270 280 290 300
CIMGEMVRHK ILFPGRSYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN
310 320 330 340 350
RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPVKRISV
360 370 380 390 400
DDALQHPYIN VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN
410 420 430 440 450
SEEKTKNGVV KSQPSPSGAA VNSSESLPPS SAVNDISSMS TDQTLASDTD
460
SSLEASAGPL GCCR
Length:464
Mass (Da):52,532
Last modified:November 1, 1997 - v2
Checksum:i4313335AC2E9D2E6
GO
Isoform Alpha-1 (identifier: Q61831-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:422
Mass (Da):48,517
Checksum:iBECC560711189590
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti267S → D in BAA85877 (PubMed:10523642).Curated1
Sequence conflicti345V → A in BAA85877 (PubMed:10523642).Curated1
Sequence conflicti412S → G in BAA85877 (PubMed:10523642).Curated1
Sequence conflicti418 – 423GAAVNS → AQVQQ (PubMed:10523642).Curated6

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004840418 – 464GAAVN…LGCCR → AQVQQ in isoform Alpha-1. CuratedAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L35236 mRNA. Translation: AAB37741.1.
AB005665 mRNA. Translation: BAA85877.1.
RefSeqiNP_001297615.1. NM_001310686.2.
XP_017176379.1. XM_017320890.1.
XP_017176380.1. XM_017320891.1.
UniGeneiMm.39253.
Mm.472459.

Genome annotation databases

GeneIDi26414.
KEGGimmu:26414.
UCSCiuc008yjg.1. mouse. [Q61831-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L35236 mRNA. Translation: AAB37741.1.
AB005665 mRNA. Translation: BAA85877.1.
RefSeqiNP_001297615.1. NM_001310686.2.
XP_017176379.1. XM_017320890.1.
XP_017176380.1. XM_017320891.1.
UniGeneiMm.39253.
Mm.472459.

3D structure databases

ProteinModelPortaliQ61831.
SMRiQ61831.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204967. 3 interactors.
IntActiQ61831. 3 interactors.
MINTiMINT-1487701.
STRINGi10090.ENSMUSP00000108468.

PTM databases

iPTMnetiQ61831.
PhosphoSitePlusiQ61831.

Proteomic databases

PaxDbiQ61831.
PeptideAtlasiQ61831.
PRIDEiQ61831.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi26414.
KEGGimmu:26414.
UCSCiuc008yjg.1. mouse. [Q61831-1]

Organism-specific databases

CTDi5602.
MGIiMGI:1346863. Mapk10.

Phylogenomic databases

eggNOGiKOG0665. Eukaryota.
ENOG410XSHI. LUCA.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ61831.
KOiK04440.
PhylomeDBiQ61831.

Enzyme and pathway databases

BRENDAi2.7.11.24. 3474.

Miscellaneous databases

ChiTaRSiMapk10. mouse.
PROiQ61831.
SOURCEiSearch...

Gene expression databases

CleanExiMM_MAPK10.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01772. JNKMAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMK10_MOUSE
AccessioniPrimary (citable) accession number: Q61831
Secondary accession number(s): Q9R0U6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.