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Q61831

- MK10_MOUSE

UniProt

Q61831 - MK10_MOUSE

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Protein
Mitogen-activated protein kinase 10
Gene
Mapk10, Jnk3, Prkm10, Serk2
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.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 HDAC9.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei93 – 931ATP By similarity
Active sitei189 – 1891Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi70 – 789ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. JUN kinase activity Source: UniProtKB
  3. protein binding Source: UniProtKB

GO - Biological processi

  1. JNK cascade Source: UniProtKB
  2. JUN phosphorylation Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

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
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:1346863. Mapk10.

Subcellular locationi

Cytoplasm. Membrane; Lipid-anchor. Nucleus. Mitochondrion
Note: Palmitoylation regulates MAPK10 trafficking to cytoskeleton By similarity. Recruited to the mitochondria in the presence of SARM1.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. mitochondrion Source: UniProtKB
  3. nucleus Source: UniProtKB-SubCell
  4. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 464464Mitogen-activated protein kinase 10
PRO_0000186278Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei154 – 1541S-nitrosocysteine By similarity
Modified residuei221 – 2211Phosphothreonine; by MAP2K7
Modified residuei223 – 2231Phosphotyrosine; by MAP2K4
Lipidationi462 – 4621S-palmitoyl cysteine By similarity
Lipidationi463 – 4631S-palmitoyl cysteine By similarity

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.
Palmitoylation regulates subcellular location and axonal development By similarity.

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein, S-nitrosylation

Proteomic databases

MaxQBiQ61831.
PaxDbiQ61831.
PRIDEiQ61831.

PTM databases

PhosphoSiteiQ61831.

Expressioni

Tissue specificityi

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 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.
GenevestigatoriQ61831.

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 SARM1.3 Publications

Protein-protein interaction databases

IntActiQ61831. 2 interactions.
MINTiMINT-1487701.

Structurei

3D structure databases

ProteinModelPortaliQ61831.
SMRiQ61831. Positions 11-429.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini64 – 359296Protein kinase
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi221 – 2233TXY

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ61831.
KOiK04440.
PhylomeDBiQ61831.

Family and domain databases

InterProiIPR011009. 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]
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. Align

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

MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSIAKHYNMS KSKVDNQFYS    50
VEVGDSTFTV LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ 100
NQTHAKRAYR ELVLMKCVNH KNIISLLNVF TPQKTLEEFQ DVYLVMELMD 150
ANLCQVIQME LDHERMSYLL YQMLCGIKHL HSAGIIHRDL KPSNIVVKSD 200
CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY KENVDIWSVG 250
CIMGEMVRHK ILFPGRSYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN 300
RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPVKRISV 350
DDALQHPYIN VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN 400
SEEKTKNGVV KSQPSPSGAA VNSSESLPPS SAVNDISSMS TDQTLASDTD 450
SSLEASAGPL GCCR 464
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei418 – 46447GAAVN…LGCCR → AQVQQ in isoform Alpha-1.
VSP_004840Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti267 – 2671S → D in BAA85877. 1 Publication
Sequence conflicti345 – 3451V → A in BAA85877. 1 Publication
Sequence conflicti412 – 4121S → G in BAA85877. 1 Publication
Sequence conflicti418 – 4236GAAVNS → AQVQQ1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L35236 mRNA. Translation: AAB37741.1.
AB005665 mRNA. Translation: BAA85877.1.
RefSeqiXP_006535014.1. XM_006534951.1.
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:
EMBL
GenBank
DDBJ
Links Updated
L35236 mRNA. Translation: AAB37741.1 .
AB005665 mRNA. Translation: BAA85877.1 .
RefSeqi XP_006535014.1. XM_006534951.1.
UniGenei Mm.39253.
Mm.472459.

3D structure databases

ProteinModelPortali Q61831.
SMRi Q61831. Positions 11-429.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q61831. 2 interactions.
MINTi MINT-1487701.

PTM databases

PhosphoSitei Q61831.

Proteomic databases

MaxQBi Q61831.
PaxDbi Q61831.
PRIDEi Q61831.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 26414.
KEGGi mmu:26414.
UCSCi uc008yjg.1. mouse. [Q61831-1 ]

Organism-specific databases

CTDi 5602.
MGIi MGI:1346863. Mapk10.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi Q61831.
KOi K04440.
PhylomeDBi Q61831.

Enzyme and pathway databases

BRENDAi 2.7.11.24. 3474.

Miscellaneous databases

ChiTaRSi MAPK10. mouse.
PROi Q61831.
SOURCEi Search...

Gene expression databases

CleanExi MM_MAPK10.
Genevestigatori Q61831.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01772. JNKMAPKINASE.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS01351. MAPK. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

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: September 3, 2014
This is version 138 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

External Data

Dasty 3

Similar proteinsi