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P49187

- MK10_RAT

UniProt

P49187 - MK10_RAT

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Protein

Mitogen-activated protein kinase 10

Gene

Mapk10

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

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. Inhibited by HDAC9 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei93 – 931ATPPROSITE-ProRule annotation
Active sitei189 – 1891Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi70 – 789ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: RGD
  2. JUN kinase activity Source: UniProtKB

GO - Biological processi

  1. JNK cascade Source: UniProtKB
  2. JUN phosphorylation Source: RGD
  3. negative regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  4. protein phosphorylation Source: RGD
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. 5301.

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):
SAPK-beta
Stress-activated protein kinase JNK3
c-Jun N-terminal kinase 3
p54-beta
Gene namesi
Name:Mapk10
Synonyms:Jnk3, Prkm10
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3663. Mapk10.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. mitochondrion Source: UniProtKB
  3. nucleus Source: UniProtKB-KW
  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 10PRO_0000186279Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei154 – 1541S-nitrosocysteineBy similarity
Modified residuei221 – 2211Phosphothreonine; by MAP2K7By similarity
Modified residuei223 – 2231Phosphotyrosine; by MAP2K4By similarity
Lipidationi462 – 4621S-palmitoyl cysteineBy similarity
Lipidationi463 – 4631S-palmitoyl cysteineBy 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).By similarity
Palmitoylation regulates subcellular location and axonal development.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein, S-nitrosylation

Proteomic databases

PaxDbiP49187.
PRIDEiP49187.

PTM databases

PhosphoSiteiP49187.

Expressioni

Gene expression databases

GenevestigatoriP49187.

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. Interacts with HDAC9 and MAPKBP1 (By similarity). Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. Interacts with SARM1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Syt4P502322EBI-7155513,EBI-540118

Protein-protein interaction databases

IntActiP49187. 1 interaction.
MINTiMINT-151503.

Structurei

3D structure databases

ProteinModelPortaliP49187.
SMRiP49187. Positions 45-400.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini64 – 359296Protein kinasePROSITE-ProRule annotationAdd
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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP49187.
KOiK04440.
PhylomeDBiP49187.

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.
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]

Sequencei

Sequence statusi: Complete.

P49187-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSVVKHYNMS 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 YQMLSAIKHL HSAGIIHRDL KPSNIVVKSD
210 220 230 240 250
CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY KENVDIWSVG
260 270 280 290 300
CIMGEMVRHK ILFPGRDYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN
310 320 330 340 350
RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPAKRISV
360 370 380 390 400
DDALQHPYIN VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN
410 420 430 440 450
SEEKTKNGVV KGQPSPSGAA VNSSESLPPS SSVNDISSMS TDQTLASDTD
460
SSLEASAGPL GCCR
Length:464
Mass (Da):52,530
Last modified:November 1, 1997 - v2
Checksum:i6D6279D7C3E68AF9
GO

Sequence cautioni

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27128 mRNA. Translation: AAA42110.1. Frameshift.
PIRiS43969.
RefSeqiNP_036938.2. NM_012806.2.
UniGeneiRn.9911.

Genome annotation databases

GeneIDi25272.
KEGGirno:25272.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27128 mRNA. Translation: AAA42110.1 . Frameshift.
PIRi S43969.
RefSeqi NP_036938.2. NM_012806.2.
UniGenei Rn.9911.

3D structure databases

ProteinModelPortali P49187.
SMRi P49187. Positions 45-400.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P49187. 1 interaction.
MINTi MINT-151503.

Chemistry

BindingDBi P49187.
ChEMBLi CHEMBL4092.

PTM databases

PhosphoSitei P49187.

Proteomic databases

PaxDbi P49187.
PRIDEi P49187.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25272.
KEGGi rno:25272.

Organism-specific databases

CTDi 5602.
RGDi 3663. Mapk10.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi P49187.
KOi K04440.
PhylomeDBi P49187.

Enzyme and pathway databases

BRENDAi 2.7.11.24. 5301.

Miscellaneous databases

NextBioi 605961.

Gene expression databases

Genevestigatori P49187.

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.
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. 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.

Entry informationi

Entry nameiMK10_RAT
AccessioniPrimary (citable) accession number: P49187
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: November 1, 1997
Last modified: November 26, 2014
This is version 129 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3