Human Gene MAPK10 (uc010ikg.3) Description and Page Index
  Description: Homo sapiens mitogen-activated protein kinase 10 (MAPK10), transcript variant 3, mRNA.
RefSeq Summary (NM_138980): The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals, and thus are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system, and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017].
Transcript (Including UTRs)
   Position: hg19 chr4:86,936,276-87,280,023 Size: 343,748 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg19 chr4:86,938,381-87,080,572 Size: 142,192 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:86,936,276-87,280,023)mRNA (may differ from genome)Protein (426 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: MK10_HUMAN
DESCRIPTION: RecName: Full=Mitogen-activated protein kinase 10; Short=MAP kinase 10; Short=MAPK 10; EC=2.7.11.24; AltName: Full=MAP kinase p49 3F12; AltName: Full=Stress-activated protein kinase 1b; Short=SAPK1b; AltName: Full=Stress-activated protein kinase JNK3; AltName: Full=c-Jun N-terminal kinase 3;
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.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium.
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. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9.
SUBUNIT: Interacts with MAPKBP1 (By similarity). 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. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5.
INTERACTION: Q04206:RELA; NbExp=2; IntAct=EBI-713543, EBI-73886;
SUBCELLULAR LOCATION: Cytoplasm. Membrane; Lipid-anchor. Nucleus. Note=Palmitoylation regulates MAPK10 trafficking to cytoskeleton.
TISSUE SPECIFICITY: Specific to a subset of neurons in the nervous system. Present in the hippocampus and areas, cerebellum, striatum, brain stem, and weakly in the spinal cord. Very weak expression in testis and kidney.
DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
PTM: 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.
PTM: Palmitoylation regulates subcellular location and axonal development.
MASS SPECTROMETRY: Mass=44070; Method=Electrospray; Range=1-464; Source=PubMed:10715136;
DISEASE: Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:606369]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
SIMILARITY: Contains 1 protein kinase domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/JNK3ID427.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MAPK10
CDC HuGE Published Literature: MAPK10
Positive Disease Associations: Asthma , Calcium-Binding Proteins
Related Studies:
  1. Asthma
    , , . [PubMed 0]
  2. Calcium-Binding Proteins
    Emelia J Benjamin et al. BMC medical genetics 2007, Genome-wide association with select biomarker traits in the Framingham Heart Study., BMC medical genetics. [PubMed 17903293]
    The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.

-  MalaCards Disease Associations
  MalaCards Gene Search: MAPK10
Diseases sorted by gene-association score: lennox-gastaut syndrome* (56), pertussis (16), pneumococcal meningitis (10), opioid abuse (10), cryptococcal meningitis (6), pheochromocytoma (2), breast cancer (2), insulin-like growth factor i (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 24.16 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 253.79 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -291.501052-0.277 Picture PostScript Text
3' UTR -592.062105-0.281 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR003527 - MAP_kinase_CS
IPR008351 - MAPK_JNK
IPR000719 - Prot_kinase_cat_dom
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF06293 - Lipopolysaccharide kinase (Kdo/WaaP) family
PF07714 - Protein tyrosine kinase

SCOP Domains:
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1JNK
- X-ray MuPIT

1PMN
- X-ray MuPIT

1PMQ
- X-ray
To conserve bandwidth, only the images from the first 3 structures are shown.
1PMU - X-ray MuPIT 1PMV - X-ray MuPIT 2B1P - X-ray MuPIT
2EXC - X-ray MuPIT 2O0U - X-ray MuPIT 2O2U - X-ray MuPIT
2OK1 - X-ray MuPIT 2P33 - X-ray MuPIT 2R9S - X-ray MuPIT
2WAJ - X-ray MuPIT 2ZDT - X-ray MuPIT 2ZDU - X-ray MuPIT
3CGF - X-ray MuPIT 3CGO - X-ray MuPIT 3DA6 - X-ray MuPIT
3FI2 - X-ray MuPIT 3FI3 - X-ray MuPIT 3FV8 - X-ray MuPIT
3G90 - X-ray MuPIT 3G9L - X-ray MuPIT 3G9N - X-ray MuPIT
3KVX - X-ray MuPIT 3OXI - X-ray MuPIT 3OY1 - X-ray MuPIT
3PTG - X-ray MuPIT 3TTI - X-ray MuPIT 3TTJ - X-ray MuPIT
3V6R - X-ray MuPIT 3V6S - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P53779
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004705 JUN kinase activity
GO:0004707 MAP kinase activity
GO:0004708 MAP kinase kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity

Biological Process:
GO:0000187 activation of MAPK activity
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0007254 JNK cascade
GO:0007258 JUN phosphorylation
GO:0009416 response to light stimulus
GO:0010468 regulation of gene expression
GO:0016310 phosphorylation
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042752 regulation of circadian rhythm
GO:0048511 rhythmic process
GO:0048666 neuron development

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0043005 neuron projection


-  Descriptions from all associated GenBank mRNAs
  JA482061 - Sequence 44 from Patent WO2011072091.
JA482062 - Sequence 45 from Patent WO2011072091.
JE980353 - Sequence 44 from Patent EP2862929.
JE980354 - Sequence 45 from Patent EP2862929.
JA482060 - Sequence 43 from Patent WO2011072091.
JE980352 - Sequence 43 from Patent EP2862929.
BC022492 - Homo sapiens mitogen-activated protein kinase 10, mRNA (cDNA clone IMAGE:4792970).
BC035057 - Homo sapiens mitogen-activated protein kinase 10, mRNA (cDNA clone MGC:41877 IMAGE:5261221), complete cds.
BC051731 - Homo sapiens mitogen-activated protein kinase 10, mRNA (cDNA clone MGC:50974 IMAGE:4838495), complete cds.
AK225974 - Homo sapiens mRNA for mitogen-activated protein kinase 10 isoform 2 variant, clone: FCC112E07.
U07620 - Human MAP kinase mRNA, complete cds.
AK124791 - Homo sapiens cDNA FLJ42801 fis, clone BRCAN2001223, highly similar to Mitogen-activated protein kinase 10 (EC 2.7.11.24).
U34820 - Human JNK3 alpha1 protein kinase (JNK3A1) mRNA, complete cds.
U34819 - Human JNK3 alpha2 protein kinase (JNK3A2) mRNA, complete cds.
AB463124 - Synthetic construct DNA, clone: pF1KB9001, Homo sapiens MAPK10 gene for mitogen-activated protein kinase 10, without stop codon, in Flexi system.
AK307129 - Homo sapiens cDNA, FLJ97077.
JA482063 - Sequence 46 from Patent WO2011072091.
JE980355 - Sequence 46 from Patent EP2862929.
BC065516 - Homo sapiens mitogen-activated protein kinase 10, mRNA (cDNA clone MGC:70580 IMAGE:5721954), complete cds.
AK091104 - Homo sapiens cDNA FLJ33785 fis, clone BRSSN2008125, highly similar to Mitogen-activated protein kinase 10 (EC 2.7.11.24).
AK057723 - Homo sapiens cDNA FLJ33161 fis, clone UTERU2000517, highly similar to Mitogen-activated protein kinase 10 (EC 2.7.11.24).
JD094529 - Sequence 75553 from Patent EP1572962.
JD338279 - Sequence 319303 from Patent EP1572962.
JD037528 - Sequence 18552 from Patent EP1572962.
JD370913 - Sequence 351937 from Patent EP1572962.
JD223689 - Sequence 204713 from Patent EP1572962.
JD280041 - Sequence 261065 from Patent EP1572962.
JD155421 - Sequence 136445 from Patent EP1572962.
JD234378 - Sequence 215402 from Patent EP1572962.
AK294125 - Homo sapiens cDNA FLJ54598 complete cds, highly similar to Mitogen-activated protein kinase 10 (EC 2.7.11.24).
JD305090 - Sequence 286114 from Patent EP1572962.
JD049317 - Sequence 30341 from Patent EP1572962.
KJ901663 - Synthetic construct Homo sapiens clone ccsbBroadEn_11057 MAPK10 gene, encodes complete protein.
KJ905294 - Synthetic construct Homo sapiens clone ccsbBroadEn_14805 MAPK10 gene, encodes complete protein.
CU688058 - Synthetic construct Homo sapiens gateway clone IMAGE:100021694 5' read MAPK10 mRNA.
KJ901664 - Synthetic construct Homo sapiens clone ccsbBroadEn_11058 MAPK10 gene, encodes complete protein.
JD329460 - Sequence 310484 from Patent EP1572962.
JD346933 - Sequence 327957 from Patent EP1572962.
JD362742 - Sequence 343766 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04012 - ErbB signaling pathway
hsa04310 - Wnt signaling pathway
hsa04510 - Focal adhesion
hsa04620 - Toll-like receptor signaling pathway
hsa04621 - NOD-like receptor signaling pathway
hsa04622 - RIG-I-like receptor signaling pathway
hsa04664 - Fc epsilon RI signaling pathway
hsa04722 - Neurotrophin signaling pathway
hsa04910 - Insulin signaling pathway
hsa04912 - GnRH signaling pathway
hsa04914 - Progesterone-mediated oocyte maturation
hsa04920 - Adipocytokine signaling pathway
hsa04930 - Type II diabetes mellitus
hsa05120 - Epithelial cell signaling in Helicobacter pylori infection
hsa05131 - Shigellosis
hsa05142 - Chagas disease
hsa05200 - Pathways in cancer
hsa05210 - Colorectal cancer
hsa05212 - Pancreatic cancer

BioCarta from NCI Cancer Genome Anatomy Project
h_mapkPathway - MAPKinase Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein P53779 (Reactome details) participates in the following event(s):

R-HSA-450348 Activated human JNKs migrate to nucleoplasm
R-HSA-168162 Phosphorylation of human JNKs by activated MKK4/MKK7
R-HSA-168136 Activated JNKs phosphorylate c-JUN
R-HSA-168053 Phosphorylated MAPKs phosphorylate ATF-2
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-450294 MAP kinase activation
R-HSA-2559583 Cellular Senescence
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-448424 Interleukin-17 signaling
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975871 MyD88 cascade initiated on plasma membrane
R-HSA-2262752 Cellular responses to stress
R-HSA-168249 Innate Immune System
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-449147 Signaling by Interleukins
R-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-168256 Immune System
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade

-  Other Names for This Gene
  Alternate Gene Symbols: A6NFS3, A6NG28, AK124791, B3KQ94, JNK3, JNK3A, MK10_HUMAN, NM_138980, NP_620446, P53779, PRKM10, Q15707, Q49AP1, SAPK1B
UCSC ID: uc010ikg.3
RefSeq Accession: NM_138980
Protein: P53779 (aka MK10_HUMAN)
CCDS: CCDS3612.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AK124791.1
exon count: 14CDS single in 3' UTR: no RNA size: 3081
ORF size: 1281CDS single in intron: no Alignment % ID: 99.81
txCdsPredict score: 2181.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.