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    Mapk10 mitogen-activated protein kinase 10 [ Mus musculus (house mouse) ]

    Gene ID: 26414, updated on 27-Nov-2024

    Summary

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    Official Symbol
    Mapk10provided by MGI
    Official Full Name
    mitogen-activated protein kinase 10provided by MGI
    Primary source
    MGI:MGI:1346863
    See related
    Ensembl:ENSMUSG00000046709 AllianceGenome:MGI:1346863
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    JNK3; Serk2; JNK3B1; JNK3B2; p493F12; p54bSAPK; SAPK(beta); C230008H04Rik
    Summary
    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 found 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]
    Expression
    Biased expression in cortex adult (RPKM 28.0), frontal lobe adult (RPKM 20.7) and 7 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Mapk10 in Genome Data Viewer
    Location:
    5 E5; 5 49.61 cM
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (103056413..103359200, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (102908547..103212604, complement)

    Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene Rho GTPase activating protein 24 Neighboring gene STARR-positive B cell enhancer ABC_E2753 Neighboring gene STARR-positive B cell enhancer ABC_E2754 Neighboring gene STARR-positive B cell enhancer ABC_E8065 Neighboring gene ferredoxin 1-like pseudogene Neighboring gene STARR-seq mESC enhancer starr_13764 Neighboring gene predicted gene, 30396 Neighboring gene STARR-seq mESC enhancer starr_13765 Neighboring gene STARR-seq mESC enhancer starr_13766 Neighboring gene STARR-seq mESC enhancer starr_13767 Neighboring gene STARR-seq mESC enhancer starr_13768 Neighboring gene STARR-seq mESC enhancer starr_13769 Neighboring gene STARR-seq mESC enhancer starr_13770 Neighboring gene STARR-seq mESC enhancer starr_13772 Neighboring gene RIKEN cDNA 4930429D17 gene Neighboring gene STARR-seq mESC enhancer starr_13773 Neighboring gene STARR-seq mESC enhancer starr_13774 Neighboring gene RIKEN cDNA 1700021F02 gene Neighboring gene STARR-seq mESC enhancer starr_13775 Neighboring gene discs, large homolog 5 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. JNK3 signaling pathway activates ceramide synthase leading to mitochondrial dysfunction. Yu J, et al. J Biol Chem, 2007 Aug 31. PMID 17609208
    2. Genetic deletion of c-Jun amino-terminal kinase 3 (JNK3) modestly increases disease severity in a mouse model of multiple sclerosis. Priego M, et al. J Neuroimmunol, 2023 Sep 15. PMID 37454525, Free PMC Article
    3. Time series RNA-seq analysis identifies MAPK10 as a critical gene in diabetes mellitus-induced atrial fibrillation in mice. Liu F, et al. J Mol Cell Cardiol, 2022 Jul. PMID 35489387
    4. Neuroprotective role of PrPC against kainate-induced epileptic seizures and cell death depends on the modulation of JNK3 activation by GluR6/7-PSD-95 binding. Carulla P, et al. Mol Biol Cell, 2011 Sep. PMID 21757544, Free PMC Article
    5. Lack of neuroprotection against experimental glaucoma in c-Jun N-terminal kinase 3 knockout mice. Quigley HA, et al. Exp Eye Res, 2011 Apr. PMID 21272576, Free PMC Article

    See all (112) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral sensitization.
      Title: Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral sensitization.
    2. Genetic deletion of c-Jun amino-terminal kinase 3 (JNK3) modestly increases disease severity in a mouse model of multiple sclerosis.
      Title: Genetic deletion of c-Jun amino-terminal kinase 3 (JNK3) modestly increases disease severity in a mouse model of multiple sclerosis.
    3. Time series RNA-seq analysis identifies MAPK10 as a critical gene in diabetes mellitus-induced atrial fibrillation in mice.
      Title: Time series RNA-seq analysis identifies MAPK10 as a critical gene in diabetes mellitus-induced atrial fibrillation in mice.
    4. JNK3 deficiency leads to upregulation of growth factors such as Vegfa, Pdgfb, Pgf, Hbegf and Tgfb3 in ischemic muscle by activation of the transcription factors Egr1/Creb1.
      Title: Neural JNK3 regulates blood flow recovery after hindlimb ischemia in mice via an Egr1/Creb1 axis.
    5. JNK isoforms are involved in the adult neurogenesis control.
      Title: JNK Isoforms Are Involved in the Control of Adult Hippocampal Neurogenesis in Mice, Both in Physiological Conditions and in an Experimental Model of Temporal Lobe Epilepsy.
    6. Together these data indicate that ONA induces APP expression and that gamma-secretase cleavage of APP releases AICD, which upregulates JNK3 leading to RGC death. This pathway may be a novel target for neuronal protection in optic neuropathies and other forms of neurotrauma.
      Title: APP upregulation contributes to retinal ganglion cell degeneration via JNK3.
    7. JNK1 and/or JNK3 are promising targets for the prevention of cell death and inflammation during epileptogenesis.
      Title: Neuroprotective Effects of the Absence of JNK1 or JNK3 Isoforms on Kainic Acid-Induced Temporal Lobe Epilepsy-Like Symptoms.
    8. Conversely, treatment with LY294002 (a selective inhibitor of Akt1) reversed the effects of quercetin. In conclusion, these findings highlight the important role of quercetin in protecting against cognitive deficits and inhibiting neuronal apoptosis via the Akt signaling pathway. We believe that quercetin might prove to be a useful therapeutic component in treating cerebral I/R diseases in the near future.
      Title: Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway.
    9. JNK3 therefore provides a mechanism that contributes to homeostatic regulation of energy balance in response to metabolic stress.
      Title: Excitatory transmission onto AgRP neurons is regulated by cJun NH2-terminal kinase 3 in response to metabolic stress.
    10. Genetic inhibition of JNK pathway in vivo by Jnk3 knockout results in amelioration of spinal muscular atrophy phenotype
      Title: Genetic inhibition of JNK3 ameliorates spinal muscular atrophy.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Endonuclease-mediated (3) 
    • Targeted (4)  1 citation

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables JUN kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables JUN kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables JUN kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in JNK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in JNK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in JNK cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in locomotor rhythm IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in neurotransmitter receptor transport to postsynaptic membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of circadian rhythm IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to light stimulus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in vesicle-mediated transport in synapse ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in glutamatergic synapse ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perikaryon ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in postsynaptic Golgi apparatus ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in postsynaptic density IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    mitogen-activated protein kinase 10
    Names
    JNK3 beta1 protein kinase
    JNK3 beta2 protein kinase
    MAP kinase 10
    MAP kinase p49 3F12
    SAPK/Erk/kinase 2
    c-Jun N-terminal kinase 3
    stress-activated protein kinase JNK3
    NP_001075036.1
    NP_001297612.1
    NP_001297614.1
    NP_001297615.1
    NP_001305031.1
    NP_001305060.1
    NP_001394501.1
    NP_001394502.1
    NP_001394503.1
    NP_001394504.1
    NP_001394505.1
    NP_001394506.1
    NP_001394507.1
    NP_001394508.1
    NP_001394509.1
    NP_001394513.1
    NP_001394515.1
    NP_001394517.1
    NP_001394518.1
    NP_001394521.1
    NP_001394524.1
    NP_001394528.1
    NP_001394529.1
    NP_001394530.1
    NP_033184.2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001081567.3 → NP_001075036.1  mitogen-activated protein kinase 10 isoform 1

      See identical proteins and their annotated locations for NP_001075036.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (1, also know as JNK3 alpha2) results from translation termination at the upstream UGA stop codon, while the longer isoform (1x) results from UGA stop codon readthrough to the downstream UGA termination codon. This RefSeq represents the shorter isoform (1).
      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      Consensus CDS
      CCDS39185.1
      UniProtKB/Swiss-Prot
      Q61831, Q9R0U6
      UniProtKB/TrEMBL
      Q8C9D4
      Related
      ENSMUSP00000108468.3, ENSMUST00000112847.9
      Conserved Domains (1) summary
      cd07850
      Location:63 → 398
      STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

    2. NM_001310683.2 → NP_001297612.1  mitogen-activated protein kinase 10 isoform 3

      See identical proteins and their annotated locations for NP_001297612.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate acceptor splice site in the 5' region, which results in translation initiation from an in-frame, downstream start codon compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/Swiss-Prot
      Q61831, Q9R0U6
      UniProtKB/TrEMBL
      Q78GB8
      Conserved Domains (1) summary
      cd07850
      Location:25 → 360
      STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

    3. NM_001310685.2 → NP_001297614.1  mitogen-activated protein kinase 10 isoform 4

      See identical proteins and their annotated locations for NP_001297614.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate in-frame coding exon compared to variant 1. The resulting isoform (4, also known as JNK3 beta2) is the same length; however, contains a different 24 aa protein segment compared to isoform 1.
      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      Consensus CDS
      CCDS80350.1
      UniProtKB/Swiss-Prot
      Q61831, Q9R0U6
      UniProtKB/TrEMBL
      Q80W80
      Related
      ENSMUSP00000084065.4, ENSMUST00000086854.10
      Conserved Domains (1) summary
      cd07850
      Location:63 → 398
      STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

    4. NM_001310686.3 → NP_001297615.1  mitogen-activated protein kinase 10 isoform 5

      See identical proteins and their annotated locations for NP_001297615.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate acceptor splice site in the 5' region and at the 3' terminal exon compared to variant 1. These differences result in translation initiation from an in-frame, downstream start codon, and an isoform (5) with a shorter N-terminus and a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/Swiss-Prot
      Q61831, Q9R0U6
      Conserved Domains (1) summary
      cd07850
      Location:25 → 360
      STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

    5. NM_001318102.1 → NP_001305031.1  mitogen-activated protein kinase 10 isoform 1x

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (1, also know as JNK3 alpha1) results from translation termination at the upstream UGA stop codon, while the longer isoform (1x) results from UGA stop codon readthrough to the downstream UGA termination codon. This RefSeq represents the longer, C-terminally extended isoform (1x). As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), the location of the upstream UGA stop codon in the longer isoform is denoted by an 'X'.
      Source sequence(s)
      AC125252, AC137121, AK082242, BC046625
      Consensus CDS
      CCDS89959.1
      UniProtKB/Swiss-Prot
      Q61831, Q9R0U6
      UniProtKB/TrEMBL
      A0A5F8MP75
      Related
      ENSMUSP00000158744.3, ENSMUST00000238446.3
      Conserved Domains (2) summary
      smart00220
      Location:64 → 359
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd07850
      Location:63 → 398
      STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

    6. NM_001318131.2 → NP_001305060.1  mitogen-activated protein kinase 10 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains an alternate in-frame coding exon and uses an alternate acceptor splice site at the 3' terminal exon (which causes a frameshift) compared to variant 1. The resulting isoform (6, also known as JNK3 beta1) has a different, internal 24 aa protein segment and a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/Swiss-Prot
      Q61831, Q9R0U6
      UniProtKB/TrEMBL
      Q80W81
      Conserved Domains (1) summary
      cd07850
      Location:63 → 398
      STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

    7. NM_001407572.1 → NP_001394501.1  mitogen-activated protein kinase 10 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121
      UniProtKB/TrEMBL
      E9QN59
      Related
      ENSMUSP00000108469.2, ENSMUST00000112848.8

    8. NM_001407573.1 → NP_001394502.1  mitogen-activated protein kinase 10 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/TrEMBL
      Q8C9D4

    9. NM_001407574.1 → NP_001394503.1  mitogen-activated protein kinase 10 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/TrEMBL
      Q8C9D4

    10. NM_001407575.1 → NP_001394504.1  mitogen-activated protein kinase 10 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/TrEMBL
      Q8C9D4

    11. NM_001407576.1 → NP_001394505.1  mitogen-activated protein kinase 10 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244

    12. NM_001407577.1 → NP_001394506.1  mitogen-activated protein kinase 10 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/TrEMBL
      Q78GB8

    13. NM_001407578.1 → NP_001394507.1  mitogen-activated protein kinase 10 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/TrEMBL
      Q78GB8

    14. NM_001407579.1 → NP_001394508.1  mitogen-activated protein kinase 10 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/TrEMBL
      Q78GB8

    15. NM_001407580.1 → NP_001394509.1  mitogen-activated protein kinase 10 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244

    16. NM_001407584.1 → NP_001394513.1  mitogen-activated protein kinase 10 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/TrEMBL
      Q80W82

    17. NM_001407586.1 → NP_001394515.1  mitogen-activated protein kinase 10 isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244

    18. NM_001407588.1 → NP_001394517.1  mitogen-activated protein kinase 10 isoform 10

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121

    19. NM_001407589.1 → NP_001394518.1  mitogen-activated protein kinase 10 isoform 11

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121

    20. NM_001407592.1 → NP_001394521.1  mitogen-activated protein kinase 10 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244

    21. NM_001407595.1 → NP_001394524.1  mitogen-activated protein kinase 10 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244

    22. NM_001407599.1 → NP_001394528.1  mitogen-activated protein kinase 10 isoform 12

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244

    23. NM_001407600.1 → NP_001394529.1  mitogen-activated protein kinase 10 isoform 13

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC137121
      UniProtKB/TrEMBL
      A0A0G2JG69
      Related
      ENSMUSP00000143448.2, ENSMUST00000128869.8

    24. NM_001407601.1 → NP_001394530.1  mitogen-activated protein kinase 10 isoform 14

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244

    25. NM_009158.4 → NP_033184.2  mitogen-activated protein kinase 10 isoform 2

      See identical proteins and their annotated locations for NP_033184.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate acceptor splice site at the 3' terminal exon, which causes a frameshift compared to variant 1. The resulting isoform (2, also know as JNK3 alpha1) has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC123664, AC125252, AC137121, AC160244
      UniProtKB/Swiss-Prot
      Q61831, Q9R0U6
      UniProtKB/TrEMBL
      Q80W82
      Related
      ENSMUSP00000159947.1, ENSMUST00000249849.1
      Conserved Domains (1) summary
      cd07850
      Location:63 → 398
      STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

    RNA

    1. NR_176398.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC123664, AC160244
      Related
      ENSMUST00000152609.2

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000071.7 Reference GRCm39 C57BL/6J

      Range
      103056413..103359200 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q61831.2 GenPept UniProtKB/Swiss-Prot:Q61831

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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