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    Map4k4 mitogen-activated protein kinase kinase kinase kinase 4 [ Rattus norvegicus (Norway rat) ]

    Gene ID: 301363, updated on 9-Dec-2024

    Summary

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    Official Symbol
    Map4k4provided by RGD
    Official Full Name
    mitogen-activated protein kinase kinase kinase kinase 4provided by RGD
    Primary source
    RGD:1305322
    See related
    EnsemblRapid:ENSRNOG00000014013 AllianceGenome:RGD:1305322
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Rattus norvegicus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
    Summary
    Predicted to enable ATP binding activity; kinase activity; and microtubule binding activity. Involved in negative regulation of insulin secretion involved in cellular response to glucose stimulus and negative regulation of neuron projection regeneration. Predicted to be located in focal adhesion. Predicted to be active in cytoplasm. Human ortholog(s) of this gene implicated in hepatocellular carcinoma and lung adenocarcinoma. Orthologous to human MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4). [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Biased expression in Thymus (RPKM 458.5), Lung (RPKM 271.0) and 9 other tissues See more
    Orthologs
    human mouse all
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    Genomic context

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    See Map4k4 in Genome Data Viewer
    Location:
    9q22
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCr8 (GCF_036323735.1) 9 NC_086027.1 (49696573..49822353)
    RS_2023_06 previous assembly mRatBN7.2 (GCF_015227675.2) 9 NC_051344.1 (42200708..42326708)
    106 previous assembly Rnor_6.0 (GCF_000001895.5) 9 NC_005108.4 (46657444..46782545)

    Chromosome 9 - NC_086027.1Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC120094674 Neighboring gene cytochrome c oxidase subunit 6A1, pseudogene 2 Neighboring gene interleukin 1 receptor type 2 Neighboring gene uncharacterized LOC120094675

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
    • Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
    • BioProject: PRJNA238328
    • Publication: PMID 24510058
    • Analysis date: Mon Jun 6 17:44:12 2016

    Bibliography

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    Related articles in PubMed

    1. Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma. Li W, et al. PeerJ, 2021. PMID 33510968, Free PMC Article
    2. Role of microRNA-141 in colorectal cancer with lymph node metastasis. Feng L, et al. Exp Ther Med, 2016 Nov. PMID 27882171, Free PMC Article
    3. A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. Yao Z, et al. J Biol Chem, 1999 Jan 22. PMID 9890973
    4. ShRNA-targeted MAP4K4 inhibits hepatocellular carcinoma growth. Liu AW, et al. Clin Cancer Res, 2011 Feb 15. PMID 21196414
    5. MAP4K4 is a novel MAPK/ERK pathway regulator required for lung adenocarcinoma maintenance. Gao X, et al. Mol Oncol, 2017 Jun. PMID 28306189, Free PMC Article

    See all (23) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4.
      Title: Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4.
    2. NIK is the first kinase shown to phosphorylate and increase the activity of the Arp2/3 complex.
      Title: The Nck-interacting kinase NIK increases Arp2/3 complex activity by phosphorylating the Arp2 subunit.
    3. Results identify MAP4K4 as a key upstream mediator of TNF-alpha action on the beta cell, preventing tumor necrosis factor-alpha-induced decrease of IRS-2 and inhibition of glucose-stimulated insulin secretion.
      Title: Silencing mitogen-activated protein 4 kinase 4 (MAP4K4) protects beta cells from tumor necrosis factor-alpha-induced decrease of IRS-2 and inhibition of glucose-stimulated insulin secretion.
    Submit: New GeneRIF Correction

    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 RGD

    Function Evidence Code Pubs
    enables ATP binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables MAP kinase kinase kinase kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables creatine kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables microtubule binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    involved_in MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular signal transduction ISO
    Inferred from Sequence Orthology
    more info
    		  
    NOT involved_in microvillus assembly ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in negative regulation of apoptotic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in negative regulation of insulin secretion involved in cellular response to glucose stimulus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of neuron projection development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of neuron projection regeneration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neuron projection morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of ARF protein signal transduction ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of GTPase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of JNK cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of cell migration ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of focal adhesion assembly ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of focal adhesion disassembly ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of hippo signaling ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of keratinocyte migration ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of JNK cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in focal adhesion ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase kinase 4
    NP_001100374.2
    NP_001388925.1
    XP_008765225.2
    XP_008765233.2
    XP_008765236.2
    XP_017451831.1
    XP_017451832.1
    XP_038939154.1
    XP_038939156.1
    XP_038939159.1
    XP_038939161.1
    XP_038939162.1
    XP_038939163.1
    XP_038939166.1
    XP_038939167.1
    XP_038939168.1
    XP_038939170.1
    XP_038939171.1
    XP_063122965.1
    XP_063122966.1
    XP_063122967.1
    XP_063122968.1
    XP_063122969.1
    XP_063122970.1
    XP_063122971.1
    XP_063122972.1
    XP_063122974.1
    XP_063122975.1
    XP_063122976.1
    XP_063122977.1
    XP_063122978.1
    XP_063122979.1
    XP_063122981.1
    XP_063122982.1
    XP_063122983.1
    XP_063122984.1
    XP_063122985.1
    XP_063122986.1
    XP_063122987.1
    XP_063122988.1
    XP_063122989.1
    XP_063122990.1
    XP_063122991.1
    XP_063122992.1
    XP_063122993.1
    XP_063122994.1
    XP_063122995.1
    XP_063122996.1
    XP_063122997.1
    XP_063122998.1
    XP_063122999.1
    XP_063123000.1

    NCBI Reference Sequences (RefSeq)

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    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_001106904.2 → NP_001100374.2  mitogen-activated protein kinase kinase kinase kinase 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000009
      UniProtKB/TrEMBL
      A6INM6

    2. NM_001401996.1 → NP_001388925.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000009
      UniProtKB/TrEMBL
      A0A8I5ZL09, A0A8I6ADP3

    RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

    Reference GRCr8

    Genomic

    1. NC_086027.1 Reference GRCr8

      Range
      49696573..49822353
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_063266904.1 → XP_063122974.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X12

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    2. XM_063266895.1 → XP_063122965.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X2

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    3. XM_063266899.1 → XP_063122969.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X7

      UniProtKB/TrEMBL
      A0A8I5ZL09

    4. XM_008767003.4 → XP_008765225.2  mitogen-activated protein kinase kinase kinase kinase 4 isoform X1

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    5. XM_063266896.1 → XP_063122966.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X3

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    6. XM_063266911.1 → XP_063122981.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X23

      UniProtKB/TrEMBL
      A6INM6

    7. XM_063266898.1 → XP_063122968.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X6

      UniProtKB/TrEMBL
      A0A8I5ZL09

    8. XM_063266906.1 → XP_063122976.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X15

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    9. XM_063266902.1 → XP_063122972.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X11

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    10. XM_039083240.2 → XP_038939168.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X28

      UniProtKB/TrEMBL
      A6INM6
      Conserved Domains (2) summary
      smart00036
      Location:912 → 1218
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    11. XM_063266908.1 → XP_063122978.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X17

      UniProtKB/TrEMBL
      A0A8I5ZL09

    12. XM_063266901.1 → XP_063122971.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X10

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    13. XM_063266905.1 → XP_063122975.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X13

      UniProtKB/TrEMBL
      A0A8I5ZLV4
      Related
      ENSRNOP00000019180.8, ENSRNOT00000019180.8

    14. XM_063266897.1 → XP_063122967.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X5

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    15. XM_039083231.2 → XP_038939159.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X14

      UniProtKB/TrEMBL
      A0A8I5ZLV4
      Conserved Domains (2) summary
      smart00036
      Location:984 → 1290
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    16. XM_063266907.1 → XP_063122977.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X16

      UniProtKB/TrEMBL
      A0A8I5ZL09

    17. XM_039083235.2 → XP_038939163.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X20

      UniProtKB/TrEMBL
      A0A8I5ZL09
      Conserved Domains (2) summary
      smart00036
      Location:966 → 1264
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    18. XM_063266917.1 → XP_063122987.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X37

      UniProtKB/TrEMBL
      A0A8I5ZL09

    19. XM_063266909.1 → XP_063122979.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X21

      UniProtKB/TrEMBL
      A0A8I5ZL09

    20. XM_063266930.1 → XP_063123000.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X50

      UniProtKB/TrEMBL
      A6INM6

    21. XM_039083226.2 → XP_038939154.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X4

      UniProtKB/TrEMBL
      A0A0G2K7W4, A0A8I5ZLV4
      Related
      ENSRNOP00000078890.2, ENSRNOT00000115451.2
      Conserved Domains (2) summary
      smart00036
      Location:1061 → 1359
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    22. XM_017596343.3 → XP_017451832.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X30

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    23. XM_063266924.1 → XP_063122994.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X44

      UniProtKB/TrEMBL
      A6INM6

    24. XM_063266912.1 → XP_063122982.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X25

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    25. XM_063266925.1 → XP_063122995.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X45

      UniProtKB/TrEMBL
      A6INM6

    26. XM_063266922.1 → XP_063122992.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X42

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    27. XM_039083228.2 → XP_038939156.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X8

      UniProtKB/TrEMBL
      A0A8I5ZL09
      Conserved Domains (2) summary
      smart00036
      Location:1030 → 1328
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    28. XM_063266900.1 → XP_063122970.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X9

      UniProtKB/TrEMBL
      A0A8I5ZL09

    29. XM_063266927.1 → XP_063122997.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X47

      UniProtKB/TrEMBL
      A6INM6

    30. XM_063266915.1 → XP_063122985.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X32

      UniProtKB/TrEMBL
      A0A8I5ZL09

    31. XM_063266913.1 → XP_063122983.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X29

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    32. XM_063266921.1 → XP_063122991.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X41

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    33. XM_063266923.1 → XP_063122993.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X43

      UniProtKB/TrEMBL
      A6INM6

    34. XM_039083238.2 → XP_038939166.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X24

      UniProtKB/TrEMBL
      A0A8I5ZLV4
      Conserved Domains (2) summary
      smart00036
      Location:930 → 1236
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    35. XM_063266918.1 → XP_063122988.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X38

      UniProtKB/TrEMBL
      A0A8I5ZLV4, A0A8I5ZYP2
      Related
      ENSRNOP00000085187.2, ENSRNOT00000111572.2

    36. XM_063266919.1 → XP_063122989.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X39

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    37. XM_008767014.4 → XP_008765236.2  mitogen-activated protein kinase kinase kinase kinase 4 isoform X34

      UniProtKB/TrEMBL
      A6INM6

    38. XM_063266926.1 → XP_063122996.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X46

      UniProtKB/TrEMBL
      A6INM6

    39. XM_039083234.2 → XP_038939162.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X19

      UniProtKB/TrEMBL
      A0A8I5ZL09
      Conserved Domains (2) summary
      smart00036
      Location:975 → 1273
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    40. XM_063266914.1 → XP_063122984.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X31

      UniProtKB/TrEMBL
      A0A8I5ZL09

    41. XM_063266920.1 → XP_063122990.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X40

      UniProtKB/TrEMBL
      A0A8I5ZLV4, A0A8I6AHN7

    42. XM_063266929.1 → XP_063122999.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X49

      UniProtKB/TrEMBL
      A0A8I5ZLV4

    43. XM_039083233.2 → XP_038939161.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X18

      UniProtKB/TrEMBL
      A0A8I5ZL09
      Conserved Domains (2) summary
      smart00036
      Location:976 → 1274
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    44. XM_008767011.4 → XP_008765233.2  mitogen-activated protein kinase kinase kinase kinase 4 isoform X22

      UniProtKB/TrEMBL
      A0A8I5ZL09
      Related
      ENSRNOP00000092349.2, ENSRNOT00000115768.2

    45. XM_039083242.2 → XP_038939170.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X35

      UniProtKB/TrEMBL
      A0A8I5ZLV4
      Related
      ENSRNOP00000097771.2, ENSRNOT00000102257.2
      Conserved Domains (2) summary
      smart00036
      Location:866 → 1164
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    46. XM_039083239.2 → XP_038939167.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X27

      UniProtKB/TrEMBL
      A0A8I5ZLV4
      Conserved Domains (2) summary
      smart00036
      Location:929 → 1227
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    47. XM_017596342.3 → XP_017451831.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X26

      UniProtKB/TrEMBL
      A0A8I5ZLV4, A0A8I6AT99

    48. XM_039083243.2 → XP_038939171.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X36

      UniProtKB/TrEMBL
      A6INM6
      Conserved Domains (2) summary
      smart00036
      Location:835 → 1133
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    49. XM_063266928.1 → XP_063122998.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X48

      UniProtKB/TrEMBL
      A0A8I5ZL09

    50. XM_063266916.1 → XP_063122986.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform X33

      UniProtKB/TrEMBL
      A0A8I5ZL09
    Nucleotide Protein Strain
    Heading Accession and Version

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