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    Map4k1 mitogen-activated protein kinase kinase kinase kinase 1 [ Mus musculus (house mouse) ]

    Gene ID: 26411, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Map4k1provided by MGI
    Official Full Name
    mitogen-activated protein kinase kinase kinase kinase 1provided by MGI
    Primary source
    MGI:MGI:1346882
    See related
    Ensembl:ENSMUSG00000037337 AllianceGenome:MGI:1346882
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Hpk1; mHPK1
    Summary
    Enables ATP binding activity and protein serine/threonine kinase activity. Involved in intracellular signal transduction and protein phosphorylation. Is expressed in several structures, including alimentary system; genitourinary system; hemolymphoid system; liver; and lung. Orthologous to human MAP4K1 (mitogen-activated protein kinase kinase kinase kinase 1). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Biased expression in spleen adult (RPKM 40.1), thymus adult (RPKM 25.1) and 10 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    7 B1; 7 16.94 cM
    Exon count:
    32
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 7 NC_000073.7 (28681506..28702704)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 7 NC_000073.6 (28982050..29003279)

    Chromosome 7 - NC_000073.7Genomic Context describing neighboring genes Neighboring gene actinin alpha 4 Neighboring gene predicted gene, 51446 Neighboring gene STARR-seq mESC enhancer starr_18451 Neighboring gene STARR-positive B cell enhancer ABC_E698 Neighboring gene STARR-positive B cell enhancer ABC_E1729 Neighboring gene eukaryotic translation initiation factor 3, subunit K Neighboring gene ryanodine receptor 1, skeletal muscle Neighboring gene STARR-positive B cell enhancer ABC_E10432 Neighboring gene predicted gene, 38979 Neighboring gene predicted gene, 26604

    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. Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia. Wang H, et al. J Clin Invest, 2023 Jun 15. PMID 37140994, Free PMC Article
    2. HPK1 Influences Regulatory T Cell Functions. Sawasdikosol S, et al. Immunohorizons, 2020 Jul 6. PMID 32631900
    3. Critical role of kinase activity of hematopoietic progenitor kinase 1 in anti-tumor immune surveillance. Liu J, et al. PLoS One, 2019. PMID 30913212, Free PMC Article
    4. The Kinase Activity of Hematopoietic Progenitor Kinase 1 Is Essential for the Regulation of T Cell Function. Hernandez S, et al. Cell Rep, 2018 Oct 2. PMID 30282040
    5. Hematopoietic progenitor kinase 1 is a negative regulator of dendritic cell activation. Alzabin S, et al. J Immunol, 2009 May 15. PMID 19414772

    See all (41) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia.
      Title: Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia.
    2. HPK1 Influences Regulatory T Cell Functions.
      Title: HPK1 Influences Regulatory T Cell Functions.
    3. Results identify the importance of HPK1 kinase activity in the negative regulation of CD8 effector functions.
      Title: The Kinase Activity of Hematopoietic Progenitor Kinase 1 Is Essential for the Regulation of T Cell Function.
    4. data provide novel findings that HKP1 kinase activity is critical in conferring suppressive functions of HPK1 in a wide range of immune cells including CD4+, CD8+, DC, NK to Tregs, and inactivation of kinase domain was sufficient to elicit robust anti-tumor immune responses.
      Title: Critical role of kinase activity of hematopoietic progenitor kinase 1 in anti-tumor immune surveillance.
    5. Introduction of three 4-R-hydroxyproline residues stabilizes the SH3m-cortactin binding of HPK1 peptide.
      Title: The impact of either 4-R-hydroxyproline or 4-R-fluoroproline on the conformation and SH3m-cort binding of HPK1 proline-rich peptide.
    6. a novel negative feedback regulation of BCR signaling by HPK1-mediated phosphorylation, ubiquitination, and subsequent degradation of the activated BLNK
      Title: Down-regulation of B cell receptor signaling by hematopoietic progenitor kinase 1 (HPK1)-mediated phosphorylation and ubiquitination of activated B cell linker protein (BLNK).
    7. HPK1 associates with SKAP1 to negatively regulate Rap1-mediated B-lymphocyte adhesion.
      Title: HPK1 associates with SKAP-HOM to negatively regulate Rap1-mediated B-lymphocyte adhesion.
    8. HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion.
      Title: HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion.
    9. Our data reveal a novel role for HPK1 as a negative regulator of dendritic cell functions
      Title: Hematopoietic progenitor kinase 1 is a negative regulator of dendritic cell activation.
    10. HPK1-C as a suppressor of antiapoptotic Bcl-2 proteins and provide a molecular basis for our understanding of CD95L-independent activation-induced cell death of lymphocytes.
      Title: Caspase-cleaved HPK1 induces CD95L-independent activation-induced cell death in T and B lymphocytes.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Gene trapped (2) 
    • Targeted (5)  1 citation
    • Chemically induced (ENU) (1) 
    • Endonuclease-mediated (4) 

    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ATP binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables MAP kinase kinase kinase kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables MAP kinase kinase kinase kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in JNK cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in cell population proliferation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in cellular response to phorbol 13-acetate 12-myristate ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-serine phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of MAPK cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein autophosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase kinase 1
    Names
    HPK
    MAPK/ERK kinase kinase kinase 1
    MEK kinase kinase 1
    MEKKK 1
    hematopoietic progenitor kinase 1
    NP_001341983.1
    NP_001414092.1
    NP_001414093.1
    NP_001414094.1
    NP_001414095.1
    NP_032305.2
    XP_006540059.1
    XP_006540061.1

    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_001355054.2 → NP_001341983.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC165142, AC166357
      Consensus CDS
      CCDS90193.1
      UniProtKB/TrEMBL
      Q3UJX3, Q3UPT4
      Related
      ENSMUSP00000146807.2, ENSMUST00000208227.2
      Conserved Domains (2) summary
      smart00036
      Location:460 → 735
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06613
      Location:1 → 228
      STKc_MAP4K3_like; Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases

    2. NM_001427163.1 → NP_001414092.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC165142, AC166357

    3. NM_001427164.1 → NP_001414093.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC165142, AC166357

    4. NM_001427165.1 → NP_001414094.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform 5

      Status: VALIDATED

      Source sequence(s)
      AC165142, AC166357

    5. NM_001427166.1 → NP_001414095.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform 6

      Status: VALIDATED

      Source sequence(s)
      AC165142, AC166357

    6. NM_008279.3 → NP_032305.2  mitogen-activated protein kinase kinase kinase kinase 1 isoform 1

      See identical proteins and their annotated locations for NP_032305.2

      Status: VALIDATED

      Source sequence(s)
      AC165142, AC166357
      Consensus CDS
      CCDS39865.1
      UniProtKB/Swiss-Prot
      P70218, Q8R3R0, Q99K62
      UniProtKB/TrEMBL
      Q3UJX3
      Related
      ENSMUSP00000082995.7, ENSMUST00000085835.8
      Conserved Domains (3) summary
      smart00036
      Location:506 → 813
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      smart00220
      Location:17 → 274
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06613
      Location:16 → 274
      STKc_MAP4K3_like; Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases

    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_000073.7 Reference GRCm39 C57BL/6J

      Range
      28681506..28702704
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006539998.3 → XP_006540061.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform X5

      UniProtKB/TrEMBL
      Q3UJX3
      Conserved Domains (2) summary
      cd06613
      Location:16 → 274
      STKc_MAP4K3_like; Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases
      cl02434
      Location:506 → 751
      CNH; CNH domain

    2. XM_006539996.2 → XP_006540059.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform X2

      UniProtKB/TrEMBL
      Q3UJX3
      Conserved Domains (2) summary
      smart00036
      Location:506 → 783
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06613
      Location:16 → 274
      STKc_MAP4K3_like; Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P70218.1 GenPept UniProtKB/Swiss-Prot:P70218

    Gene LinkOut

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

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