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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

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