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MAP4K1 mitogen-activated protein kinase kinase kinase kinase 1 [ Homo sapiens (human) ]

Gene ID: 11184, updated on 27-Nov-2024

Summary

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Official Symbol
MAP4K1provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase kinase 1provided by HGNC
Primary source
HGNC:HGNC:6863
See related
Ensembl:ENSG00000104814 MIM:601983; AllianceGenome:HGNC:6863
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HPK1
Summary
Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Nov 2024]
Expression
Biased expression in lymph node (RPKM 28.4), spleen (RPKM 19.4) and 10 other tissues See more
Orthologs
mouse all
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Genomic context

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See MAP4K1 in Genome Data Viewer
Location:
19q13.2
Exon count:
33
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (38587641..38617953, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (41391622..41421931, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (39078281..39108593, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10574 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38917687-38918201 Neighboring gene MPRA-validated peak3471 silencer Neighboring gene family with sequence similarity 98 member C Neighboring gene RAS guanyl releasing protein 4 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10575 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38925085-38925660 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:38932363-38932538 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38932982-38933942 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38943427-38943954 Neighboring gene MPRA-validated peak3472 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38953733-38954234 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38954745-38955341 Neighboring gene ryanodine receptor 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:38969337-38969680 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38986475-38987366 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr19:38995830-38997029 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10576 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14572 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14573 Neighboring gene uncharacterized LOC124904710 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14574 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14575 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14576 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10577 Neighboring gene MPRA-validated peak3473 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39070191-39070692 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14578 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39087374-39087874 Neighboring gene MAP4K1 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39098110-39098610 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39098611-39099111 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39103339-39103839 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14579 Neighboring gene NANOG hESC enhancer GRCh37_chr19:39112860-39113720 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39114367-39114868 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr19:39121815-39122606 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr19:39122654-39123853 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39125282-39126240 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39127485-39128424 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39130305-39131243 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10578 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10579 Neighboring gene Sharpr-MPRA regulatory region 11915 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:39139812-39140010 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14582 Neighboring gene eukaryotic translation initiation factor 3 subunit K Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39142765-39143374 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39143375-39143983 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39144522-39145390 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:39145391-39146259 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10580 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39148471-39149116 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39150898-39151588 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39155729-39156418 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39156419-39157108 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39157109-39157798 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14583 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14585 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14586 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14587 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39168839-39169424 Neighboring gene actinin alpha 4 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39173979-39174762 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14590 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39184359-39184950 Neighboring gene uncharacterized LOC107985291 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39193145-39193645 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39195255-39196024 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39198444-39199230 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39208396-39209241 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39209276-39209996 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39217269-39218152

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Hematopoietic progenitor kinase 1 (HPK1) negatively regulates prostaglandin E2-induced fos gene transcription. Sawasdikosol S, et al. Blood, 2003 May 1. PMID 12522005
  2. The pan-caspase inhibitor Q-VD-OPh has anti-leukemia effects and can interact with vitamin D analogs to increase HPK1 signaling in AML cells. Chen-Deutsch X, et al. Leuk Res, 2012 Jul. PMID 22541691, Free PMC Article
  3. Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of 1α,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML cells and as a mediator of vitamin D resistance. Chen-Deutsch X, et al. Cell Cycle, 2012 Apr 1. PMID 22421156, Free PMC Article
  4. Release of serine/threonine-phosphorylated adaptors from signaling microclusters down-regulates T cell activation. Lasserre R, et al. J Cell Biol, 2011 Nov 28. PMID 22105350, Free PMC Article
  5. Proteasome-mediated degradation and functions of hematopoietic progenitor kinase 1 in pancreatic cancer. Wang H, et al. Cancer Res, 2009 Feb 1. PMID 19141650, Free PMC Article

See all (73) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.
    Title: HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.
  2. Glioblastoma cellular MAP4K1 facilitates tumor growth and disrupts T effector cell infiltration.
    Title: Glioblastoma cellular MAP4K1 facilitates tumor growth and disrupts T effector cell infiltration.
  3. Decoding the signaling profile of hematopoietic progenitor kinase 1 (HPK1) in innate immunity: A proteomic approach.
    Title: Decoding the signaling profile of hematopoietic progenitor kinase 1 (HPK1) in innate immunity: A proteomic approach.
  4. The Kinase MAP4K1 Inhibits Cytosolic RNA-Induced Antiviral Signaling by Promoting Proteasomal Degradation of TBK1/IKKepsilon.
    Title: The Kinase MAP4K1 Inhibits Cytosolic RNA-Induced Antiviral Signaling by Promoting Proteasomal Degradation of TBK1/IKKε.
  5. Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1).
    Title: Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1).
  6. MAP4K1 functions as a tumor promotor and drug mediator for AML via modulation of DNA damage/repair system and MAPK pathway.
    Title: MAP4K1 functions as a tumor promotor and drug mediator for AML via modulation of DNA damage/repair system and MAPK pathway.
  7. MAP4K Interactome Reveals STRN4 as a Key STRIPAK Complex Component in Hippo Pathway Regulation.
    Title: MAP4K Interactome Reveals STRN4 as a Key STRIPAK Complex Component in Hippo Pathway Regulation.
  8. Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies.
    Title: Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies.
  9. Hematopoietic progenitor kinase 1 down-regulates the oncogenic receptor tyrosine kinase AXL in pancreatic cancer.
    Title: Hematopoietic progenitor kinase 1 down-regulates the oncogenic receptor tyrosine kinase AXL in pancreatic cancer.
  10. Interactions between HPK1 and its adaptor proteins related to immunity has been discussed (Review).
    Title: Interactions between hematopoietic progenitor kinase 1 and its adaptor proteins (Review).
Submit: New GeneRIF Correction See all GeneRIFs (29)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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 GOA

Function Evidence Code Pubs
enables 3-phosphoinositide-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables AMP-activated protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-dependent protein kinase activity IEA
Inferred from Electronic Annotation
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 IDA
Inferred from Direct Assay
more info
 PubMed 
enables Rho-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables eukaryotic translation initiation factor 2alpha kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AS1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AS121 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AT120 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AXS139 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2BS14 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2BS36 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S10 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S28 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S57 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T11 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T3 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T45 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T6 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H4S1 kinase activity IEA
Inferred from Electronic Annotation
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
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ribosomal protein S6 kinase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in JNK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to phorbol 13-acetate 12-myristate IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane HDA PubMed 

General protein information

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Preferred Names
mitogen-activated protein kinase kinase kinase kinase 1
Names
MAPK/ERK kinase kinase kinase 1
MEK kinase kinase 1
MEKKK 1
hematopoietic progenitor kinase 1
NP_001036065.1
NP_009112.1
XP_011524706.1
XP_054175655.1
XP_054175656.1
XP_054175657.1

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_001042600.3 → NP_001036065.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform 1

    See identical proteins and their annotated locations for NP_001036065.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 2. The encoded isoform (1) has a shorter and distinct C-terminus, compared to isoform 2.
    Source sequence(s)
    HY074876, U66464
    Consensus CDS
    CCDS42564.1
    UniProtKB/TrEMBL
    K7ER95
    Related
    ENSP00000380066.1, ENST00000396857.7
    Conserved Domains (3) summary
    smart00036
    Location:500 → 807
    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

  2. NM_007181.6 → NP_009112.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform 2

    See identical proteins and their annotated locations for NP_009112.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) represents the longer transcript and encodes the longer isoform (2).
    Source sequence(s)
    HY074876, U66464
    Consensus CDS
    CCDS59385.1
    UniProtKB/Swiss-Prot
    Q92918
    UniProtKB/TrEMBL
    K7ER95
    Related
    ENSP00000465039.1, ENST00000591517.5
    Conserved Domains (3) summary
    smart00036
    Location:500 → 807
    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_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    38587641..38617953 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011526404.2 → XP_011524706.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform X1

    UniProtKB/TrEMBL
    K7ER95
    Conserved Domains (3) summary
    smart00036
    Location:540 → 847
    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

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_014040929.1 Reference GRCh38.p14 PATCHES

    Range
    1476..27589 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    41391622..41421931 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054319680.1 → XP_054175655.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform X1

  2. XM_054319681.1 → XP_054175656.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform X2

  3. XM_054319682.1 → XP_054175657.1  mitogen-activated protein kinase kinase kinase kinase 1 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q92918.1 GenPept UniProtKB/Swiss-Prot:Q92918

Gene LinkOut

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