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

Summary

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. Predicted to be active in cytoplasm. 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, Dec 2024]
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

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_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
HPK1 Influences Regulatory T Cell Functions.
Title: HPK1 Influences Regulatory T Cell Functions.
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.
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.
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.
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).
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (5)
Gene trapped (2)
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI528790 (e-PCR)
- UniSTS:185702

Map4k1 (e-PCR), detects polymorphism
- UniSTS:507050

Gene Ontology Provided by MGI

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 ATP binding	ISO Inferred from Sequence Orthology more info
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	IEA Inferred from Electronic Annotation more info
enables MAP kinase kinase kinase kinase activity	ISO Inferred from Sequence Orthology more info
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 protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
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 cell population proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to phorbol 13-acetate 12-myristate	IEA Inferred from Electronic Annotation more info
involved_in cellular response to phorbol 13-acetate 12-myristate	ISO Inferred from Sequence Orthology more info
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 intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in peptidyl-serine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of MAPK cascade	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 autophosphorylation	ISS Inferred from Sequence or Structural Similarity 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

EC 2.7.11.1

NP_001414092.1

EC 2.7.11.1

NP_001414093.1

EC 2.7.11.1

NP_001414094.1

EC 2.7.11.1

NP_001414095.1

EC 2.7.11.1

NP_032305.2

EC 2.7.11.1

XP_006540059.1

EC 2.7.11.1

XP_006540061.1

EC 2.7.11.1

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)

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

Status: VALIDATED

Source sequence(s)

AC165142, AC166357

UniProtKB/TrEMBL

Q3UJX3
NM_001427164.1 → NP_001414093.1 mitogen-activated protein kinase kinase kinase kinase 1 isoform 4

Status: VALIDATED

Source sequence(s)

AC165142, AC166357

UniProtKB/TrEMBL

Q3UJX3
NM_001427165.1 → NP_001414094.1 mitogen-activated protein kinase kinase kinase kinase 1 isoform 5

Status: VALIDATED

Source sequence(s)

AC165142, AC166357

UniProtKB/TrEMBL

Q3UJX3
NM_001427166.1 → NP_001414095.1 mitogen-activated protein kinase kinase kinase kinase 1 isoform 6

Status: VALIDATED

Source sequence(s)

AC165142, AC166357

UniProtKB/TrEMBL

Q3UJX3

Related

ENSMUSP00000147189.2, ENSMUST00000207185.2
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

NC_000073.7 Reference GRCm39 C57BL/6J

Range

28681506..28702704

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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