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

Summary

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, Apr 2022]
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

Location:: 19q13.2

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (38587641..38617953, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (41391622..41421931, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (39078281..39108593, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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).
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.
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.
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.
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.
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).
HPK1 protein expression, which is expressed at significantly higher levels in NATs compared with paired IDC-NOS tissues, is significantly negatively associated with ER positivity and is positively associated with OS duration, suggesting that HPK1 may exhibit anticancer activities.
Title: HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.

Submit: New GeneRIF Correction See all GeneRIFs (28)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH71249 (e-PCR)
- UniSTS:61819

GDB:182154 (e-PCR)
- UniSTS:155359

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
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 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

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 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	IBA Inferred from Biological aspect of Ancestor more info
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 more info	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

EC 2.7.11.1

NP_009112.1

EC 2.7.11.1

XP_011524706.1

EC 2.7.11.1

XP_054175655.1

EC 2.7.11.1

XP_054175656.1

EC 2.7.11.1

XP_054175657.1

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_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
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

38587641..38617953 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NW_014040929.1 Reference GRCh38.p14 PATCHES

Range

1476..27589 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

41391622..41421931 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054319680.1 → XP_054175655.1 mitogen-activated protein kinase kinase kinase kinase 1 isoform X1
XM_054319681.1 → XP_054175656.1 mitogen-activated protein kinase kinase kinase kinase 1 isoform X2
XM_054319682.1 → XP_054175657.1 mitogen-activated protein kinase kinase kinase kinase 1 isoform X3