Aliases for MAP4K1 Gene

Aliases for MAP4K1 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1 2 3 4 5
  • Hematopoietic Progenitor Kinase 1 2 3
  • MAPK/ERK Kinase Kinase Kinase 1 3 4
  • MEK Kinase Kinase 1 3 4
  • EC 2.7.11.1 4 54
  • MEKKK 1 3 4
  • HPK1 3 4
  • Hematopoietic Progenitor Kinase 4
  • EC 2.7.11 54

External Ids for MAP4K1 Gene

Previous GeneCards Identifiers for MAP4K1 Gene

  • GC19M039692
  • GC19M039469
  • GC19M043754
  • GC19M043770
  • GC19M039078
  • GC19M035526

Summaries for MAP4K1 Gene

GeneCards Summary for MAP4K1 Gene

MAP4K1 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1) is a Protein Coding gene. Diseases associated with MAP4K1 include Multiminicore Disease and Malignant Hyperthermia Susceptibility. Among its related pathways are Signal transduction_JNK pathway and TGF-Beta Pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP4K3.

UniProtKB/Swiss-Prot Summary for MAP4K1 Gene

  • Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.

Gene Wiki entry for MAP4K1 Gene

Additional gene information for MAP4K1 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP4K1 Gene

Genomics for MAP4K1 Gene

GeneHancer (GH) Regulatory Elements for MAP4K1 Gene

Promoters and enhancers for MAP4K1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP4K1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MAP4K1 gene promoter:
  • ATF-2
  • c-Ets-1
  • c-Jun
  • CUTL1
  • E47
  • Hand1
  • SRF
  • SRF (504 AA)
  • YY1

Genomic Locations for MAP4K1 Gene

Genomic Locations for MAP4K1 Gene
chr19:38,587,640-38,618,882
(GRCh38/hg38)
Size:
31,243 bases
Orientation:
Minus strand
chr19:39,078,281-39,109,522
(GRCh37/hg19)
Size:
31,242 bases
Orientation:
Minus strand

Genomic View for MAP4K1 Gene

Genes around MAP4K1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP4K1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP4K1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP4K1 Gene

Proteins for MAP4K1 Gene

  • Protein details for MAP4K1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92918-M4K1_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 1
    Protein Accession:
    Q92918

    Protein attributes for MAP4K1 Gene

    Size:
    833 amino acids
    Molecular mass:
    91296 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with MAP3K1. Interacts with FBXW8.

    Three dimensional structures from OCA and Proteopedia for MAP4K1 Gene

    Alternative splice isoforms for MAP4K1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP4K1 Gene

Selected DME Specific Peptides for MAP4K1 Gene

Q92918:
  • FIGTPYWMAPEV
  • MEFCGAGS
  • MDGSVKL
  • LFLMTKS
  • CDIWSLG
  • GITAIEL
  • HRDIKGANI
  • GTPYWMAPE

Post-translational modifications for MAP4K1 Gene

  • Autophosphorylates: phosphorylation promotes ubiquitination by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.
  • Ubiquitinated by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex following autophosphorylation, leading to its degradation by the proteasome.
  • Ubiquitination at Lys139
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Abcam antibodies for MAP4K1
  • Boster Bio Antibodies for MAP4K1

Domains & Families for MAP4K1 Gene

Gene Families for MAP4K1 Gene

Protein Domains for MAP4K1 Gene

Suggested Antigen Peptide Sequences for MAP4K1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ50326, highly similar to Mitogen-activated protein kinase kinase kinase kinase 1 (EC 2.7.11.1) (B4E087_HUMAN)
  • MAPK/ERK kinase kinase kinase 1 (M4K1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q92918

UniProtKB/Swiss-Prot:

M4K1_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
genes like me logo Genes that share domains with MAP4K1: view

Function for MAP4K1 Gene

Molecular function for MAP4K1 Gene

UniProtKB/Swiss-Prot Function:
Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence=. ;.
GENATLAS Biochemistry:
mitogen-activated kinase kinase kinase kinase 1,nuclear,predominantly expressed in hematopoietic cells,binding MAP3K1 (MEKK1) activating the JNK/SAPK kinase pathway

Enzyme Numbers (IUBMB) for MAP4K1 Gene

Phenotypes From GWAS Catalog for MAP4K1 Gene

Gene Ontology (GO) - Molecular Function for MAP4K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA,TAS 8824585
GO:0004674 protein serine/threonine kinase activity IBA,IDA 8824585
GO:0005515 protein binding IPI 9346925
GO:0005524 ATP binding IDA,IEA 8824585
genes like me logo Genes that share ontologies with MAP4K1: view
genes like me logo Genes that share phenotypes with MAP4K1: view

Animal Models for MAP4K1 Gene

MGI Knock Outs for MAP4K1:

Animal Model Products

  • Taconic Biosciences Mouse Models for MAP4K1

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for MAP4K1 Gene

Localization for MAP4K1 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MAP4K1 gene
Compartment Confidence
nucleus 3
cytosol 3
plasma membrane 2
cytoskeleton 1
mitochondrion 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (1)
  • Plasma membrane (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MAP4K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0016020 membrane HDA 19946888
genes like me logo Genes that share ontologies with MAP4K1: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for MAP4K1 Gene

Pathways & Interactions for MAP4K1 Gene

genes like me logo Genes that share pathways with MAP4K1: view

Pathways by source for MAP4K1 Gene

3 Qiagen pathways for MAP4K1 Gene
  • JNK Pathway
  • MAPK Family Pathway
  • TGF-Beta Pathway
1 Cell Signaling Technology pathway for MAP4K1 Gene

SIGNOR curated interactions for MAP4K1 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for MAP4K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000185 activation of MAPKKK activity IEA,IC 11053428
GO:0006468 protein phosphorylation IEA,IDA 8824585
GO:0007257 activation of JUN kinase activity IDA 8824585
GO:0008283 cell proliferation IMP 24362026
GO:0016310 phosphorylation IEA --
genes like me logo Genes that share ontologies with MAP4K1: view

Drugs & Compounds for MAP4K1 Gene

(5) Drugs for MAP4K1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved, Experimental, Investigational Pharma 0
genes like me logo Genes that share compounds with MAP4K1: view

Transcripts for MAP4K1 Gene

mRNA/cDNA for MAP4K1 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MAP4K1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17
SP1: - - -
SP2: -
SP3:
SP4:
SP5:
SP6: -

Relevant External Links for MAP4K1 Gene

GeneLoc Exon Structure for
MAP4K1
ECgene alternative splicing isoforms for
MAP4K1

Expression for MAP4K1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MAP4K1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP4K1 Gene

This gene is overexpressed in Whole Blood (x9.0), Spleen (x8.5), and Small Intestine - Terminal Ileum (x4.2).

Protein differential expression in normal tissues from HIPED for MAP4K1 Gene

This gene is overexpressed in Lymph node (30.4), Peripheral blood mononuclear cells (16.5), and CD8 Tcells (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MAP4K1 Gene



Protein tissue co-expression partners for MAP4K1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MAP4K1 Gene:

MAP4K1

SOURCE GeneReport for Unigene cluster for MAP4K1 Gene:

Hs.95424

mRNA Expression by UniProt/SwissProt for MAP4K1 Gene:

Q92918-M4K1_HUMAN
Tissue specificity: Expressed primarily in hematopoietic organs, including bone marrow, spleen and thymus. Also expressed at very low levels in lung, kidney, mammary glands and small intestine.

Evidence on tissue expression from TISSUES for MAP4K1 Gene

  • Blood(2.4)
  • Lymph node(2.3)
genes like me logo Genes that share expression patterns with MAP4K1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP4K1 Gene

Orthologs for MAP4K1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MAP4K1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP4K1 33 32
  • 99.47 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MAP4K1 33 32
  • 89.8 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MAP4K1 33 32
  • 89.8 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map4k1 32
  • 84.98 (n)
mouse
(Mus musculus)
Mammalia Map4k1 17 33 32
  • 84.41 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia MAP4K1 33
  • 75 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MAP4K1 33
  • 74 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP4K1 33
  • 55 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia map4k1 32
  • 57.69 (n)
zebrafish
(Danio rerio)
Actinopterygii MAP4K1 33
  • 65 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG7097 34
  • 52 (a)
hppy 33
  • 29 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea gck-2 33
  • 35 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KIC1 33
  • 17 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 37 (a)
OneToMany
Species where no ortholog for MAP4K1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MAP4K1 Gene

ENSEMBL:
Gene Tree for MAP4K1 (if available)
TreeFam:
Gene Tree for MAP4K1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MAP4K1: view image

Paralogs for MAP4K1 Gene

(59) SIMAP similar genes for MAP4K1 Gene using alignment to 6 proteins:

  • M4K1_HUMAN
  • B4E087_HUMAN
  • K7EJS6_HUMAN
  • K7EKT6_HUMAN
  • K7ER95_HUMAN
  • K7ERT2_HUMAN
genes like me logo Genes that share paralogs with MAP4K1: view

Variants for MAP4K1 Gene

Sequence variations from dbSNP and Humsavar for MAP4K1 Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs1057519258 uncertain-significance, Malignant hyperthermia, susceptibility to, 1 38,587,376(-) G/A downstream_transcript_variant
rs1238066548 A metastatic melanoma sample 38,595,699(-) G/A/T coding_sequence_variant, missense_variant
rs1555806119 likely-pathogenic, Myopathy, Central Core 38,587,350(-) AA/ downstream_transcript_variant
rs1555806206 uncertain-significance, RYR1-Related Disorders 38,587,418(-) T/A downstream_transcript_variant
rs188314477 likely-benign, Neuromuscular disease, congenital, with uniform type 1 fiber, Myopathy, Central Core, Multiminicore Disease, Malignant hyperthermia susceptibility 38,587,555(-) C/T downstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for MAP4K1 Gene

Variant ID Type Subtype PubMed ID
dgv1780n106 CNV duplication 24896259
dgv3526n100 CNV gain 25217958
nsv1114005 CNV deletion 24896259
nsv1125672 CNV tandem duplication 24896259
nsv470140 CNV gain 18288195
nsv833824 CNV loss 17160897
nsv833826 CNV loss 17160897
nsv833827 CNV gain 17160897
nsv833828 CNV loss 17160897
nsv953298 CNV deletion 24416366

Variation tolerance for MAP4K1 Gene

Residual Variation Intolerance Score: 44.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.19; 39.55% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP4K1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP4K1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP4K1 Gene

Disorders for MAP4K1 Gene

MalaCards: The human disease database

(2) MalaCards diseases for MAP4K1 Gene - From: GeneCards

Disorder Aliases PubMed IDs
multiminicore disease
  • minicore myopathy with external ophthalmoplegia
malignant hyperthermia susceptibility
  • malignant hyperpyrexia due to anesthesia
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP4K1

genes like me logo Genes that share disorders with MAP4K1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP4K1 Gene

Publications for MAP4K1 Gene

  1. Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. (PMID: 8824585) Hu MC … Tan TH (Genes & development 1996) 2 3 4 23 56
  2. The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1. (PMID: 24362026) Wang H … Wang H (The Journal of biological chemistry 2014) 3 4 56
  3. Proteasome-mediated degradation and functions of hematopoietic progenitor kinase 1 in pancreatic cancer. (PMID: 19141650) Wang H … Wang H (Cancer research 2009) 3 23 56
  4. Phosphorylation of CARMA1 by HPK1 is critical for NF-kappaB activation in T cells. (PMID: 19706536) Brenner D … Arnold R (Proceedings of the National Academy of Sciences of the United States of America 2009) 3 23 56
  5. Recruitment of Sprouty1 to immune synapse regulates T cell receptor signaling. (PMID: 19915061) Lee JS … Choi K (Journal of immunology (Baltimore, Md. : 1950) 2009) 3 23 56

Products for MAP4K1 Gene