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Aliases for STK4 Gene

Aliases for STK4 Gene

  • Serine/Threonine Kinase 4 2 3
  • KRS2 3 4 6
  • MST1 3 4 6
  • Mammalian STE20-Like Protein Kinase 1 3 4
  • Serine/Threonine-Protein Kinase Krs-2 3 4
  • Kinase Responsive To Stress 2 2 3
  • Mammalian Sterile 20-Like 1 2 3
  • STE20-Like Kinase MST1 3 4
  • EC 2.7.11.1 4 63
  • TIIAC 3 6
  • MST-1 3 4
  • DJ211D12.2 (Serine/Threonine Kinase 4 (MST1, KRS2)) 3
  • Serine/Threonine-Protein Kinase 4 3
  • Yeast Ste20-Like 2
  • EC 2.7.11 63
  • YSK3 3

External Ids for STK4 Gene

Previous GeneCards Identifiers for STK4 Gene

  • GC20P043323
  • GC20P044233
  • GC20P044280
  • GC20P043028
  • GC20P043595
  • GC20P040336

Summaries for STK4 Gene

Entrez Gene Summary for STK4 Gene

  • The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process. [provided by RefSeq, Jul 2008]

GeneCards Summary for STK4 Gene

STK4 (Serine/Threonine Kinase 4) is a Protein Coding gene. Diseases associated with STK4 include t-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations and combined immunodeficiency due to stk4 deficiency. Among its related pathways are MAPK signaling pathway and Ras signaling pathway. GO annotations related to this gene include protein homodimerization activity and protein serine/threonine kinase activity. An important paralog of this gene is STK26.

UniProtKB/Swiss-Prot for STK4 Gene

  • Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates Ser-14 of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on Ser-212 and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on Ser-650 and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.

Gene Wiki entry for STK4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for STK4 Gene

Genomics for STK4 Gene

Regulatory Elements for STK4 Gene

Genomic Location for STK4 Gene

Start:
44,966,474 bp from pter
End:
45,079,959 bp from pter
Size:
113,486 bases
Orientation:
Plus strand

Genomic View for STK4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for STK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for STK4 Gene

Proteins for STK4 Gene

  • Protein details for STK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13043-STK4_HUMAN
    Recommended name:
    Serine/threonine-protein kinase 4
    Protein Accession:
    Q13043
    Secondary Accessions:
    • B2RCR8
    • Q15802
    • Q4G156
    • Q5H982
    • Q6PD60
    • Q9BR32
    • Q9NTZ4

    Protein attributes for STK4 Gene

    Size:
    487 amino acids
    Molecular mass:
    55630 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RASSF1. Interacts with FOXO3. Interacts with RASSF2 (via SARAH domain). Interacts with AR, PKB/AKT1, TNNI3 and SIRT1.
    SequenceCaution:
    • Sequence=AAH29511.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH58916.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for STK4 Gene

    Alternative splice isoforms for STK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for STK4 Gene

Proteomics data for STK4 Gene at MOPED

Post-translational modifications for STK4 Gene

  • Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-120 and Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183. It also diminishes its cleavage by caspases and its ability to phosphorylate FOXO3.
  • Proteolytically cleaved by caspase-3 during apoptosis at Asp-326 and Asp-349 resulting in a 37 kDa or a 39 kDa subunit respectively. The 39 kDa subunit is further cleaved into the 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). It is less likely that cleavage at Asp-349 is a prerequisite for activation as this site is not conserved in the murine ortholog.
  • Ubiquitination at Lys180
  • Modification sites at PhosphoSitePlus

Other Protein References for STK4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for STK4 Gene

Gene Families for STK4 Gene

Suggested Antigen Peptide Sequences for STK4 Gene

Graphical View of Domain Structure for InterPro Entry

Q13043

UniProtKB/Swiss-Prot:

STK4_HUMAN :
  • Q13043
Domain:
  • Contains 1 protein kinase domain.
  • Contains 1 SARAH domain.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
genes like me logo Genes that share domains with STK4: view

Function for STK4 Gene

Molecular function for STK4 Gene

GENATLAS Biochemistry: serine/threonine kinase 4,65kDa,mainly expressed in pancreas,heart and skeletal muscle,highly homolog to the DM protein kinase
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-183. Activated by RASSF1 which acts by preventing its dephosphorylation.
UniProtKB/Swiss-Prot Function: Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates Ser-14 of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on Ser-212 and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on Ser-650 and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.
UniProtKB/Swiss-Prot Induction: Activity increases during mitosis

Enzyme Numbers (IUBMB) for STK4 Gene

Gene Ontology (GO) - Molecular Function for STK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 8566796
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity IDA 11805089
GO:0004702 receptor signaling protein serine/threonine kinase activity IBA --
GO:0004713 protein tyrosine kinase activity --
genes like me logo Genes that share ontologies with STK4: view
genes like me logo Genes that share phenotypes with STK4: view

Animal Models for STK4 Gene

MGI Knock Outs for STK4:

miRNA for STK4 Gene

miRTarBase miRNAs that target STK4

No data available for Transcription Factor Targeting and HOMER Transcription for STK4 Gene

Localization for STK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for STK4 Gene

Cytoplasm. Nucleus. Note=The caspase-cleaved form cycles between the nucleus and cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for STK4 Gene COMPARTMENTS Subcellular localization image for STK4 gene
Compartment Confidence
nucleus 5
cytosol 4
cytoskeleton 2
extracellular 1

Gene Ontology (GO) - Cellular Components for STK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with STK4: view

Pathways for STK4 Gene

genes like me logo Genes that share pathways with STK4: view

Pathways by source for STK4 Gene

Gene Ontology (GO) - Biological Process for STK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000902 cell morphogenesis IDA 11805089
GO:0001569 patterning of blood vessels IEA --
GO:0001841 neural tube formation IEA --
GO:0003157 endocardium development IEA --
GO:0006468 protein phosphorylation IDA 11805089
genes like me logo Genes that share ontologies with STK4: view

Compounds for STK4 Gene

(3) HMDB Compounds for STK4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(3) Novoseek inferred chemical compound relationships for STK4 Gene

Compound -log(P) Hits PubMed IDs
leptomycin b 68.1 3
threonine 66.9 8
serine 54.4 9
genes like me logo Genes that share compounds with STK4: view

Transcripts for STK4 Gene

Unigene Clusters for STK4 Gene

Serine/threonine kinase 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for STK4 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13
SP1: - - -
SP2: -
SP3:

Relevant External Links for STK4 Gene

GeneLoc Exon Structure for
STK4
ECgene alternative splicing isoforms for
STK4

Expression for STK4 Gene

mRNA expression in normal human tissues for STK4 Gene

mRNA differential expression in normal tissues according to GTEx for STK4 Gene

This gene is overexpressed in Whole Blood (8.3).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for STK4 Gene

SOURCE GeneReport for Unigene cluster for STK4 Gene Hs.472838

mRNA Expression by UniProt/SwissProt for STK4 Gene

Q13043-STK4_HUMAN
Tissue specificity: Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed.
genes like me logo Genes that share expressions with STK4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for STK4 Gene

Orthologs for STK4 Gene

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

Orthologs for STK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia STK4 35
  • 99.59 (n)
  • 99.76 (a)
STK4 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia STK4 35
  • 91.79 (n)
  • 97.13 (a)
STK4 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia STK4 35
  • 91.92 (n)
  • 97.33 (a)
STK4 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Stk4 35
  • 90.9 (n)
  • 97.33 (a)
Stk4 16
Stk4 36
  • 97 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia STK4 36
  • 95 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 96 (a)
OneToMany
-- 36
  • 71 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Stk4 35
  • 89.39 (n)
  • 95.89 (a)
chicken
(Gallus gallus)
Aves STK4 35
  • 82.17 (n)
  • 92.39 (a)
STK4 36
  • 93 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia STK4 36
  • 87 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia MGC68762 35
tropical clawed frog
(Silurana tropicalis)
Amphibia MGC75656 35
stk4 35
  • 72.58 (n)
  • 77.11 (a)
fruit fly
(Drosophila melanogaster)
Insecta hpo 36
  • 43 (a)
OneToMany
CG11228 37
  • 50 (a)
worm
(Caenorhabditis elegans)
Secernentea cst-1 36
  • 53 (a)
ManyToMany
cst-2 36
  • 55 (a)
ManyToMany
C24A8.4a 37
  • 61 (a)
F14H12.4a 37
  • 52 (a)
C24A8.4b 37
  • 61 (a)
F14H12.4b 37
  • 52 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CDC15 38
SPS1 36
  • 28 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8767 36
  • 67 (a)
OneToMany
Species with no ortholog for STK4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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)
  • zebrafish (Danio rerio)

Evolution for STK4 Gene

ENSEMBL:
Gene Tree for STK4 (if available)
TreeFam:
Gene Tree for STK4 (if available)

Paralogs for STK4 Gene

Paralogs for STK4 Gene

genes like me logo Genes that share paralogs with STK4: view

Variants for STK4 Gene

Sequence variations from dbSNP and Humsavar for STK4 Gene

SNP ID Clin Chr 20 pos Sequence Context AA Info Type MAF
rs8000 -- 45,079,656(-) AGCAA(A/C)AACAT utr-variant-3-prime
rs910671 -- 44,973,280(-) TGACT(A/C/T)ATGTT intron-variant, upstream-variant-2KB
rs927000 -- 44,970,064(-) GATCC(A/G)GGGCT intron-variant
rs1014905 -- 45,011,731(+) TATAT(A/T)TTTTT intron-variant
rs1015519 -- 45,002,795(-) CTTTT(C/T)ATGGC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for STK4 Gene

Variant ID Type Subtype PubMed ID
nsv179332 CNV Loss 16902084

Relevant External Links for STK4 Gene

HapMap Linkage Disequilibrium report
STK4
Human Gene Mutation Database (HGMD)
STK4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for STK4 Gene

Disorders for STK4 Gene

(1) OMIM Diseases for STK4 Gene (604965)

UniProtKB/Swiss-Prot

STK4_HUMAN
  • T-cell immunodeficiency, recurrent infections, and autoimmunity with or without cardiac malformations (TIIAC) [MIM:614868]: A primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T-cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect. {ECO:0000269 PubMed:22294732}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(3) Novoseek inferred disease relationships for STK4 Gene

Disease -log(P) Hits PubMed IDs
tumors 37.2 14
cancer 21.6 2
shock 4.88 2

Relevant External Links for STK4

Genetic Association Database (GAD)
STK4
Human Genome Epidemiology (HuGE) Navigator
STK4
genes like me logo Genes that share disorders with STK4: view

Publications for STK4 Gene

  1. Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. (PMID: 11517310) Ura S. … Gotoh Y. (Proc. Natl. Acad. Sci. U.S.A. 2001) 2 3 4 23
  2. Cloning and characterization of a human protein kinase with homology to Ste20. (PMID: 7665586) Creasy C.L. … Chernoff J. (J. Biol. Chem. 1995) 3 4 23
  3. MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation. (PMID: 11278283) Lee K.-K. … Yonehara S. (J. Biol. Chem. 2001) 3 4 23
  4. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. (PMID: 15109305) Praskova M. … Avruch J. (Biochem. J. 2004) 3 4 23
  5. Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. (PMID: 16510573) Oh H.J. … Lim D.-S. (Cancer Res. 2006) 3 4 23

Products for STK4 Gene

  • Addgene plasmids for STK4

Sources for STK4 Gene

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