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Aliases for ZAK Gene

Aliases for ZAK Gene

  • Sterile Alpha Motif And Leucine Zipper Containing Kinase AZK 3
  • MLK-Like Mitogen-Activated Protein Triple Kinase 3 4
  • Human Cervical Cancer Suppressor Gene 4 Protein 3 4
  • HCCS-4 3 4
  • MLTK 3 4
  • MRK 3 4
  • Mixed Lineage Kinase With A Leucine Zipper And A Sterile Alpha Motif 3
  • Sterile Alpha Motif- And Leucine Zipper-Containing Kinase AZK 4
  • Leucine Zipper- And Sterile Alpha Motif-Containing Kinase 4
  • Mitogen-Activated Protein Kinase Kinase Kinase MLT 5
  • Mixed Lineage Kinase-Related Kinase MRK-Beta 3
  • Mixed Lineage Kinase-Related Kinase 4
  • Mixed Lineage Kinase 7 3
  • MLK-Related Kinase 4
  • EC 2.7.11.25 4
  • AC013461.1 5
  • EC 2.7.11 63
  • Mlklak 3
  • SFMMP 3
  • MLK7 3
  • MLT 3
  • AZK 3
  • PK 3

External Ids for ZAK Gene

Previous GeneCards Identifiers for ZAK Gene

  • GC02P171993
  • GC02P172601
  • GC02P173904
  • GC02P174143
  • GC02P173766
  • GC02P173648
  • GC02P165819
  • GC02P173940

Summaries for ZAK Gene

Entrez Gene Summary for ZAK Gene

  • This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

GeneCards Summary for ZAK Gene

ZAK (Sterile Alpha Motif And Leucine Zipper Containing Kinase AZK) is a Protein Coding gene. Among its related pathways are Sertoli-Sertoli Cell Junction Dynamics and Tight junction. GO annotations related to this gene include poly(A) RNA binding and protein kinase activity. An important paralog of this gene is KSR1.

UniProtKB/Swiss-Prot for ZAK Gene

  • Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at Ser-28.

Gene Wiki entry for ZAK Gene

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

Genomics for ZAK Gene

Regulatory Elements for ZAK Gene

Promoters for ZAK Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around ZAK on UCSC Golden Path with GeneCards custom track

Genomic Location for ZAK Gene

Chromosome:
2
Start:
173,075,435 bp from pter
End:
173,268,010 bp from pter
Size:
192,576 bases
Orientation:
Plus strand

Genomic View for ZAK Gene

Genes around ZAK on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for ZAK Gene

Proteins for ZAK Gene

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

    Protein Symbol:
    Q9NYL2-MLTK_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase MLT
    Protein Accession:
    Q9NYL2
    Secondary Accessions:
    • B3KPG2
    • Q53SX1
    • Q580W8
    • Q59GY5
    • Q86YW8
    • Q9HCC4
    • Q9HCC5
    • Q9HDD2
    • Q9NYE9

    Protein attributes for ZAK Gene

    Size:
    800 amino acids
    Molecular mass:
    91155 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer. Interacts with PKN1 and ZNF33A.
    SequenceCaution:
    • Sequence=BAD92211.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for ZAK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ZAK Gene

Proteomics data for ZAK Gene at MOPED

Selected DME Specific Peptides for ZAK Gene

Post-translational modifications for ZAK Gene

  • Ubiquitination at Lys 321
  • Modification sites at PhosphoSitePlus

Other Protein References for ZAK Gene

Antibody Products

Domains & Families for ZAK Gene

Suggested Antigen Peptide Sequences for ZAK Gene

Graphical View of Domain Structure for InterPro Entry

Q9NYL2

UniProtKB/Swiss-Prot:

MLTK_HUMAN :
  • Contains 1 protein kinase domain.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Domain:
  • Contains 1 protein kinase domain.
  • Contains 1 SAM (sterile alpha motif) domain.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
genes like me logo Genes that share domains with ZAK: view

Function for ZAK Gene

Molecular function for ZAK Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphorylation by PKN1 and autophosphorylation on Thr-161 and Ser-165.
UniProtKB/Swiss-Prot Function:
Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at Ser-28.

Enzyme Numbers (IUBMB) for ZAK Gene

Gene Ontology (GO) - Molecular Function for ZAK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IEA,IDA 11836244
GO:0005515 protein binding IEA,IPI 12761180
genes like me logo Genes that share ontologies with ZAK: view
genes like me logo Genes that share phenotypes with ZAK: view

Animal Model Products

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ZAK Gene

Localization for ZAK Gene

Subcellular locations from UniProtKB/Swiss-Prot for ZAK Gene

Cytoplasm. Nucleus. Note=Translocates to the nucleus upon ultraviolet B irradiation.

No data available for Subcellular locations from COMPARTMENTS and Gene Ontology (GO) - Cellular Components for ZAK Gene

Pathways & Interactions for ZAK Gene

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

Pathways by source for ZAK Gene

SIGNOR curated interactions for ZAK Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for ZAK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000075 cell cycle checkpoint IDA 15342622
GO:0000077 DNA damage checkpoint IMP 11836244
GO:0006468 protein phosphorylation IEA,IDA 11836244
GO:0006950 response to stress NAS 11836244
GO:0007050 cell cycle arrest IMP 11836244
genes like me logo Genes that share ontologies with ZAK: view

Drugs & Compounds for ZAK Gene

(5) Drugs for ZAK Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Magnesium Nutra 0

(1) Additional Compounds for ZAK Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with ZAK: view

Transcripts for ZAK Gene

Unigene Clusters for ZAK Gene

Sterile alpha motif and leucine zipper containing kinase AZK:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

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

No ASD Table

Relevant External Links for ZAK Gene

GeneLoc Exon Structure for
ZAK

Expression for ZAK Gene

mRNA expression in normal human tissues for ZAK Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Muscle - Skeletal (x8.2) and Heart - Left Ventricle (x4.7).

Protein differential expression in normal tissues from HIPED for ZAK Gene

This gene is overexpressed in Heart (10.0), Lung (8.7), and Ovary (6.4).

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



SOURCE GeneReport for Unigene cluster for ZAK Gene Hs.444451

mRNA Expression by UniProt/SwissProt for ZAK Gene

Q9NYL2-MLTK_HUMAN
Tissue specificity: Ubiquitously expressed. Isoform 2 is the predominant form in all tissues examined, except for liver, in which isoform 1 is more highly expressed.
genes like me logo Genes that share expression patterns with ZAK: view

Protein tissue co-expression partners for ZAK Gene

- Elite partner

Primer Products

In Situ Assay Products

Orthologs for ZAK Gene

This gene was present in the common ancestor of chordates.

Orthologs for ZAK Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LOC459745 35
  • 99.54 (n)
  • 99.5 (a)
ZAK 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia -- 36
  • 92 (a)
OneToOne
ZAK 35
  • 90.92 (n)
  • 92.62 (a)
dog
(Canis familiaris)
Mammalia ZAK 35
  • 91.12 (n)
  • 92.12 (a)
-- 36
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Zak 16
Zak 36
  • 92 (a)
OneToOne
Zak 35
  • 87.65 (n)
  • 92.24 (a)
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 83 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Zak 35
  • 86.13 (n)
  • 91.86 (a)
chicken
(Gallus gallus)
Aves -- 36
  • 72 (a)
OneToOne
ZAK 35
  • 75.02 (n)
  • 76.46 (a)
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100495797 35
  • 70.25 (n)
  • 72.32 (a)
zebrafish
(Danio rerio)
Actinopterygii zak 36
  • 59 (a)
OneToMany
zak 36
  • 63 (a)
OneToMany
si:dkey-15i8.3 35
  • 63.16 (n)
  • 63.29 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 58 (a)
OneToOne
Species with no ortholog for ZAK:
  • 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)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for ZAK Gene

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

Paralogs for ZAK Gene

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

Variants for ZAK Gene

Sequence variations from dbSNP and Humsavar for ZAK Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs722864 -- 173,118,476(-) CCCCC(A/C/G/T)CAAAA intron-variant
rs734993 -- 173,161,271(+) AGTGA(A/C)CTAGT intron-variant
rs746179 -- 173,161,596(+) ATTTT(A/G)TAAGA intron-variant
rs935005 -- 173,156,640(+) cctct(A/G)agaat intron-variant
rs935006 -- 173,172,763(+) AAGCC(A/G)AAAGA intron-variant

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

Variant ID Type Subtype PubMed ID
nsv834460 CNV Gain 17160897
nsv3036 CNV Insertion 18451855
nsv834461 CNV Loss 17160897
nsv3037 CNV Insertion 18451855

Variation tolerance for ZAK Gene

Residual Variation Intolerance Score: 17% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.70; 78.63% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ZAK Gene

HapMap Linkage Disequilibrium report
ZAK

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

Disorders for ZAK Gene

Relevant External Links for ZAK

Genetic Association Database (GAD)
ZAK
Human Genome Epidemiology (HuGE) Navigator
ZAK

No disorders were found for ZAK Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for ZAK Gene

Publications for ZAK Gene

  1. MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest. (PMID: 11836244) Gross E.A. … Ruggieri R. (J. Biol. Chem. 2002) 3 4 23 67
  2. ZAK re-programs atrial natriuretic factor expression and induces hypertrophic growth in H9c2 cardiomyoblast cells. (PMID: 15485649) Huang C.Y. … Yang J.J. (Biochem. Biophys. Res. Commun. 2004) 3 23
  3. Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK. (PMID: 15465036) Huang C.Y. … Yang J.J. (Biochem. Biophys. Res. Commun. 2004) 3 23
  4. Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN. (PMID: 12761180) Takahashi M. … Ono Y. (J. Biochem. 2003) 3 23
  5. Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N-terminal kinase and playing a role in the cell arrest. (PMID: 12220515) Yang J.J. (Biochem. Biophys. Res. Commun. 2002) 3 23

Products for ZAK Gene

Sources for ZAK Gene

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