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MAP3K20 mitogen-activated protein kinase kinase kinase 20 [ Homo sapiens (human) ]

Gene ID: 51776, updated on 2-Nov-2024

Summary

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Official Symbol
MAP3K20provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase 20provided by HGNC
Primary source
HGNC:HGNC:17797
See related
Ensembl:ENSG00000091436 MIM:609479; AllianceGenome:HGNC:17797
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
pk; AZK; MLT; MRK; ZAK; CNM6; MLK7; MLTK; SFMMP; mlklak; MLTKbeta; MLTKalpha
Summary
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]
Expression
Broad expression in heart (RPKM 51.0), fat (RPKM 33.9) and 21 other tissues See more
Orthologs
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Genomic context

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See MAP3K20 in Genome Data Viewer
Location:
2q31.1
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (173075517..173268015)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (173561966..173754582)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (173940574..174132743)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene pyruvate dehydrogenase kinase 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:173590766-173591266 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:173591267-173591767 Neighboring gene RAPGEF4 antisense RNA 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:173607526-173608725 Neighboring gene Rap guanine nucleotide exchange factor 4 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:173668092-173668282 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:173770903-173771408 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:173771409-173771912 Neighboring gene aldehyde dehydrogenase 7 family member A1 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12112 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12113 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56377 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56397 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:174056283-174056864 Neighboring gene MAP3K20 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16764 Neighboring gene VISTA enhancer hs242 Neighboring gene NANOG hESC enhancer GRCh37_chr2:174129200-174129707 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16765 Neighboring gene uncharacterized LOC105373743 Neighboring gene ribosomal protein S2 pseudogene 18

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. Mixed lineage kinase ZAK promotes epithelial-mesenchymal transition in cancer progression. Li L, et al. Cell Death Dis, 2018 Feb 2. PMID 29396440, Free PMC Article
  2. Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion. Vasli N, et al. Brain, 2017 Jan. PMID 27816943, Free PMC Article
  3. Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate. Wu CC, et al. Cell, 2020 Jul 23. PMID 32610081, Free PMC Article
  4. The MAP3K ZAK, a novel modulator of ERK-dependent migration, is upregulated in colorectal cancer. Rey C, et al. Oncogene, 2016 Jun 16. PMID 26522728
  5. Long non-coding RNA URHC regulates cell proliferation and apoptosis via ZAK through the ERK/MAPK signaling pathway in hepatocellular carcinoma. Xu WH, et al. Int J Biol Sci, 2014. PMID 25013376, Free PMC Article

See all (86) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies.
    Title: Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies.
  2. Myofibrillar myopathy hallmarks associated with ZAK deficiency.
    Title: Myofibrillar myopathy hallmarks associated with ZAK deficiency.
  3. ZAKalpha-driven ribotoxic stress response activates the human NLRP1 inflammasome.
    Title: ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome.
  4. ZAK Gene Expression in Patients with Helicobacter pylori Infection.
    Title: ZAK Gene Expression in Patients with Helicobacter pylori Infection.
  5. Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
    Title: Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
  6. Selective Activation of ZAK beta Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation.
    Title: Selective Activation of ZAK β Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation.
  7. MicroRNA-335 inhibits the growth, chemo-sensitivity, and metastasis of human breast cancer cells by targeting MAP3K2.
    Title: MicroRNA-335 inhibits the growth, chemo-sensitivity, and metastasis of human breast cancer cells by targeting MAP3K2.
  8. miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3.
    Title: miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3.
  9. promoting epithelial mesenchymal transition is the primary role for ZAK in cancer progression.
    Title: Mixed lineage kinase ZAK promotes epithelial-mesenchymal transition in cancer progression.
  10. MLK7AS1 has potential as a biomarker and may promote proliferation in CRC partially through downregulating p21 expression.
    Title: Long non‑coding RNA MLK7‑AS1 promotes proliferation in human colorectal cancer via downregulation of p21 expression.
Submit: New GeneRIF Correction See all GeneRIFs (29)

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

Associated conditions

Description Tests
Myopathy, centronuclear, 6, with fiber-type disproportion
MedGen: C4540345 OMIM: 617760 GeneReviews: Not available
Compare labs
Split-foot malformation-mesoaxial polydactyly syndrome
MedGen: C5567487 OMIM: 616890 GeneReviews: Not available
Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables JUN kinase kinase kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables MAP kinase kinase kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables RNA binding HDA PubMed 
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ribosome binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables small ribosomal subunit rRNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables stalled ribosome sensor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA damage checkpoint signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of GCN2-mediated signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in JNK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in cell death NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in cell differentiation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in cellular response to UV-B IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to gamma radiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in chromosome segregation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cytoskeleton organization IEA
Inferred from Electronic Annotation
more info
  
involved_in embryonic digit morphogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in inflammatory response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in limb development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of stress-activated protein kinase signaling cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of translation in response to endoplasmic reticulum stress IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in p38MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of mitotic DNA damage checkpoint IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of positive regulation of programmed cell death IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_positive_effect pyroptotic inflammatory response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of mitotic metaphase/anaphase transition IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in stress-activated MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in stress-activated protein kinase signaling cascade IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
mitogen-activated protein kinase kinase kinase 20
Names
HCCS-4
MLK-like mitogen-activated protein triple kinase
ZAK1 homolog, leucine zipper and sterile-alpha motif kinase
human cervical cancer suppressor gene 4 protein
mitogen-activated protein kinase kinase kinase MLT
mixed lineage kinase 7
mixed lineage kinase with a leucine zipper and a sterile alpha motif
mixed lineage kinase-related kinase MRK-beta
sterile alpha motif and leucine zipper containing kinase AZK
NP_057737.2
NP_598407.1
XP_005246697.1
XP_016859812.1
XP_016859813.1
XP_047300702.1
XP_047300703.1
XP_047300704.1
XP_054198527.1
XP_054198528.1
XP_054198529.1
XP_054198530.1
XP_054198531.1
XP_054198532.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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.

Genomic

  1. NG_029373.2 RefSeqGene

    Range
    5331..197500
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_016653.3 → NP_057737.2  mitogen-activated protein kinase kinase kinase 20 isoform 1

    See identical proteins and their annotated locations for NP_057737.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1, also referred to as MRK-alpha and MLTK-alpha).
    Source sequence(s)
    AC013461, AC019046, AC092573
    Consensus CDS
    CCDS42777.1
    UniProtKB/Swiss-Prot
    B3KPG2, Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9, Q9NYL2
    Related
    ENSP00000364361.3, ENST00000375213.8
    Conserved Domains (3) summary
    cd09529
    Location:338 → 408
    SAM_MLTK; SAM domain of MLTK subfamily
    smart00221
    Location:23 → 260
    STYKc; Protein kinase; unclassified specificity
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

  2. NM_133646.3 → NP_598407.1  mitogen-activated protein kinase kinase kinase 20 isoform 2

    See identical proteins and their annotated locations for NP_598407.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks several exons in the coding region and contains a different 3' exon compared to variant 1. The resulting protein (isoform 2, also referred to as MRK-beta, MLTK-beta and MLK7) is shorter and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC013461, AC019046
    Consensus CDS
    CCDS2251.1
    UniProtKB/TrEMBL
    A8K710, D4Q8H0
    Related
    ENSP00000340257.3, ENST00000338983.7
    Conserved Domains (1) summary
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    173075517..173268015
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047444746.1 → XP_047300702.1  mitogen-activated protein kinase kinase kinase 20 isoform X1

    UniProtKB/Swiss-Prot
    B3KPG2, Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9, Q9NYL2

  2. XM_017004324.2 → XP_016859813.1  mitogen-activated protein kinase kinase kinase 20 isoform X2

    UniProtKB/TrEMBL
    A8K710, D4Q8H0
    Related
    ENSP00000439414.1, ENST00000539448.5
    Conserved Domains (1) summary
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

  3. XM_047444747.1 → XP_047300703.1  mitogen-activated protein kinase kinase kinase 20 isoform X1

    UniProtKB/Swiss-Prot
    B3KPG2, Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9, Q9NYL2

  4. XM_047444748.1 → XP_047300704.1  mitogen-activated protein kinase kinase kinase 20 isoform X2

    UniProtKB/TrEMBL
    D4Q8H0

  5. XM_005246640.3 → XP_005246697.1  mitogen-activated protein kinase kinase kinase 20 isoform X1

    See identical proteins and their annotated locations for XP_005246697.1

    UniProtKB/Swiss-Prot
    B3KPG2, Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9, Q9NYL2
    Related
    ENSP00000387259.2, ENST00000409176.6
    Conserved Domains (3) summary
    cd09529
    Location:338 → 408
    SAM_MLTK; SAM domain of MLTK subfamily
    smart00221
    Location:23 → 260
    STYKc; Protein kinase; unclassified specificity
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

  6. XM_017004323.2 → XP_016859812.1  mitogen-activated protein kinase kinase kinase 20 isoform X2

    UniProtKB/TrEMBL
    A8K710, D4Q8H0
    Conserved Domains (1) summary
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    173561966..173754582
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054342552.1 → XP_054198527.1  mitogen-activated protein kinase kinase kinase 20 isoform X1

    UniProtKB/Swiss-Prot
    B3KPG2, Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9, Q9NYL2

  2. XM_054342556.1 → XP_054198531.1  mitogen-activated protein kinase kinase kinase 20 isoform X2

    UniProtKB/TrEMBL
    D4Q8H0

  3. XM_054342553.1 → XP_054198528.1  mitogen-activated protein kinase kinase kinase 20 isoform X1

    UniProtKB/Swiss-Prot
    B3KPG2, Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9, Q9NYL2

  4. XM_054342557.1 → XP_054198532.1  mitogen-activated protein kinase kinase kinase 20 isoform X2

    UniProtKB/TrEMBL
    D4Q8H0

  5. XM_054342554.1 → XP_054198529.1  mitogen-activated protein kinase kinase kinase 20 isoform X1

    UniProtKB/Swiss-Prot
    B3KPG2, Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9, Q9NYL2

  6. XM_054342555.1 → XP_054198530.1  mitogen-activated protein kinase kinase kinase 20 isoform X2

    UniProtKB/TrEMBL
    D4Q8H0
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NYL2.3 GenPept UniProtKB/Swiss-Prot:Q9NYL2

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