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

Summary

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: mouse all
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Genomic context

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_000002.12 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 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?

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.
Myofibrillar myopathy hallmarks associated with ZAK deficiency.
Title: Myofibrillar myopathy hallmarks associated with ZAK deficiency.
ZAKalpha-driven ribotoxic stress response activates the human NLRP1 inflammasome.
Title: ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome.
ZAK Gene Expression in Patients with Helicobacter pylori Infection.
Title: ZAK Gene Expression in Patients with Helicobacter pylori Infection.
Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
Title: Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
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.
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.
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.
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.
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	not available
Split-foot malformation-mesoaxial polydactyly syndrome MedGen: C5567487 OMIM: 616890 GeneReviews: Not available	not available

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

GDB:434012 (e-PCR)
- UniSTS:157204

SHGC-79584 (e-PCR)
- UniSTS:103702

RH69341 (e-PCR)
- UniSTS:45593

PMC156606P1 (e-PCR)
- UniSTS:271408

A009I04 (e-PCR)
- UniSTS:38449

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

RH102508 (e-PCR)
- UniSTS:96842

D1S1423 (e-PCR)
- UniSTS:149619

RH11697 (e-PCR)
- UniSTS:83321

SHGC-67307 (e-PCR)
- UniSTS:89991

G32560 (e-PCR)
- UniSTS:117144

D13S1568 (e-PCR)
- UniSTS:473497

L18441 (e-PCR)
- UniSTS:71348

RH118970 (e-PCR)
- UniSTS:138938

SHGC-82889 (e-PCR)
- UniSTS:103359

RH80553 (e-PCR)
- UniSTS:88774

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 more info	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 kinase regulator 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

EC 2.7.11.25

NP_598407.1

EC 2.7.11.25

XP_005246697.1

EC 2.7.11.25

XP_016859812.1

EC 2.7.11.25

XP_016859813.1

EC 2.7.11.25

XP_047300702.1

EC 2.7.11.25

XP_047300703.1

EC 2.7.11.25

XP_047300704.1

EC 2.7.11.25

XP_054198527.1

EC 2.7.11.25

XP_054198528.1

EC 2.7.11.25

XP_054198529.1

EC 2.7.11.25

XP_054198530.1

EC 2.7.11.25

XP_054198531.1

EC 2.7.11.25

XP_054198532.1

EC 2.7.11.25

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.

Genomic

NG_029373.2 RefSeqGene

Range

5331..197500

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

173075517..173268015

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

D4Q8H0
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
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

NC_060926.1 Alternate T2T-CHM13v2.0

Range

173561966..173754582

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

D4Q8H0
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
XM_054342557.1 → XP_054198532.1 mitogen-activated protein kinase kinase kinase 20 isoform X2

UniProtKB/TrEMBL

D4Q8H0
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
XM_054342555.1 → XP_054198530.1 mitogen-activated protein kinase kinase kinase 20 isoform X2

UniProtKB/TrEMBL

D4Q8H0