MAPK12 mitogen-activated protein kinase 12 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAPK12provided by HGNC
Official Full Name: mitogen-activated protein kinase 12provided by HGNC
Primary source: HGNC:HGNC:6874
See related: Ensembl:ENSG00000188130 MIM:602399; AllianceGenome:HGNC:6874
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: ERK3; ERK6; ERK-6; SAPK3; PRKM12; SAPK-3; MAPK 12; P38GAMMA
Summary: Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in brain (RPKM 6.0), prostate (RPKM 5.7) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q13.33

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (50252901..50261683, complement)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (50759904..50768686, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (50691330..50700112, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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?

The pro-tumorigenic activity of p38gamma overexpression in nasopharyngeal carcinoma.
Title: The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.
Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice.
Title: Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice.
P38GAMMA silencing inhibits colorectal cancer (CRC) cell growth and migration. P38GAMMA silencing induces apoptosis activation in CRC cells. Ectopic P38GAMMA overexpression promotes CRC cell progression in vitro.
Title: Targeting p38γ to inhibit human colorectal cancer cell progression.
these results indicate that ERK3 acts as a potent suppressor of melanoma cell growth and invasiveness
Title: The atypical MAPK ERK3 potently suppresses melanoma cell growth and invasiveness.
p38 MAPK gamma (p38gamma) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle; p38gamma shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members; biopsies of human hepatocellular carcinoma show high expression of p38gamma, suggesting that p38gamma could be a therapeutic target in the treatment of this disease
Title: p38γ is essential for cell cycle progression and liver tumorigenesis.
IFN-gamma receptor stimulation requires ULK1-mediated activation of MLK3 and ERK5
Title: IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5.
p38gamma was up-regulated in breast cancer, which exerts a great influence on the cell growth, cell mobility, invasiveness, and apoptosis of MDA-MB-231 cells and also affected the metabolism
Title: Impact of p38γ mitogen-activated protein kinase (MAPK) on MDA-MB-231 breast cancer cells using metabolomic approach.
Our findings suggest that L290P/V mutations of ERK3 may confer increased invasiveness to cancers.
Title: L290P/V mutations increase ERK3's cytoplasmic localization and migration/invasion-promoting capability in cancer cells.
importance of Ser(189) phosphorylation for intramolecular regulation of ERK3 kinase activity and invasiveness-promoting ability in lung cancer cells.
Title: Activation loop phosphorylation of ERK3 is important for its kinase activity and ability to promote lung cancer cell invasiveness.
Study established an important role of p38gamma MAPK in epithelial-mesenchymal transition (EMT) and identified a novel signaling pathway for p38gamma MAPK-mediated tumor promotion. p38gamma MAPK regulated miR-200b through inhibiting GATA3 by inducing its ubiquitination, leading proteasome-dependent degradation.
Title: Role of p38γ MAPK in regulation of EMT and cancer stem cells.

Submit: New GeneRIF Correction See all GeneRIFs (44)

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

EBI GWAS Catalog

Description
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 binding to CD4 results in activation of the mitogen-activated protein kinase (MAPK) in CD4(+) lymphocytes prestimulated through their T-cell receptor (TCR)	PubMed
reverse transcriptase	gag-pol	MEK1 in HIV-1 producer cells is able to activate virion-associated MAPK in trans, and the activated MAPK facilitates efficient disengagement of the HIV-1 reverse transcription complex from the cell membrane and subsequent nuclear translocation	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH65991 (e-PCR)
- UniSTS:85026

D8S2279 (e-PCR)
- UniSTS:473907

G67870 (e-PCR)
- UniSTS:225622

G67895 (e-PCR)
- UniSTS:225623

G67897 (e-PCR)
- UniSTS:225624

L18426 (e-PCR)
- UniSTS:34648

G67863 (e-PCR)
- UniSTS:225625

D11S3114 (e-PCR)
- UniSTS:152207

Homology

Homologs of the MAPK12 gene: The MAPK12 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 319 organisms have orthologs with human gene MAPK12
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables MAP kinase activity	IEA Inferred from Electronic Annotation more info
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 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	PubMed
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in MAPK cascade	TAS Traceable Author Statement more info
involved_in cell cycle	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in muscle organ development	TAS Traceable Author Statement more info	PubMed
involved_in myoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell cycle	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of muscle cell differentiation	TAS Traceable Author Statement more info
involved_in positive regulation of peptidase activity	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in signal transduction in response to DNA damage	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: mitogen-activated protein kinase 12

Names: MAP kinase 12; MAP kinase p38 gamma; extracellular signal-regulated kinase 6; mitogen-activated protein kinase 3; mitogen-activated protein kinase p38 gamma; stress-activated protein kinase 3

NP_001290181.1

EC 2.7.11.24

NP_002960.2

EC 2.7.11.24

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.

mRNA and Protein(s)

NM_001303252.3 → NP_001290181.1 mitogen-activated protein kinase 12 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region compared to variant 1. This difference results in a shorter isoform (2), compared to isoform 1.

Source sequence(s)

BC015741, BX640648, CB123561, N94360, U66243, Y10487

Consensus CDS

CCDS77688.1

UniProtKB/Swiss-Prot

P53778

UniProtKB/TrEMBL

Q6N076

Related

ENSP00000479972.1, ENST00000622558.4

Conserved Domains (2) summary

cd07880
Location:11 → 343

STKc_p38gamma; Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12)

smart00220
Location:27 → 301

S_TKc; Serine/Threonine protein kinases, catalytic domain
NM_002969.6 → NP_002960.2 mitogen-activated protein kinase 12 isoform 1

See identical proteins and their annotated locations for NP_002960.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BC015741, CB123561, N94360, U66243, Y10487

Consensus CDS

CCDS14089.1

UniProtKB/Swiss-Prot

P53778, Q99672

Related

ENSP00000215659.8, ENST00000215659.13

Conserved Domains (1) summary

cd07880
Location:11 → 353

STKc_p38gamma; Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12)