MAPK13 mitogen-activated protein kinase 13 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAPK13provided by HGNC
Official Full Name: mitogen-activated protein kinase 13provided by HGNC
Primary source: HGNC:HGNC:6875
See related: Ensembl:ENSG00000156711 MIM:602899; AllianceGenome:HGNC:6875
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: SAPK4; PRKM13; MAPK 13; MAPK-13; p38delta
Summary: This gene encodes a member of the mitogen-activated protein (MAP) kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]
Expression: Broad expression in skin (RPKM 21.7), small intestine (RPKM 17.1) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.31

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (36130513..36144521)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (35950829..35964842)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (36098290..36112298)

Chromosome 6 - NC_000006.12 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?

MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer.
Title: MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer.
p38delta promotes micro-aggregate transport by phosphorylating SQSTM1, a major scaffold protein that assembles soluble ubiquitylated proteins into micro-aggregates.
Title: p38δ MAPK regulates aggresome biogenesis by phosphorylating SQSTM1 in response to proteasomal stress.
Study identified p38alpha and p38delta as critical regulators of ASC oligomerization, inflammasome activation, and IL-1beta secretion in keratinocytes. Furthermore, data suggest that the nature of the mitogen-activated protein kinase regulating inflammasome activity exhibits a certain cell specificity, with p38 playing a predominant role in keratinocytes and Jun N-terminal kinase 1 in cells of myeloid origin.
Title: The p38 Mitogen-Activated Protein Kinase Critically Regulates Human Keratinocyte Inflammasome Activation.
These observations indicate that p38alpha probably blocks brown adipose tissue thermogenesis through p38delta inhibition.
Title: p38α blocks brown adipose tissue thermogenesis through p38δ inhibition.
Mitogen-activated protein kinases p38gamma/p38delta deficiency protects against Candida albicans infection by increasing reactive oxygen species and iNOS enzyme production and thus the antifungal capacity of neutrophils and macrophages.
Title: Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity.
The knockdown of MAPK13 also blocked the effect of miR23a5p in osteogenic differentiation of bone marrow-derived mesenchymal stem cells.
Title: MicroRNA-23a-5p regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting mitogen-activated protein kinase-13.
expression of claudin-11 in cutaneous squamous cell carcinoma cells depended on the activity of p38delta MAPK
Title: Expression of claudin-11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38δ.
Study proposes MAPK p38delta protein as a key factor in breast cancer.
Title: P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.
The p38delta mitogen-activated protein kinase was identified as a novel regulator of NLRP3 inflammasome activation in primary human macrophages, and thus, represents a potential target for modulation of atherosclerotic inflammation.
Title: p38δ MAPK: A Novel Regulator of NLRP3 Inflammasome Activation With Increased Expression in Coronary Atherogenesis.
p38delta expression was significantly higher in esophageal squamous cell carcinoma tissues compared with paired normal controls. No significant association was found for p38delta between its expression and other clinicopathological parameters. In Eca109 cells, p38delta can promote the cell growth and motility. p38delta overexpression promotes tumorigenesis in nude mice when p38delta was stably over-expressed and p38ga...
Title: Clinicopathological significance of p38β, p38γ, and p38δ and its biological roles in esophageal squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (35)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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
Nef	nef	HIV-1 Nef involves MAPK13 in the regulation of IL6 expression	PubMed
	nef	Knockdown of p38 MAPK alpha or delta by siRNA shows significant reduction of CCL5 levels, suggesting that p38 MAPK alpha and delta proteins are involved in Nef-mediated upregulation of CCL5	PubMed
Pr55(Gag)	gag	The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with p38delta	PubMed
Tat	tat	HIV-1 Tat-mediated upregulation of CCL5 involves JAK2/3, AKT2/3, p38delta, NF-kappaB (p65/p50), C/EBP alpha/gamma, and AP-1 proteins	PubMed
Vpr	vpr	p38-MAPK13 (delta isoform of p38-MAPK) is involved in Vpr-mediated IL6 induction in astrocytes	PubMed
	vpr	HIV-1 Vpr-induced upregulation of CCL5 requires p50 and p65 subunits of NF-kappaB, p38delta MAPK, Akt-2 and Akt-3, and AP-1 transcription factor in HIV-1 Vpr transfected astrocytes	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

RH46763 (e-PCR)
- UniSTS:12696

MAPK13_919 (e-PCR)
- UniSTS:277475

MAPK13_V206 (e-PCR)
- UniSTS:277475

WI-17354 (e-PCR)
- UniSTS:82917

MARC2561-2562 (e-PCR)
- UniSTS:207083

MARC_2561-2562:966881345:1 (e-PCR)
- UniSTS:207083

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in cellular response to UV	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to anisomycin	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to interleukin-1	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to sodium arsenite	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to sorbitol	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
involved_in positive regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to osmotic stress	IDA Inferred from Direct Assay more info	PubMed
involved_in stress-activated MAPK cascade	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: mitogen-activated protein kinase 13

Names: MAP kinase 13; MAP kinase p38 delta; mitogen-activated protein kinase p38 delta; stress-activated protein kinase 4

NP_002745.1

EC 2.7.11.24

XP_054211903.1

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_002754.5 → NP_002745.1 mitogen-activated protein kinase 13

See identical proteins and their annotated locations for NP_002745.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and is protein-coding.

Source sequence(s)

AF092535, DB335275, DB473379, DR006449, U93232, Z95152

Consensus CDS

CCDS4818.1

UniProtKB/Swiss-Prot

O14739, O15124, O15264, Q5U4A5, Q6FI46, Q9UNU0

UniProtKB/TrEMBL

A0A024RD04, B5BTY5

Related

ENSP00000211287.4, ENST00000211287.9

Conserved Domains (1) summary

cd07879
Location:9 → 351

STKc_p38delta; Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13)

RNA

NR_072996.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two consecutive internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC085196, DB335275, DB473379, DR006449, Z95152

Related

ENST00000373766.9