MAPKAPK5 MAPK activated protein kinase 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAPKAPK5provided by HGNC
Official Full Name: MAPK activated protein kinase 5provided by HGNC
Primary source: HGNC:HGNC:6889
See related: Ensembl:ENSG00000089022 MIM:606723; AllianceGenome:HGNC:6889
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: MK5; MK-5; NCFD; PRAK; MAPKAP-K5
Summary: The protein encoded by this gene is a tumor suppressor and member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. The encoded protein is found in the nucleus but translocates to the cytoplasm upon phosphorylation and activation. This kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2012]
Expression: Ubiquitous expression in small intestine (RPKM 3.1), colon (RPKM 2.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.12-q24.13

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (111842228..111902222)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (111819139..111879131)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (112280032..112340026)

Chromosome 12 - NC_000012.12 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?

Consolidating the association of biallelic MAPKAPK5 pathogenic variants with a distinct syndromic neurodevelopmental disorder.
Title: Consolidating the association of biallelic MAPKAPK5 pathogenic variants with a distinct syndromic neurodevelopmental disorder.
The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-beta/beta-catenin signaling in HCC.
Title: The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-β/β-catenin signaling in HCC.
Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19 months of follow-up.
Title: Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19 months of follow-up.
TLK1-mediated MK5-S354 phosphorylation drives prostate cancer cell motility and may signify distinct pathologies.
Title: TLK1-mediated MK5-S354 phosphorylation drives prostate cancer cell motility and may signify distinct pathologies.
MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis.
Title: MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis.
Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly.
Title: Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly.
Study identified the serine/threonine kinase MK5 as a positive regulator of YAP. MK5 physically interacted with YAP and counteracted CK1delta/epsilon-mediated YAP ubiquitination and degradation independent of LATS1/2. MK5 upregulation was associated with high levels of YAP expression and poor prognosis in clinical tumor samples, confirming its important role for YAP activity in human cancer.
Title: MK5 Regulates YAP Stability and Is a Molecular Target in YAP-Driven Cancers.
MK5 is being discussed as a putative novel regulator of cardiac fibroblast function. (Review)
Title: MK5: A novel regulator of cardiac fibroblast function?
PRAK might be a potential therapeutic target of Alzheimer's disease involved in receptor for advanced glycation end products-mediated cell signaling induced by Abeta
Title: The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer's disease pathogenesis.
Plasma MAPKAPK5 protein was found to positively associate with the 10-year change in paired associates learning assessment in asymptomatic older twins.
Title: Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes.

Submit: New GeneRIF Correction See all GeneRIFs (22)

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
Neurocardiofaciodigital syndrome MedGen: C5677020 OMIM: 619869 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

A009W37 (e-PCR)
- UniSTS:60933

MARC_4607-4608:966894545:1 (e-PCR)
- UniSTS:269407

D12S1333 (e-PCR)
- UniSTS:77957

RH17458 (e-PCR)
- UniSTS:15606

G32924 (e-PCR)
- UniSTS:117502

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables MAP kinase kinase activity	TAS Traceable Author Statement more info	PubMed
enables calcium-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium/calmodulin-dependent protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables mitogen-activated protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables p53 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	EXP Inferred from Experiment 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

Process	Evidence Code	Pubs
involved_in MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular senescence	TAS Traceable Author Statement more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of dendritic spine development	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of signal transduction by p53 class mediator	TAS Traceable Author Statement more info
involved_in regulation of translation	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in stress-induced premature senescence	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	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
part_of protein-containing complex	IEA Inferred from Electronic Annotation more info
located_in septin cytoskeleton	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: MAP kinase-activated protein kinase 5

Names: MAPKAP kinase 5; MAPKAPK-5; mitogen-activated protein kinase-activated protein kinase 5; p38-regulated/activated protein kinase

NP_001358408.1

EC 2.7.11.1

NP_001358409.1

EC 2.7.11.1

NP_001358410.1

EC 2.7.11.1

NP_001358411.1

EC 2.7.11.1

NP_001358412.1

EC 2.7.11.1

NP_001358413.1

EC 2.7.11.1

NP_001358414.1

EC 2.7.11.1

NP_001358415.1

EC 2.7.11.1

NP_001358416.1

EC 2.7.11.1

NP_003659.2

EC 2.7.11.1

NP_620777.1

EC 2.7.11.1

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_001371479.1 → NP_001358408.1 MAP kinase-activated protein kinase 5 isoform 3

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cd14171
Location:15 → 304

STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5
NM_001371480.1 → NP_001358409.1 MAP kinase-activated protein kinase 5 isoform 4

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cd14171
Location:15 → 304

STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5
NM_001371481.1 → NP_001358410.1 MAP kinase-activated protein kinase 5 isoform 5

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cl21453
Location:15 → 277

PKc_like; Protein Kinases, catalytic domain
NM_001371482.1 → NP_001358411.1 MAP kinase-activated protein kinase 5 isoform 6

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cl21453
Location:15 → 274

PKc_like; Protein Kinases, catalytic domain
NM_001371483.1 → NP_001358412.1 MAP kinase-activated protein kinase 5 isoform 7

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cl21453
Location:15 → 274

PKc_like; Protein Kinases, catalytic domain
NM_001371484.1 → NP_001358413.1 MAP kinase-activated protein kinase 5 isoform 8

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cl21453
Location:15 → 270

PKc_like; Protein Kinases, catalytic domain
NM_001371485.1 → NP_001358414.1 MAP kinase-activated protein kinase 5 isoform 9

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cl21453
Location:15 → 235

PKc_like; Protein Kinases, catalytic domain
NM_001371486.1 → NP_001358415.1 MAP kinase-activated protein kinase 5 isoform 10

Status: REVIEWED

Source sequence(s)

AC003029

Conserved Domains (1) summary

cl21453
Location:15 → 235

PKc_like; Protein Kinases, catalytic domain
NM_001371487.1 → NP_001358416.1 MAP kinase-activated protein kinase 5 isoform 11

Status: REVIEWED

Source sequence(s)

AC003029

UniProtKB/TrEMBL

R4GN33

Related

ENSP00000473467.1, ENST00000549875.1

Conserved Domains (1) summary

cl21453
Location:15 → 205

PKc_like; Protein Kinases, catalytic domain
NM_003668.4 → NP_003659.2 MAP kinase-activated protein kinase 5 isoform 1

See identical proteins and their annotated locations for NP_003659.2

Status: REVIEWED

Source sequence(s)

AC003029

Consensus CDS

CCDS44976.1

UniProtKB/Swiss-Prot

Q8IW41

Related

ENSP00000449667.2, ENST00000550735.7

Conserved Domains (1) summary

cd14171
Location:15 → 304

STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5
NM_139078.3 → NP_620777.1 MAP kinase-activated protein kinase 5 isoform 2

See identical proteins and their annotated locations for NP_620777.1

Status: REVIEWED

Source sequence(s)

AC003029

Consensus CDS

CCDS44975.1

UniProtKB/Swiss-Prot

B3KVA5, O60491, Q86X46, Q8IW41, Q9BVX9, Q9UG86

Related

ENSP00000449381.2, ENST00000551404.7

Conserved Domains (1) summary

cd14171
Location:15 → 304

STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5