MAPKAPK5

Chr 12q24.12-q24.13

MAPK activated protein kinase 5

Aliases:: PRAK, MK5
MANE:: ENST00000550735.7

OMIM: 606723 ↗NCBI: 8550 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

MAPKAPK5 · Q8IW41

v62025-08-01

Predicted Aligned Error matrix for MAPKAPK5 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

78.7/ 100

Confident

473 residues

Confidence breakdown

Very high(≥ 90)39%
Confident(70–90)35%
Low(50–70)14%
Very low(< 50)13%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Limb disorders
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

neurocardiofaciodigital syndrome
0.69
chronic obstructive pulmonary disease
0.34
alcohol drinking
0.26
coronary artery disorder
0.26
gout
0.26
hypothyroidism
0.23
hepatocellular carcinoma
0.11
neoplasm
0.11
rheumatoid arthritis
0.10
colorectal carcinoma
0.10

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

MAP kinase-activated protein kinase 5

Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement