Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

NUAK1 (O60285) - Overview - Molecular Target Synopsis

Protein


NUAK1, NUAK family SNF1-like kinase 1
Enzyme Classification 2.7.11.1
UniProt O60285

Also Known as NUAK1_HUMAN, NUAK1, ARK5, KIAA0537, OMPHK1

Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate to transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). Interact (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A. Interacts with CDKN1A.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: NUAK1 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: NUAK1 is active in the following subcellular-locations: cytoplasm, fibrillar center, microtubule cytoskeleton, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project NUAK1 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 1005 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_268, IGROV1, BT_549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H209, NCI-H1882, G22

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, SK-N-SH, BJ

(see details)

RNA Interference


NUAK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H2228, JHESOAD1. (see details)

3D Structures


At greater than 35% identity similarity to NUAK1 there are:
148 structures (222 chains) solved
117 are solved in complex with at least one small molecule ligand
2 are solved with an approved drug

NUAK1 is solved in complex with the approved drug(s):

AMP/ADENOSINE PHOSPHATE (4Y5Q_A),
XIN/NINTEDANIB (5MAF_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


NUAK1 has been screened with 859 compounds (1464 bioactivities), 22 compounds have bioactivities that show binding affinity of <= 500nM (32 bioactivities). (see details)