NUAK1

Summary

NUAK1 (NUAK family kinase 1, HGNC:14311) is a protein-coding gene on chromosome 12q23.3, encoding NUAK family SNF1-like kinase 1 (O60285). Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression.

Enables p53 binding activity and protein serine/threonine kinase activity. Involved in protein phosphorylation; regulation of cell adhesion; and regulation of cellular senescence. Located in cytoplasm; microtubule cytoskeleton; and nuclear lumen. Implicated in uterine fibroid. Biomarker of uterine fibroid.

Source: NCBI Gene 9891 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 88 total
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14311
Approved symbol	NUAK1
Name	NUAK family kinase 1
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	ARK5, KIAA0537
Ensembl gene	ENSG00000074590
Ensembl biotype	protein_coding
OMIM	608130
Entrez	9891

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000261402, ENST00000548902, ENST00000549704, ENST00000553094

RefSeq mRNA: 1 — MANE Select: NM_014840 NM_014840

CCDS: CCDS31892

Canonical transcript exons

ENST00000261402 — 7 exons

Exon	Start	End
ENSE00001099252	106106405	106106525
ENSE00001099255	106083864	106083929
ENSE00001099261	106086734	106086885
ENSE00001199745	106063345	106067955
ENSE00001316787	106138414	106138954
ENSE00003560155	106070774	106070906
ENSE00003657151	106072724	106072843

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5878 / max 144.2957, expressed in 1456 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133051	3.6873	954
133049	3.6872	1069
133054	2.6039	1196
133050	1.5522	806
133047	1.0156	511
133046	0.8932	441
133052	0.7476	424
133042	0.3822	124
133048	0.2189	88
133053	0.2088	90

Top tissues by expression

297 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.13	gold quality
middle temporal gyrus	UBERON:0002771	98.91	gold quality
hair follicle	UBERON:0002073	98.64	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.55	gold quality
parietal lobe	UBERON:0001872	98.49	gold quality
postcentral gyrus	UBERON:0002581	98.41	gold quality
frontal pole	UBERON:0002795	98.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.34	gold quality
endothelial cell	CL:0000115	98.08	gold quality
orbitofrontal cortex	UBERON:0004167	98.00	gold quality
superior frontal gyrus	UBERON:0002661	97.84	gold quality
cerebellar vermis	UBERON:0004720	97.44	gold quality
entorhinal cortex	UBERON:0002728	97.14	gold quality
visceral pleura	UBERON:0002401	97.06	gold quality
tendon of biceps brachii	UBERON:0008188	96.82	gold quality
heart right ventricle	UBERON:0002080	96.81	gold quality
cranial nerve II	UBERON:0000941	96.43	gold quality
medial globus pallidus	UBERON:0002477	96.35	gold quality
occipital lobe	UBERON:0002021	96.25	gold quality
pons	UBERON:0000988	96.14	gold quality
pleura	UBERON:0000977	96.11	gold quality
globus pallidus	UBERON:0001875	95.95	gold quality
parietal pleura	UBERON:0002400	95.91	gold quality
paraflocculus	UBERON:0005351	95.89	gold quality
primary visual cortex	UBERON:0002436	95.43	gold quality
inferior vagus X ganglion	UBERON:0005363	95.29	gold quality
skin of hip	UBERON:0001554	95.28	gold quality
buccal mucosa cell	CL:0002336	95.10	gold quality
adult organism	UBERON:0007023	95.07	gold quality
CA1 field of hippocampus	UBERON:0003881	94.88	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	19.92
E-ANND-3	yes	15.43
E-GEOD-124858	no	492.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAFB, TP53

miRNA regulators (miRDB)

140 targeting NUAK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 40)

• Data suggest that a novel AMPK family member, ARK5, is the tumor cell survival factor activated by Akt and acts as an ATM kinase under the conditions of nutrient starvation. (PMID:12409306)
• ARK5 suppresses the apoptosis induced by nutrient starvation and death receptors via inhibition of caspase 8 activation. (PMID:13679856)
• Results report that a novel AMPK catalytic subunit family member, ARK5, plays a key role in tumor malignancy downstream of Akt. (PMID:15060171)
• ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system. (PMID:15273717)
• overexpression of ARK5 is associated with tumor invasion and metastasis (PMID:15354411)
• ARK5 is a transcriptional target of the Large-MAF family through MARE sequence and that ARK5 may in part mediate the aggressive phenotype associated with c-MAF- and MAFB-expressing myelomas (PMID:16044163)
• NDR2 is an upstream kinase of ARK5 that plays an essential role in tumor progression through ARK5 (PMID:16488889)
• NUAK1 and MARK4 are substrates of USP9X (PMID:18254724)
• Cells that constitutively express NUAK1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator LATS1, whereas depletion of NUAK1 with shRNA exerts opposite effects. (PMID:19927127)
• the LKB1-NUAK pathway has roles in controlling myosin phosphatase complexes and cell adhesion (PMID:20354225)
• A novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53. (PMID:21317932)
• NUAK1 and PPP1CC are identified as positional candidate loci for skeletal muscle strength phenotypes. (PMID:21750233)
• ARK5 enhanced the invasive and metastatic potential of MDA-MB-231 cells under regulation by Akt. (PMID:22105900)
• in human and murine cell lines, oncogenic levels of MYC establish a dependence on AMPK-related kinase 5 for maintaining metabolic homeostasis and for cell survival; ARK5 is an upstream regulator of AMPK and limits protein synthesis via inhibition of the mammalian target of rapamycin 1 (mTORC1) signalling pathway (PMID:22460906)
• ARK5 can promote glioma cell invasion by regulating cytoskeleton rearrangement and matrix metalloproteinase activation. (PMID:23063350)
• High NUAK1 expression correlates with poor prognosis and involved in human nonsmall cell lung cancer cells migration and invasion. (PMID:23215946)
• Overexpression of ARK5 is associated with hepatocellular carcinoma. (PMID:23516026)
• We demonstrate that miR-211 contributes to melanoma adhesion by directly targeting a gene, NUAK1. (PMID:23934065)
• Expression of NUAK1 is controlled by cyclin-dependent kinase, PLK1, and the SCFbetaTrCP (Skp, Cullin and F-boxbetaTrCP) E3 ubiquitin ligase complex. (PMID:24785407)
• Overexpression of NUAK1 is associated with disease-free survival and overall survival in patients with gastric cancer. (PMID:24943992)
• Data indicate that miR-96 suppresses the expression of (nua) kinase family 1 (NUAK1) by targeting its 3’ untranslated region (3’ UTR). (PMID:25242509)
• Results indicate that NUAK1 is excessively expressed in NSCLC and plays important roles in NSCLC invasion. (PMID:25412236)
• ARK5 was upregulated in ovarian cancer tissues, promoted epithelialmesenchymal transition and inhibited miR-1181 expression in ovarian cancer cells (PMID:26151663)
• MiR-145 functions as a tumor suppressor targeting NUAK1 in human intrahepatic cholangiocarcinoma. (PMID:26255969)
• High NUAK1 expression are correlated with epithelial-mesenchymal transition induction in head and neck cancer. (PMID:26882562)
• ARK5 confers doxorubicin resistance in hepatocellular carcinoma by inducing epithelial-mesenchymal transition. (PMID:27126361)
• Nuak1 downregulation decreases tau levels in a human cell line. (PMID:27720485)
• The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in Gastric Cancer cells migration and invasion via epithelial-mesenchymal transition alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1. (PMID:28662499)
• High NUAK1 expression is associated with cancer. (PMID:29106388)
• This work identifies NUAK1 as a key facilitator of the adaptive antioxidant response that is associated with aggressive disease and worse outcome in human colorectal cancer. Our data suggest that transient NUAK1 inhibition may provide a safe and effective means for treatment of human colorectal cancer via disruption of intrinsic antioxidant defenses (PMID:29500295)
• Confirmation studies (step 4) provided additional evidence that NUAK1 and STK11 have PTEN-SSL patterns of activity. Consistent with PTEN-SSL status, inhibition of the NUAK1 protein kinase by the small molecule drug HTH-01-015 selectively impaired viability in multiple PTEN-deficient breast cancer cell lines, while mutations affecting STK11 and PTEN were largely mutually exclusive across large pan-cancer data sets. (PMID:29566768)
• the impaired cell migration and invasion by SNHG1 siRNA could be rescued by cotransfection of miR-145-5p in CNE and HNE-1 cells. LncRNA SNHG1 promoted the expression of NUAK1 by down-regulating miR-145-5p and thus promoted the aggressiveness of nasopharyngeal carcinoma cells through AKT signalling pathway and induced epithelial-mesenchymal transition (EMT). (PMID:29575772)
• NUAK1 is excessively expressed in NPC and may serve as a potential predictor of prognosis for NPC. (PMID:30121842)
• The current study demonstrated that ARK5 is a critical factor involved in SKOV3 cell invasion and ARK5 increases invasive potential by promoting EMT and activating the AktmTORMMPs pathway. (PMID:30720082)
• Identification of a nuclear localization signal and importin beta members mediating NUAK1 nuclear import inhibited by oxidative stress. (PMID:31090959)
• miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase. (PMID:32418991)
• AMPactivated protein kinase family member 5 is an independent prognostic indicator of pancreatic adenocarcinoma: A study based on The Cancer Genome Atlas. (PMID:33000197)
• LINC00922 promotes the proliferation, migration, invasion and EMT process of liver cancer cells by regulating miR-424-5p/ARK5. (PMID:34097192)
• Loss of LKB1-NUAK1 signalling enhances NF-kappaB activity in a spheroid model of high-grade serous ovarian cancer. (PMID:35194062)
• Circ_0003998 upregulates ARK5 expression to elevate 5-Fluorouracil resistance in hepatocellular carcinoma through binding to miR-513a-5p. (PMID:36255069)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	nuak1a	ENSDARG00000020086
danio_rerio	nuak1b	ENSDARG00000028676
mus_musculus	Nuak1	ENSMUSG00000020032
rattus_norvegicus	Nuak1	ENSRNOG00000008061
drosophila_melanogaster	Snrk	FBGN0033915
drosophila_melanogaster	Nuak	FBGN0262617
caenorhabditis_elegans		WBGENE00012638
caenorhabditis_elegans	ZK524.4	WBGENE00013994
caenorhabditis_elegans	tag-344	WBGENE00015230
caenorhabditis_elegans		WBGENE00044388

Paralogs (17): PRKAA1 (ENSG00000132356), TSSK4 (ENSG00000139908), HUNK (ENSG00000142149), SIK1 (ENSG00000142178), BRSK1 (ENSG00000160469), SIK3 (ENSG00000160584), PRKAA2 (ENSG00000162409), TSSK3 (ENSG00000162526), NUAK2 (ENSG00000163545), SNRK (ENSG00000163788), MELK (ENSG00000165304), SIK2 (ENSG00000170145), BRSK2 (ENSG00000174672), NIM1K (ENSG00000177453), TSSK6 (ENSG00000178093), TSSK2 (ENSG00000206203), TSSK1B (ENSG00000212122)

Protein

Protein identifiers

NUAK family SNF1-like kinase 1 — O60285 (reviewed: O60285)

Alternative names: AMPK-related protein kinase 5, Omphalocele kinase 1

All UniProt accessions (4): O60285, F8VSH4, F8VXF0, F8VZ96

UniProt curated annotations — full annotation on UniProt →

Function. 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 in 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.

Subunit / interactions. Interacts (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A. Interacts with CDKN1A.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed at high levels in heart and brain, and at lower levels in skeletal muscle, kidney, ovary, placenta, lung and liver. Highly up-regulated in colorectal cancer cell lines.

Post-translational modifications. Ubiquitinated with ‘Lys-29’- and ‘Lys-33’-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X. Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not dephosphorylated by the myosin PP1 complex when regulating its activity, due to the presence of PPP1R12A, which prevents myosin PP1 from dephosphorylating NUAK1. Phosphorylated by STK38L upon stimulation with IGF1.

Activity regulation. Activated by phosphorylation on Thr-211. Activated by phosphorylation at Ser-600 AKT1 during glucose starvation; the relevance of such activation in normal cells is however unsure.

Domain organisation. The GILK motif mediates interaction with PPP1CB.

Induction. Transcriptionally regulated by members of the MAF family.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O60285-1	1	yes
O60285-2	2

RefSeq proteins (1): NP_055655* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (25 total): modified residue 5, mutagenesis site 4, region of interest 3, binding site 2, splice variant 2, sequence variant 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60285-F1	62.48	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 178 (proton acceptor)

Ligand- & substrate-binding residues (2): 84; 61–69

Post-translational modifications (5): 1, 22, 211, 455, 600

Mutagenesis-validated functional residues (4):

Position	Phenotype
84	abolishes kinase activity and ability to induce senescence.
211	prevents phosphorylation and activation by stk11/lkb1 complex. abolishes ability to induce senescence.
400–401	abolishes interaction with ppp1cb and ability to regulate myosin pp1 activity.
600	abrogates phosphorylation by pkb/akt1. does not affect ability to induce senescence.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation

MSigDB gene sets: 229 (showing top): TAATAAT_MIR126, PEREZ_TP63_TARGETS, ZHAN_MULTIPLE_MYELOMA_MF_UP, GOZGIT_ESR1_TARGETS_DN, TATTATA_MIR374, GOBP_CELLULAR_SENESCENCE, CATTTCA_MIR203, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, BACH2_01, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (7): protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), cell adhesion (GO:0007155), regulation of cell adhesion (GO:0030155), regulation of cell population proliferation (GO:0042127), regulation of signal transduction by p53 class mediator (GO:1901796), regulation of cellular senescence (GO:2000772)

GO Molecular Function (10): p53 binding (GO:0002039), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), microtubule cytoskeleton (GO:0015630)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of TP53 Activity	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	3
cellular anatomical structure	3
protein kinase activity	2
phosphorylation	1
protein modification process	1
cellular response to stress	1
cellular process	1
cell adhesion	1
cell population proliferation	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
cellular senescence	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoskeleton	1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUAK1	USP9X	Q93008	694
NUAK1	SIK2	Q9H0K1	517
NUAK1	STK11	Q15831	510
NUAK1	SNPH	O15079	480
NUAK1	SIK3	Q9Y2K2	478
NUAK1	ATM	Q13315	420
NUAK1	CAB39	Q9Y376	407
NUAK1	PPP1R12A	O14974	401
NUAK1	PPP1CB	P37140	365
NUAK1	BLTP3A	Q6BDS2	346
NUAK1	MELK	Q14680	337
NUAK1	ITGB7	P26010	336
NUAK1	C12orf75	Q8TAD7	324
NUAK1	MYC	P01106	305
NUAK1	PAFAH2	Q99487	305

IntAct

27 interactions, top by confidence:

A	B	Type	Score
NUAK1	TP53	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
TP53	NUAK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
TP53	NUAK1	psi-mi:“MI:0915”(physical association)	0.590
NUAK1	SRRM2	psi-mi:“MI:0915”(physical association)	0.560
NUAK1	USP9X	psi-mi:“MI:0915”(physical association)	0.560
LATS1	NUAK1	psi-mi:“MI:0915”(physical association)	0.400
NUAK1	FBXW11	psi-mi:“MI:0914”(association)	0.350
NUAK1	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
ESR1	ARPC1B	psi-mi:“MI:0914”(association)	0.350
NUAK1		psi-mi:“MI:0914”(association)	0.350
NUAK1	DOCK1	psi-mi:“MI:0914”(association)	0.350
FBXW11	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
MAGEA10	KANSL1L	psi-mi:“MI:0914”(association)	0.350
P4HA3	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
NUAK1		psi-mi:“MI:0915”(physical association)	0.000
NUAK1	IGHA2	psi-mi:“MI:0915”(physical association)	0.000
NUAK1	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.000
NUAK1	S100A9	psi-mi:“MI:0915”(physical association)	0.000
NUAK1	PRPSAP1	psi-mi:“MI:0915”(physical association)	0.000
NUAK1	S100A8	psi-mi:“MI:0915”(physical association)	0.000
FYN	NUAK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (123): SRRM2 (Affinity Capture-MS), BTRC (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), S100A8 (Affinity Capture-MS), PRKAR1A (Affinity Capture-MS), S100A9 (Affinity Capture-MS), NUAK1 (Affinity Capture-RNA), TP53 (Affinity Capture-Western), TP53 (Biochemical Activity), TP53 (Co-localization), NUAK1 (Positive Genetic), NUAK1 (Affinity Capture-RNA)

ESM2 similar proteins: A0AUV4, A1A5Q6, A1A5R7, A2KF29, B1WAS2, C0HKC8, C0HKC9, D3ZML2, O60285, O74536, O88831, O88866, P41279, P51956, P57058, P97756, Q20443, Q2T9U5, Q5R7G9, Q5XHI9, Q60670, Q63562, Q641K5, Q66HE5, Q68UT7, Q6P431, Q6VZ17, Q7T0B0, Q7T0B1, Q7TNJ7, Q7TNL4, Q8BHI9, Q8BZN4, Q8C078, Q8C0N0, Q8C0V7, Q8C0X8, Q8CIP4, Q8IY84, Q8K4K4

Diamond homologs: A0AUV4, A1A5Q6, A2KF29, A2XFF4, A8WRV1, A8WYE4, B2DD29, B7XHR6, B8BBT7, C0HKC8, C0HKC9, F1QGZ6, O08678, O08679, O22932, O22971, O60285, O65554, O74536, P0DP15, P27448, P57059, P92958, Q02723, Q03141, Q05512, Q0D4B2, Q0JI49, Q10SC8, Q14680, Q19469, Q21017, Q28GW8, Q2QY53, Q2RAX3, Q2V452, Q38997, Q54DF2, Q54TA3, Q54YF2

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
STK11	up-regulates	NUAK1	phosphorylation
NUAK1	down-regulates	LATS1	phosphorylation
NUAK1	down-regulates	PPP1R12A	phosphorylation
NUAK1	up-regulates	TP53	phosphorylation
AKT1	up-regulates	NUAK1	phosphorylation
NUAK1	“up-regulates quantity”	MAPT	phosphorylation
NUAK1	“up-regulates activity”	PPP1R10	phosphorylation
AKT	up-regulates	NUAK1	phosphorylation
NUAK1	“down-regulates activity”	CASP6	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

88 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1242 predictions. Top by Δscore:

Variant	Effect	Δscore
12:106070769:CGCA:C	donor_loss	1.0000
12:106070770:GCACC:G	donor_loss	1.0000
12:106070771:CACC:C	donor_loss	1.0000
12:106070772:ACC:A	donor_loss	1.0000
12:106072718:GCTCA:G	donor_loss	1.0000
12:106072719:CTCA:C	donor_loss	1.0000
12:106072720:TCAC:T	donor_loss	1.0000
12:106072721:CA:C	donor_loss	1.0000
12:106072722:A:AC	donor_gain	1.0000
12:106072722:ACC:A	donor_loss	1.0000
12:106072723:C:CA	donor_loss	1.0000
12:106072723:C:CC	donor_gain	1.0000
12:106072723:CCT:C	donor_gain	1.0000
12:106083925:CCGTT:C	acceptor_gain	1.0000
12:106083926:CGTT:C	acceptor_gain	1.0000
12:106083926:CGTTC:C	acceptor_gain	1.0000
12:106083927:GTT:G	acceptor_gain	1.0000
12:106083928:TT:T	acceptor_gain	1.0000
12:106083928:TTCTG:T	acceptor_loss	1.0000
12:106083929:TC:T	acceptor_loss	1.0000
12:106083930:C:CC	acceptor_gain	1.0000
12:106083931:T:G	acceptor_loss	1.0000
12:106083935:A:AC	acceptor_gain	1.0000
12:106086728:CCATA:C	donor_loss	1.0000
12:106086729:CATAC:C	donor_loss	1.0000
12:106086730:ATACC:A	donor_loss	1.0000
12:106086731:TACC:T	donor_loss	1.0000
12:106086732:ACC:A	donor_loss	1.0000
12:106086733:C:G	donor_loss	1.0000
12:106086881:AAACA:A	acceptor_gain	1.0000

AlphaMissense

4362 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:106067873:C:A	W305C	1.000
12:106067873:C:G	W305C	1.000
12:106067875:A:G	W305R	1.000
12:106067875:A:T	W305R	1.000
12:106067904:G:T	A295D	1.000
12:106067928:A:G	L287P	1.000
12:106067928:A:T	L287Q	1.000
12:106070803:C:T	G268E	1.000
12:106070812:A:C	I265S	1.000
12:106070812:A:G	I265T	1.000
12:106070812:A:T	I265N	1.000
12:106070815:T:G	Q264P	1.000
12:106070824:A:G	L261P	1.000
12:106070824:A:T	L261H	1.000
12:106070847:G:C	F253L	1.000
12:106070847:G:T	F253L	1.000
12:106070848:A:C	F253C	1.000
12:106070848:A:G	F253S	1.000
12:106070849:A:C	F253V	1.000
12:106070849:A:G	F253L	1.000
12:106070849:A:T	F253I	1.000
12:106070851:G:C	P252R	1.000
12:106070851:G:T	P252H	1.000
12:106070852:G:A	P252S	1.000
12:106070852:G:T	P252T	1.000
12:106070869:A:G	L246P	1.000
12:106070878:A:G	L243P	1.000
12:106070881:A:C	L242W	1.000
12:106070887:C:A	G240V	1.000
12:106070887:C:T	G240D	1.000

dbSNP variants (sampled 300 via entrez): RS1000014436 (12:106101668 T>C), RS1000059002 (12:106093846 G>T), RS1000130854 (12:106110823 C>G), RS1000138043 (12:106088886 A>G), RS1000199334 (12:106069375 C>T), RS1000209693 (12:106088620 C>T), RS1000267046 (12:106111165 G>A,C), RS1000334193 (12:106074143 A>G), RS1000441409 (12:106082853 C>A,G), RS1000577504 (12:106139631 G>A,T), RS1000589843 (12:106132995 A>T), RS1000618808 (12:106064694 C>A,T), RS1000678589 (12:106104363 G>A), RS1000707308 (12:106113602 C>T), RS1000764080 (12:106098533 T>C)

Disease associations

OMIM: gene MIM:608130 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001868_8	Alzheimer’s disease biomarkers	4.000000e-06
GCST002408_11	Response to methotrexate in juvenile idiopathic arthritis	4.000000e-06
GCST003025_11	Attention function in attention deficit hyperactive disorder	3.000000e-06
GCST003025_21	Attention function in attention deficit hyperactive disorder	6.000000e-07
GCST007147_4	Lateral ventricular volume in normal aging	3.000000e-13
GCST007182_2	Two-hour glucose in pregnancy (gestational week 30-32)	3.000000e-08
GCST007184_1	General glucose level in pregnancy (gestational week 30-32)	2.000000e-08
GCST010703_94	Brain morphology (MOSTest)	6.000000e-52
GCST012010_2	Medial thalamic nuclei volume	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005194	amyloid-beta measurement
EFO:0007636	attention function measurement
EFO:0008487	lateral ventricle volume measurement
EFO:0004346	neuroimaging measurement
EFO:0006935	thalamus volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5784 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 236,526 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL50	QUERCETIN	3	74,559
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL3115681	NARAZACICLIB	2	287
CHEMBL3544911	PREXASERTIB	2	699
CHEMBL4116008	CERDULATINIB	2	2,083
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL575448	BMS-754807	2	406
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL4169078	SRA-737	1	529
CHEMBL4482864	TIZATERKIB	1
CHEMBL494089	GSK-690693	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — NuaK subfamily

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
cerdulatinib	Inhibition	8.4	pIC50
narazaciclib	Inhibition	8.31	pIC50
HTH-02-006	Inhibition	8.1	pIC50
WZ4003	Inhibition	7.7	pIC50
compound 25b [PMID: 22564207]	Inhibition	7.59	pIC50
WZ4002	Inhibition	7.04	pKd
HTH-01-015	Inhibition	7.0	pIC50

Binding affinities (BindingDB)

8 measured of 8 human assays (8 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

225 potent at pChembl≥5 of 235 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.07943	nM	CHEMBL6078515
9.90	IC50	0.1259	nM	CHEMBL6145232
9.80	IC50	0.1585	nM	CHEMBL6144894
9.60	IC50	0.2512	nM	CHEMBL6078155
9.60	IC50	0.2512	nM	CHEMBL6083111
9.60	IC50	0.2512	nM	CHEMBL6082932
9.30	IC50	0.5012	nM	CHEMBL6147297
8.90	IC50	1.259	nM	CHEMBL6134733
8.90	IC50	1.259	nM	CHEMBL6078515
8.88	IC50	1.31	nM	STAUROSPORINE
8.88	IC50	1.32	nM	STAUROSPORINE
8.87	IC50	1.35	nM	STAUROSPORINE
8.85	IC50	1.41	nM	STAUROSPORINE
8.85	IC50	1.4	nM	CHEMBL5176650
8.82	IC50	1.5	nM	CHEMBL4303523
8.82	IC50	1.5	nM	CHEMBL5303523
8.80	IC50	1.585	nM	CHEMBL6145990
8.80	IC50	1.585	nM	CHEMBL6144894
8.77	Ki	1.7	nM	CHEMBL1908392
8.70	IC50	2	nM	CHEMBL3780091
8.60	IC50	2.512	nM	CHEMBL6173351
8.60	IC50	2.512	nM	CHEMBL6167944
8.52	IC50	3	nM	CHEMBL5199998
8.52	IC50	3	nM	CHEMBL5305160
8.50	IC50	3.162	nM	CHEMBL6102086
8.50	IC50	3.162	nM	CHEMBL6091821
8.50	IC50	3.162	nM	CHEMBL6133470
8.50	IC50	3.162	nM	CHEMBL6103014
8.50	IC50	3.162	nM	CHEMBL6145232
8.50	IC50	3.162	nM	CHEMBL6078155
8.50	IC50	3.162	nM	CHEMBL6177408
8.50	IC50	3.162	nM	CHEMBL6171771
8.43	IC50	3.7	nM	CHEMBL5173501
8.43	Kd	3.7	nM	LESTAURTINIB
8.40	IC50	4	nM	CERDULATINIB
8.40	IC50	3.981	nM	CHEMBL6082932
8.40	IC50	3.981	nM	CHEMBL6176672
8.40	IC50	3.981	nM	CHEMBL6170125
8.38	IC50	4.2	nM	CHEMBL4568087
8.36	Kd	4.4	nM	STAUROSPORINE
8.32	IC50	4.8	nM	CHEMBL5196626
8.30	IC50	4.95	nM	NARAZACICLIB
8.30	IC50	5	nM	CHEMBL3884319
8.30	IC50	5	nM	BX-795
8.30	IC50	5.012	nM	CHEMBL6145553
8.30	IC50	5.012	nM	CHEMBL6145677
8.30	IC50	5.012	nM	CHEMBL6083111
8.30	IC50	5.012	nM	CHEMBL190684
8.30	IC50	5.012	nM	CHEMBL6167301
8.30	IC50	5.012	nM	CHEMBL6175168

PubChem BioAssay actives

115 with measured affinity, of 990 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1612690: Inhibition of human ARK5 using KKKVSRSGLYRSPSMPENLNRPR as substrate by [gamma-33P]-ATP assay	ic50	0.0013	uM
5-[2-(dimethylamino)ethoxy]-13-methyl-11,15-diazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2(7),3,5,8,12(17),13-heptaen-16-one	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0014	uM
N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]propanamide	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0015	uM
5,11-dimethyl-2-[(1-piperidin-4-ylpyrazol-4-yl)amino]pyrimido[4,5-b][1,4]benzodiazepin-6-one	2186795: Inhibition of GST-tagged NUAK1 (unknown origin) expressed in HEK293 cells using ALNRTSSDSALHRRR as substrate incubated for 30 mins in presence of [gamma-32P]-ATP by Cerenkov counting method	ic50	0.0015	uM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	1474642: Inhibition of full length recombinant human N-terminal GST-tagged NUAK1 expressed in baculovirus infected Sf9 insect cells using CHK peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0017	uM
4-[(4-aminocyclohexyl)amino]-3-(1H-benzimidazol-2-yl)-1H-pyridin-2-one	1287935: Inhibition of NUAK1 (unknown origin)	ic50	0.0020	uM
7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-2-methylsulfonylpyrrolo[2,3-d]pyrimidin-6-one	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0030	uM
7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-2-[3-(pyrrolidin-1-ylmethyl)anilino]pyrrolo[2,3-d]pyrimidin-6-one	1992920: Inhibition of NUAK1 (unknown origin)	ic50	0.0030	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507833: Binding affinity to ARK5	kd	0.0037	uM
(2R,15S)-19-fluoro-2,15-dimethyl-16-oxa-3,6,8,9,13-pentazatetracyclo[15.3.1.14,8.07,11]docosa-1(21),4(22),5,7(11),9,17,19-heptaen-12-one	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0037	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0040	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637116: Inhibition of full-length recombinant human His-tagged NUAK1 expressed in baculovirus expression system by Adapta assay	ic50	0.0042	uM
13-methyl-5-(2-piperidin-1-ylethoxy)-11,15-diazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2(7),3,5,8,12(17),13-heptaen-16-one	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0048	uM
N-[3-[[5-iodo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0050	uM
8-cyclopentyl-2-[4-(4-methylpiperazin-1-yl)anilino]-7-oxopyrido[2,3-d]pyrimidine-6-carbonitrile	1069223: Inhibition of ARK5 (unknown origin)	ic50	0.0050	uM
2-anilino-7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one	1336002: Inhibition of human recombinant full length His-tagged NUAK1 expressed in baculovirus expression system	ic50	0.0050	uM
5,11-dimethyl-2-[3-methyl-4-(4-methylpiperazine-1-carbonyl)anilino]pyrimido[4,5-b][1,4]benzodiazepin-6-one	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0060	uM
5,8,11-trimethyl-2-[(1-piperidin-4-ylpyrazol-4-yl)amino]pyrimido[4,5-b][1,4]benzodiazepin-6-one	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0070	uM
4-[2-(butylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1185907: Inhibition of Nuak1 (unknown origin) by Off-chip Mobility Shift Assay	ic50	0.0080	uM
2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylic acid	1474642: Inhibition of full length recombinant human N-terminal GST-tagged NUAK1 expressed in baculovirus infected Sf9 insect cells using CHK peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0086	uM
5-(4-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0091	uM
(2R,3R)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0100	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylate	1474642: Inhibition of full length recombinant human N-terminal GST-tagged NUAK1 expressed in baculovirus infected Sf9 insect cells using CHK peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0110	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526250: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged NUAK1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0130	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1845590: Binding affinity to NUAK1 (unknown origin) assessed as dissociation constant	kd	0.0130	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526250: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged NUAK1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0150	uM
5,8,11-trimethyl-2-[(2-oxo-3,4-dihydro-1H-quinolin-7-yl)amino]pyrimido[4,5-b][1,4]benzodiazepin-6-one	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0150	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637116: Inhibition of full-length recombinant human His-tagged NUAK1 expressed in baculovirus expression system by Adapta assay	ic50	0.0150	uM
4,5,11-trimethyl-2-[(1-piperidin-4-ylpyrazol-4-yl)amino]pyrimido[4,5-b][1,4]benzodiazepin-6-one	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0170	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637116: Inhibition of full-length recombinant human His-tagged NUAK1 expressed in baculovirus expression system by Adapta assay	ic50	0.0190	uM
N-[5-[[4-[[(3R,3aR,6R,6aR)-3-methoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-5-chloropyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]phenyl]prop-2-enamide	1885423: Inhibition of human ARK5	ic50	0.0250	uM
N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0250	uM
(1S,2S,3R,4R)-3-[[5-chloro-2-[[(7S)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide	676085: Inhibition of human ARK5	ic50	0.0260	uM
2,9-dimethyl-5-[(1-piperidin-4-ylpyrazol-4-yl)amino]-2,4,6,9-tetrazatetracyclo[9.8.0.03,8.013,18]nonadeca-1(19),3,5,7,11,13,15,17-octaen-10-one	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0300	uM
N-[3-[[2-[4-(4-methylpiperazin-1-yl)anilino]-7H-purin-6-yl]oxy]phenyl]prop-2-enamide	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0330	uM
Fedratinib	625088: Binding constant for ARK5 kinase domain	kd	0.0340	uM
6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-[(4-fluorophenyl)methyl]imidazo[4,5-b]pyridin-5-amine	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0349	uM
Midostaurin	435150: Binding constant for ARK5 kinase domain	kd	0.0410	uM
9-(cyclohexylmethyl)-4,5-dimethoxy-9,14,16-triazatetracyclo[8.7.0.02,7.011,15]heptadeca-1(17),2,4,6,10,12,15-heptaen-8-one	1415049: Binding affinity to DNA-tagged recombinant human ARK5 (25 to 332 residues) expressed in bacterial expression system by KINOMEscan assay	kd	0.0420	uM
Brigatinib	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0470	uM
Sunitinib	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0480	uM
5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]pyrazine-2-carbonitrile	1845556: Inhibition of NUAK1 (unknown origin)	ic50	0.0640	uM
N-tert-butyl-3-[[5-chloro-2-[(1-piperidin-4-ylpyrazol-4-yl)amino]pyrimidin-4-yl]amino]benzenesulfonamide	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.0670	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625088: Binding constant for ARK5 kinase domain	kd	0.0750	uM
2,7,9-trimethyl-5-[(1-piperidin-4-ylpyrazol-4-yl)amino]-2,4,6,9-tetrazatetracyclo[9.8.0.03,8.013,18]nonadeca-1(19),3,5,7,11,13,15,17-octaen-10-one	1845553: Inhibition of N-terminal GST-tagged wild type human NUAK1 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis	ic50	0.1000	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide	507833: Binding affinity to ARK5	kd	0.1100	uM
2-[3-[(6-ethynyl-7H-purin-2-yl)amino]phenyl]acetamide	1695312: Inhibition of human NAUK1 by kinase-profiling analysis	ic50	0.1200	uM
N-[(1R)-1-(3,5-difluorophenyl)ethyl]-3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-5-amine	1741247: Binding affinity to wild-type human partial length ARK5 (E25 to I332 residues) expressed in bacterial expression system by Kinomescan method relative to control	kd	0.1400	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625088: Binding constant for ARK5 kinase domain	kd	0.1600	uM
4-[[[5-bromo-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]methyl]benzenesulfonamide	1823784: Inhibition of recombinant human ARK5 (2 to end residues) using KKKVSRSGLYRSPSMPENLNRPR as substrate incubated for 40 mins in presence of [gamma-33ATP] by scintillation counting based radiometry assay	ic50	0.1710	uM

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
cobaltous chloride	decreases expression, increases expression	2
WZ4003	decreases activity, decreases response to substance, decreases reaction, increases activity, increases phosphorylation	2
HTH-01-015	increases phosphorylation, decreases activity, decreases response to substance, decreases reaction, increases activity	2
Benzo(a)pyrene	increases methylation, affects methylation	2
Estradiol	increases expression, decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	increases methylation, decreases expression, increases expression	2
Aflatoxin B1	increases methylation, decreases expression, increases expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
GSK-J4	increases expression	1
ON123300	decreases phosphorylation	1
TAK-243	increases sumoylation	1
chloroacetaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sulforaphane	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
Dasatinib	increases expression	1
Rosiglitazone	decreases expression	1

ChEMBL screening assays

342 unique, capped per target: 342 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1025529	Binding	Inhibition of ARK5 at 1 uM	3-amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK profile. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TB31	HAP1 NUAK1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.