STK17A

Summary

STK17A (serine/threonine kinase 17a, HGNC:11395) is a protein-coding gene on chromosome 7p13, encoding Serine/threonine-protein kinase 17A (Q9UEE5). Acts as a positive regulator of apoptosis.

This gene is a member of the DAP kinase-related apoptosis-inducing protein kinase family and encodes an autophosphorylated nuclear protein with a protein kinase domain. The protein has apoptosis-inducing activity.

Source: NCBI Gene 9263 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 19 total
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004760

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11395
Approved symbol	STK17A
Name	serine/threonine kinase 17a
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	DRAK1
Ensembl gene	ENSG00000164543
Ensembl biotype	protein_coding
OMIM	604726
Entrez	9263

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000319357, ENST00000462448, ENST00000474211, ENST00000648544, ENST00000869874, ENST00000938960, ENST00000950254

RefSeq mRNA: 1 — MANE Select: NM_004760 NM_004760

CCDS: CCDS5470

Canonical transcript exons

ENST00000319357 — 7 exons

Exon	Start	End
ENSE00001085350	43583108	43583449
ENSE00001240034	43624518	43627379
ENSE00001240052	43623709	43623888
ENSE00001748848	43623572	43623620
ENSE00003594099	43619597	43619723
ENSE00003615135	43608256	43608400
ENSE00003639671	43595901	43596113

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 96.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5021 / max 670.0068, expressed in 1807 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78356	27.6969	1804
78357	0.8051	408

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	96.33	gold quality
epithelium of nasopharynx	UBERON:0001951	96.12	gold quality
granulocyte	CL:0000094	95.53	gold quality
vermiform appendix	UBERON:0001154	95.02	gold quality
blood	UBERON:0000178	94.91	gold quality
bone marrow	UBERON:0002371	94.41	gold quality
ganglionic eminence	UBERON:0004023	94.30	gold quality
ventricular zone	UBERON:0003053	93.18	gold quality
caecum	UBERON:0001153	92.73	gold quality
vena cava	UBERON:0004087	92.64	gold quality
calcaneal tendon	UBERON:0003701	92.07	gold quality
spleen	UBERON:0002106	91.83	gold quality
islet of Langerhans	UBERON:0000006	91.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.53	gold quality
bone marrow cell	CL:0002092	91.43	gold quality
heart right ventricle	UBERON:0002080	91.16	gold quality
cartilage tissue	UBERON:0002418	90.93	gold quality
superficial temporal artery	UBERON:0001614	90.91	gold quality
tonsil	UBERON:0002372	90.91	gold quality
trabecular bone tissue	UBERON:0002483	90.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.74	gold quality
placenta	UBERON:0001987	90.69	gold quality
saphenous vein	UBERON:0007318	90.40	gold quality
bronchial epithelial cell	CL:0002328	89.49	gold quality
oral cavity	UBERON:0000167	89.05	gold quality
descending thoracic aorta	UBERON:0002345	88.95	gold quality
ascending aorta	UBERON:0001496	88.73	gold quality
thoracic aorta	UBERON:0001515	88.69	gold quality
superior surface of tongue	UBERON:0007371	88.59	gold quality
pancreas	UBERON:0001264	88.51	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	859.29
E-MTAB-6701	yes	107.64
E-CURD-122	yes	46.72
E-MTAB-10287	yes	39.96
E-GEOD-135922	yes	29.45
E-MTAB-8410	yes	27.43
E-HCAD-10	yes	24.94
E-HCAD-9	yes	19.36
E-CURD-88	yes	18.39
E-HCAD-1	yes	18.29
E-CURD-46	yes	13.38
E-MTAB-10042	yes	11.89
E-CURD-112	yes	5.24
E-MTAB-9067	yes	4.03
E-MTAB-7381	no	230.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting STK17A, 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-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4503	99.85	71.45	1869

Literature-anchored findings (GeneRIF, showing 12)

• identified STK17A as a novel direct target of p53 and a modulator of cisplatin toxicity and reactive oxygen species in testicular cancer cells. (PMID:21489989)
• When analyzing STK17A haplotypes distribution, we found association between TGGTC, TAGTC and AAGAT haplotypes and risk to develop SLE (PMID:23860322)
• STK17A provides a proliferative and survival advantage to GBM cells (PMID:24312360)
• DRAK1 was predominantly localized in the cytoplasm and bound to Smad3, thereby interrupting Smad3/Smad4 complex formation, which is the core process for the induction of tumor suppressor genes by TGF-beta1 (PMID:25531329)
• the present study was the first to find localization of STK17A in normal bile canaliculi. (PMID:26305096)
• These findings suggest that DRAK1 translocates in response to stimuli and induces apoptosis through its interaction with specific binding partners, p53 and/or ANT2. (PMID:29397938)
• High STK17A expression is associated with glioma. (PMID:30530503)
• Loss of serine threonine kinase 17A occurs in colorectal cancer metastasis, induces mesenchymal morphologies, and contributes to tumor cell invasion and migration in colorectal cancer. (PMID:30655319)
• Destablilization of TRAF6 by DRAK1 Suppresses Tumor Growth and Metastasis in Cervical Cancer Cells. (PMID:32265222)
• Genome-wide association study of non-tuberculous mycobacterial pulmonary disease. (PMID:33115937)
• Predictive significance of STK17A in patients with gastric cancer and association with gastric cancer cell proliferation and migration. (PMID:33955523)
• Degradation of DRAK1 by CUL3/SPOP E3 Ubiquitin ligase promotes tumor growth of paclitaxel-resistant cervical cancer cells. (PMID:35194034)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk17a	ENSDARG00000074715
drosophila_melanogaster	Drak	FBGN0052666

Paralogs (1): STK17B (ENSG00000081320)

Protein

Protein identifiers

Serine/threonine-protein kinase 17A — Q9UEE5 (reviewed: Q9UEE5)

Alternative names: DAP kinase-related apoptosis-inducing protein kinase 1

All UniProt accessions (1): Q9UEE5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in placenta. Lower levels in heart, lung, skeletal muscle, kidney and pancreas.

Post-translational modifications. Autophosphorylated.

Activity regulation. Inhibited by thiazolidinedione-type compounds: inhibited by furan- and pyridone- thiazolidinediones.

Induction. Directly regulated by p53/TP53: induced following cisplatin treatment in a p53/TP53-dependent manner. p53/TP53 activates expression by directly binding to its regulatory regions.

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

RefSeq proteins (1): NP_004751* (*=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
IPR042704	DRAK1_STKc	Domain

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

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 (42 total): helix 15, strand 9, sequence variant 4, turn 3, modified residue 3, region of interest 2, binding site 2, chain 1, domain 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7QUE	X-RAY DIFFRACTION	2.4
7QUF	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UEE5-F1	75.58	0.54

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): 186 (proton acceptor)

Ligand- & substrate-binding residues (2): 67–75; 90

Post-translational modifications (3): 9, 13, 28

Mutagenesis-validated functional residues (1):

Position	Phenotype
90	loss of activity and of apoptotic function.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 207 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MORF_FLT1, MODULE_169, MORF_ESR1, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, BROWNE_HCMV_INFECTION_48HR_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, SASSON_RESPONSE_TO_FORSKOLIN_DN, SU_THYMUS, GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, LEE_EARLY_T_LYMPHOCYTE_DN, GARY_CD5_TARGETS_DN

GO Biological Process (6): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), intracellular signal transduction (GO:0035556), positive regulation of apoptotic process (GO:0043065), positive regulation of fibroblast apoptotic process (GO:2000271), regulation of reactive oxygen species metabolic process (GO:2000377)

GO Molecular Function (7): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), plasma membrane (GO:0005886), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
intracellular anatomical structure	1
signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
positive regulation of apoptotic process	1
fibroblast apoptotic process	1
regulation of fibroblast apoptotic process	1
regulation of metabolic process	1
reactive oxygen species metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK17A	PLEKHF1	Q96S99	588
STK17A	DAP	P51397	572
STK17A	COL21A1	Q96P44	447
STK17A	C7orf25	Q9BPX7	408
STK17A	FHL2	Q14192	401
STK17A	CDC7	O00311	360
STK17A	NME5	P56597	353
STK17A	EFNB2	P52799	352
STK17A	LANCL2	Q9NS86	348
STK17A	MMP3	P08254	336
STK17A	MRPS24	P82668	332
STK17A	CCDC117	Q8IWD4	330
STK17A	NME3	Q13232	328
STK17A	OR7G1	Q8NGA0	323
STK17A	MFSD6	Q6ZSS7	316

IntAct

5 interactions, top by confidence:

A	B	Type	Score
	STK17A	psi-mi:“MI:0915”(physical association)	0.000
yopM	STK17A	psi-mi:“MI:0915”(physical association)	0.000
STK17A		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): STK17A (Affinity Capture-RNA), TRAF6 (Affinity Capture-Western), TRAF6 (Two-hybrid), STK17A (Affinity Capture-Western), STK17A (Affinity Capture-Western), STK17A (Affinity Capture-RNA), STK17A (Biochemical Activity), STK17A (Affinity Capture-MS), PRPF31 (Affinity Capture-MS), SDAD1 (Affinity Capture-MS), DCAF7 (Affinity Capture-MS), GPATCH2L (Affinity Capture-MS), GPATCH2 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), GNL1 (Affinity Capture-MS)

ESM2 similar proteins: D4A7V9, F1QGZ6, O15530, O54785, O54863, O94768, O96017, P53351, P53666, P53670, P53671, P92958, Q14680, Q20443, Q28GW8, Q32L23, Q38997, Q3SZW1, Q5HZ38, Q5RBJ6, Q5SUV5, Q61241, Q61846, Q6DE87, Q6SA08, Q7RTN6, Q7TNJ7, Q7TNZ6, Q852Q2, Q86YV6, Q8BG48, Q8C1R0, Q8NG66, Q8VDF3, Q8WNU8, Q91821, Q91VB2, Q91XS8, Q93V58, Q96NX5

Diamond homologs: A0A509AFG4, A0A5K1K8H0, A2AAJ9, A2ZVI7, A4IFM7, A8C984, A8WXF6, B9FKW9, C0HKC8, C0HKC9, E9PT87, O02827, O43293, O44997, O54784, O62305, O70150, O75147, O80673, O88764, O94768, P07313, P08414, P11801, P13234, P15735, P18653, P20689, P29294, P31325, P34101, P43292, P53355, P53681, Q00168, Q00771, Q0KHT7, Q0V7M1, Q10KY3, Q14012

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STK17A	up-regulates	TP53	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2149 predictions. Top by Δscore:

Variant	Effect	Δscore
7:43586368:G:GT	donor_gain	1.0000
7:43595896:TCTAG:T	acceptor_loss	1.0000
7:43595897:CTAGG:C	acceptor_loss	1.0000
7:43595898:TA:T	acceptor_loss	1.0000
7:43595899:A:AC	acceptor_loss	1.0000
7:43595899:A:AG	acceptor_gain	1.0000
7:43595899:AG:A	acceptor_gain	1.0000
7:43595899:AGGG:A	acceptor_gain	1.0000
7:43595899:AGGGG:A	acceptor_gain	1.0000
7:43595900:G:GT	acceptor_gain	1.0000
7:43595900:GG:G	acceptor_gain	1.0000
7:43595900:GGGG:G	acceptor_gain	1.0000
7:43595900:GGGGG:G	acceptor_gain	1.0000
7:43596109:GAATA:G	donor_gain	1.0000
7:43596110:AATA:A	donor_gain	1.0000
7:43596111:ATA:A	donor_gain	1.0000
7:43596111:ATAGT:A	donor_loss	1.0000
7:43596112:TA:T	donor_gain	1.0000
7:43596112:TAG:T	donor_loss	1.0000
7:43596113:AGT:A	donor_loss	1.0000
7:43596114:G:A	donor_loss	1.0000
7:43596114:G:GG	donor_gain	1.0000
7:43596115:TAA:T	donor_loss	1.0000
7:43608251:TCTAG:T	acceptor_loss	1.0000
7:43608253:TA:T	acceptor_loss	1.0000
7:43608254:A:AG	acceptor_gain	1.0000
7:43608255:G:A	acceptor_loss	1.0000
7:43608255:G:GA	acceptor_gain	1.0000
7:43608255:GT:G	acceptor_gain	1.0000
7:43608255:GTGCT:G	acceptor_gain	1.0000

AlphaMissense

2711 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:43595908:T:C	F72L	1.000
7:43595910:T:A	F72L	1.000
7:43595910:T:G	F72L	1.000
7:43595964:G:C	K90N	1.000
7:43595964:G:T	K90N	1.000
7:43596017:A:T	E108V	1.000
7:43608393:A:T	D186V	1.000
7:43608400:G:C	K188N	1.000
7:43608400:G:T	K188N	1.000
7:43619651:G:C	D207H	1.000
7:43619652:A:C	D207A	1.000
7:43619652:A:T	D207V	1.000
7:43619653:T:A	D207E	1.000
7:43619653:T:G	D207E	1.000
7:43619705:G:C	G225R	1.000
7:43623619:T:A	W247R	1.000
7:43623619:T:C	W247R	1.000
7:43623717:G:A	G250E	1.000
7:43595902:G:A	G70R	0.999
7:43595902:G:C	G70R	0.999
7:43595902:G:T	G70W	0.999
7:43595903:G:A	G70E	0.999
7:43595903:G:T	G70V	0.999
7:43595912:C:A	A73E	0.999
7:43595957:C:A	A88D	0.999
7:43595959:G:C	A89P	0.999
7:43595960:C:A	A89E	0.999
7:43595962:A:C	K90Q	0.999
7:43595962:A:G	K90E	0.999
7:43596017:A:C	E108A	0.999

dbSNP variants (sampled 300 via entrez): RS1000008037 (7:43615780 A>G), RS1000122265 (7:43602505 A>G), RS1000124924 (7:43590692 A>G), RS1000176967 (7:43591129 G>A), RS1000234734 (7:43583949 T>C,G), RS1000371042 (7:43581202 T>A,C), RS1000380196 (7:43599620 A>T), RS1000430053 (7:43625969 T>C), RS1000436364 (7:43597936 A>G), RS1000509570 (7:43607909 C>T), RS1000556924 (7:43615801 G>A), RS1000563677 (7:43614371 G>T), RS1000578952 (7:43606415 A>G), RS1000608997 (7:43616041 A>C), RS1000642061 (7:43607640 TC>T)

Disease associations

OMIM: gene MIM:604726 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST011743_76	HDL cholesterol levels in HIV infection	5.000000e-06
GCST90002396_384	Mean reticulocyte volume	2.000000e-18
GCST90002397_501	Mean spheric corpuscular volume	9.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4525 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 530,230 (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
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL2005186	BELUMOSUDIL	4	1,817
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL941	IMATINIB	4	111,611
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2
CHEMBL362558	LY-2090314	2
CHEMBL4073443	TOMIVOSERTIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL572878	TOZASERTIB	2
CHEMBL607707	PELITINIB	2
CHEMBL1084546	PF-00562271	1
CHEMBL1908397	KW-2449	1
CHEMBL1969664	AZD-1080	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Death-associated kinase (DAPK) family

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
AT-9283	Inhibition	8.0	pIC50
compound 7 [PMID: 34333981]	Inhibition	6.9	pIC50
tomivosertib	Inhibition	6.89	pIC50
BAY-985	Inhibition	6.51	pIC50

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
SCH772984	IC50	580 nM
BMS-387072	KD	1800 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer
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
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 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

486 potent at pChembl≥5 of 488 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	SUNITINIB
8.60	Ki	2.512	nM	CHEMBL1980995
8.54	Kd	2.9	nM	KW-2449
8.50	Ki	3.162	nM	CHEMBL1983111
8.50	Ki	3.162	nM	CHEMBL1984548
8.47	Kd	3.4	nM	LESTAURTINIB
8.40	Ki	3.981	nM	CHEMBL1973540
8.35	IC50	4.47	nM	CHEMBL5085430
8.31	Kd	4.9	nM	CHEMBL3334979
8.30	Kd	5	nM	CHEMBL4435393
8.20	Ki	6.31	nM	CHEMBL1994669
8.10	Ki	7.943	nM	CENISERTIB
8.10	Ki	7.943	nM	CHEMBL1992363
8.10	Ki	7.943	nM	CHEMBL379975
8.10	Ki	7.943	nM	CHEMBL1972290
8.05	Kd	9	nM	CHEMBL4549459
8.05	Kd	9	nM	CHEMBL5191892
8.00	IC50	10	nM	CHEMBL4126445
8.00	Kd	10	nM	CHEMBL4553949
8.00	IC50	10	nM	AT-9283
8.00	Ki	10	nM	CHEMBL1999931
7.96	IC50	11	nM	CHEMBL6042561
7.92	IC50	12	nM	CHEMBL3799585
7.92	IC50	12	nM	CHEMBL5573038
7.90	Ki	12.59	nM	CHEMBL1966343
7.90	Ki	12.59	nM	CHEMBL1966204
7.90	Ki	12.59	nM	CHEMBL2005475
7.90	Ki	12.59	nM	CHEMBL1985723
7.89	Kd	13	nM	CHEMBL3334980
7.89	IC50	12.8	nM	CHEMBL3774448
7.85	IC50	14	nM	CHEMBL4744680
7.85	IC50	14	nM	CHEMBL5995328
7.85	Kd	14	nM	STAUROSPORINE
7.82	IC50	15	nM	CHEMBL4436188
7.82	IC50	15	nM	CHEMBL5191892
7.82	IC50	15	nM	CHEMBL5895021
7.80	IC50	16	nM	CHEMBL5775584
7.80	Ki	15.85	nM	CHEMBL2001751
7.80	Ki	15.85	nM	CHEMBL1990162
7.80	Ki	15.85	nM	CHEMBL1972142
7.80	Ki	15.85	nM	CHEMBL2005718
7.80	Ki	15.85	nM	CHEMBL1987261
7.77	IC50	17	nM	CHEMBL5579785
7.75	IC50	18	nM	CHEMBL5574990
7.72	IC50	19	nM	CHEMBL5564156
7.72	IC50	19	nM	CHEMBL5785929
7.72	IC50	19	nM	CHEMBL5857177
7.72	IC50	19	nM	CHEMBL5946905
7.70	IC50	20	nM	CHEMBL5569603
7.70	IC50	20	nM	CHEMBL5571334

PubChem BioAssay actives

161 with measured affinity, of 1704 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
Sunitinib	435790: Binding constant for DRAK1 kinase domain	kd	0.0010	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624968: Binding constant for DRAK1 kinase domain	kd	0.0029	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	507903: Binding affinity to DRAK1	kd	0.0034	uM
N-[3-[[5-bromo-4-[3-(cyclobutanecarbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1823772: Displacement of tracer K9 from NLuc fused DRAK1 (unknown origin) expressed in HEK293 cells by NanoBRET assay	ic50	0.0045	uM
N-[5-(3,4-dimethoxyphenyl)thieno[2,3-b]pyridin-3-yl]cyclohexanecarboxamide	1162293: Binding affinity to DRAK1 (unknown origin)	kd	0.0049	uM
1-[4-[(1R)-1-[2-[[6-[1-(cyclopropylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582169: Inhibition of wild-type human partial length DRAK1 (R32 to E363 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0050	uM
3,3,3-trifluoro-1-[4-[[2-[[6-(3-methyl-1,2,4-oxadiazol-5-yl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]propan-1-one	1582169: Inhibition of wild-type human partial length DRAK1 (R32 to E363 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0090	uM
N-[(1S)-1-pyridin-4-ylethyl]-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.12,6.017,20]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide	1911001: Binding affinity to human N-terminal His-tagged/ TEV cleavage fused DRAK1 (39 to 369 residues) expressed in Escherichia coli by isothermal titration calorimetry	kd	0.0090	uM
3,3,3-trifluoro-1-[4-[(1R)-1-[2-[[6-(3-methyl-1,2,4-oxadiazol-5-yl)-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]propan-1-one	1582169: Inhibition of wild-type human partial length DRAK1 (R32 to E363 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0100	uM
N-[5-[2-[(1S)-1-cyclopropylethyl]-7-methyl-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]acetamide	1497498: Inhibition of recombinant human full length GST-tagged DRAK1 expressed in baculovirus expression system	ic50	0.0100	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	412608: Inhibition of DRAK1	ic50	0.0100	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]butanamide	1298194: Inhibition of DRAK1 (unknown origin)	ic50	0.0120	uM
N-propan-2-yl-5-[[4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]pyridine-2-carboxamide	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0120	uM
(5Z)-5-(quinolin-6-ylmethylidene)-2-sulfanylidene-1,3-thiazolidin-4-one	1284873: Inhibition of STK17A (unknown origin)	ic50	0.0128	uM
N-[2-(3,4-dimethoxyphenyl)thieno[2,3-b]pyrazin-7-yl]cyclohexanecarboxamide	1162293: Binding affinity to DRAK1 (unknown origin)	kd	0.0130	uM
N-[(1S)-1-cyclopropyl-2,2,2-trifluoroethyl]-4-[6-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	2156563: Inhibition of human recombinant DRAK1	ic50	0.0140	uM
(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	435790: Binding constant for DRAK1 kinase domain	kd	0.0140	uM
1-[4-[(1R)-1-[2-[[6-[1-(cyclobutylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582169: Inhibition of wild-type human partial length DRAK1 (R32 to E363 residues) expressed in bacterial expression system by Kinomescan method	ic50	0.0150	uM
2-[4-[5-[[4-[2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]quinazolin-6-yl]pyrimidin-2-yl]amino]-2-pyridinyl]piperidin-1-yl]ethanol	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0170	uM
N-(6-piperazin-1-yl-3-pyridinyl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0180	uM
4-(2-morpholin-4-ylquinazolin-6-yl)-N-(1-piperidin-4-ylpyrazol-4-yl)pyrimidin-2-amine	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0190	uM
4-[[4-(2-morpholin-4-ylquinazolin-6-yl)pyrimidin-2-yl]amino]-N-propan-2-ylbenzamide	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0200	uM
N-(1-piperidin-4-ylpyrazol-4-yl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0200	uM
4-(2-morpholin-4-ylquinazolin-6-yl)-N-(4-piperazin-1-ylphenyl)pyrimidin-2-amine	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0200	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]cyclopropanecarboxamide	1298194: Inhibition of DRAK1 (unknown origin)	ic50	0.0210	uM
N-tert-butyl-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.12,6.017,20]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide	1911001: Binding affinity to human N-terminal His-tagged/ TEV cleavage fused DRAK1 (39 to 369 residues) expressed in Escherichia coli by isothermal titration calorimetry	kd	0.0210	uM
2-[4-[4-[[5-fluoro-4-(2-morpholin-4-ylquinazolin-6-yl)pyrimidin-2-yl]amino]pyrazol-1-yl]piperidin-1-yl]ethanol	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0210	uM
N-propan-2-yl-4-[[4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]benzamide	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0230	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435790: Binding constant for DRAK1 kinase domain	kd	0.0240	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]-3,3-dimethylbutanamide	1298194: Inhibition of DRAK1 (unknown origin)	ic50	0.0240	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]-3,5-dinitrobenzamide	1298194: Inhibition of DRAK1 (unknown origin)	ic50	0.0240	uM
3,3,3-trifluoro-1-[4-[[2-[[6-[6-(methylamino)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]methyl]piperazin-1-yl]propan-1-one	1582169: Inhibition of wild-type human partial length DRAK1 (R32 to E363 residues) expressed in bacterial expression system by Kinomescan method	ic50	0.0250	uM
4-[[5-fluoro-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]-N-propan-2-ylbenzamide	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0250	uM
methyl 4-[5-[[4-[2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]quinazolin-6-yl]pyrimidin-2-yl]amino]-2-pyridinyl]piperidine-1-carboxylate	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0290	uM
3,3,3-trifluoro-1-[4-[(1R)-1-[2-[[6-[6-(methoxymethyl)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]propan-1-one	1582169: Inhibition of wild-type human partial length DRAK1 (R32 to E363 residues) expressed in bacterial expression system by Kinomescan method	ic50	0.0300	uM
N-(1-phenylethyl)-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.12,6.017,20]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide	1911002: Inhibition of human N-terminal His-tagged/ TEV cleavage fused DRAK1 (39 to 369 residues) expressed in Escherichia coli using KKLNRTLSFAEPG peptide as substrate in presence of [gamma-33P]ATP by radiometric based scintillation proximity assay	ic50	0.0310	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	624968: Binding constant for DRAK1 kinase domain	kd	0.0320	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]-2,2-dimethylpropanamide	1298194: Inhibition of DRAK1 (unknown origin)	ic50	0.0320	uM
N-(4-morpholin-4-ylphenyl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0430	uM
N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	1823772: Displacement of tracer K9 from NLuc fused DRAK1 (unknown origin) expressed in HEK293 cells by NanoBRET assay	ic50	0.0432	uM
2-[(1S,4S)-5-[5-[[5-fluoro-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanol	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0480	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]pentanamide	1298194: Inhibition of DRAK1 (unknown origin)	ic50	0.0510	uM
N-[4-(4-methylpiperazin-1-yl)phenyl]-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0510	uM
N-(4-piperazin-1-ylphenyl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0550	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256568: Average Binding Constant for STK17A; NA=Not Active at 10 uM	kd	0.0570	uM
N-[3-[[4-[3-(cyclobutanecarbonylamino)propylamino]-5-cyclopropylpyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1823772: Displacement of tracer K9 from NLuc fused DRAK1 (unknown origin) expressed in HEK293 cells by NanoBRET assay	ic50	0.0582	uM
methyl 4-[5-[[4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]-2-pyridinyl]piperidine-1-carboxylate	2094978: Inhibition of STK17A (unknown origin) in presence of ATP	ic50	0.0660	uM
(15R)-15-methyl-5-(6-methyl-3-pyridinyl)-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	2167728: Inhibition of DRAK1 (unknown origin)	ic50	0.0710	uM
4-[[5-(4-fluorophenyl)-1H-pyrazol-3-yl]amino]benzamide	389090: Binding affinity to human DRAK1	kd	0.0960	uM
5-(3-amino-5-thiophen-3-ylthieno[2,3-b]pyridin-2-yl)-3H-1,3,4-oxadiazole-2-thione	1446748: Binding affinity to DRAK1 (unknown origin)	kd	0.0990	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Benzo(a)pyrene	increases expression	4
Aflatoxin B1	affects expression, decreases methylation, increases expression	4
mercuric bromide	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Estradiol	affects expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
sotorasib	decreases expression, affects cotreatment	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
glycidyl methacrylate	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
periodate-oxidized adenosine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

305 unique, capped per target: 304 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009907	Binding	Inhibition of DRAK1	Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. — J Med Chem
CHEMBL1963717	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK17A	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HN	Abcam HeLa STK17A KO	Cancer cell line	Female
CVCL_TQ75	HAP1 STK17A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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