Details of the Target

General Information of Target

Target ID LDTP02293
Target Name Tyrosine-protein kinase HCK (HCK)
Gene Name HCK
Gene ID 3055
Synonyms
Tyrosine-protein kinase HCK; EC 2.7.10.2; Hematopoietic cell kinase; Hemopoietic cell kinase; p59-HCK/p60-HCK; p59Hck; p61Hck
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIK
PGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSL
ATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSY
SLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVP
CMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVE
AFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLID
FSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFP
IKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPE
NCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP
Target Type
Patented-recorded
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Tyr protein kinase family, SRC subfamily
Subcellular location
Lysosome; Cell membrane; Cytoplasmic vesicle, secretory vesicle
Function
Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.
TTD ID
T31406
Uniprot ID
P08631
DrugMap ID
TT42OGM
Ensemble ID
ENST00000375852.5
HGNC ID
HGNC:4840
ChEMBL ID
CHEMBL3234

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
IGROV1 SNV: p.R156C .
JHH7 SNV: p.L355F .
MELHO SNV: p.I59N .
NCIH146 SNV: p.E90D .
NCIH2291 SNV: p.P464T .
NUGC3 SNV: p.A403V .
PANC0403 SNV: p.A391T .
SW1783 SNV: p.R190Q .
SW756 SNV: p.E140A .
TOV21G SNV: p.R478S .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C482(1.91)  LDD3333  [1]
ATP probe
 Probe Info  		N.A.  LDD0199  [2]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DA-2
 Probe Info  		N.A.  LDD0072  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 EoL-1 C395(1.74)  LDD2324  [1]
 LDCM0023  KB03 EoL-1 C395(2.60)  LDD2741  [1]
 LDCM0024  KB05 MOLM-13 C482(1.91)  LDD3333  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 13 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Anterior gradient protein 2 homolog (AGR2) AGR family O95994
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5) Lipoxygenase family P09917
Serine/threonine-protein kinase PAK 2 (PAK2) STE Ser/Thr protein kinase family Q13177
Mast/stem cell growth factor receptor Kit (KIT) Tyr protein kinase family P10721
Epidermal growth factor receptor (EGFR) Tyr protein kinase family P00533
Receptor tyrosine-protein kinase erbB-3 (ERBB3) Tyr protein kinase family P21860
Focal adhesion kinase 1 (PTK2) Tyr protein kinase family Q05397
Zinc finger protein RFP (TRIM27) TRIM/RBCC family P14373
Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) . O14672
Disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) . O43184
Disintegrin and metalloproteinase domain-containing protein 15 (ADAM15) . Q13444
E3 ubiquitin-protein ligase CBL (CBL) . P22681
Probable E3 ubiquitin-protein ligase makorin-3 (MKRN3) . Q13064
Transporter and channel
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Heat shock protein HSP 90-beta (HSP90AB1) Heat shock protein 90 family P08238
AP-4 complex accessory subunit Tepsin (TEPSIN) . Q96N21
Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC) . Q9HD26
Wolframin (WFS1) . O76024
Transcription factor
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Oligodendrocyte transcription factor 1 (OLIG1) . Q8TAK6
Zinc finger and SCAN domain-containing protein 4 (ZSCAN4) . Q8NAM6
Other
Click To Hide/Show 37 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
BPI fold-containing family A member 1 (BPIFA1) Plunc family Q9NP55
Coiled-coil domain-containing protein 88B (CCDC88B) CCDC88 family A6NC98
Cancer/testis antigen 1 (CTAG1A; CTAG1B) CTAG/PCC1 family P78358
Cysteine-rich tail protein 1 (CYSRT1) CYSRT1 family A8MQ03
Neuferricin (CYB5D2) Cytochrome b5 family Q8WUJ1
Protein INCA1 (INCA1) INCA family Q0VD86
Keratin, type I cuticular Ha1 (KRT31) Intermediate filament family Q15323
Keratin, type I cuticular Ha4 (KRT34) Intermediate filament family O76011
Keratin, type I cuticular Ha5 (KRT35) Intermediate filament family Q92764
Keratin, type I cytoskeletal 40 (KRT40) Intermediate filament family Q6A162
KH domain-containing, RNA-binding, signal transduction-associated protein 1 (KHDRBS1) KHDRBS family Q07666
Keratin-associated protein 1-1 (KRTAP1-1) KRTAP type 1 family Q07627
Keratin-associated protein 1-3 (KRTAP1-3) KRTAP type 1 family Q8IUG1
Keratin-associated protein 10-7 (KRTAP10-7) KRTAP type 10 family P60409
Keratin-associated protein 10-8 (KRTAP10-8) KRTAP type 10 family P60410
Keratin-associated protein 10-9 (KRTAP10-9) KRTAP type 10 family P60411
Keratin-associated protein 3-1 (KRTAP3-1) KRTAP type 3 family Q9BYR8
Microtubule-associated tumor suppressor candidate 2 (MTUS2) MTUS1 family Q5JR59
NACHT, LRR and PYD domains-containing protein 12 (NLRP12) NLRP family P59046
Notch homolog 2 N-terminal-like protein A (NOTCH2NLA) NOTCH family Q7Z3S9
Notch homolog 2 N-terminal-like protein C (NOTCH2NLC) NOTCH family P0DPK4
Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3) PI3K p85 subunit family Q92569
Midkine (MDK) Pleiotrophin family P21741
Paraneoplastic antigen Ma1 (PNMA1) PNMA family Q8ND90
Tektin-4 (TEKT4) Tektin family Q8WW24
WAS/WASL-interacting protein family member 1 (WIPF1) Verprolin family O43516
Thyroid receptor-interacting protein 6 (TRIP6) Zyxin/ajuba family Q15654
Actin nucleation-promoting factor WAS (WAS) . P42768
Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 (ASAP1) . Q9ULH1
Engulfment and cell motility protein 1 (ELMO1) . Q92556
Fibroblast growth factor receptor substrate 3 (FRS3) . O43559
Four and a half LIM domains protein 5 (FHL5) . Q5TD97
Heat shock factor 2-binding protein (HSF2BP) . O75031
Keratinocyte proline-rich protein (KPRP) . Q5T749
Programmed cell death 6-interacting protein (PDCD6IP) . Q8WUM4
Puratrophin-1 (PLEKHG4) . Q58EX7
Son of sevenless homolog 1 (SOS1) . Q07889

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bosutinib Small molecular drug DB06616
Fostamatinib Small molecular drug DB12010
Investigative
Click To Hide/Show 5 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Phosphonotyrosine Small molecular drug DB01962
Pmid15546730c2 Small molecular drug D08RZB
Pp121 Small molecular drug D03EHM
Quercetin Small molecular drug DB04216
1-ter-butyl-3-p-tolyl-1h-pyrazolo[34-d]Pyrimidin-4-ylamine . DB01809
Patented
Click To Hide/Show 9 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
3-(6-allyloxy-2-naphthyl)-1-(4-piperidylmethyl)Pyrazolo[3,4-d]Pyrimidin-4-amine Small molecular drug D07FAF
Bk3 Small molecular drug D04XHJ
Bk7 Small molecular drug D0Y9PK
Doramapimod Small molecular drug D05CDF
Sb19065 Small molecular drug D0D5PL
Unii-i92mu0v408 Small molecular drug D07PDQ
Us8933228, 3 Small molecular drug D0B7VP
Us8933228, Ref 2 Small molecular drug D0Y4TK
Us9108950, 1 Small molecular drug D0H0SM

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
3 Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes. J Am Chem Soc. 2012 Feb 15;134(6):3001-14. doi: 10.1021/ja208518u. Epub 2012 Feb 1.