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

HCK (P08631) - Overview - Molecular Target Synopsis

Protein


HCK, Tyrosine-protein kinase HCK
Enzyme Classification 2.7.10.2
UniProt P08631

Also Known as HCK_HUMAN, HCK

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. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with VAV1, WAS and RAPGEF1 (By similarity). This interaction stimulates its tyrosine-kinase activity. Interacts with ARRB1 and ARRB2. Interacts with ADAM15. Interacts with FASLG. Interacts with CBL. Interacts with FCGR1A; the interaction may be indirect. Interacts with IL6ST. Interacts (via SH3 domain) with ELMO1. Interacts (via SH3 domain) with TP73. Interacts with YAP1. Interacts with ABL1 and ITGB1, and thereby recruits ABL1 to activated ITGB1. Interacts (via SH3 domain) with WDCP.

5ZJ6
CRYSTAL STRUCTURE OF HCK KINASE COMPLEXED WITH A PYRROLO-PYRIMIDINE INHIBITOR 7-[TRANS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL]-5-(4- PHENOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE
RCSB/PDB
Inspect Structure
See all 3D Structures for HCK

Isoforms / Transcripts (Protein Coding)


Drugs


HCK is targeted by Approved Drugs Dasatinib, Bosutinib, Vandetanib. (see details)
Dasatinib
Bosutinib
Vandetanib

Sub-cellular localization


UniProt: HCK is active in the following subcellular-locations: caveola, cell junction, cell membrane, cell projection, cytoplasm, cytoplasmic vesicle, cytoskeleton, cytosol, focal adhesion, golgi apparatus, lysosome, membrane, nucleus, podosome membrane, secretory vesicle.
GO terms: HCK is active in the following subcellular-locations: caveola, cell projection, cytoskeleton, cytosol, extrinsic component of cytoplasmic side of plasma membrane, focal adhesion, Golgi apparatus, lysosome, nucleoplasm, plasma membrane, transport vesicle.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project HCK has gain in 7 cell-lines, loss in 0 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SR, HL_60, OVCAR_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: TMD8, OCI-LY-3, MV-4-11

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: CD14-positive monocyte, CD20-positive B cell, SK-N-SH

(see details)

RNA Interference


HCK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB134VI, MCF7. (see details)

3D Structures


For HCK there are:
38 structures (66 chains) solved
25 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


HCK has been screened with 1167 compounds (2146 bioactivities), 221 compounds have bioactivities that show binding affinity of <= 500nM (242 bioactivities). (see details)