PLEK Gene (Pleckstrin) - NCBI, Ensembl, UniProt, OMIM, HGNC, ClinVar, COSMIC

PLEK (pleckstrin) is a protein-coding gene located on chromosome 2p14. It encodes pleckstrin, a 47 kDa protein predominantly expressed in platelets and leukocytes. Pleckstrin contains two pleckstrin homology (PH) domains and a DEP domain, and serves as a major substrate for protein kinase C (PKC) during platelet activation. It plays a critical role in cytoskeletal reorganization, cell adhesion, and signal transduction pathways involving phosphoinositides. Mutations in PLEK have been associated with immune and hematologic disorders, including Wiskott-Aldrich syndrome and leukocyte adhesion deficiency type III.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Platelet activation

• signaling and aggregation (Reactome: R-HSA-76002)

• Fcgamma receptor (FCGR) dependent phagocytosis (Reactome: R-HSA-2029480)

• Signaling by GPCR (Reactome: R-HSA-372790)

Pleckstrin is a 350-amino acid protein with two PH domains (N-terminal and C-terminal) and a central DEP domain. It is a major PKC substrate in platelets, where phosphorylation at Ser113, Ser117, and Thr114 regulates its membrane localization and interaction with phosphoinositides. Pleckstrin links receptor activation to cytoskeletal remodeling, cell spreading, and granule secretion. In leukocytes, it modulates integrin activation and chemotaxis. Structural studies show that the N-terminal PH domain binds PIP3 with high affinity, while the C-terminal PH domain binds PIP2. The DEP domain is involved in membrane targeting and protein-protein interactions.