Function: Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca2+ while binding to PIP2 is Ca2+ insensitive. Ref.1 Ref.9 Ref.10
Subunit structure: Monomer. Binds NRXN1. Interacts with RAB27B
By similarity. Binds RAB27A that has been activated by GTP-binding. Ref.1 Ref.11
Subcellular location: Isoform 1: Cytoplasm. Cell membrane. Note: Recruited on vesicular structures in cytotoxic T-lymphocytes (CTL) by RAB27A. Ref.1 Ref.9 Ref.10Isoform 4: Cell membrane. Note: In the pancreatic alpha cells distributed in both peripheral and anterior regions. Localizes on the glucagon granules in the cell periphery. Ref.1 Ref.9 Ref.10
Tissue specificity: Isoform 1 is expressed in hematopoietic lineages with a strong expression in CD4 and CD8 T-lymphocytes. It is also widely expressed in nonhematopoietic tissues. Isoform 5 is expressed only in nonhematopoietic tissues. Isoform 4 is expressed in pancreatic alpha cells. Ref.1 Ref.9 Ref.10
Domain: The RabBD domain mediates interaction with RAB27A and recruitment on to vesicular structures in cytotoxic T-lymphocytes (CTL). Ref.1 Ref.9The C2 1 domain mediates binding to phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2) and localization to the cell membrane. Ref.1 Ref.9
Post-translational modification: Isoform 1 is highly susceptible to proteolytic degradation and is stabilized by the interaction with RAB27A.
Sequence similarities: Contains 2 C2 domains.Contains 1 RabBD (Rab-binding) domain.
Sequence caution: The sequence AAR25619.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence BAA90989.1 differs from that shown. Reason: Probable cloning artifact.The sequence BAB13423.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.The sequence BAB13423.1 differs from that shown. Reason: Frameshift at position 13. The sequence BAB13423.1 differs from that shown. Reason: Sequencing errors.The sequence BAD18516.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
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