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Ank2

Developmental stage

Expressed in neonatal developing ventricular cardiomyocytes as well as adult cardiomyocytes.

Domain

The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin's function other than binding to spectrin (By similarity).

Function

Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions (PubMed:19109891). In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites (PubMed:12571597). Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:15262991). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (PubMed:19007774). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (PubMed:27718357).

Post-translational modifications

Phosphorylated at multiple sites by different protein kinases and each phosphorylation event regulates the protein's structure and function.

Tissue Specificity

Detected in eye lens fiber cells (at protein level) (PubMed:21745462). In the retina, expressed in the inner segments of rod photoreceptors (PubMed:19007774). Expressed in cardiomyocytes, as well as in skeletal muscles (PubMed:12571597, PubMed:17940615, PubMed:27718357). Also detected in brain and pancreas, as well as in kidney and spleen (at protein level) (PubMed:12571597, PubMed:17940615, PubMed:8253844). In the pancreas, highly expressed in islets, predominantly in beta cells, but low expression, if any in acinar cells (at protein level) (PubMed:17940615). In the central nervous system, expressed in the corpus callosum and in cerebellar Purkinje neurons (at protein level) (PubMed:17940615, PubMed:27718357). Expressed in lung and, at low levels, in testes (at protein level) (PubMed:17940615).

Cellular localization

Alternative names

AnkB, Ank2, Ankyrin-2, ANK-2, Ankyrin-B, Brain ankyrin

swissprot:Q8C8R3