PPP3CA Antibody - #DF6208

Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Many of the substrates contain a PxIxIT motif and/or a LxVP motif. In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation. In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion. Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1. In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32. May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins.

Cytoplasm. Cell membrane>Peripheral membrane protein. Cell membrane>Sarcolemma. Cytoplasm>Myofibril>Sarcomere>Z line. Cell projection>Dendritic spine.
Note: Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle (By similarity). Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel activation (PubMed:22343722).

Expressed in keratinocytes (at protein level).

Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CA/calcineurin A, calcineurin B and calmodulin (By similarity). Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B. Interacts (via calmodulin-binding domain) with CALM1/calmodulin; the interaction depends on calmodulin binding to Ca(2+) Ref.30,. Forms a complex composed of MYOZ2 and ACTN1 (By similarity). Within the complex interacts with MYOZ2. Interacts with MYOZ1. Interacts with MYOZ3. Interacts with CIB1; the interaction increases upon cardiomyocyte hypertrophy (By similarity). Interacts with CHP1 and CHP2 (By similarity). Interacts with CRTC1. Interacts with CRTC2. Interacts with DNM1L; the interaction dephosphorylates DNM1L and promotes its translocation to mitochondria. Interacts with CMYA5; this interaction represses calcineurin activity in muscle (By similarity). Interacts (constitutively active form) with SYNPO2. Interacts with scaffold protein AKAP5 (via IAIIIT motif); the interaction recruits PPP3CA to the plasma membrane following L-type Ca(2+)-channel activation. Interacts with NFATC2. Interacts with RCAN3. Interacts with PPIA. Interacts with RCAN1. Interacts with UNC119 (By similarity).

The autoinhibitory domain prevents access to the catalytic site.

The autoinhibitory segment prevents access to the substrate binding site.

Possible isomerization of Pro-309 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.

Belongs to the PPP phosphatase family. PP-2B subfamily.