PPP1R12A

PPP1R12A (Protein Phosphatase 1 Regulatory Subunit 12A) is a protein coding gene. Diseases associated with PPP1R12A include Infratentorial Cancer and Lacrimal Apparatus Disease. Among its related pathways are Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases and Focal Adhesion. Gene Ontology annotations related to this gene include protein kinase binding and enzyme inhibitor activity. An important paralog of the gene is PPP1R12B.

Full Name

Protein Phosphatase 1 Regulatory Subunit 12A

Function

Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity.

Biological Process

Cellular response to xenobiotic stimulusIEA:Ensembl
Centrosome cycleManual Assertion Based On ExperimentIMP:UniProtKB
Mitotic cell cycleManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of catalytic activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of myosin-light-chain-phosphatase activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Protein dephosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cell adhesionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of myosin-light-chain-phosphatase activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of nucleocytoplasmic transportIEA:Ensembl
Signal transductionIEA:InterPro

Cellular Location

Cytoplasm
Cytoplasm, cytoskeleton, stress fiber
Also along actomyosin filaments.

Involvement in disease

Genitourinary and/or brain malformation syndrome (GUBS):
An autosomal dominant syndrome characterized by multiple congenital anomalies including urogenital malformations and brain abnormalities ranging from agenesis of the corpus callosum to anencephaly.

PTM

Phosphorylated by CIT (Rho-associated kinase) (By similarity).
Phosphorylated cooperatively by ROCK1 and CDC42BP on Thr-696. Phosphorylated on upon DNA damage, probably by ATM or ATR. In vitro, phosphorylation of Ser-695 by PKA and PKG appears to prevent phosphorylation of the inhibitory site Thr-696, probably mediated by PRKG1. Phosphorylation at Ser-445, Ser-472 and Ser-910 by NUAK1 promotes interaction with 14-3-3, leading to inhibit interaction with myosin light chain MLC2, preventing dephosphorylation of MLC2. May be phosphorylated at Thr-696 by DMPK; may inhibit the myosin phosphatase activity. Phosphorylated at Ser-473 by CDK1 during mitosis, creating docking sites for the POLO box domains of PLK1. Subsequently, PLK1 binds and phosphorylates PPP1R12A.