UniProt functional annotation for P30153



	UniProt functional annotation for P30153

UniProt code: P30153.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887). {ECO:0000269|PubMed:15525651, ECO:0000269|PubMed:16580887}.

Subunit: PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites (By similarity). Interacts with IPO9 (PubMed:12670497). Interacts with TP53 and SGO1 (PubMed:17245430, PubMed:16580887). Interacts with PLA2G16; this interaction might decrease PP2A activity (PubMed:17374643). Interacts with CTTNBP2NL (PubMed:18782753). Interacts with GNA12; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (PubMed:15525651). Interacts with CIP2A; this interaction stabilizes CIP2A (PubMed:28174209). Interacts with PABIR1/FAM122A (PubMed:27588481). Interacts with ADCY8; antagonizes interaction between ADCY8 and calmodulin (By similarity). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2 (PubMed:17974561). {ECO:0000250|UniProtKB:Q32PI5, ECO:0000250|UniProtKB:Q76MZ3, ECO:0000269|PubMed:12670497, ECO:0000269|PubMed:15525651, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17245430, ECO:0000269|PubMed:17374643, ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18394995, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:27588481, ECO:0000269|PubMed:28174209, ECO:0000269|PubMed:30611118}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q32PI5}. Nucleus {ECO:0000269|PubMed:30611118}. Chromosome, centromere {ECO:0000269|PubMed:16580887}. Lateral cell membrane {ECO:0000269|PubMed:15525651}. Cell projection, dendrite {ECO:0000269|PubMed:15525651}. Note=Centromeric localization requires the presence of BUB1. {ECO:0000269|PubMed:16580887}.

Domain: Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.

Disease: Mental retardation, autosomal dominant 36 (MRD36) [MIM:616362]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:26168268}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the phosphatase 2A regulatory subunit A family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887). {ECO:0000269\|PubMed:15525651, ECO:0000269\|PubMed:16580887}.


Subunit:		PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites (By similarity). Interacts with IPO9 (PubMed:12670497). Interacts with TP53 and SGO1 (PubMed:17245430, PubMed:16580887). Interacts with PLA2G16; this interaction might decrease PP2A activity (PubMed:17374643). Interacts with CTTNBP2NL (PubMed:18782753). Interacts with GNA12; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (PubMed:15525651). Interacts with CIP2A; this interaction stabilizes CIP2A (PubMed:28174209). Interacts with PABIR1/FAM122A (PubMed:27588481). Interacts with ADCY8; antagonizes interaction between ADCY8 and calmodulin (By similarity). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2 (PubMed:17974561). {ECO:0000250\|UniProtKB:Q32PI5, ECO:0000250\|UniProtKB:Q76MZ3, ECO:0000269\|PubMed:12670497, ECO:0000269\|PubMed:15525651, ECO:0000269\|PubMed:16580887, ECO:0000269\|PubMed:17245430, ECO:0000269\|PubMed:17374643, ECO:0000269\|PubMed:17974561, ECO:0000269\|PubMed:18394995, ECO:0000269\|PubMed:18782753, ECO:0000269\|PubMed:27588481, ECO:0000269\|PubMed:28174209, ECO:0000269\|PubMed:30611118}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q32PI5}. Nucleus {ECO:0000269\|PubMed:30611118}. Chromosome, centromere {ECO:0000269\|PubMed:16580887}. Lateral cell membrane {ECO:0000269\|PubMed:15525651}. Cell projection, dendrite {ECO:0000269\|PubMed:15525651}. Note=Centromeric localization requires the presence of BUB1. {ECO:0000269\|PubMed:16580887}.
Domain:		Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.
Disease:		Mental retardation, autosomal dominant 36 (MRD36) [MIM:616362]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269\|PubMed:25533962, ECO:0000269\|PubMed:26168268}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the phosphatase 2A regulatory subunit A family. {ECO:0000305}.