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FLASH GENE

Symbol

PPP1R1B

contributors: mct/npt - updated : 19-07-2008

HGNC name	protein phosphatase 1, regulatory (inhibitor) subunit 1B
HGNC id	9287

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	97.00 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed DARPP-32 or variant 1 - - 1841 - 204 expressed in medium-sized spiny neurons and overexpressed in gastric carcinoma Beckler, Belkhiri (2008) DARRPt or variant 2 - - 1502 - 168 overexpressed in gastric cancers EL Rifai, Belkhiri (2008) lacks the phosphorylation site related to protein phosphatase 1 inhibition but maintains the phosphorylation site with the protein kinase A inhibitory effect promotes cancer cell survival by up-regulation of BCL2 through AKT-dependent mechanism

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine       highly   stomach       highly Nervous brain basal nuclei caudate nucleus   highly   brain forebrain cerebral cortex   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

Other

HOMOLOGY

interspecies	homolog to murine Ppp1r1b
	homolog to C.elegans T23B3.5

Homologene

FAMILY

protein phosphatase inhibitor 1 family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	mainly nuclear when Ser 97 is dephosphorylated, whereas it is preferentially cytoplasmic when phosphorylated by CNSK2A1
	drugs of abuse and food self-administration induce nuclear accumulation in striatal neurons

basic FUNCTION	inhibitor of protein phosphatase 1 and PKA
	playing a central role in regulating the efficacy of dopaminergic neurotransmission
	a key factor in the phosphorylation of histone H3, a component of the nucleosomal response that is essential for gene expression
	may be a tumor suppressor in oral premalignant and malignant lesions
	playing a role in the interactions of dopamine and glutamate in the neostriatum
	antiapoptotic gene in upper gastrointestinal carcinomas
	may be a tumor suppressor in in oral premalignant and malignant lesions
	dual-function protein kinase/phosphatase inhibitor that is involved in striatal signaling
	pivotal integrator of information in dopaminoceptive neurons, regulating the response to neuroleptics, psychotomimetics, and drugs of abuse, and affecting striatal function and plasticity (Meyer-Lindenberg 2007)
	might mediate multidrug resistance of gastric cancer through regulation of permeability glycoprotein (P-gp) and ZNRD1 (Hong 2007)
	plays a pivotal role in cognitive function and possibly in the pathogenesis of schizophrenia (Meyer-Lindenberg 2007)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	PP1
	changes the usage of TRA2B dependent alternative exons in a concentration-dependent manner, suggesting that the PPP1R1B:TRA2B interaction is a molecular link between signaling pathways and pre-mRNA processing

cell & other

REGULATION

activated by

CAMP dependent phosphorylation produced by dopamine stimulation

inhibited by

NMDA-induced dephosphorylation

Other	phosphorylation on threonine 75 by CDK5 leads PPP1R1B inhibitor of PKA
	phosphorylation on threonine 34 by PKA leads to PPP1R1B inhibitor of protein phosphatase 1
	regulated by glutamate in neostriatal neurons involving activation of multiple signaling cascades
	phosphorylation at threonine 34 is essential for mediating the effects of both psychostimulant and antipsychotic drugs
	regulation of its phosphorylation in striatal neurons, by cocaine and haloperidol and a variety of agents

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in leukoplakia, and oral squamous cell carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target	regulation of the nuclear accumulation of PPP1R1B may be important to the functions or dysfunctions of dopamine that involve transcription-dependent long-term plasticity, including neuroleptic- and L-DOPA-induced dyskinesia, and other diseases of the basal ganglia

ANIMAL & CELL MODELS

Darpp 32 knockout mice