PPP1R1B (protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein, DARPP-32))

2007-12-01   Wael El-Rifai , Abbes Belkhiri 

Department of Surgery, Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee


Atlas Image
Genomic localization of DARPP-32, with FISH using BAC clone CTD-2019C10 (Research Genetics) that contains DARPP-32, using fluorescent in situ hybridization (FISH) on a normal metaphase spread. Arrows indicate the green FITC hybridization signals. The ideogram of chromosome 17 together with the inverted DAPI banding and FISH hybridization signals on the two chromosome 17. The FISH signals localize to chromosome band 17q12-q21.


Atlas Image
This schematic illustration shows the genomic structure of DARPP-32 and its transcriptional splice variant that encodes a truncated DARPP-32 protein (t-DARPP). The sequence length of the mRNA of DARPP-32 is 1,841 bp, including the untranslated 3 and 5 ends. The length of the transcriptional splice variant of DARPP-32 that encodes a truncated DARPP-32 protein (t-DARPP) is 1,502 bp. DARPP-32 and t-DARPP share an identical sequence from exon 2 to the 3 end. Each of them has seven exons. Each of DARPP-32 and t-DARPP transcripts has its own unique exon 1, where exon1 in DARPP-32 includes 548 bp whereas exon1 in t-DARPP consists of unique 207 bp that does not match with exon1 of DARPP-32.


DARPP-32 gene is located at 17q12. Both full length DARPP-32 and its transcriptional splice variant (t-DARPP) consist of seven exons where only exon 1 is unique in each of the two transcripts.


2 alternative transcripts





DARPP-32 encodes a protein of 204 amino acids (about 32 kD), whereas t-DARPP encodes a 168 amino acid protein (about 28 kD). DARPP-32 contains four phosphorylation sites at Thr34, Thr75, Ser102, and Ser137, whereas t-DARPP lacks the Thr34 phosphorylation site of DARPP-32. The schematic illustration, shown above, demonstrates the phosphorylation sites of DARPP-32 and t-DARPP shown in yellow color.


DARPP-32 protein is highly expressed in medium-sized spiny neurons of the neostriatum. DARPP-32 was characterized as a major target for dopamine and protein kinase A signaling. Modulation of DARPP-32 phosphorylation state provides a molecular mechanism for integrating signals through several neurotransmitters and steroid hormones that stimulate dopaminoceptic neurons in various regions of the brain. Activation of PKA or PKG leads to phosphorylation of DARPP-32 at Thr34 and subsequently converts DARPP-32 into a potent inhibitor of protein phosphatase-1 (PP-1). Cdk5 can also phosphorylate DARPP-32 at Thr75 and this converts DARPP-32 into a PKA inhibitor. Expression of t-DARPP in the brain was not reported.
Protein and mRNA expression of both DARPP-32 and t-DARPP are expressed at varying levels in several types of normal epithelial tissues outside the brain. DARPP-32 and t-DARPP are over-expressed in carcinomas of the breast, prostate, colon, and stomach compared with normal tissue samples. The observation that DARPP-32 and t-DARPP are frequently over-expressed in common subtypes of human cancers suggests that these proteins may play a role in tumorigenesis. The expression of t-DARPP has been shown to increase the AKT kinase activity and regulate the levels of BCL2 in cancer cells. This effect is believed to mediate resistance to drug-induced apoptosis.








Implicated in

Entity name
Dopaminergic disorders
DARPP-32 plays a key role in cognitive function, and multiple brain functions. DARPP-32 is a key mediator of the biochemical, electrophysiological, transcriptional, and behavioral effects of dopamine. In this respect, DARPP-32 plays a critical role in dopaminoceptive neurons in the neostriatum (and likely in other brain regions) in signal transduction pathways regulated by a variety of neurotransmitters, neuromodulators, and neuropeptides. Abnormal signaling through DARPP-32 has been implicated in several major neurologic and psychiatric disorders. DARPP-32 may be involved in the pathogenesis of schizophrenia and plays a role in mediating the actions of a broad range of drugs of abuse.
Entity name
Over-expression of DARPP-32 and t-DARPP are associated with gastric cancer, and confer a potent anti-apoptotic function in cancer cells through a p53-independent mechanism that involves preservation of mitochondrial membrane potential and increased Bcl2 expression levels. t-DARPP transcriptionally up-regulates Bcl2 by an Akt-dependent mechanism through activation of CREB/ATF-1 transcription factors in gastric cancer. DARPP-32 is frequently over-expressed in multiple human adenocarcinomas suggesting that DARPP-32 proteins may be important in tumorigenesis. Decreased expression of DARPP-32, however, in oral premalignant and malignant lesions was observed, and thereby suggested that DARPP-32 may be a tumor suppressor in this particular malignancy. In addition, phosphorylation of DARPP-32 at Thr34 or Thr75 appears to regulate breast cancer cell migration downstream of the receptor tyrosine kinase DDR1.


Pubmed IDLast YearTitleAuthors
145088442003Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein in common adenocarcinomas.Beckler A et al
181995332008t-Darpp promotes cancer cell survival by up-regulation of Bcl2 through Akt-dependent mechanism.Belkhiri A et al
106044731999Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons.Bibb JA et al
81206381994Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human brain tissue.Brené S et al
121243422002Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP.El-Rifai W et al
96946581998DARPP-32: regulator of the efficacy of dopaminergic neurotransmission.Fienberg AA et al
160204822005DARPP-32 (dopamine and 3',5'-cyclic adenosine monophosphate-regulated neuronal phosphoprotein) is essential for the maintenance of thyroid differentiation.García-Jiménez C et al
29082931987Neuronal phosphoproteins. Mediators of signal transduction.Greengard P et al
104332571999Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade.Greengard P et al
21539351990Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices.Halpain S et al
60871601984DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1.Hemmings HC Jr et al
121815662002Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine.Lindskog M et al
106694192000Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice.Mani SK et al
99200931999Functional dopamine-1 receptors and DARPP-32 are expressed in human ovary and granulosa luteal cells in vitro.Mayerhofer A et al
172903032007Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition.Meyer-Lindenberg A et al
154641222004The role of DARPP-32 in the actions of drugs of abuse.Nairn AC et al
93343901997Bidirectional regulation of DARPP-32 phosphorylation by dopamine.Nishi A et al
157074662005Overexpression of DARPP-32 in colorectal adenocarcinoma.Wang MS et al

Other Information

Locus ID:

NCBI: 84152
MIM: 604399
HGNC: 9287
Ensembl: ENSG00000131771


dbSNP: 84152
ClinVar: 84152
TCGA: ENSG00000131771


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Dopaminergic synapseKEGGko04728
Dopaminergic synapseKEGGhsa04728
Cocaine addictionKEGGhsa05030
Cocaine addictionKEGGko05030
Amphetamine addictionKEGGhsa05031
Amphetamine addictionKEGGko05031
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
Opioid SignallingREACTOMER-HSA-111885
DARPP-32 eventsREACTOMER-HSA-180024

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
198745742009Genetical genomic determinants of alcohol consumption in rats and humans.93
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
206316842011Neurogenetics and pharmacology of learning, motivation, and cognition.75
172903032007Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition.73
232502042013Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons.60
210416082011Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up.48
191561682009Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.46
190771152009Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936.40
190860532009Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.34
181995332008t-Darpp promotes cancer cell survival by up-regulation of Bcl2 through Akt-dependent mechanism.33


Wael El-Rifai ; Abbes Belkhiri

PPP1R1B (protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein, DARPP-32))

Atlas Genet Cytogenet Oncol Haematol. 2007-12-01

Online version: http://atlasgeneticsoncology.org/gene/44096/ppp1r1b