PTPA

Summary

PTPA (protein phosphatase 2 phosphatase activator, HGNC:9308) is a protein-coding gene on chromosome 9q34.11, encoding Serine/threonine-protein phosphatase 2A activator (Q15257). PPIases accelerate the folding of proteins.

Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B’/PR61, and B’’/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B’ family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 5524 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Parkinson disease (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 30 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_178000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9308
Approved symbol	PTPA
Name	protein phosphatase 2 phosphatase activator
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	PR53
Ensembl gene	ENSG00000119383
Ensembl biotype	protein_coding
OMIM	600756
Entrez	5524

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 29 protein_coding

ENST00000337738, ENST00000347048, ENST00000348141, ENST00000355007, ENST00000357197, ENST00000358994, ENST00000393370, ENST00000411917, ENST00000414331, ENST00000414510, ENST00000417504, ENST00000419582, ENST00000423100, ENST00000432124, ENST00000432651, ENST00000434095, ENST00000435132, ENST00000435305, ENST00000436883, ENST00000440346, ENST00000452489, ENST00000453358, ENST00000455240, ENST00000455292, ENST00000868578, ENST00000918673, ENST00000918674, ENST00000918675, ENST00000918676

RefSeq mRNA: 6 — MANE Select: NM_178000 NM_001193397, NM_001271832, NM_021131, NM_178000, NM_178001, NM_178003

CCDS: CCDS65156, CCDS6920, CCDS75917

Canonical transcript exons

ENST00000393370 — 10 exons

Exon	Start	End
ENSE00001457949	129147387	129148946
ENSE00001597590	129134795	129134894
ENSE00001711396	129136471	129136595
ENSE00001760922	129137592	129137692
ENSE00001804284	129128985	129129110
ENSE00001930387	129111415	129111631
ENSE00003576525	129120513	129120610
ENSE00003687161	129123052	129123138
ENSE00003785540	129142445	129142552
ENSE00003788994	129131522	129131639

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3710 / max 144.9108, expressed in 1766 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98879	39.9218	1823
98877	8.4013	1738
98883	5.6379	1471
98880	5.0931	1634
98889	1.4921	738
98876	0.9251	487
98878	0.7351	478
98890	0.5695	329
98894	0.3332	151
205631	0.0022	1

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.53	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.26	gold quality
apex of heart	UBERON:0002098	98.77	gold quality
frontal pole	UBERON:0002795	98.77	gold quality
middle frontal gyrus	UBERON:0002702	98.30	gold quality
right frontal lobe	UBERON:0002810	98.24	gold quality
anterior cingulate cortex	UBERON:0009835	98.20	gold quality
cingulate cortex	UBERON:0003027	98.18	gold quality
right testis	UBERON:0004534	98.07	gold quality
left testis	UBERON:0004533	98.03	gold quality
prefrontal cortex	UBERON:0000451	98.02	gold quality
paraflocculus	UBERON:0005351	97.96	gold quality
amygdala	UBERON:0001876	97.49	gold quality
right adrenal gland	UBERON:0001233	97.47	gold quality
right adrenal gland cortex	UBERON:0035827	97.33	gold quality
left adrenal gland	UBERON:0001234	97.30	gold quality
heart left ventricle	UBERON:0002084	97.28	gold quality
left adrenal gland cortex	UBERON:0035825	97.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.20	gold quality
frontal cortex	UBERON:0001870	97.11	gold quality
metanephros cortex	UBERON:0010533	97.11	gold quality
cardiac ventricle	UBERON:0002082	97.10	gold quality
right atrium auricular region	UBERON:0006631	97.09	gold quality
cerebellar hemisphere	UBERON:0002245	97.08	gold quality
cerebellar cortex	UBERON:0002129	97.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.04	gold quality
nucleus accumbens	UBERON:0001882	97.03	gold quality
neocortex	UBERON:0001950	97.00	gold quality
adrenal cortex	UBERON:0001235	96.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting PTPA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514

Literature-anchored findings (GeneRIF, showing 40)

• Protein phosphatase 2A regulates estrogen receptor alpha (ER) expression through modulation of ER mRNA stability. (PMID:15965230)
• Activation of erbB1 leads to phosphorylation of protein phosphatase 2A, inhibiting its activity, which provides a rapid means of sensing the loss of epithelial integrity and subsequently restoring barrier function. (PMID:16293617)
• PTPA belongs to a novel peptidyl-prolyl cis/trans-isomerase (PPIase) family (PMID:16380387)
• crystal structure of PTPA, a human PP2A phosphatase activator (PMID:16782712)
• The crystal structures of PTPA was determined, revealing an all alpha-helical protein fold that is radically different from other PPIases. (PMID:16885030)
• These observations reveal significant insights into the function and mechanism of PTPA and have important ramifications for understanding PP2A function. (PMID:16916641)
• In retinoic acid treated ovarian cancer cells PP2A, a serine/threonine phosphatase, binds and dephosphorylates Rb2/p130. (review) (PMID:16936753)
• These observations suggest that PP2A, via the dephosphorylation of multiple serines including the 14-3-3 binding sites and serine 298, controls HDAC4 nuclear import. (PMID:18045992)
• PP2A may regulate cytokinesis by dephosphorylating MgcRacGAP and its interacting partners (PMID:18201571)
• Phosphorylated PP2A is associated with Alzheimer neurofibrillary pathology (PMID:18208556)
• PP2A and AIP1 cooperatively induce activation of ASK1-JNK signaling and vascular endothelial cell apoptosis. (PMID:18292600)
• PP2Ac (alpha) can negatively regulate integrin alpha(IIb)beta(3) signaling by suppressing the ERK1/2 signaling pathway (PMID:18334487)
• Hepatitis C virus-induced over-expression of PP2A in the liver contributes to the pathogenesis of insulin resistance in patients with chronic hepatitis C. (PMID:18486982)
• Increased demethylation of PP2A mediated by Abeta overproduction or estrogen deficiency may contribute to the reduced PP2A activity observed in the AD brain, resulting in the compromised dephosphorylation of abnormally hyperphosphorylated tau. (PMID:18586097)
• The TBP-PP2A mitotic complex bookmarks genes by preventing condensin action. (PMID:18931662)
• These results indicate that HDAC3 may act as a scaffold protein for PP2A to regulate the LIF/STAT3-mediated signaling pathway. (PMID:19121623)
• B56epsilon is alternatively translated adds a new level of regulation to PP2A holoenzymes (PMID:19129191)
• Lyn is downstream of Jak2, and Jak2 maintains activated Lyn kinase in CML through the SET-PP2A-Shp1 pathway. (PMID:19234487)
• These data suggest that ceramide plays a role in activating PP2A to terminate ongoing IL-8 production. (PMID:19286927)
• important for CTLA-4-mediated T cell activation (PMID:19405949)
• oxidative stress regulates the phosphorylation status of nonribosomal rpS3 by both activating PKCdelta and blocking the PP2A interaction with rpS3 (PMID:19458393)
• These data highlight the existence of a feedback loop in normal cells whereby ERK silencing is associated with decreased PP2A activity and consequent MEK activation. (PMID:19465001)
• Constitutive basal activity of PKR is required for leukemic cell homeostasis and growth and functions as a negative regulator of AKT, thereby increasing the pool of potentially active GSK-3. (PMID:19507191)
• These data indicate that PP2A-mediated RPA32 dephosphorylation is required for the efficient DNA damage repair. (PMID:19704001)
• Women who had both the PPP2R1A risk haplotype and a history of proliferative breast disease had an odds ratio of 2.44 (95% CI, 1.7-3.5) for the subsequent development of breast cancer. (PMID:19890961)
• We show here that protein phosphatase 2A (PP2A), which interacts with condensin II but not condensin I, plays an essential role in targeting condensin II to chromosomes. (PMID:19915589)
• This study highlights a novel signaling role of PP2A by Pin1 and implicates Pin1 as a therapeutic target to reduce aberrant phosphorylation of NF proteins in neurodegenerative disorders such as AD, PD, and ALS. (PMID:19940183)
• Data show that distinct phosphatases dephosphorylate conserved AKT motifs within the FOXO family and that PP2A is entwined in a dynamic interplay with AKT and 14-3-3 to directly regulate FOXO3a subcellular localization and transcriptional activation. (PMID:20110348)
• A critical role of PP2A is uncovered in maintaining embryonic stem cell self-renewal capability, and a defined medium has been developed for their culture. (PMID:20306465)
• Because the impacts of tau phosphorylation on its biological activity and on neurofibrillary degeneration are site-specific, this study provides a new insight into the role of PP2A down-regulation in neurofibrillary degeneration in Alzheimers disease. (PMID:20308788)
• Protein phosphatase 2A has an essential role in the activation of gamma-irradiation-induced G2/M checkpoint response. (PMID:20498628)
• Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells. (PMID:20558741)
• cyclin dependent kinase 5 interacts with p53 to phosphorylate it at Serine20 and Serine46 residues thereby promoting its recruitment on p21 and bax promoters (PMID:20673369)
• Loss of PP2A is associated with acute myeloid leukemia. (PMID:21233840)
• findings suggest that decreased B55alpha expression in AML is at least partially responsible for increased AKT signaling in AML and suggests that therapeutic targeting of PP2A could counteract this (PMID:21660042)
• Compared with healthy individuals, the activity of PP2A in AML patients is obviously lower. (PMID:21729530)
• when lung fibroblasts are attached to collagen matrix, the beta1 integrin/Src/PP2A-mediated 4EBP-1 regulatory pathway is activated (PMID:21784851)
• Striatin orchestrates the regulation of Mst3 by PP2A. (PMID:21985334)
• Data reveal that the tumour suppressor PP2A may act via S369 to regulated NEDD9-mediated cell spreading. (PMID:22061964)
• PP2A activity predicts poor survival in glioblastoma multiforme. (PMID:22253878)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpa	ENSDARG00000031985
mus_musculus	Ptpa	ENSMUSG00000039515
rattus_norvegicus	Ptpa	ENSRNOG00000018457
drosophila_melanogaster	Ptpa	FBGN0016698
drosophila_melanogaster	CG8509	FBGN0030696
drosophila_melanogaster	CG2104	FBGN0037365
caenorhabditis_elegans		WBGENE00022185

Protein

Protein identifiers

Serine/threonine-protein phosphatase 2A activator — Q15257 (reviewed: Q15257)

Alternative names: PP2A, subunit B’, PR53 isoform, Phosphotyrosyl phosphatase activator, Serine/threonine-protein phosphatase 2A regulatory subunit 4, Serine/threonine-protein phosphatase 2A regulatory subunit B'

All UniProt accessions (16): A0A804CD06, A6PVN5, A6PVN6, A6PVN7, A6PVN8, B4DDQ6, B7ZBP7, B7ZBP9, B7ZBQ0, C9IZ76, Q15257, F6WIT2, H0Y562, H0Y6E5, Q5T949, Q68CR8

UniProt curated annotations — full annotation on UniProt →

Function. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A). Modulates PP2A activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A.

Subunit / interactions. Associates with PP2A heterodimeric core enzyme PP2A(D), composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A). Interacts with the catalytic subunit PPP2CA (via C-terminus). Interacts with PPP2CB.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed.

Disease relevance. Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development (PARK25) [MIM:620482] An autosomal recessive, early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK25 is characterized by onset of parkinsonism in late childhood or adolescence, developmental delay and intellectual disability. Cognitive impairment is mild to moderate and non-progressive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PTPA-type PPIase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15257-1	2, Beta	yes
Q15257-2	1, Alpha
Q15257-3	3, Delta
Q15257-4	4, Epsilon

RefSeq proteins (6): NP_001180326, NP_001258761, NP_066954, NP_821067, NP_821068, NP_821070 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004327	Phstyr_phstse_ac	Family
IPR037218	PTPA_sf	Homologous_superfamily
IPR043170	PTPA_C_lid	Homologous_superfamily

Pfam: PF03095

Catalyzed reactions (Rhea), 1 shown:

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (61 total): helix 20, mutagenesis site 9, binding site 8, sequence variant 5, strand 5, turn 4, splice variant 3, sequence conflict 3, initiator methionine 1, chain 1, modified residue 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2IXM	X-RAY DIFFRACTION	1.5
2G62	X-RAY DIFFRACTION	1.6
4NY3	X-RAY DIFFRACTION	1.8
2HV6	X-RAY DIFFRACTION	1.9
2HV7	X-RAY DIFFRACTION	2.5
4LAC	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15257-F1	87.76	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 343; 183; 188; 189; 243; 249; 339; 342

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (9):

Position	Phenotype
185	impairs atpase activity of the pp2a(d):ppp2r4 complex; no effect on interaction with the pp2a(d) complex.
239	impairs atpase activity of the pp2a(d):ppp2r4 complex; no effect on interaction with the pp2a(d) complex.
240	impairs atpase activity of the pp2a(d):ppp2r4 complex; no effect on interaction with the pp2a(d) complex.
244	impairs interaction with the pp2a(d) complex.
305	abolishes interaction with the pp2a(d) complex.
316	impairs interaction with the pp2a(d) complex.
325	abolishes interaction with the pp2a(d) complex.
329	abolishes interaction with the pp2a(d) complex.
337	impairs interaction with the pp2a(d) complex.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 248 (showing top): CMYB_01, AAAYRNCTG_UNKNOWN, ONKEN_UVEAL_MELANOMA_UP, MORF_ATOX1, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_PPP2R4, LIAO_METASTASIS, GOBP_MITOTIC_CELL_CYCLE, MYOD_Q6, GOMF_SIGNALING_RECEPTOR_BINDING, DANG_BOUND_BY_MYC, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3, GOCC_CATION_CHANNEL_COMPLEX, GOCC_ATPASE_COMPLEX, GOCC_TRANSPORTER_COMPLEX

GO Biological Process (2): mitotic spindle organization (GO:0007052), positive regulation of apoptotic process (GO:0043065)

GO Molecular Function (14): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), protein tyrosine phosphatase activator activity (GO:0008160), protein phosphatase regulator activity (GO:0019888), phosphatase binding (GO:0019902), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), protein phosphatase 2A binding (GO:0051721), nucleotide binding (GO:0000166), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), isomerase activity (GO:0016853), phosphatase activator activity (GO:0019211)

GO Cellular Component (7): protein phosphatase type 2A complex (GO:0000159), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), calcium channel complex (GO:0034704), extracellular exosome (GO:0070062), ATPase complex (GO:1904949)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity, acting on a protein	2
phosphatase regulator activity	2
protein phosphatase binding	2
phosphatase activity	2
cellular anatomical structure	2
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cis-trans isomerase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein tyrosine phosphatase activity	1
protein phosphatase activator activity	1
phosphoprotein phosphatase activity	1
enzyme binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
enzyme activator activity	1
protein serine/threonine phosphatase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cation channel complex	1
extracellular vesicle	1
catalytic complex	1

Protein interactions and networks

STRING

1020 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPA	PPP2CA	P05323	920
PTPA	PPP2R1A	P30153	899
PTPA	LCMT1	Q9UIC8	744
PTPA	PPME1	Q9Y570	726
PTPA	AXIN1	O15169	707
PTPA	PPP2R5C	Q13362	705
PTPA	CSNK1A1	P48729	703
PTPA	GSK3B	P49841	631
PTPA	PPP2R3A	Q06190	627
PTPA	PPP2R3B	Q9Y5P8	574
PTPA	ABL1	P00519	573
PTPA	PPP2CB	P11082	540
PTPA	PPP6C	O00743	530
PTPA	PPP2R2A	P50409	528
PTPA	TIPRL	O75663	516

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PPP4R3A	PPP4C	psi-mi:“MI:0914”(association)	0.920
PTPA	PPP4C	psi-mi:“MI:0915”(physical association)	0.620
AMOT	PTPA	psi-mi:“MI:0915”(physical association)	0.560
PTPA	PPP4R2	psi-mi:“MI:0915”(physical association)	0.500
PTPA	BRINP1	psi-mi:“MI:0915”(physical association)	0.400
AMOT	PTPA	psi-mi:“MI:0915”(physical association)	0.370
PTPA	AMOT	psi-mi:“MI:0915”(physical association)	0.370
Bltp1	DRC1	psi-mi:“MI:0914”(association)	0.350
PTPA	TCP1	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
PPP2CB	ENSA	psi-mi:“MI:0914”(association)	0.350
CT45A6	AP3B1	psi-mi:“MI:0914”(association)	0.350
PPP4C	MID1	psi-mi:“MI:0914”(association)	0.350
PPP4R3A	GRK6	psi-mi:“MI:0914”(association)	0.350
PPP4R2	METTL15	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
PPP4C	ISG15	psi-mi:“MI:0914”(association)	0.350
UBAC1	PTPA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (155): PPP2R4 (Biochemical Activity), AMOT (Two-hybrid), PPP2R4 (Affinity Capture-RNA), PPP2R4 (Affinity Capture-RNA), PPP2R4 (Affinity Capture-Western), FAM110C (Affinity Capture-Western), TUBA1A (Affinity Capture-Western), PPP4R2 (Affinity Capture-MS), ANXA3 (Co-fractionation), PPP2R4 (Co-fractionation), PPP2R4 (Co-fractionation), BRINP1 (Affinity Capture-MS), PPP2R4 (Affinity Capture-MS), PPP2R4 (Affinity Capture-MS), PPP2R4 (Reconstituted Complex)

ESM2 similar proteins: A0A1S4BZI5, A0A1S4CB73, A2VE39, A2X8Q3, D2HRF1, D3Z6H8, E9Q4Z2, F1MF74, F1R777, F1RA39, F4JVN6, O00763, O23979, O48556, O82597, O82793, O94851, P0DMN7, P17707, P17708, P21216, P28918, P42898, P50243, P79888, P82185, Q04499, Q0DYB1, Q0J6P7, Q0WWQ1, Q15257, Q2QTL0, Q3B8I4, Q43187, Q5BJ48, Q5R981, Q5ZJT0, Q60HE5, Q641Y5, Q86U44

Diamond homologs: O36016, P0C153, P0CQ00, P0CQ01, P0CQ02, P0CQ03, P40454, P58389, Q12461, Q15257, Q28717, Q2KJ44, Q2UCL6, Q2UN27, Q4I0M9, Q4INW6, Q4P4W3, Q4PCR0, Q4WMU5, Q4WSA8, Q54WH6, Q55CJ3, Q59ST6, Q5ADP9, Q5B6C5, Q6BNW4, Q6BU97, Q6C712, Q6CFX5, Q6CKF0, Q6CYH1, Q6FK00, Q6FRQ9, Q753L9, Q75BY1, Q7S6M5, Q7SEF9, Q8SVB5, Q9P7H4, Q9VQQ0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PTPA	down-regulates	AKT	dephosphorylation
PTPA	down-regulates	AKT1	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

30 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	4
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2576988	NM_178000.3(PTPA):c.788T>G (p.Met263Arg)	Pathogenic
2576989	NM_178000.3(PTPA):c.407C>A (p.Ala136Asp)	Pathogenic

SpliceAI

2165 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129111628:CCAGG:C	donor_loss	1.0000
9:129111630:AGG:A	donor_loss	1.0000
9:129111631:GGTAA:G	donor_loss	1.0000
9:129111632:G:GA	donor_loss	1.0000
9:129120498:T:G	acceptor_gain	1.0000
9:129120511:A:G	acceptor_gain	1.0000
9:129123047:GGTA:G	acceptor_loss	1.0000
9:129123048:GTAG:G	acceptor_loss	1.0000
9:129123049:TAGG:T	acceptor_loss	1.0000
9:129123050:A:AT	acceptor_loss	1.0000
9:129123051:GGCAT:G	acceptor_gain	1.0000
9:129131635:CACAG:C	donor_loss	1.0000
9:129131636:ACAGG:A	donor_loss	1.0000
9:129131637:CAGGT:C	donor_loss	1.0000
9:129131638:AGGT:A	donor_loss	1.0000
9:129131639:GGTA:G	donor_loss	1.0000
9:129131640:GT:G	donor_loss	1.0000
9:129131641:T:C	donor_loss	1.0000
9:129134793:AG:A	acceptor_gain	1.0000
9:129134794:GG:G	acceptor_gain	1.0000
9:129134794:GGGC:G	acceptor_gain	1.0000
9:129134893:CGG:C	donor_loss	1.0000
9:129134894:GG:G	donor_loss	1.0000
9:129134895:GTGAG:G	donor_loss	1.0000
9:129136532:G:GT	donor_gain	1.0000
9:129142442:CAG:C	acceptor_loss	1.0000
9:129142443:A:AG	acceptor_gain	1.0000
9:129142443:A:G	acceptor_loss	1.0000
9:129142443:AGAT:A	acceptor_gain	1.0000
9:129142444:G:GT	acceptor_gain	1.0000

AlphaMissense

2132 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129120596:T:A	W39R	1.000
9:129120596:T:C	W39R	1.000
9:129120597:G:C	W39S	1.000
9:129129066:T:A	F135I	1.000
9:129129066:T:C	F135L	1.000
9:129129067:T:C	F135S	1.000
9:129129067:T:G	F135C	1.000
9:129129068:T:A	F135L	1.000
9:129129068:T:G	F135L	1.000
9:129129070:G:A	G136E	1.000
9:129131609:G:A	G179R	1.000
9:129131609:G:C	G179R	1.000
9:129131609:G:T	G179W	1.000
9:129131610:G:A	G179E	1.000
9:129131610:G:T	G179V	1.000
9:129131621:C:A	R183S	1.000
9:129131621:C:G	R183G	1.000
9:129131622:G:C	R183P	1.000
9:129131627:G:C	D185H	1.000
9:129131628:A:C	D185A	1.000
9:129131628:A:T	D185V	1.000
9:129131629:C:A	D185E	1.000
9:129131629:C:G	D185E	1.000
9:129131633:G:C	G187R	1.000
9:129131633:G:T	G187C	1.000
9:129131634:G:A	G187D	1.000
9:129131634:G:T	G187V	1.000
9:129131639:G:A	G189R	1.000
9:129131639:G:C	G189R	1.000
9:129131639:G:T	G189W	1.000

dbSNP variants (sampled 300 via entrez): RS1000015998 (9:129110230 CT>C), RS1000067347 (9:129121371 A>C,G), RS1000087902 (9:129121262 G>A), RS1000177380 (9:129126280 G>A), RS1000294266 (9:129132789 C>G,T), RS1000470535 (9:129132051 C>G,T), RS1000504033 (9:129121616 G>A), RS1000509287 (9:129116945 G>A), RS1000510347 (9:129125199 T>C), RS1000525200 (9:129130950 G>A), RS1000653793 (9:129146255 G>A), RS1000693913 (9:129122590 G>A), RS1000704542 (9:129146112 G>A,C,T), RS1000737854 (9:129116239 C>T), RS1000790462 (9:129116648 G>A)

Disease associations

OMIM: gene MIM:600756 | disease phenotypes: MIM:620482

GenCC curated gene-disease

Disease	Classification	Inheritance
Parkinson disease	Moderate	Autosomal dominant
Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development	Moderate	Autosomal recessive

Mondo (2): Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development (MONDO:0957576), Parkinson disease (MONDO:0005180)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001971_4	Hypersomnia (HLA-DQB1*06:02 negative)	3.000000e-06
GCST006879_1	Blood metabolite levels	1.000000e-09
GCST006879_18	Blood metabolite levels	3.000000e-43
GCST006879_19	Blood metabolite levels	4.000000e-83
GCST006879_2	Blood metabolite levels	2.000000e-12
GCST006879_20	Blood metabolite levels	5.000000e-12
GCST006879_21	Blood metabolite levels	2.000000e-22
GCST006879_22	Blood metabolite levels	2.000000e-20
GCST007191_1	Hypersomnia (HLA-DQB1*06:02 negative)	8.000000e-09
GCST009733_142	Urinary metabolite levels in chronic kidney disease	6.000000e-30
GCST009735_9	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	2.000000e-14
GCST010143_23	Meat-related diet	6.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0008111	diet measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010300	Parkinson Disease	C10.228.140.079.862.500; C10.228.662.600.400; C10.574.928.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2505 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

8 measured of 13 human assays (13 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Calyculinamide A (18)	IC50	5 nM
C1/C34-Calyculin A (15)	IC50	9 nM
Des-N-methylcalyculin A (20)	IC50	11 nM
Calyculin A 21-acetate (13)	IC50	13 nM
Hemicalyculin A (5)	IC50	14 nM
Calyculin C (24)	IC50	29 nM
Calyculin J (14)	IC50	105 nM
Calyculin A (4)	IC50	112 nM

ChEMBL bioactivities

3 potent at pChembl≥5 of 8 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.30	IC50	500	nM	CHEMBL40248
5.40	IC50	4000	nM	CHEMBL295239
5.03	IC50	9400	nM	TAUTOMYCIN

PubChem BioAssay actives

16 with measured affinity, of 49 total; 13 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(2R,3R,7R,8S)-2-[(1S,3S,5R,7E,9E,11E,13E)-14-cyano-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyltetradeca-7,9,11,13-tetraenyl]-9-[(E)-3-[2-[4-[[(2S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoyl]amino]butan-2-yl]-1,3-oxazol-4-yl]prop-2-enyl]-7-hydroxy-4,4,8-trimethyl-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0010	uM
[(2R,3R,7R,8S)-2-[(1S,3S,5R,7E,9E,11E,13E)-14-cyano-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyltetradeca-7,9,11,13-tetraenyl]-9-[(E)-3-cyanoprop-2-enyl]-7-hydroxy-4,4,8-trimethyl-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0010	uM
[(2R,3R,7R,8S)-2-[(1S,3S,5R,7E,9E,11E,13E)-14-cyano-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyltetradeca-7,9,11,13-tetraenyl]-9-[(E)-3-[2-[4-[[(2S,4S)-2,3-dihydroxy-5-methoxy-4-(methylamino)pentanoyl]amino]butan-2-yl]-1,3-oxazol-4-yl]prop-2-enyl]-7-hydroxy-4,4,8-trimethyl-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0010	uM
[(2R,3R,7R,8S)-2-[(1S,3S,5R,7E,9E,11E,13E)-14-cyano-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyltetradeca-7,9,11,13-tetraenyl]-7-hydroxy-9-[(E)-3-[2-[4-[(2-hydroxyacetyl)amino]butan-2-yl]-1,3-oxazol-4-yl]prop-2-enyl]-4,4,8-trimethyl-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0011	uM
[(2R,3R,7R,8S)-2-[(1S,3S,5R,7E,9E,11E,13E)-15-amino-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyl-15-oxopentadeca-7,9,11,13-tetraenyl]-9-[(E)-3-[2-[4-[[(2S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoyl]amino]butan-2-yl]-1,3-oxazol-4-yl]prop-2-enyl]-7-hydroxy-4,4,8-trimethyl-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0015	uM
[(2R,3R,7R,8R)-2-[(1S,3S,5R,7E,9E,11E,13E)-14-cyano-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyltetradeca-7,9,11,13-tetraenyl]-9-[(E)-3-[2-[4-[[(2S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoyl]amino]butan-2-yl]-1,3-oxazol-4-yl]prop-2-enyl]-4,4,8-trimethyl-3-phosphonooxy-1,10-dioxaspiro[4.5]decan-7-yl] acetate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0021	uM
[(2R,3R,7R,8S)-2-[(1S,3S,5R,7E,9E,11E,13E)-14-cyano-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyltetradeca-7,9,11,13-tetraenyl]-9-[(E)-3-[2-[4-[[(2S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoyl]amino]pentan-2-yl]-1,3-oxazol-4-yl]prop-2-enyl]-7-hydroxy-4,4,8-trimethyl-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0026	uM
[(2R,3R)-2-[(1S,3S)-4-[(3S,4R)-4-bromo-5-[(2E,4E,6E)-7-cyano-6-methylhepta-2,4,6-trien-2-yl]-3,5-dimethyloxolan-2-yl]-3-hydroxy-1-methoxypentyl]-5-[(E)-4-[2-[4-[[(2S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoyl]amino]butan-2-yl]-1,3-oxazol-4-yl]but-3-enoxy]-5-[(2S)-2-hydroxybutyl]-4,4-dimethyloxolan-3-yl] dihydrogen phosphate	1799476: Inhibition Assay from Article 10.1016/S1074-5521(02)00118-7: “Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A.”	ic50	0.0200	uM
[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-3,9-dimethyl-8-[(3S)-3-methyl-4-oxopentyl]-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl] (3S)-3-hydroxy-3-(4-methyl-2,5-dioxofuran-3-yl)propanoate	164525: Inhibition of protein phosphatase 2A (PP2A) was determined by standard phosphorylase a inhibition assay	ic50	0.5000	uM
(E,4R)-6-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-3,9-dimethyl-8-[(3S)-3-methyl-4-oxopentyl]-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-4-hydroxy-2-methyl-6-oxohex-2-enoic acid	164525: Inhibition of protein phosphatase 2A (PP2A) was determined by standard phosphorylase a inhibition assay	ic50	4.0000	uM
[(3R,4R,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-3,9-dimethyl-8-[(3S)-3-methyl-4-oxopentyl]-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl] (3R)-3-hydroxy-3-(4-methyl-2,5-dioxofuran-3-yl)propanoate	164525: Inhibition of protein phosphatase 2A (PP2A) was determined by standard phosphorylase a inhibition assay	ic50	9.4000	uM
(2S,5S)-2-[(4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyloxan-2-yl]-8a-methyl-4a,6,7,8-tetrahydro-4H-pyrano[3,2-b]pyran-2-yl]-5-[(2R,5R)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]pentane-1,2,5-triol	164527: Inhibitory activity against protein phosphatase (PP2A) using fluorescein diphosphate as substrate	ic50	10.0000	uM
(1S,3S)-4-[(2R,4aS,6R,8aR)-2-[(2S,5R)-5-bromo-2,6,6-trimethyloxan-2-yl]-4a-methyl-3,4,6,7,8,8a-hexahydro-2H-pyrano[3,2-b]pyran-6-yl]-1-[(2R,5R)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]pent-4-ene-1,3-diol	164527: Inhibitory activity against protein phosphatase (PP2A) using fluorescein diphosphate as substrate	ic50	10.0000	uM

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Smoke	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression, decreases reaction, increases abundance	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Vehicle Emissions	affects expression, increases abundance	1
Azacitidine	increases expression	1
Calcitriol	decreases expression	1
Bucladesine	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Oils, Volatile	decreases reaction, increases abundance, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Quercetin	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Thiram	decreases expression	1

ChEMBL screening assays

17 unique, capped per target: 16 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1067751	Binding	Inhibition of PTPalpha expressed in Escherichia coli BL21 (DE3) after 10 mins by spectrophotometry	Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity. — Bioorg Med Chem
CHEMBL4626314	ADMET	Inhibition of PTPA (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method	Highly Potent and Selective N-Aryl Oxamic Acid-Based Inhibitors for Mycobacterium tuberculosis Protein Tyrosine Phosphatase B. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1Q9	Abcam K-562 PTPA KO	Cancer cell line	Female
CVCL_D2LV	Abcam Raji PTPA KO	Cancer cell line	Male
CVCL_TG03	HAP1 PPP2R4 (-) 1	Cancer cell line	Male
CVCL_TG04	HAP1 PPP2R4 (-) 2	Cancer cell line	Male
CVCL_WQ43	Abcam Jurkat PTPA KO	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00030979	PHASE4	COMPLETED	Donepezil to Treat Dementia in Parkinson’s Disease
NCT00043849	PHASE4	COMPLETED	Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)
NCT00095810	PHASE4	COMPLETED	Aripiprazole in Patients With Psychosis Associated With Parkinson’s Disease
NCT00125567	PHASE4	COMPLETED	Stalevo in Early Wearing-Off Patients
NCT00143026	PHASE4	COMPLETED	Study to Compare the Effect of Treatment With Carbidopa/Levodopa/Entacapone on the Quality of Life of Patients With Parkinson’s Disease. This Study is Not Recruiting in the United States
NCT00144300	PHASE4	COMPLETED	Ophthalmologic Safety Study of Pramipexole Immediate Release (IR) Versus Ropinirole in Early Parkinson’s Disease (PD) Patients
NCT00153972	PHASE4	COMPLETED	Dopamine Turnover Rate as Surrogate Parameter for Diagnosis of Early Parkinson’s Disease
NCT00174239	PHASE4	TERMINATED	Study Of Cabaser and Sinemet CR For The Treatment Of Nighttime Symptoms Associated With Parkinson’s Disease.
NCT00215904	PHASE4	COMPLETED	D-serine Adjuvant Treatment for Parkinson’s Disease
NCT00247247	PHASE4	COMPLETED	Comtess® Versus Cabaseril® as Add-on to Levodopa in the Treatment of Parkinsonian Patients Suffering From Wearing- Off.
NCT00272688	PHASE4	COMPLETED	Continuous Delivery of Levodopa in Patients With Advanced Idiopathic Parkinsons Disease - Cost-benefit
NCT00297778	PHASE4	COMPLETED	Pramipexole Versus Placebo in Parkinson’s Disease (PD) Patients With Depressive Symptoms
NCT00304161	PHASE4	COMPLETED	Effectiveness of Antidepressant Treatment for Depression in People With Parkinson’s Disease
NCT00307450	PHASE4	COMPLETED	Efficacy and Safety of Levetiracetam Versus Placebo on Levodopa-induced Dyskinesias in Advanced Parkinson’s Disease
NCT00321854	PHASE4	COMPLETED	Study of (Mirapex) Pramipexole for the Early Treatment of Parkinsons Disease (PD)
NCT00354133	PHASE4	UNKNOWN	Controlled Trial With Deep Brain Stimulation in Patients With Early Parkinson’s Disease
NCT00373087	PHASE4	COMPLETED	COMT Polymorphism and Entacapone Efficacy
NCT00391898	PHASE4	COMPLETED	Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson’s Disease Patients With Early Wearing-off
NCT00399477	PHASE4	COMPLETED	A Non-Blinded Study Demonstrating the Effectiveness and Safety of Azilect Alone or in Combination Therapy in Parkinson’s Disease
NCT00402233	PHASE4	COMPLETED	A Randomized, Double-blind, Active (Pramipexole 0.5 mg Tid) and Placebo Controlled, Study of Pramipexole Given 0.5 mg and 0.75 mg Bid Over 12-week Treatment in Early Parkinson’s Disease (PD) Patients
NCT00437125	PHASE4	COMPLETED	Study on the Tolerability of Duloxetine in Depressed Patients With Parkinson’s Disease
NCT00443872	PHASE4	COMPLETED	Efficacy of Orally Disintegrating Selegiline in Parkinson’s Patients Experiencing Adverse Effects With Dopamine Agonists
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00462007	PHASE4	COMPLETED	Study to Evaluate Initiation of Stalevo in Early Wearing-off
NCT00462254	PHASE4	TERMINATED	Ramelteon (ROZEREM) in the Treatment of Sleep Disturbances Associated With Parkinson’s Disease
NCT00477802	PHASE4	TERMINATED	Botulinum Toxin Type A (Botox) in the Management of Levodopa-Induced Peak-Dose Dyskinesias in Parkinson’s Disease
NCT00485069	PHASE4	COMPLETED	REQUIP (Ropinirole Hydrochloride) IR Long-Term Phase 4 Study
NCT00489255	PHASE4	COMPLETED	Safety/Efficacy of Tigan® to Control Nausea/Vomiting Experienced During Apokyn® Initiation and Treatment
NCT00526630	PHASE4	COMPLETED	Methylphenidate for the Treatment of Gait Impairment in Parkinson’s Disease
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT00571285	PHASE4	TERMINATED	Clinical Effects of Vitamin D Repletion in Patients With Parkinson’s Disease
NCT00584025	PHASE4	WITHDRAWN	Keppra IV for the Treatment of Motor Fluctuations in Parkinson’s Disease
NCT00584090	PHASE4	WITHDRAWN	Solifenacin Succinate (VESIcare) for the Treatment of Urinary Incontinence in Parkinson’s Disease
NCT00590122	PHASE4	COMPLETED	Parcopa Versus Carbidopa-levodopa in a Single Dose Cross-over Comparison Study
NCT00594464	PHASE4	COMPLETED	A Trial of Neupro® (Rotigotine Transdermal Patch) in Patients With Parkinson’s Disease Undergoing Surgery
NCT00601978	PHASE4	WITHDRAWN	Carbidopa/Levodopa Versus Carbidopa/Levodopa/Entacapone on Markers of Event Related Potentials (ERPs) in Patients With Idiopathic Parkinson’s Disease (PD) and End-of-dose Wearing Off
NCT00632762	PHASE4	COMPLETED	Long-Term Effects of Amantadine in Parkinsonian (AMANDYSK)
NCT00640159	PHASE4	COMPLETED	Selegiline to Zelapar Switch Study in Parkinson Disease Patients
NCT00642356	PHASE4	TERMINATED	Carbidopa/Levodopa/Entacapone Versus Immediate Release (IR) Carbidopa/Levodopa on Non-motor Symptoms in Patients With Idiopathic Parkinson’s Disease and Demonstrating Non-motor Symptoms of Wearing Off
NCT00646204	PHASE4	COMPLETED	Namenda (Memantine) for Non-motor Symptoms in Parkinson’s Disease