PPP6R3 (protein phosphatase 6 regulatory subunit 3)

2019-03-01   Luigi Cristiano 

Aesthetic and medical biotechnologies research unit, Prestige, Terranuova Bracciolini, Italy. prestige.infomed@gmail.com; luigicristiano@libero.it




Protein phosphatase 6 regulatory subunit 3 (PPP6R3) is a regulatory subunit of the PP6 holoenzyme complex involved in the turnover of serine and threonine phosphorylation events during mitosis. PPP6R3 shows abundant mRNA splicing variants and numerous functional protein isoforms. PPP6R3 gene is often involved in abnormal chromosomal translocations and it is found as a fusion gene partner in different kind of cancers.


Atlas Image
Figure. 1. PPP6R3 gene and splicing variants/isoforms. The figure shows the locus on chromosome 11 of the PPP6R3 gene (reworked from https://www.ncbi.nlm.nih.gov/gene; http://grch37.ensembl.org; www.genecards.org)


PPP6R3, alias protein phosphatase 6 regulatory subunit 3, is a protein coding gene that starts at 68,460,718 nt and ends at 68,615,334 nt from qter (RefSeq NC_000011.10) and with a length of 154617 bp. It is proximal to LRP5 (LDL receptor related protein 5) gene. Around the genomic locus of PPP6R3 take place different promoter or enhancer transcriptional elements that are located at +0.5 kb, +837.9 kb and -359.7 kb.


Exists a high number of spliced version of PPP6R3 (Stefansson and Brautigan, 2006) and their main characteristics are reported in Table.1
Name Variant RefSeq (1) Transcript ID Exons Type Lenght (bp) Isoform Alias RefSeq (2) Lenght (aa) MW (kDa) pI
PPP6R3-201 (PPP6R3-003)Var.5 NM_018312ENST00000265636.923protein coding4992Isoform 5-NP_06078279388.954.49
PPP6R3-202  (PPP6R3-021)Var.44NR_147968.1ENST00000265637.822ncRNA5124------
PPP6R3-203 (PPP6R3-001)Var.6NM_001164161ENST00000393800.624protein coding5127Isoform 6-NP_00115763387397.674.50
Var.21NM_0013523614873Isoform 18-NP_00133929078286.884.52
Var.28NM_0013523685211Isoform 6-NP_00133929787397.674.50
Var. 35NM_0013523755233Isoform 6-NP_00133930487397.674.50
Var.45NR_147969 5235------
Var.46NR_147970 4978------
PPP6R3-204 (PPP6R3-005)Var.4NM_001164160 ENST00000393801.725protein coding5145Isoform 4A, C11orf23a, SAPLaNP_001157632 87998.494.54
Var.7NM_001352347 5052Isoform 7-NP_001339276 66473.154.44
Var.10NM_001352350 5037Isoform 8-NP_001339279 85095.264.55
Var.12NM_001352352 5073Isoform 10-NP_001339281 86296.454.55
Var.13NM_001352353 4704Isoform 11-NP_001339282 71779.534.49
Var.14NM_001352354 5281Isoform 12-NP_001339283 88999.474.53
Var.16NM_001352356 5154Isoform 12-NP_001339285 88999.474.53
Var.20NM_001352360 5194Isoform 17-NP_001339289 86096.254.54
Var.24NM_001352364 5251Isoform 4A, C11orf23a, SAPLaNP_001339293 87998.494.54
Var.29NM_001352369 5149Isoform 20-NP_001339298 65472.164.45
Var.30NM_001352370 4891Isoform 21-NP_001339299 78887.694.56
Var.31NM_001352371 5200Isoform 10-NP_001339300 86296.454.55
Var.32NM_001352372 5233Isoform 24-NP_001339301 87397.734.54
Var.33NM_001352373 5067Isoform 17-NP_001339302 86096.254.54
Var.34NM_001352374 4804Isoform 22-NP_001339303 75984.474.58
Var.36NM_001352376 5164Isoform 8-NP_001339305 85095.264.55
Var.37NM_001352377 5106Isoform 24-NP_001339306 87397.734.54
Var.38NM_001352378 4931Isoform 22-NP_001339307 75984.474.58
Var.39NM_001352379 5390Isoform 4A, C11orf23a, SAPLaNP_001339308 87998.494.54
Var.40NM_001352380 5142Isoform 8-NP_001339309 85095.264.55
PPP6R3-205 (PPP6R3-026)Var.2NM_001164163 ENST00000524845.5 23protein coding5040Isoform 2-NP_001157635 84494.444.51
Var.15NM_001352355 4786Isoform 13-NP_001339284 75383.654.54
Var.23NM_0013523635146Isoform 2-NP_00133929284494.444.51
PPP6R3-206  (PPP6R3-007)Var.1NM_001164162 ENST00000524904.524protein coding5109Isoform 1-NP_001157634 86796.964.51
Var.8NM_001352348 5284Isoform 1-NP_001339277 86796.964.51
Var.11NM_001352351 4822Isoform 9-NP_001339280 76584.844.54
Var.18NM_001352358 4902Isoform 15-NP_001339287 80590.144.49
Var.19NM_001352359 4885Isoform 16-NP_001339288 78687.154.52
Var.22NM_001352362 5129Isoform 19-NP_001339291 85695.634.52
Var.25NM_0013523655055Isoform 19-NP_00133929485695.634.52
PPP6R3-207--ENST00000525050.5 4retained intron513------
PPP6R3-208--ENST00000525152.12retained intron582------
PPP6R3-209--ENST00000525421.5 8nonsense md830------
PPP6R3-210--ENST00000526307.510retained intron4134------
PPP6R3-211--ENST00000526574.1 4retained intron489------
PPP6R3-212--ENST00000526593.15nonsense md570------
PPP6R3-213--ENST00000527069.5 4retained intron573------
PPP6R3-214  (PPP6R3-020)Var.26NM_001352366ENST00000527403.622protein coding5019Isoform 23-NP_00133929584494.554.56
PPP6R3-215  (PPP6R3-012)--ENST00000528635.55(?)538------
PPP6R3-216--ENST00000529172.1 4retained intron500------
PPP6R3-217  (PPP6R3-011)--ENST00000529344.5 4(?)603------
PPP6R3-218  (PPP6R3-004)Var.3NM_001164164ENST00000529710.5 23protein coding3426Isoform 3B, C11orf23b, SAPLbNP_00115763679188.914.48
PPP6R3-219  (PPP6R3-009)--ENST00000529907.5 7(?)826------
PPP6R3-220--ENST00000530427.55processed transcript560------
PPP6R3-221 (PPP6R3-025)--ENST00000530734.1 2(?)576------
PPP6R3-222  (PPP6R3-013)--ENST00000531244.1 5(?)687------
PPP6R3-223--ENST00000531432.12retained intron590------
PPP6R3-224 (PPP6R3-027)--ENST00000533127.5 4(?)551------
PPP6R3-225  (PPP6R3-018)Var.17NM_001352357ENST00000534190.5 16protein coding5150Isoform 14-NP_00133928661968.124.42
PPP6R3-226  (PPP6R3-008)--ENST00000534534.5 19(?)2968------

Table.1 Alterative splicing variants and isoforms of PPP6R3. (reworked from http://grch37.ensembl.org; ttps://www.ncbi.nlm.nih.gov; https://web.expasy.org/protparam/; https://www.uniprot.org)
ncRNA = non-coding RNA; nonsense md = nonsense mediated decay; (?) = undetermined; MW = molecular weight; pI = theoretical pI.


Currently, pseudogenes for PPP6R3 have not been detected in the human genome.


Atlas Image
Figure.2 PPP6R3 protein isoforms. Graphical representation of the PPP6R3 protein isoforms with highlight of the main verified post-translational modifications (reworked from http://grch37.ensembl.org; https://www.ncbi.nlm.nih.gov; Stefansson and Brautigan, 2006).


PPP6R3 encodes the protein phosphatase 6 regulatory subunit 3, which belongs to protein phosphatase 6 (PP6) complex (York et al., 2014; Guergnon et al., 2009) in which there are also PPP6R1, PPP6R2 and PPP6C proteins. PP6 complex is a member of the PP2A subfamily of protein phosphatases and shows a Sit4-associated protein domain (SAPS domain) (Stefansson and Brautigan, 2006). There are evidence about many functioning isoforms for PPP6R3 protein (Table.1) that maintain the SAPS main domain.


PPP6R3 is ubiquitously expressed in human tissues and mRNA levels are highly expressed in heart (Ziembik et al., 2017; Stefansson and Brautigan, 2006) and also in immune cells and lymphoid tissues, in particular in T helper cells, cytotoxic T cells and monocytes (Ziembik et al., 2017). On the contrary, PPP6R3 protein is found at high levels in lung, bladder, spleen and pancreas (Ziembik et al., 2017).


PPP6R3 localize in various subcellular compartments: it is present mainly in the cytoplasm but it is also found in Golgi apparatus, nucleoplasm, nucleus and associated with the plasma membrane (Stefansson et al., 2008; https://www.ncbi.nlm.nih.gov).


PPP6R3 is a subunit of protein phosphatase 6 (PP6), a trimeric holoenzyme of the family of phosphoprotein phosphatases (PPPs), involved in the turnover of serine and threonine phosphorylation events during mitosis so much to be able to regulate the cell cycle progression (Stefansson and Brautigan, 2007). PPP6R3 acts as a regulatory element in the PP6 protein complex and could function as a scaffold for PP6 subunits. It was observed that a high amount of PPP6R3 in cell result in a great destabilization, upon depletion, of the catalytic subunit of PP6 (Rusin et al.,2017). Moreover, PPP6R3 could have an important role in maintaining immune self-tolerance through the control of the nuclear factor kappaB (NF-kB) (Ziembik et al., 2017) and the TNF- α/NF-kB pathway (Bouwmeester et al., 2004).
Pediatric musculoskeletal development. PPP6R3, along with other genes, seems to be involved in bone mineralization and myogenensis during pediatric development (Medina-Gomez et al., 2017). However, the inner significance of this relation, such as the impact on musculoskeletal structure, on strength or weakness and on the predisposition to develop the related pathologies, needs to be clarified.
Interactions with the influenza A virus transcription/replication machinery. PPP6R3 is a member of PP6 complex and some authors found that PP6 interact directly with two subunits, i.e. PB1 and PB2, of the viral RNA-dependent RNA polymerase (RdRP) of the influenza A virus. This suggest a role of PP6 complex, and for regulatory subunit PPP6R3, in the regulation of phosphorylation also in the influenza A virus transcription/replication machinery (York et al., 2014).


PPP6R3 is highly and abundant conserved in many species and its homology between the species is reported in Table.2
OrganismSpeciesSymbol DNA Identity (%)Prot Identity (%)
Mouse M.musculus Ppp6r390.596.3
RatR.norvegicus Ppp6r390.695.5
Xenopus tropicalisX.tropicalis Ppp6r375.680.3
Zebrafish D.rerio Ppp6r371.679.0

Table.2 PPP6R3 homology (reworked from ps://www.ncbi.nlm.nih.gov/homologene)

Implicated in

Top note
PPP6R3 is involved in many and heterogeneous genomic translocations in different kind of tumors (Table. 3) and it has been proposed that this happens because it possess a potent promotor activity (Guo et al., 2016).
Name 5 end 3 end Loc1 Loc2 Description Type Disease Organ Code Ref.
RNF121/PPP6R3 RNF121PPP6R311q13.411q13.2t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015

 Chronic myeloid leukemiaBloodCMLStopera et al., 1990 TNFRSF21/PPP6R3TNFRSF21PPP6R3 6p12.3 11q13.2t(6;11)(p12;q13)TranslocationAdenocarcinomaBreastBRCABanerji et al., 2012 PPP6R3/YAP1PPP6R3YAP111q13.211q22.1 t(11;11)(q13;q22)Fusion gene Transitional cell carcinomaBladderBLCAYoshihara et al., 2015 PPP6R3/EIF4G3PPP6R3EIF4G311q13.2 1p36.12t(1;11)(p36;q13)TranslocationMalignant melanomaSkinSKCM- NADSYN1/PPP6R3NADSYN1PPP6R3 11q13.411q13.2t(11;11)(q13;q13)Fusion geneMalignant melanomaSkinSKCMHu et al., 2018; Klijn et al., 2015 PPP6R3/MTL5PPP6R3MTL511q13.211q13.3 t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015 PPP6R3/INTS4 PPP6R3INTS4 11q13.2 11q14.1t(11;11)(q13;q14) Fusion geneAcute lymphoblastic leukemia/lymphoblastic lymphoma (T-Lineage)BloodT-ALLLiu et al., 2017 PPP6R3/SSH2PPP6R3SSH211q13.217q11.2t(11;17)(q13;q11)TranslocationAdenocarcinomaBreastBRCAYoshihara et al., 2015 TMPRSS6/PPP6R3TMPRSS6PPP6R3 22q12.311q13.2t(11;22)(q13;q12)TranslocationLiver hepatocellular carcinomaLiver LIHC- PPP6R3/USP6 PPP6R3USP6 11q13.2 17p13.2 t(11;17)(q13;p13) TranslocationNodular fasciitisSoft tissueNFGuo et al., 2016 Multiple myelomaBloodMMSawyer et al., 1995; Sawyer et al., 2014 Table.3 PPP6R3 rearrangements: translocations and fusion genes (reworked from ps://www.ncbi.nlm.nih.gov/homologene; http://www.tumorfusions.org; https://cgap.nci.nih.gov/Chromosomes; http://quiver.archerdx.com)
[ (?) ] unknown; [ - ] no reference
Entity name
Acute lymphoblastic leukemia (ALL)
Hybrid gene
The fusion gene PPP6R3/ INTS4 has been found in T-ALL (Liu et al., 2017), while a t(11;17)(q13;q11) PPP6R3/ SSH2 was discovered in a childhood T/BCP (T/ B-cell precursor) ALL (Schmiegelow et al., 2012).
Entity name
Bladder cancer
Hybrid gene
The fusion genes PPP6R3/ SHANK2 and PPP6R3/ YAP1 have been found in transitional cell carcinoma of the bladder (Hu et al., 2018; Yoshihara et al., 2015; http://www.tumorfusions.org).
Entity name
Breast cancer
Hybrid gene
Many fusion genes and abnormal translocation was discovered. C11orf80 /PPP6R3, KDM2A/PPP6R3, PC/PPP6R3, PPP6R3/ FADD, PPP6R3/ MTL5, PPP6R3/ POLD3, PPP6R3/ SPTBN2, t(11;17)(q13;q11) PPP6R3/SSH2, RNF121/PPP6R3, t(11;14)(q13;q12) STRN3/PPP6R3 and t(6;11)(p12;q13) TNFRSF21/PPP6R3 have been found in breast adenocarcinoma (Hu et al., 2018; Yoshihara et al., 2015; http://www.tumorfusions.org)
Entity name
Cervical carcinoma
Hybrid gene
A t(11;15)(q13;q22) RAB11A/PPP6R3 has been found in cervical carcinoma (http://www.tumorfusions.org).
Entity name
Gastric cancer
Hybrid gene
The fusion gene PPP6R3/ RHOD has been found in gastric adenocarcinoma (Hu et al., 2018; http://www.tumorfusions.org)
Entity name
t(11;17)(q13;p13)PPP6R3/USP6 in hematological malignancies.
Hybrid gene
A t(11;17)(q13;p13)PPP6R3/ USP6 has been found in Hairy cell leukemia, Multiple myeloma, and Chronic myeloid leukemia (Sawyer et al., 2014 ; Sawyer et al., 1995 ; Nacheva et al., 1992; Stopera et al., 1990 http://www.tumorfusions.org)
Entity name
Hepatocellular carcinoma
Hybrid gene
A t(11;22)(q13;q12) TMPRSS6/PPP6R3 has been found in hepatocellular carcinoma (http://www.tumorfusions.org).
Entity name
Lung squamous cell carcinoma
Hybrid gene
In squamous cell carcinoma of the lung was discovered the fusion gene EEF1G/PPP6R3 (Hammerman et al., 2012). Other detected are: a t(7;11)(q21;q13) CCDC132/PPP6R3, PPP6R3/ ARHGAP1 fusion gene, PPP6R3/ CNTN5 fusion gene, PPP6R3/ LRP5 fusion gene, a t(7;11)(q13;q34)PPP6R3/ MGAM and a t(7;11)(q34;q13) SSBP1/PPP6R3 (Yoshihara et al., 2015; Hammerman et al., 2012; http://www.tumorfusions.org)
In squamous cell carcinoma of the lung was found the presence of the fusion gene 5 EEF1G- 3 PPP6R3 deriving by the genomic translocation and fusion of a part of EEF1G gene with a portion of PPP6R3 gene, both located on chromosome 11 (Hammerman et al., 2012).
Entity name
Malignant melanoma
Hybrid gene
The fusion genes CTTN/PPP6R3, NADSYN1/PPP6R3 and PPP6R3/ ACER3 have been found in malignant melanoma. In addition, a t(1;11)( p36;q13) PPP6R3/ EIF4G3 has also been found (Hu et al., 2018; Klijn et al., 2015; http://www.tumorfusions.org)
Entity name
Malignant Nodular Fasciitis
Nodular fasciitis (NF) occurs in subcutaneous tissue and it is generally a benign self-limiting myofibroblastic proliferation (Bernstein and Lattes, 1982). Sometimes was found USP6 gene rearrangements (Erickson-Johnson et al., 2011) and surprendently in one case was revealed the presence of PPP6R3/USP6 fusion gene with both genomic amplification and overexpression (Guo et al., 2016) that could explain the more aggressive behavior seen in malignant NF case report.
Hybrid gene
It was described the fusion gene 5 PPP6R3 / 3 USP6 deriving by the genomic translocation and fusion of a part of PPP6R3 gene, situated on chromosome 11, with a portion of USP6 gene, instead located on chromosome 17. In particular, the breakpoint reside at the end of exon 1 of PPP6R3 (non-coding) and 155 bp upstream of coding sequence of USP6 gene (Guo et al., 2016).
The presence of the novel PPP6R3/USP6 fusion gene was linked to the increase of malignancy of the nodular faciitis (NF). Other tumors were tested for the presence of this chimeric gene, such as aggressive angiomyxoma , malignant peripheral nerve sheath tumor, dermatofibroma/ benign fibrous histiocytoma and melanoma. In that cases the results were negatives (Guo et al., 2016). Some authors detect PPP6R3/USP6 in hairy cell leukemia, multiple myeloma and chronic myeloid leukemia (Sawyer et al., 2014; Sawyer et al., 1995; Nacheva et al., 1992 ; Stopera et al., 1990).
Entity name
Nervous system tumors
Malignant peripheral nerve sheath tumors (MPNSTs), also called neurofibrosarcomas, are a rare aggressive, metastatic, nerve-associated cancer type. It was found that in about 10% of this malignancy there are mutations on PPP6R3 gene that cause disrupt gene transcription (Rahrmann et al., 2013). In addition a t(8;11)(q21;q13)PPP6R3/ ATP6V0D2 is found in sarcoma (http://www.tumorfusions.org) and a t(11;17)(q13;q11)PPP6R3/SSH2 is detected in neuroblastoma (McRobert et al., 1992).
Entity name
Ovarian carcinoma
Ovarian malignancies, a type of gynecological cancer, show high genomic instability and structural chromosomal aberrations which are believed to be common mechanisms for both the inactivation of tumour suppressor genes and the production of fusion genes useful for cancer vitality. The precise roles and functions of these chimeric gene are not always understood (Smebye et al., 2017). The fusion gene DPP9 /PPP6R3 play a role in tumorigenesis and/or cancer progression through the loss-of-function of the DPP9 protein, a serine protease that act as a tumour suppressor and is a inducer of apoptosis.
Hybrid gene
A fusion gene 5 DPP9 / 3 PPP6R3 deriving from the genomic translocation and fusion of a part of DPP9 (dipeptidyl peptidase 9) gene, situated on chromosome 19 with a portion of PPP6R3 gene, located on chromosome 11 was found in a high-grade serous ovarian carcinoma. The fusion occured between DPP9 exon 11 and PPP6R3 exon 18. DPP9 is a serine protease that act as a tumor suppressor and as a inducer of apoptosis (Smebye et al., 2017).
Fusion protein
The fusion between DPP9 and PPP6R3 leads to disruption and deregulation of expression of DPP9 gene due to the introduction of a stop codon (TAG) directly after the junction that leads to the production of truncated form of DPP9 protein. This protein loss some functional domains, i.e. the peptidase and esterase-lipase domains (Smebye et al., 2017) and this causes its loss-of-function.
Entity name
Pancreatic cancer
Hybrid gene
The fusion genes PPP6R3/LRP5 and PPP6R3/ SSH3 have been found in pancreas adenocarcinoma (Hu et al., 2018; http://www.tumorfusions.org)
Entity name
Testicular germ cell tumors
Testicular germ cell tumors (TGCTs) are the most frequently diagnosed solid malignancies in young males and men by 15 to 44 years old and that includes two main subtypes: seminomas and non-seminomas (Hoff et al., 2016; Znaor et al., 2014). Some authors found a novel fusion gene 5 PPP6R3 - 3 DPP3 in pluripotent embryonal carcinomas (EC) cell lines (Hoff et al., 2016).
Hybrid gene
The fusion gene 5 PPP6R3 / 3 DPP3 resulting by the translocation t(11;11)(q13;q13) and PPP6R3/DPP3 is a novel genomic chimeric rearrangement occurs in vitro. However more studies are need to characterize it and to elucidate its exact role in testicular germ cell tumors.
Fusion protein
PPP6R3-DPP3 fusion gene encodes a protein of 198 amino acids long (Hoff et al., 2016). The functions of this chimeric protein are unknown.
Entity name
Type 1 diabetes mellitus 4
The IDDM4 locus has been localized to chromosome 11q13 and PPP6R3 gene is linked with type 1 diabetes mellitus 4 (Twells et al., 2001).
Entity name
Effects on HIV-1 replication
Knockdown of PPP6R3 by short interfering RNAs (siRNA) library screening inhibits HIV-1 replication in cultured Jurkat T-cells (Yeung et al., 2009).


Pubmed IDLast YearTitleAuthors
227222022012Sequence analysis of mutations and translocations across breast cancer subtypes.Banerji S et al
62792731982Nodular (pseudosarcomatous) fasciitis, a nonrecurrent lesion: clinicopathologic study of 134 cases.Bernstein KE et al
147432162004A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.Bouwmeester T et al
229607452012Comprehensive genomic characterization of squamous cell lung cancers.
218260562011Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion.Erickson-Johnson MR et al
198356102009Mapping of protein phosphatase-6 association with its SAPS domain regulatory subunit using a model of helical repeats.Guergnon J et al
271132712016PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis.Guo R et al
266595752016Identification of Novel Fusion Genes in Testicular Germ Cell Tumors.Hoff AM et al
290999512018TumorFusions: an integrative resource for cancer-associated transcript fusions.Hu X et al
254856192015A comprehensive transcriptional portrait of human cancer cell lines.Klijn C et al
286716882017The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia.Liu Y et al
15818791992Detection of MYCN amplification in three neuroblastoma cell lines by non-radioactive chromosomal in situ hybridization.McRobert TL et al
287438602017Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.Medina-Gomez C et al
13941071992Complex chromosomal rearrangements in an unusual variant of hairy cell leukemia.Nacheva E et al
236857472013Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis.Rahrmann EP et al
264627362015Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.Rusin SF et al
244975332014Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease.Sawyer JR et al
76279331995Cytogenetic findings in 200 patients with multiple myeloma.Sawyer JR et al
220057842012High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia.Schmiegelow K et al
288932312017Involvement of DPP9 in gene fusions in serous ovarian carcinoma.Smebye ML et al
181866512008Protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains.Stefansson B et al
114014382001The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13.Twells RC et al
194607522009A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication.Yeung ML et al
251875372014Interactome analysis of the influenza A virus transcription/replication machinery identifies protein phosphatase 6 as a cellular factor required for efficient virus replication.York A et al
255005442015The landscape and therapeutic relevance of cancer-associated transcript fusions.Yoshihara K et al
286200302017Functions of protein phosphatase-6 in NF-κB signaling and in lymphocytes.Ziembik MA et al
242685062014International variations and trends in testicular cancer incidence and mortality.Znaor A et al

Other Information

Locus ID:

NCBI: 55291
MIM: 610879
HGNC: 1173
Ensembl: ENSG00000110075


dbSNP: 55291
ClinVar: 55291
TCGA: ENSG00000110075


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Asparagine N-linked glycosylationREACTOMER-HSA-446203
Transport to the Golgi and subsequent modificationREACTOMER-HSA-948021
ER to Golgi Anterograde TransportREACTOMER-HSA-199977
COPII (Coat Protein 2) Mediated Vesicle TransportREACTOMER-HSA-204005
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
262882492015Variability of Gene Expression Identifies Transcriptional Regulators of Early Human Embryonic Development.17
288932312017Involvement of DPP9 in gene fusions in serous ovarian carcinoma.3
271132712016PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis.1
319048302020Protein kinase CK2 phosphorylation of SAPS3 subunit increases PP6 phosphatase activity with Aurora A kinase.0


Luigi Cristiano

PPP6R3 (protein phosphatase 6 regulatory subunit 3)

Atlas Genet Cytogenet Oncol Haematol. 2019-03-01

Online version: http://atlasgeneticsoncology.org/gene/54550/ppp6r3