PPP6R3 (protein phosphatase 6 regulatory subunit 3)

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PPP6R3 (protein phosphatase 6 regulatory subunit 3)

Written	2019-03	Luigi Cristiano
		Aesthetic and medical biotechnologies research unit, Prestige, Terranuova Bracciolini, Italy. prestige.infomed@gmail.com; luigicristiano@libero.it

Abstract

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.

Keywords

PPP6R3, protein phosphatase 6 regulatory subunit 3, C11orf23, SAPS, phosphorylation, breast cancer, bladder cancer, lung cancer, nodular fasciitis

(Note : for Links provided by Atlas : click)

Identity

Alias_names	C11orf23
	SAPS3
	chromosome 11 open reading frame 23
	SAPS domain family, member 3
	protein phosphatase 6, regulatory subunit 3
Alias_symbol (synonym)	SAPLa
	DKFZp781E2374
	DKFZp781O2362
	DKFZp781E17107
	SAP190
	SAPL
	PP6R3
	FLJ11058
	FLJ43065
	KIAA1558
	MGC125711
	MGC125712
Other alias	Serine/threonine-protein phosphatase 6 regulatory subunit 3
	chromosome 11 open reading frame 23 C11orf23
	SAPS domain family member 3, SAPS3
	sporulation-induced transcript 4-associated protein
HGNC (Hugo)	PPP6R3
LocusID (NCBI)	55291
Atlas_Id	54550
Location	11q13.2 [Link to chromosome band 11q13]
Location_base_pair	Starts at 68460718 and ends at 68615333 bp from pter ( according to hg19-Feb_2009) [Mapping PPP6R3.png]

Fusion genes
(updated 2017)

Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

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)

Description

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.

Transcription

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_018312	ENST00000265636.9	23	protein coding	4992	Isoform 5	-	NP_060782	793	88.95	4.49
PPP6R3-202 (PPP6R3-021)	Var.44	NR_147968.1	ENST00000265637.8	22	ncRNA	5124	-	-	-	-	-	-
PPP6R3-203 (PPP6R3-001)	Var.6	NM_001164161	ENST00000393800.6	24	protein coding	5127	Isoform 6	-	NP_001157633	873	97.67	4.50
	Var.21	NM_001352361				4873	Isoform 18	-	NP_001339290	782	86.88	4.52
	Var.28	NM_001352368				5211	Isoform 6	-	NP_001339297	873	97.67	4.50
	Var. 35	NM_001352375				5233	Isoform 6	-	NP_001339304	873	97.67	4.50
	Var.41	NR_147965			ncRNA	4942	-	-	-	-	-	-
	Var.43	NR_147967				5401	-	-	-	-	-	-
	Var.45	NR_147969				5235	-	-	-	-	-	-
	Var.46	NR_147970				4978	-	-	-	-	-	-
	Var.47	NR_147971				5362	-	-	-	-	-	-
PPP6R3-204 (PPP6R3-005)	Var.4	NM_001164160	ENST00000393801.7	25	protein coding	5145	Isoform 4	A, C11orf23a, SAPLa	NP_001157632	879	98.49	4.54
	Var.7	NM_001352347				5052	Isoform 7	-	NP_001339276	664	73.15	4.44
	Var.10	NM_001352350				5037	Isoform 8	-	NP_001339279	850	95.26	4.55
	Var.12	NM_001352352				5073	Isoform 10	-	NP_001339281	862	96.45	4.55
	Var.13	NM_001352353				4704	Isoform 11	-	NP_001339282	717	79.53	4.49
	Var.14	NM_001352354				5281	Isoform 12	-	NP_001339283	889	99.47	4.53
	Var.16	NM_001352356				5154	Isoform 12	-	NP_001339285	889	99.47	4.53
	Var.20	NM_001352360				5194	Isoform 17	-	NP_001339289	860	96.25	4.54
	Var.24	NM_001352364				5251	Isoform 4	A, C11orf23a, SAPLa	NP_001339293	879	98.49	4.54
	Var.29	NM_001352369				5149	Isoform 20	-	NP_001339298	654	72.16	4.45
	Var.30	NM_001352370				4891	Isoform 21	-	NP_001339299	788	87.69	4.56
	Var.31	NM_001352371				5200	Isoform 10	-	NP_001339300	862	96.45	4.55
	Var.32	NM_001352372				5233	Isoform 24	-	NP_001339301	873	97.73	4.54
	Var.33	NM_001352373				5067	Isoform 17	-	NP_001339302	860	96.25	4.54
	Var.34	NM_001352374				4804	Isoform 22	-	NP_001339303	759	84.47	4.58
	Var.36	NM_001352376				5164	Isoform 8	-	NP_001339305	850	95.26	4.55
	Var.37	NM_001352377				5106	Isoform 24	-	NP_001339306	873	97.73	4.54
	Var.38	NM_001352378				4931	Isoform 22	-	NP_001339307	759	84.47	4.58
	Var.39	NM_001352379				5390	Isoform 4	A, C11orf23a, SAPLa	NP_001339308	879	98.49	4.54
	Var.40	NM_001352380				5142	Isoform 8	-	NP_001339309	850	95.26	4.55
	Var.42	NR_147966			ncRNA	5392	-	-	-	-	-	-
PPP6R3-205 (PPP6R3-026)	Var.2	NM_001164163	ENST00000524845.5	23	protein coding	5040	Isoform 2	-	NP_001157635	844	94.44	4.51
	Var.15	NM_001352355				4786	Isoform 13	-	NP_001339284	753	83.65	4.54
	Var.23	NM_001352363				5146	Isoform 2	-	NP_001339292	844	94.44	4.51
PPP6R3-206 (PPP6R3-007)	Var.1	NM_001164162	ENST00000524904.5	24	protein coding	5109	Isoform 1	-	NP_001157634	867	96.96	4.51
	Var.8	NM_001352348				5284	Isoform 1	-	NP_001339277	867	96.96	4.51
	Var.11	NM_001352351				4822	Isoform 9	-	NP_001339280	765	84.84	4.54
	Var.18	NM_001352358				4902	Isoform 15	-	NP_001339287	805	90.14	4.49
	Var.19	NM_001352359				4885	Isoform 16	-	NP_001339288	786	87.15	4.52
	Var.22	NM_001352362				5129	Isoform 19	-	NP_001339291	856	95.63	4.52
	Var.25	NM_001352365				5055	Isoform 19	-	NP_001339294	856	95.63	4.52
PPP6R3-207	-	-	ENST00000525050.5	4	retained intron	513	-	-	-	-	-	-
PPP6R3-208	-	-	ENST00000525152.1	2	retained intron	582	-	-	-	-	-	-
PPP6R3-209	-	-	ENST00000525421.5	8	nonsense md	830	-	-	-	-	-	-
PPP6R3-210	-	-	ENST00000526307.5	10	retained intron	4134	-	-	-	-	-	-
PPP6R3-211	-	-	ENST00000526574.1	4	retained intron	489	-	-	-	-	-	-
PPP6R3-212	-	-	ENST00000526593.1	5	nonsense md	570	-	-	-	-	-	-
PPP6R3-213	-	-	ENST00000527069.5	4	retained intron	573	-	-	-	-	-	-
PPP6R3-214 (PPP6R3-020)	Var.26	NM_001352366	ENST00000527403.6	22	protein coding	5019	Isoform 23	-	NP_001339295	844	94.55	4.56
PPP6R3-215 (PPP6R3-012)	-	-	ENST00000528635.5	5	(?)	538	-	-	-	-	-	-
PPP6R3-216	-	-	ENST00000529172.1	4	retained intron	500	-	-	-	-	-	-
PPP6R3-217 (PPP6R3-011)	-	-	ENST00000529344.5	4	(?)	603	-	-	-	-	-	-
PPP6R3-218 (PPP6R3-004)	Var.3	NM_001164164	ENST00000529710.5	23	protein coding	3426	Isoform 3	B, C11orf23b, SAPLb	NP_001157636	791	88.91	4.48
PPP6R3-219 (PPP6R3-009)	-	-	ENST00000529907.5	7	(?)	826	-	-	-	-	-	-
PPP6R3-220	-	-	ENST00000530427.5	5	processed transcript	560	-	-	-	-	-	-
PPP6R3-221 (PPP6R3-025)	-	-	ENST00000530734.1	2	(?)	576	-	-	-	-	-	-
PPP6R3-222 (PPP6R3-013)	-	-	ENST00000531244.1	5	(?)	687	-	-	-	-	-	-
PPP6R3-223	-	-	ENST00000531432.1	2	retained intron	590	-	-	-	-	-	-
PPP6R3-224 (PPP6R3-027)	-	-	ENST00000533127.5	4	(?)	551	-	-	-	-	-	-
PPP6R3-225 (PPP6R3-018)	Var.17	NM_001352357	ENST00000534190.5	16	protein coding	5150	Isoform 14	-	NP_001339286	619	68.12	4.42
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.

Pseudogene

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

Protein

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).

Description

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.

Expression

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).

Localisation

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).

Function

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).

Homology

PPP6R3 is highly and abundant conserved in many species and its homology between the species is reported in Table.2

Organism	Species	Symbol	DNA Identity (%)	Prot Identity (%)
Human	H.sapiens	PPP6R3	100	100
Chimpanzee	P.troglodytes	LOC710120	99.6	99.8
Macaco	M.mulatta	PPP6R3	95.6	96.4
Wolf	C.lupus	PPP6R3	92.8	92.2
Cattle	B.taurus	PPP6R3	91.8	96.0
Mouse	M.musculus	Ppp6r3	90.5	96.3
Rat	R.norvegicus	Ppp6r3	90.6	95.5
Chicken	G.gallus	PPP6R3	82.8	91.5
Xenopus tropicalis	X.tropicalis	Ppp6r3	75.6	80.3
Zebrafish	D.rerio	Ppp6r3	71.6	79.0

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

Implicated in

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.
C11orf80/PPP6R3	C11orf80	PPP6R3	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Hu et al., 2018
CCDC132/PPP6R3	CCDC132	PPP6R3	7q21.2	11q13.2	t(7;11)(q21;q13)	Translocation	Adenocarcinoma	Lung	LUAD	-
CTTN/PPP6R3	CTTN	PPP6R3	17q23.3	11q13.2	t(11;11)(q13;q13)	Fusion gene	Malignant melanoma	Skin	SKCM	Hu et al., 2018
CSHL1/PPP6R3	CSHL1	PPP6R3	17q23.3	11q13.2	t(11:17)(q13;q23)	Translocation	(?)	(?)	(?)	-
DPP9/PPP6R3	DPP9	PPP6R3	19p13.3	11q13.2	t(11;19)(q13;p13)	Translocation	Adenocarcinoma	Ovary	OVCA	Smebye et al., 2017
EEF1G/PPP6R3	EEF1G	PPP6R3	11q12.3	11q13.2	t(11;11)(q12;q13)	Fusion gene	Squamous cell carcinoma	Lung	LUSC	Hammerman et al., 2012
ITGB5 /PPP6R3	ITGB5	PPP6R3	3q21.2	11q13.2	t(3;11)(q21;q13)	Translocation	(?)	(?)	(?)	-
KDM2A/PPP6R3	KDM2A	PPP6R3	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
KRT5/PPP6R3	KRT5	PPP6R3	12q13.13	11q13.2	t(11;12)(q13;q13)	Translocation	(?)	(?)	(?)	-
MKL2/PPP6R3	MKL2	PPP6R3	16p13.12	11q13.2	t(11;16)(q13;p13)	Translocation	(?)	(?)	(?)	-
NADSYN1/PPP6R3	NADSYN1	PPP6R3	11q13.4	11q13.2	t(11;11)(q13;q13)	Fusion gene	Malignant melanoma	Skin	SKCM	Hu et al., 2018; Klijn et al., 2015
PC/PPP6R3	PC	PPP6R3	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
PPP6R3/ACER3	PPP6R3	ACER3	11q13.2	11q13.5	t(11;11)(q13;q13)	Fusion gene	Malignant melanoma	Skin	SKCM	Hu et al., 2018
PPP6R3/ARHGAP1	PPP6R3	ARHGAP1	11q13.2	11p11.2	t(11;11)(p11;q13)	Fusion gene	Squamous cell carcinoma	Lung	LUSC	Yoshihara et al., 2015
PPP6R3/ATP6V0D2	PPP6R3	ATP6V0D2	11q13.2	8q21.3	t(8;11)(q21;q13)	Translocation	Sarcoma	Soft tissue	SARC	-
PPP6R3/CNTN5	PPP6R3	CNTN5	11q13.2	11q22.1	t(11;11)(q13;q22)	Fusion gene	Squamous cell carcinoma	Lung	LUSC	Hammerman et al., 2012
PPP6R3/DPP3	PPP6R3	DPP3	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Germ cell tumor, NOS	Testis	TGCT	Hoff et al., 2016
PPP6R3/FADD	PPP6R3	FADD	11q13.2	11q13.3	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
PPP6R3/EIF4G3	PPP6R3	EIF4G3	11q13.2	1p36.12	t(1;11)(p36;q13)	Translocation	Malignant melanoma	Skin	SKCM	-
PPP6R3/INTS4	PPP6R3	INTS4	11q13.2	11q14.1	t(11;11)(q13;q14)	Fusion gene	Acute lymphoblastic leukemia/lymphoblastic lymphoma (T-Lineage)	Blood	T-ALL	Liu et al., 2017
PPP6R3/LRP5	PPP6R3	LRP5	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Squamous cell carcinoma	Lung	LUSC	Yoshihara et al., 2015
PPP6R3/LRP5	PPP6R3	LRP5	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Pancreas	PAAD	-
PPP6R3/MGAM	PPP6R3	MGAM	11q13.2	7q34	t(7;11)(q34;q13)	Translocation	Squamous cell carcinoma	Lung	LUSC	-
PPP6R3/MTL5	PPP6R3	MTL5	11q13.2	11q13.3	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
PPP6R3/POLD3	PPP6R3	POLD3	11q13.2	11q13.4	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
PPP6R3/PREPL	PPP6R3	PREPL	11q13.2	2p21	t(2;11)(p21;q13)	Translocation	(?)	(?)	(?)	-
PPP6R3/RHOD	PPP6R3	RHOD	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Stomach	STAD	Hu et al., 2018
PPP6R3/SHANK2	PPP6R3	SHANK2	11q13.2	11q13.3	t(11;11)(q13;q13)	Fusion gene	Transitional cell carcinoma	Bladder	BLCA	Hu et al., 2018
PPP6R3/SPTBN2	PPP6R3	SPTBN2	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
PPP6R3/SSH2	PPP6R3	SSH2	11q13.2	17q11.2	t(11;17)(q13;q11)	Translocation	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
							Neuroblastoma	Soft tissue	NBL	McRobert et al., 1992
							Acute lymphoblastic leukemia/lymphoblastic lymphoma	Blood	ALL	Schmiegelow et al., 2012
PPP6R3/SSH3	PPP6R3	SSH3	11q13.2	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Pancreas	PAAD	Hu et al., 2018
PPP6R3/USP6	PPP6R3	USP6	11q13.2	17p13.2	t(11;17)(q13;p13)	Translocation	Nodular fasciitis	Soft tissue	NF	Guo et al., 2016
							Hairy cell leukemia	Blood	HCL	Nacheva et al., 1992
							Multiple myeloma	Blood	MM	Sawyer et al., 1995; Sawyer et al., 2014
							Chronic myeloid leukemia	Blood	CML	Stopera et al., 1990
PPP6R3/YAP1	PPP6R3	YAP1	11q13.2	11q22.1	t(11;11)(q13;q22)	Fusion gene	Transitional cell carcinoma	Bladder	BLCA	Yoshihara et al., 2015
RAB11A/PPP6R3	RAB11A	PPP6R3	15q22.31	11q13.2	t(11;15)(q13;q22)	Translocation	Cell carcinoma and endocervical adenocarcinoma	Cervical	CESC	-
RNF121/PPP6R3	RNF121	PPP6R3	11q13.4	11q13.2	t(11;11)(q13;q13)	Fusion gene	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
SH3RF1/PPP6R3	SH3RF1	PPP6R3	4q32.3	11q13.2	t(4;11)(q32;q13)	Translocation	(?)	(?)	(?)	-
SMAD2/PPP6R3	SMAD2	PPP6R3	18q21.1	11q13.2	t(11;18)(q13;q21)	Translocation	(?)	(?)	(?)	-
SSBP1/PPP6R3	SSBP1	PPP6R3	7q34	11q13.2	t(7;11)(q34;q13)	Translocation	Squamous cell carcinoma	Lung	LUSC	-
STRN3/PPP6R3	STRN3	PPP6R3	14q12	11q13.2	t(11;14)(q13;q12)	Translocation	Adenocarcinoma	Breast	BRCA	Yoshihara et al., 2015
TMPRSS6/PPP6R3	TMPRSS6	PPP6R3	22q12.3	11q13.2	t(11;22)(q13;q12)	Translocation	Liver hepatocellular carcinoma	Liver	LIHC	-
TNFRSF21/PPP6R3	TNFRSF21	PPP6R3	6p12.3	11q13.2	t(6;11)(p12;q13)	Translocation	Adenocarcinoma	Breast	BRCA	Banerji et al., 2012
VPS50/PPP6R3	VPS50	PPP6R3	7q21.3	11q13.2	t(7;11)(q21;q13)	Translocation	(?)	(?)	(?)	-

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

Acute lymphoblastic leukemia (ALL)

Hybrid/Mutated 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

Bladder cancer

Hybrid/Mutated 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

Breast cancer

Hybrid/Mutated 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

Cervical carcinoma

Hybrid/Mutated Gene

A t(11;15)(q13;q22) RAB11A/PPP6R3 has been found in cervical carcinoma (http://www.tumorfusions.org).

Entity

Gastric cancer

Hybrid/Mutated Gene

The fusion gene PPP6R3/ RHOD has been found in gastric adenocarcinoma (Hu et al., 2018; http://www.tumorfusions.org)

Entity

t(11;17)(q13;p13)PPP6R3/USP6 in hematological malignancies.

Hybrid/Mutated 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

Hepatocellular carcinoma

Hybrid/Mutated Gene

A t(11;22)(q13;q12) TMPRSS6/PPP6R3 has been found in hepatocellular carcinoma (http://www.tumorfusions.org).

Entity

Lung squamous cell carcinoma

Hybrid/Mutated 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

Malignant melanoma

Hybrid/Mutated 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

Malignant Nodular Fasciitis

Disease

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/Mutated 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).

Oncogenesis

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

Nervous system tumors

Disease

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

Ovarian carcinoma

Disease

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/Mutated 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).

Abnormal 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

Pancreatic cancer

Hybrid/Mutated Gene

The fusion genes PPP6R3/LRP5 and PPP6R3/ SSH3 have been found in pancreas adenocarcinoma (Hu et al., 2018; http://www.tumorfusions.org)

Entity

Testicular germ cell tumors

Disease

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/Mutated 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.

Abnormal 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

Type 1 diabetes mellitus 4

Note

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

Effects on HIV-1 replication

Note

Knockdown of PPP6R3 by short interfering RNAs (siRNA) library screening inhibits HIV-1 replication in cultured Jurkat T-cells (Yeung et al., 2009).

Bibliography

Sequence analysis of mutations and translocations across breast cancer subtypes

Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L, Cortes ML, Fernandez-Lopez JC, Peng S, Ardlie KG, Auclair D, Bautista-Piña V, Duke F, Francis J, Jung J, Maffuz-Aziz A, Onofrio RC, Parkin M, Pho NH, Quintanar-Jurado V, Ramos AH, Rebollar-Vega R, Rodriguez-Cuevas S, Romero-Cordoba SL, Schumacher SE, Stransky N, Thompson KM, Uribe-Figueroa L, Baselga J, Beroukhim R, Polyak K, Sgroi DC, Richardson AL, Jimenez-Sanchez G, Lander ES, Gabriel SB, Garraway LA, Golub TR, Melendez-Zajgla J, Toker A, Getz G, Hidalgo-Miranda A, Meyerson M

Nature 2012 Jun 20;486(7403):405-9

PMID 22722202

Nodular (pseudosarcomatous) fasciitis, a nonrecurrent lesion: clinicopathologic study of 134 cases

Bernstein KE, Lattes R

Cancer 1982 Apr 15;49(8):1668-78

PMID 6279273

A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway

Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G

Nat Cell Biol 2004 Feb;6(2):97-105

PMID 14743216

Comprehensive genomic characterization of squamous cell lung cancers

Cancer Genome Atlas Research Network

Nature 2012 Sep 27;489(7417):519-25

PMID 22960745

Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion

Erickson-Johnson MR, Chou MM, Evers BR, Roth CW, Seys AR, Jin L, Ye Y, Lau AW, Wang X, Oliveira AM

Lab Invest 2011 Oct;91(10):1427-33

PMID 21826056

Mapping of protein phosphatase-6 association with its SAPS domain regulatory subunit using a model of helical repeats

Guergnon J, Derewenda U, Edelson JR, Brautigan DL

BMC Biochem 2009 Oct 16;10:24

PMID 19835610

PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis

Guo R, Wang X, Chou MM, Asmann Y, Wenger DE, Al-Ibraheemi A, Molavi DW, Aboulafia A, Jin L, Fritchie K, Oliveira JL, Jenkins RB, Westendorf JJ, Dong J, Oliveira AM

Genes Chromosomes Cancer 2016 Aug;55(8):640-9

PMID 27113271

Identification of Novel Fusion Genes in Testicular Germ Cell Tumors

Hoff AM, Alagaratnam S, Zhao S, Bruun J, Andrews PW, Lothe RA, Skotheim RI

Cancer Res 2016 Jan 1;76(1):108-16

PMID 26659575

TumorFusions: an integrative resource for cancer-associated transcript fusions

Hu X, Wang Q, Tang M, Barthel F, Amin S, Yoshihara K, Lang FM, Martinez-Ledesma E, Lee SH, Zheng S, Verhaak RGW

Nucleic Acids Res 2018 Jan 4;46(D1):D1144-D1149

PMID 29099951

A comprehensive transcriptional portrait of human cancer cell lines

Klijn C, Durinck S, Stawiski EW, Haverty PM, Jiang Z, Liu H, Degenhardt J, Mayba O, Gnad F, Liu J, Pau G, Reeder J, Cao Y, Mukhyala K, Selvaraj SK, Yu M, Zynda GJ, Brauer MJ, Wu TD, Gentleman RC, Manning G, Yauch RL, Bourgon R, Stokoe D, Modrusan Z, Neve RM, de Sauvage FJ, Settleman J, Seshagiri S, Zhang Z

Nat Biotechnol 2015 Mar;33(3):306-12

PMID 25485619

The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia

Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, McCastlain K, Edmonson M, Pounds SB, Shi L, Zhou X, Ma X, Sioson E, Li Y, Rusch M, Gupta P, Pei D, Cheng C, Smith MA, Auvil JG, Gerhard DS, Relling MV, Winick NJ, Carroll AJ, Heerema NA, Raetz E, Devidas M, Willman CL, Harvey RC, Carroll WL, Dunsmore KP, Winter SS, Wood BL, Sorrentino BP, Downing JR, Loh ML, Hunger SP, Zhang J, Mullighan CG

Nat Genet 2017 Aug;49(8):1211-1218

PMID 28671688

Detection of MYCN amplification in three neuroblastoma cell lines by non-radioactive chromosomal in situ hybridization

McRobert TL, Rudduck C, Kees UR, Garson OM

Cancer Genet Cytogenet 1992 Apr;59(2):128-34

PMID 1581879

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

Medina-Gomez C, Kemp JP, Dimou NL, Kreiner E, Chesi A, Zemel BS, Bønnelykke K, Boer CG, Ahluwalia TS, Bisgaard H, Evangelou E, Heppe DHM, Bonewald LF, Gorski JP, Ghanbari M, Demissie S, Duque G, Maurano MT, Kiel DP, Hsu YH, C J van der Eerden B, Ackert-Bicknell C, Reppe S, Gautvik KM, Raastad T, Karasik D, van de Peppel J, Jaddoe VWV, Uitterlinden AG, Tobias JH, Grant SFA, Bagos PG, Evans DM, Rivadeneira F

Nat Commun 2017 Jul 25;8(1):121

PMID 28743860

Complex chromosomal rearrangements in an unusual variant of hairy cell leukemia

Nacheva E, Fischer P, O'Connor S, Bloxham D, Hoggarth C, Marcus R

Cancer Genet Cytogenet 1992 Sep;62(2):186-90

PMID 1394107

Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis

Rahrmann EP, Watson AL, Keng VW, Choi K, Moriarity BS, Beckmann DA, Wolf NK, Sarver A, Collins MH, Moertel CL, Wallace MR, Gel B, Serra E, Ratner N, Largaespada DA

Nat Genet 2013 Jul;45(7):756-66

PMID 23685747

Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells

Rusin SF, Schlosser KA, Adamo ME, Kettenbach AN

Sci Signal 2015 Oct 13;8(398):rs12

PMID 26462736

Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease

Sawyer JR, Tian E, Heuck CJ, Epstein J, Johann DJ, Swanson CM, Lukacs JL, Johnson M, Binz R, Boast A, Sammartino G, Usmani S, Zangari M, Waheed S, van Rhee F, Barlogie B

Blood 2014 Apr 17;123(16):2504-12

PMID 24497533

Cytogenetic findings in 200 patients with multiple myeloma

Sawyer JR, Waldron JA, Jagannath S, Barlogie B

Cancer Genet Cytogenet 1995 Jul 1;82(1):41-9

PMID 7627933

High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia

Schmiegelow K, Lausten Thomsen U, Baruchel A, Pacheco CE, Pieters R, Pombo-de-Oliveira MS, Andersen EW, Rostgaard K, Hjalgrim H, Pui CH

Leukemia 2012 Apr;26(4):675-81

PMID 22005784

Involvement of DPP9 in gene fusions in serous ovarian carcinoma

Smebye ML, Agostini A, Johannessen B, Thorsen J, Davidson B, Tropé CG, Heim S, Skotheim RI, Micci F

BMC Cancer 2017 Sep 11;17(1):642

PMID 28893231

Protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains

Stefansson B, Ohama T, Daugherty AE, Brautigan DL

Biochemistry 2008 Feb 5;47(5):1442-51

PMID 18186651

Variant Philadelphia translocations in chronic myeloid leukemia: correlation with cancer breakpoints, fragile sites and oncogenes

Stopera SA, Ray M, Riordan D, Christie N, Wickstrom D

Cancer Lett 1990 Dec 17;55(3):249-53

The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13

Twells RC, Metzker ML, Brown SD, Cox R, Garey C, Hammond H, Hey PJ, Levy E, Nakagawa Y, Philips MS, Todd JA, Hess JF

Genomics 2001 Mar 15;72(3):231-42

PMID 11401438

A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication

Yeung ML, Houzet L, Yedavalli VS, Jeang KT

J Biol Chem 2009 Jul 17;284(29):19463-73

PMID 19460752

Interactome analysis of the influenza A virus transcription/replication machinery identifies protein phosphatase 6 as a cellular factor required for efficient virus replication

York A, Hutchinson EC, Fodor E

J Virol 2014 Nov;88(22):13284-99

PMID 25187537

The landscape and therapeutic relevance of cancer-associated transcript fusions

Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RG

Oncogene 2015 Sep 10;34(37):4845-54

PMID 25500544

Functions of protein phosphatase-6 in NF-κB signaling and in lymphocytes

Ziembik MA, Bender TP, Larner JM, Brautigan DL

Biochem Soc Trans 2017 Jun 15;45(3):693-701

PMID 28620030

International variations and trends in testicular cancer incidence and mortality

Znaor A, Lortet-Tieulent J, Jemal A, Bray F

Eur Urol 2014 Jun;65(6):1095-106

PMID 24268506

Citation

This paper should be referenced as such :

Cristiano L.

PPP6R3 (protein phosphatase 6 regulatory subunit 3);

Atlas Genet Cytogenet Oncol Haematol. in press

On line version : http://AtlasGeneticsOncology.org/Genes/PPP6R3ID54550ch11q13.html

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]

t(11;11)(q13;q14) PPP6R3/INTS4

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 17 ]

EEF1G/PPP6R3 (11q12-13)
Lung: Translocations in Squamous Cell Carcinoma
t(11;11)(p11;q13) PPP6R3/ARHGAP1
t(11;11)(q12;q13) EEF1G/PPP6R3
KDM2A/PPP6R3 (11q13)
PC/PPP6R3 (11q13)
PPP6R3/DPP3 (11q13)
PPP6R3/FADD (11q13)
PPP6R3/LRP5 (11q13)
PPP6R3/POLD3 (11q13)
PPP6R3/SPTBN2 (11q13)
RNF121/PPP6R3 (11q13)
t(11;11)(q13;q22) PPP6R3/YAP1
t(11;11)(q13;q22) PPP6R3/CNTN5
t(11;14)(q13;q12) STRN3/PPP6R3
t(11;17)(q13;p13) PPP6R3/USP6
t(11;17)(q13;q11) PPP6R3/SSH2

External links

	Nomenclature
HGNC (Hugo)	PPP6R3 1173
	Cards
Atlas	PPP6R3ID54550ch11q13
Entrez_Gene (NCBI)	PPP6R3 55291 protein phosphatase 6 regulatory subunit 3
Aliases	C11orf23; PP6R3; SAP190; SAPL;
	SAPLa; SAPS3
GeneCards (Weizmann)	PPP6R3
Ensembl hg19 (Hinxton)	ENSG00000110075 [Gene_View]
Ensembl hg38 (Hinxton)	ENSG00000110075 [Gene_View] ENSG00000110075 [Sequence] chr11:68460718-68615333 [Contig_View] PPP6R3 [Vega]
ICGC DataPortal	ENSG00000110075
TCGA cBioPortal	PPP6R3
AceView (NCBI)	PPP6R3
Genatlas (Paris)	PPP6R3
WikiGenes	55291
SOURCE (Princeton)	PPP6R3
Genetics Home Reference (NIH)	PPP6R3
	Genomic and cartography
GoldenPath hg38 (UCSC)	PPP6R3 - chr11:68460718-68615333 + 11q13.2 [Description] (hg38-Dec_2013)
GoldenPath hg19 (UCSC)	PPP6R3 - 11q13.2 [Description] (hg19-Feb_2009)
GoldenPath	PPP6R3 - 11q13.2 [CytoView hg19] PPP6R3 - 11q13.2 [CytoView hg38]
ImmunoBase	ENSG00000110075
Mapping of homologs : NCBI	PPP6R3 [Mapview hg19] PPP6R3 [Mapview hg38]
OMIM	610879
	Gene and transcription
Genbank (Entrez)	AB046778 AF264779 AF264780 AK001920 AK023950
RefSeq transcript (Entrez)	NM_001164160 NM_001164161 NM_001164162 NM_001164163 NM_001164164 NM_001352347 NM_001352348 NM_001352350 NM_001352351 NM_001352352 NM_001352353 NM_001352354 NM_001352355 NM_001352356 NM_001352357 NM_001352358 NM_001352359 NM_001352360 NM_001352361 NM_001352362 NM_001352363 NM_001352364 NM_001352365 NM_001352366 NM_001352368 NM_001352369 NM_001352370 NM_001352371 NM_001352372 NM_001352373 NM_001352374 NM_001352375 NM_001352376 NM_001352377 NM_001352378 NM_001352379 NM_001352380 NM_018312
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)	PPP6R3
Cluster EST : Unigene	Hs.503022 [ NCBI ]
CGAP (NCI)	Hs.503022
Alternative Splicing Gallery	ENSG00000110075
Gene Expression	PPP6R3 [ NCBI-GEO ] PPP6R3 [ EBI - ARRAY_EXPRESS ] PPP6R3 [ SEEK ] PPP6R3 [ MEM ]
Gene Expression Viewer (FireBrowse)	PPP6R3 [ Firebrowse - Broad ]
SOURCE (Princeton)	Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60]
Genevestigator	Expression in : [tissues] [cell-lines] [cancer] [perturbations]
BioGPS (Tissue expression)	55291
GTEX Portal (Tissue expression)	PPP6R3
Human Protein Atlas	ENSG00000110075-PPP6R3 [pathology] [cell] [tissue]
	Protein : pattern, domain, 3D structure
UniProt/SwissProt	Q5H9R7 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction]
NextProt	Q5H9R7 [Sequence] [Exons] [Medical] [Publications]
With graphics : InterPro	Q5H9R7
Splice isoforms : SwissVar	Q5H9R7
PhosPhoSitePlus	Q5H9R7
Domains : Interpro (EBI)	ARM-type_fold SAPS
Domain families : Pfam (Sanger)	SAPS (PF04499)
Domain families : Pfam (NCBI)	pfam04499
Conserved Domain (NCBI)	PPP6R3
DMDM Disease mutations	55291
Blocks (Seattle)	PPP6R3
Superfamily	Q5H9R7
Human Protein Atlas [tissue]	ENSG00000110075-PPP6R3 [tissue]
Peptide Atlas	Q5H9R7
HPRD	10703
IPI	IPI00719821 IPI00719553 IPI00719345 IPI00019540 IPI00719725 IPI00030624 IPI00909546 IPI00975695 IPI01015850 IPI00985268 IPI00976160 IPI00984704 IPI00985128 IPI00983215 IPI00977455 IPI00983893 IPI00983242 IPI00976813 IPI00985067
	Protein Interaction databases
DIP (DOE-UCLA)	Q5H9R7
IntAct (EBI)	Q5H9R7
FunCoup	ENSG00000110075
BioGRID	PPP6R3
STRING (EMBL)	PPP6R3
ZODIAC	PPP6R3
	Ontologies - Pathways
QuickGO	Q5H9R7
Ontology : AmiGO	Golgi membrane protein binding nucleoplasm cytosol cytosol plasma membrane protein phosphatase binding regulation of phosphoprotein phosphatase activity COPII vesicle coating
Ontology : EGO-EBI	Golgi membrane protein binding nucleoplasm cytosol cytosol plasma membrane protein phosphatase binding regulation of phosphoprotein phosphatase activity COPII vesicle coating
REACTOME	Q5H9R7 [protein]
REACTOME Pathways	R-HSA-204005 [pathway]
NDEx Network	PPP6R3
Atlas of Cancer Signalling Network	PPP6R3
Wikipedia pathways	PPP6R3
	Orthology - Evolution
OrthoDB	55291
GeneTree (enSembl)	ENSG00000110075
Phylogenetic Trees/Animal Genes : TreeFam	PPP6R3
HOGENOM	Q5H9R7
Homologs : HomoloGene	PPP6R3
Homology/Alignments : Family Browser (UCSC)	PPP6R3
	Gene fusions - Rearrangements
Fusion : Mitelman	CCDC132/11q13.2 [PPP6R3/t(7;11)(q21;q13)]
Fusion : Mitelman	EEF1G/PPP6R3 [11q12.3/11q13.2] [t(11;11)(q12;q13)]
Fusion : Mitelman	KDM2A/PPP6R3 [11q13.2/11q13.2] [t(11;11)(q13;q13)]
Fusion : Mitelman	PC/PPP6R3 [11q13.2/11q13.2] [t(11;11)(q13;q13)]
Fusion : Mitelman	PPP6R3/ARHGAP1 [11q13.2/11p11.2] [t(11;11)(p11;q13)]
Fusion : Mitelman	PPP6R3/CNTN5 [11q13.2/11q22.1] [t(11;11)(q13;q22)]
Fusion : Mitelman	PPP6R3/FADD [11q13.2/11q13.3] [t(11;11)(q13;q13)]
Fusion : Mitelman	PPP6R3/LRP5 [11q13.2/11q13.2] [t(11;11)(q13;q13)]
Fusion : Mitelman	PPP6R3/MTL5 [11q13.2/11q13.3] [t(11;11)(q13;q13)]
Fusion : Mitelman	PPP6R3/POLD3 [11q13.2/11q13.4] [t(11;11)(q13;q13)]
Fusion : Mitelman	PPP6R3/SPTBN2 [11q13.2/11q13.2] [t(11;11)(q13;q13)]
Fusion : Mitelman	PPP6R3/SSH2 [11q13.2/17q11.2] [t(11;17)(q13;q11)]
Fusion : Mitelman	PPP6R3/YAP1 [11q13.2/11q22.1] [t(11;11)(q13;q22)]
Fusion : Mitelman	RNF121/PPP6R3 [11q13.4/11q13.2] [t(11;11)(q13;q13)]
Fusion : Mitelman	STRN3/PPP6R3 [14q12/11q13.2] [t(11;14)(q13;q12)]
Fusion Portal	CCDC132 PPP6R3 11q13.2 LUAD
Fusion Portal	KDM2A 11q13.2 PPP6R3 11q13.2 BRCA
Fusion Portal	PC 11q13.2 PPP6R3 11q13.2 BRCA
Fusion Portal	PPP6R3 11q13.2 ARHGAP1 11p11.2 LUSC
Fusion Portal	PPP6R3 11q13.2 FADD 11q13.3 BRCA
Fusion Portal	PPP6R3 11q13.2 LRP5 11q13.2 LUSC
Fusion Portal	PPP6R3 11q13.2 MTL5 11q13.3 BRCA
Fusion Portal	PPP6R3 11q13.2 POLD3 11q13.4 BRCA
Fusion Portal	PPP6R3 11q13.2 SPTBN2 11q13.2 BRCA
Fusion Portal	PPP6R3 11q13.2 SSH2 17q11.2 BRCA
Fusion Portal	PPP6R3 11q13.2 YAP1 11q22.1 BLCA
Fusion Portal	RNF121 11q13.4 PPP6R3 11q13.2 BRCA
Fusion Portal	STRN3 14q12 PPP6R3 11q13.2 BRCA
Fusion : FusionGDB	17886 18409 19272 22089 23362 26332 28532 28533 28534 28535 28536 28537 28538 28539 28540
	28541 28542 28543 28544 28545 28546 28547 28548 28549 29870 31401 33690 34732 38775 43074
	4651 8606 8955
Fusion : Fusion_Hub	ANTXR1--PPP6R3 BCCIP--PPP6R3 C11ORF80--PPP6R3 CCDC132--PPP6R3 CSHL1--PPP6R3 CTTN--PPP6R3 DDAH1--PPP6R3 DPP3--PPP6R3 DPP9--PPP6R3 FAM168A--PPP6R3 FCHSD2--PPP6R3 FGFR1OP2--PPP6R3 FOXJ3--PPP6R3 ITGB5--PPP6R3 KDM2A--PPP6R3
	KDM4C--PPP6R3 KRT5--PPP6R3 LRP5--PPP6R3 MKL2--PPP6R3 NADSYN1--PPP6R3 NAPG--PPP6R3 OPA1--PPP6R3 PC--PPP6R3 PHF21A--PPP6R3 PPP6R3--ACER3 PPP6R3--ACTB PPP6R3--ANAPC4 PPP6R3--ARHGAP1 PPP6R3--ATG2A PPP6R3--ATP6V0D2
	PPP6R3--C11ORF63 PPP6R3--C17ORF67 PPP6R3--CAPZB PPP6R3--CDK19 PPP6R3--CHMP3 PPP6R3--DPP3 PPP6R3--DRG1 PPP6R3--EIF4G3 PPP6R3--FADD PPP6R3--GNB2L1 PPP6R3--GOLGA8A PPP6R3--KDM2A PPP6R3--KLC1 PPP6R3--LOC338694 PPP6R3--LRP5
	PPP6R3--LRTM1 PPP6R3--MGAM PPP6R3--MTL5 PPP6R3--POLD3 PPP6R3--PPFIA1 PPP6R3--PPP1CB PPP6R3--PREPL PPP6R3--RHOD PPP6R3--SERINC1 PPP6R3--SHANK2 PPP6R3--SIK2 PPP6R3--SPTBN2 PPP6R3--SS18 PPP6R3--SSH2 PPP6R3--SSH3
	PPP6R3--TBC1D15 PPP6R3--YAP1 RAB11A--PPP6R3 RNF121--PPP6R3 SCARB1--PPP6R3 SCCPDH--PPP6R3 SH3RF1--PPP6R3 SHANK2--PPP6R3 SMAD2--PPP6R3 SSBP1--PPP6R3 STRN3--PPP6R3 TMPRSS6--PPP6R3
Fusion : Quiver	PPP6R3
	Polymorphisms : SNP and Copy number variants
NCBI Variation Viewer	PPP6R3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)	PPP6R3
dbVar	PPP6R3
ClinVar	PPP6R3
1000_Genomes	PPP6R3
Exome Variant Server	PPP6R3
ExAC (Exome Aggregation Consortium)	ENSG00000110075
GNOMAD Browser	ENSG00000110075
Varsome Browser	PPP6R3
Genetic variants : HAPMAP	55291
Genomic Variants (DGV)	PPP6R3 [DGVbeta]
DECIPHER	PPP6R3 [patients] [syndromes] [variants] [genes]
CONAN: Copy Number Analysis	PPP6R3
	Mutations
ICGC Data Portal	PPP6R3
TCGA Data Portal	PPP6R3
Broad Tumor Portal	PPP6R3
OASIS Portal	PPP6R3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMIC	PPP6R3 [overview] [genome browser] [tissue] [distribution]
Somatic Mutations in Cancer : COSMIC3D	PPP6R3
Mutations and Diseases : HGMD	PPP6R3
LOVD (Leiden Open Variation Database)	Whole genome datasets
LOVD (Leiden Open Variation Database)	LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)	LOVD 3.0 shared installation
BioMuta	search PPP6R3
DgiDB (Drug Gene Interaction Database)	PPP6R3
DoCM (Curated mutations)	PPP6R3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)	PPP6R3 (select a term)
intoGen	PPP6R3
NCG5 (London)	PPP6R3
Cancer3D	PPP6R3(select the gene name)
Impact of mutations	[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
	Diseases
OMIM	610879
Orphanet
DisGeNET	PPP6R3
Medgen	PPP6R3
Genetic Testing Registry	PPP6R3
NextProt	Q5H9R7 [Medical]
TSGene	55291
GENETests	PPP6R3
Target Validation	PPP6R3
Huge Navigator	PPP6R3 [HugePedia]
snp3D : Map Gene to Disease	55291
BioCentury BCIQ	PPP6R3
ClinGen	PPP6R3
	Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD	55291
Chemical/Pharm GKB Gene	PA25487
Clinical trial	PPP6R3
	Miscellaneous
canSAR (ICR)	PPP6R3 (select the gene name)
DataMed Index	PPP6R3
	Probes
	Litterature
PubMed	74 Pubmed reference(s) in Entrez
GeneRIFs	Gene References Into Functions (Entrez)
CoreMine	PPP6R3
EVEX	PPP6R3
GoPubMed	PPP6R3
iHOP	PPP6R3

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI NCBI

indexed on : Wed Nov 13 21:50:55 CET 2019

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