ID P2R3C_HUMAN Reviewed; 453 AA. AC Q969Q6; B4DEN7; D3DS97; D3DS98; Q5GJ55; Q5GJ56; Q6P4G2; Q86TZ3; Q9NWR9; DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 174. DE RecName: Full=Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma; DE AltName: Full=Protein phosphatase subunit G5PR; DE AltName: Full=Rhabdomyosarcoma antigen MU-RMS-40.6A/6C; GN Name=PPP2R3C; Synonyms=C14orf10, G5PR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL RP STAGE, AND SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=15820313; DOI=10.1016/j.ygeno.2005.01.010; RA Kamnasaran D., Chen C.-P., Devriendt K., Mehta L., Cox D.W.; RT "Defining a holoprosencephaly locus on human chromosome 14q13 and RT characterization of potential candidate genes."; RL Genomics 85:608-621(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cerebellum, and Gastric carcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Bone marrow, Brain, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-167 (ISOFORM 1). RC TISSUE=Placenta; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-453 (ISOFORM 1). RC TISSUE=Embryonic rhabdomyosarcoma; RA Behrends U., Gotz C., Mautner J.; RT "SEREX-defined rhabdomyosarcoma antigens."; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP INTERACTION WITH PPP2CA; PPP2R1A AND PPP5C, AND TISSUE SPECIFICITY. RX PubMed=12167160; DOI=10.1046/j.1365-2443.2002.00562.x; RA Kono Y., Maeda K., Kuwahara K., Yamamoto H., Miyamoto E., Yonezawa K., RA Takagi K., Sakaguchi N.; RT "MCM3-binding GANP DNA-primase is associated with a novel phosphatase RT component G5PR."; RL Genes Cells 7:821-834(2002). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [9] RP INTERACTION WITH TFPI2 AND ABCB1, AND FUNCTION. RX PubMed=24333728; DOI=10.1016/j.canlet.2013.12.007; RA Katayama K., Yamaguchi M., Noguchi K., Sugimoto Y.; RT "Protein phosphatase complex PP5/PPP2R3C dephosphorylates P- RT glycoprotein/ABCB1 and down-regulates the expression and function."; RL Cancer Lett. 345:124-131(2014). RN [10] RP INVOLVEMENT IN MEGD, INVOLVEMENT IN SPGF36, AND VARIANTS MEGD PRO-103; RP SER-193 AND SER-350. RX PubMed=30893644; DOI=10.1530/eje-19-0067; RA Guran T., Yesil G., Turan S., Atay Z., Bozkurtlar E., Aghayev A., Gul S., RA Tinay I., Aru B., Arslan S., Koroglu M.K., Ercan F., Demirel G.Y., RA Eren F.S., Karademir B., Bereket A.; RT "PPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and RT impaired spermatogenesis in humans."; RL Eur. J. Endocrinol. 180:291-309(2019). CC -!- FUNCTION: May regulate MCM3AP phosphorylation through phosphatase CC recruitment (By similarity). May act as a negative regulator of ABCB1 CC expression and function through the dephosphorylation of ABCB1 by CC TFPI2/PPP2R3C complex (PubMed:24333728). May play a role in the CC activation-induced cell death of B-cells (By similarity). CC {ECO:0000250|UniProtKB:Q9JK24, ECO:0000269|PubMed:24333728}. CC -!- SUBUNIT: Interacts with MCM3AP/GANP. Interacts with PPP5C, and the CC phosphatase 2A core enzyme composed of the PPP2CA catalytic subunit and CC the constant regulatory subunit PPP2R1A. Finds in a complex with ABCB1, CC TFPI2 and PPP2R3C; leading to the dephosphorylation of ABCB1. CC {ECO:0000250|UniProtKB:Q9JK24, ECO:0000269|PubMed:12167160, CC ECO:0000269|PubMed:24333728}. CC -!- INTERACTION: CC Q969Q6; Q8IYE0: CCDC146; NbExp=3; IntAct=EBI-2561661, EBI-10749669; CC Q969Q6; Q96DZ9: CMTM5; NbExp=3; IntAct=EBI-2561661, EBI-2548702; CC Q969Q6; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-2561661, EBI-744099; CC Q969Q6; Q3B820: FAM161A; NbExp=3; IntAct=EBI-2561661, EBI-719941; CC Q969Q6; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-2561661, EBI-7225287; CC Q969Q6; Q96BY2: MOAP1; NbExp=3; IntAct=EBI-2561661, EBI-739825; CC Q969Q6; O15160: POLR1C; NbExp=5; IntAct=EBI-2561661, EBI-1055079; CC Q969Q6; Q8WWY3: PRPF31; NbExp=3; IntAct=EBI-2561661, EBI-1567797; CC Q969Q6; O95197: RTN3; NbExp=3; IntAct=EBI-2561661, EBI-740467; CC Q969Q6; Q9H0W8: SMG9; NbExp=3; IntAct=EBI-2561661, EBI-2872322; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15820313}. Cytoplasm CC {ECO:0000269|PubMed:15820313}. Note=Excluded from the nucleoli. CC Localization is cell cycle-dependent. Localizes to the cytoplasm during CC cytokinesis. {ECO:0000269|PubMed:15820313}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q969Q6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q969Q6-2; Sequence=VSP_023113; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in brain and other tissues. CC {ECO:0000269|PubMed:12167160, ECO:0000269|PubMed:15820313}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain. CC {ECO:0000269|PubMed:15820313}. CC -!- DISEASE: Myoectodermal gonadal dysgenesis syndrome (MEGD) [MIM:618419]: CC An autosomal recessive disorder characterized by 46,XY complete gonadal CC dysgenesis and extragonadal anomalies, including typical facial CC gestalt, low birth weight, myopathy, rod and cone dystrophy, anal CC atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, CC skeletal abnormalities, renal agenesis and neuromotor delay. CC {ECO:0000269|PubMed:30893644}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spermatogenic failure 36 (SPGF36) [MIM:618420]: An autosomal CC dominant infertility disorder due to teratozoospermia, with spermatozoa CC showing anomalies of the head, acrosome, and nucleus. CC {ECO:0000269|PubMed:30893644}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAT44532.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAT44533.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY157304; AAO17045.1; -; mRNA. DR EMBL; AK000651; BAA91308.1; -; mRNA. DR EMBL; AK293717; BAG57148.1; -; mRNA. DR EMBL; CH471078; EAW65886.1; -; Genomic_DNA. DR EMBL; CH471078; EAW65887.1; -; Genomic_DNA. DR EMBL; CH471078; EAW65889.1; -; Genomic_DNA. DR EMBL; CH471078; EAW65890.1; -; Genomic_DNA. DR EMBL; BC006823; AAH06823.1; -; mRNA. DR EMBL; BC010293; AAH10293.1; -; mRNA. DR EMBL; BC012563; AAH12563.1; -; mRNA. DR EMBL; BC063438; AAH63438.1; -; mRNA. DR EMBL; BX248043; CAD62352.1; -; mRNA. DR EMBL; AY518535; AAT44532.1; ALT_INIT; mRNA. DR EMBL; AY518537; AAT44533.1; ALT_INIT; mRNA. DR CCDS; CCDS9654.1; -. [Q969Q6-1] DR RefSeq; NP_001292084.1; NM_001305155.1. [Q969Q6-2] DR RefSeq; NP_001292085.1; NM_001305156.1. [Q969Q6-2] DR RefSeq; NP_060387.2; NM_017917.3. [Q969Q6-1] DR RefSeq; XP_005267839.1; XM_005267782.3. [Q969Q6-1] DR AlphaFoldDB; Q969Q6; -. DR SMR; Q969Q6; -. DR BioGRID; 120344; 55. DR CORUM; Q969Q6; -. DR IntAct; Q969Q6; 36. DR MINT; Q969Q6; -. DR STRING; 9606.ENSP00000261475; -. DR iPTMnet; Q969Q6; -. DR PhosphoSitePlus; Q969Q6; -. DR BioMuta; PPP2R3C; -. DR DMDM; 74762643; -. DR EPD; Q969Q6; -. DR jPOST; Q969Q6; -. DR MassIVE; Q969Q6; -. DR MaxQB; Q969Q6; -. DR PaxDb; 9606-ENSP00000261475; -. DR PeptideAtlas; Q969Q6; -. DR ProteomicsDB; 75817; -. [Q969Q6-1] DR ProteomicsDB; 75818; -. [Q969Q6-2] DR Pumba; Q969Q6; -. DR Antibodypedia; 23186; 185 antibodies from 28 providers. DR DNASU; 55012; -. DR Ensembl; ENST00000261475.10; ENSP00000261475.5; ENSG00000092020.11. [Q969Q6-1] DR GeneID; 55012; -. DR KEGG; hsa:55012; -. DR MANE-Select; ENST00000261475.10; ENSP00000261475.5; NM_017917.4; NP_060387.2. DR UCSC; uc001wss.4; human. [Q969Q6-1] DR AGR; HGNC:17485; -. DR CTD; 55012; -. DR DisGeNET; 55012; -. DR GeneCards; PPP2R3C; -. DR HGNC; HGNC:17485; PPP2R3C. DR HPA; ENSG00000092020; Low tissue specificity. DR MalaCards; PPP2R3C; -. DR MIM; 615902; gene. DR MIM; 618419; phenotype. DR MIM; 618420; phenotype. DR neXtProt; NX_Q969Q6; -. DR OpenTargets; ENSG00000092020; -. DR PharmGKB; PA162400008; -. DR VEuPathDB; HostDB:ENSG00000092020; -. DR eggNOG; KOG2562; Eukaryota. DR GeneTree; ENSGT00940000155583; -. DR HOGENOM; CLU_035365_1_0_1; -. DR InParanoid; Q969Q6; -. DR OMA; HKFWAYE; -. DR OrthoDB; 196875at2759; -. DR PhylomeDB; Q969Q6; -. DR TreeFam; TF318412; -. DR PathwayCommons; Q969Q6; -. DR SignaLink; Q969Q6; -. DR SIGNOR; Q969Q6; -. DR BioGRID-ORCS; 55012; 435 hits in 1089 CRISPR screens. DR ChiTaRS; PPP2R3C; human. DR GeneWiki; PPP2R3C; -. DR GenomeRNAi; 55012; -. DR Pharos; Q969Q6; Tbio. DR PRO; PR:Q969Q6; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q969Q6; Protein. DR Bgee; ENSG00000092020; Expressed in right testis and 194 other cell types or tissues. DR ExpressionAtlas; Q969Q6; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001782; P:B cell homeostasis; IBA:GO_Central. DR GO; GO:0030865; P:cortical cytoskeleton organization; IBA:GO_Central. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central. DR GO; GO:0045579; P:positive regulation of B cell differentiation; IBA:GO_Central. DR GO; GO:0002759; P:regulation of antimicrobial humoral response; IEA:Ensembl. DR GO; GO:0035303; P:regulation of dephosphorylation; IEA:InterPro. DR GO; GO:0051900; P:regulation of mitochondrial depolarization; IEA:Ensembl. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR GO; GO:0043029; P:T cell homeostasis; IBA:GO_Central. DR CDD; cd21505; PPP2R3C; 1. DR Gene3D; 1.10.238.220; -; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR041534; EF-hand_13. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR039865; PPP2R3C. DR PANTHER; PTHR12085; SERINE/THREONINE-PROTEIN PHOSPHATASE 2A REGULATORY SUBUNIT B'' SUBUNIT GAMMA; 1. DR PANTHER; PTHR12085:SF3; SERINE_THREONINE-PROTEIN PHOSPHATASE 2A REGULATORY SUBUNIT B'' SUBUNIT GAMMA; 1. DR Pfam; PF17958; EF-hand_13; 1. DR SUPFAM; SSF47473; EF-hand; 2. DR PROSITE; PS00018; EF_HAND_1; 1. DR Genevisible; Q969Q6; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cone-rod dystrophy; Cytoplasm; Deafness; KW Disease variant; Metal-binding; Nucleus; Reference proteome; Repeat. FT CHAIN 1..453 FT /note="Serine/threonine-protein phosphatase 2A regulatory FT subunit B"" subunit gamma" FT /id="PRO_0000277833" FT DOMAIN 273..308 FT /note="EF-hand 1" FT DOMAIN 341..376 FT /note="EF-hand 2" FT BINDING 286 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT BINDING 288 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT BINDING 290 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT BINDING 292 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT BINDING 297 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT VAR_SEQ 1..110 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_023113" FT VARIANT 103 FT /note="L -> P (in MEGD; dbSNP:rs754106837)" FT /evidence="ECO:0000269|PubMed:30893644" FT /id="VAR_082202" FT VARIANT 193 FT /note="L -> S (in MEGD; dbSNP:rs1566411552)" FT /evidence="ECO:0000269|PubMed:30893644" FT /id="VAR_082203" FT VARIANT 350 FT /note="F -> S (in MEGD; dbSNP:rs1566684983)" FT /evidence="ECO:0000269|PubMed:30893644" FT /id="VAR_082204" FT CONFLICT 106 FT /note="H -> R (in Ref. 2; BAA91308)" FT /evidence="ECO:0000305" FT CONFLICT 240 FT /note="I -> T (in Ref. 6; AAT44532)" FT /evidence="ECO:0000305" FT CONFLICT 301 FT /note="Y -> H (in Ref. 2; BAA91308)" FT /evidence="ECO:0000305" SQ SEQUENCE 453 AA; 53316 MW; 9749B7188B2F7599 CRC64; MDWKEVLRRR LATPNTCPNK KKSEQELKDE EMDLFTKYYS EWKGGRKNTN EFYKTIPRFY YRLPAEDEVL LQKLREESRA VFLQRKSREL LDNEELQNLW FLLDKHQTPP MIGEEAMINY ENFLKVGEKA GAKCKQFFTA KVFAKLLHTD SYGRISIMQF FNYVMRKVWL HQTRIGLSLY DVAGQGYLRE SDLENYILEL IPTLPQLDGL EKSFYSFYVC TAVRKFFFFL DPLRTGKIKI QDILACSFLD DLLELRDEEL SKESQETNWF SAPSALRVYG QYLNLDKDHN GMLSKEELSR YGTATMTNVF LDRVFQECLT YDGEMDYKTY LDFVLALENR KEPAALQYIF KLLDIENKGY LNVFSLNYFF RAIQELMKIH GQDPVSFQDV KDEIFDMVKP KDPLKISLQD LINSNQGDTV TTILIDLNGF WTYENREALV ANDSENSADL DDT //