P2R3C_HUMAN
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 03-AUG-2022, entry version 165.
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 GDRM, INVOLVEMENT IN SPGF36, AND VARIANTS GDRM 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: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and
CC myopathy (GDRM) [MIM:618419]: An autosomal recessive disorder
CC characterized by 46,XY complete gonadal dysgenesis and extragonadal
CC anomalies, including typical facial gestalt, low birth weight,
CC myopathy, rod and cone dystrophy, anal atresia, omphalocele,
CC sensorineural hearing loss, dry and scaly skin, skeletal abnormalities,
CC renal agenesis and neuromotor delay. {ECO:0000269|PubMed:30893644}.
CC Note=The disease is caused by variants affecting the gene represented
CC 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};
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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; 46.
DR CORUM; Q969Q6; -.
DR IntAct; Q969Q6; 35.
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; Q969Q6; -.
DR PeptideAtlas; Q969Q6; -.
DR PRIDE; Q969Q6; -.
DR ProteomicsDB; 75817; -. [Q969Q6-1]
DR ProteomicsDB; 75818; -. [Q969Q6-2]
DR Antibodypedia; 23186; 171 antibodies from 27 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 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 OMA; HKFWAYE; -.
DR OrthoDB; 541286at2759; -.
DR PhylomeDB; Q969Q6; -.
DR TreeFam; TF318412; -.
DR PathwayCommons; Q969Q6; -.
DR SignaLink; Q969Q6; -.
DR BioGRID-ORCS; 55012; 419 hits in 1041 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 192 other tissues.
DR ExpressionAtlas; Q969Q6; baseline and differential.
DR Genevisible; Q969Q6; HS.
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:0032147; P:activation of protein kinase activity; IEA:Ensembl.
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 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; PTHR12085; 1.
DR Pfam; PF17958; EF-hand_13; 1.
DR SUPFAM; SSF47473; SSF47473; 2.
DR PROSITE; PS00018; EF_HAND_1; 1.
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 GDRM; unknown pathological significance;
FT dbSNP:rs754106837)"
FT /evidence="ECO:0000269|PubMed:30893644"
FT /id="VAR_082202"
FT VARIANT 193
FT /note="L -> S (in GDRM; unknown pathological significance;
FT dbSNP:rs1566411552)"
FT /evidence="ECO:0000269|PubMed:30893644"
FT /id="VAR_082203"
FT VARIANT 350
FT /note="F -> S (in GDRM; unknown pathological significance;
FT 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
