PR15A_RAT
ID PR15A_RAT Reviewed; 578 AA.
AC Q6IN02; O88344; Q7TQC2;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Protein phosphatase 1 regulatory subunit 15A;
DE AltName: Full=Growth arrest and DNA damage-inducible protein GADD34;
DE AltName: Full=Myeloid differentiation primary response protein MyD116 homolog;
DE AltName: Full=Progression elevated gene 3 protein;
DE Short=PEG-3;
GN Name=Ppp1r15a; Synonyms=Gadd34, Myd116, Peg3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=9256446; DOI=10.1073/pnas.94.17.9125;
RA Su Z.-Z., Shi Y., Fisher P.B.;
RT "Subtraction hybridization identifies a transformation progression-
RT associated gene PEG-3 with sequence homology to a growth arrest and DNA
RT damage-inducible gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9125-9130(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND MUTANT PEG-3.
RC STRAIN=Sprague-Dawley;
RX PubMed=12813455; DOI=10.1038/sj.onc.1206567;
RA Hollander M.C., Poola-Kella S., Fornace A.J. Jr.;
RT "Gadd34 functional domains involved in growth suppression and apoptosis.";
RL Oncogene 22:3827-3832(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [4]
RP INDUCTION.
RX PubMed=8139541; DOI=10.1128/mcb.14.4.2361-2371.1994;
RA Zhan Q., Lord K.A., Alamo I. Jr., Hollander M.C., Carrier F., Ron D.,
RA Kohn K.W., Hoffman B., Liebermann D.A., Fornace A.J. Jr.;
RT "The gadd and MyD genes define a novel set of mammalian genes encoding
RT acidic proteins that synergistically suppress cell growth.";
RL Mol. Cell. Biol. 14:2361-2371(1994).
RN [5]
RP MUTANT PEG-3.
RX PubMed=10611347; DOI=10.1073/pnas.96.26.15115;
RA Su Z.-Z., Goldstein N.I., Jiang H., Wang M.-N., Duigou G.J., Young C.S.H.,
RA Fisher P.B.;
RT "PEG-3, a nontransforming cancer progression gene, is a positive regulator
RT of cancer aggressiveness and angiogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:15115-15120(1999).
RN [6]
RP FUNCTION, AND MUTANT PEG-3.
RX PubMed=15674324; DOI=10.1038/sj.onc.1208420;
RA Su Z.-Z., Emdad L., Sarkar D., Randolph A., Valerie K., Yacoub A., Dent P.,
RA Fisher P.B.;
RT "Potential molecular mechanism for rodent tumorigenesis: mutational
RT generation of Progression Elevated Gene-3 (PEG-3).";
RL Oncogene 24:2247-2255(2005).
CC -!- FUNCTION: Recruits the serine/threonine-protein phosphatase PPP1CA to
CC prevents excessive phosphorylation of the translation initiation factor
CC eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis
CC initiated by stress-inducible kinases and facilitating recovery of
CC cells from stress. Down-regulates the TGF-beta signaling pathway by
CC promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by
CC inducing TP53 phosphorylation on 'Ser-15'. Plays an essential role in
CC autophagy by tuning translation during starvation, thus enabling
CC lysosomal biogenesis and a sustained autophagic flux.
CC {ECO:0000250|UniProtKB:O75807, ECO:0000269|PubMed:15674324}.
CC -!- SUBUNIT: Interacts with PPP1CA. Interacts with EIF2S1 (By similarity).
CC Interacts with PCNA (By similarity). Interacts with LYN and KMT2A/MLL1.
CC Interacts with PPP1R1A and SMARCB1. Interacts with SMAD7. Interacts
CC with BAG1. Interacts with NOX4 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:O75807}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein; Cytoplasmic side {ECO:0000250|UniProtKB:O75807}.
CC Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic
CC side {ECO:0000250|UniProtKB:O75807}. Note=Associates with membranes via
CC an N-terminal amphipathic intramembrane region.
CC {ECO:0000250|UniProtKB:O75807}.
CC -!- INDUCTION: By lipopolysaccharide. {ECO:0000269|PubMed:8139541}.
CC -!- PTM: Phosphorylated at multiple Ser/Thr residues. Phosphorylated on
CC tyrosine by LYN; which impairs its antiproliferative activity.
CC Phosphorylation at Tyr-236 enhances proteasomal degradation, this
CC position is dephosphorylated by PTPN2. {ECO:0000250|UniProtKB:O75807}.
CC -!- PTM: Polyubiquitinated. Exhibits a rapid proteasomal degradation with a
CC half-life under 1 hour, ubiquitination depends on endoplasmic reticulum
CC association. {ECO:0000250|UniProtKB:O75807}.
CC -!- SIMILARITY: Belongs to the PPP1R15 family. {ECO:0000305}.
CC -!- CAUTION: The sequence described initially (PubMed:9256446) corresponds
CC to a mutant, frameshifted form named PEG-3 that frequently arises
CC during cell transformation and does not seem to exist in normal cells.
CC PEG-3 functions as a dominant negative of GADD34-mediated pro-apoptotic
CC pathway and promotes cancer aggressiveness.
CC {ECO:0000305|PubMed:9256446}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC24980.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF020618; AAC24980.1; ALT_FRAME; mRNA.
DR EMBL; AY128642; AAM77795.1; -; Genomic_DNA.
DR EMBL; BC072513; AAH72513.1; -; mRNA.
DR RefSeq; NP_598230.2; NM_133546.3.
DR AlphaFoldDB; Q6IN02; -.
DR SMR; Q6IN02; -.
DR STRING; 10116.ENSRNOP00000048451; -.
DR PaxDb; Q6IN02; -.
DR PRIDE; Q6IN02; -.
DR GeneID; 171071; -.
DR KEGG; rno:171071; -.
DR CTD; 23645; -.
DR RGD; 621526; Ppp1r15a.
DR eggNOG; ENOG502S745; Eukaryota.
DR InParanoid; Q6IN02; -.
DR OrthoDB; 391948at2759; -.
DR PhylomeDB; Q6IN02; -.
DR TreeFam; TF105547; -.
DR PRO; PR:Q6IN02; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IDA:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0019888; F:protein phosphatase regulator activity; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:0072732; P:cellular response to calcium ion starvation; IEP:RGD.
DR GO; GO:0071322; P:cellular response to carbohydrate stimulus; IEP:RGD.
DR GO; GO:1904310; P:cellular response to cordycepin; IEP:RGD.
DR GO; GO:1904308; P:cellular response to desipramine; IEP:RGD.
DR GO; GO:1904312; P:cellular response to gold(3+); IEP:RGD.
DR GO; GO:1904314; P:cellular response to methamphetamine hydrochloride; IEP:RGD.
DR GO; GO:0072703; P:cellular response to methyl methanesulfonate; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; IEP:RGD.
DR GO; GO:0034644; P:cellular response to UV; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEP:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; ISO:RGD.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:RGD.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; ISO:RGD.
DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; ISO:RGD.
DR GO; GO:0010955; P:negative regulation of protein processing; IMP:RGD.
DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:1990441; P:negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR GO; GO:1903917; P:positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:1902310; P:positive regulation of peptidyl-serine dephosphorylation; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:RGD.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; ISO:RGD.
DR GO; GO:0070972; P:protein localization to endoplasmic reticulum; ISO:RGD.
DR GO; GO:0045765; P:regulation of angiogenesis; IMP:RGD.
DR GO; GO:0060734; P:regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; ISO:RGD.
DR GO; GO:0036496; P:regulation of translational initiation by eIF2 alpha dephosphorylation; ISO:RGD.
DR GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEP:RGD.
DR GO; GO:0090648; P:response to environmental enrichment; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR InterPro; IPR019523; Prot_Pase1_reg-su15A/B_C.
DR Pfam; PF10488; PP1c_bdg; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Endoplasmic reticulum; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Phosphoprotein; Reference proteome; Repeat;
KW Stress response; Translation regulation; Ubl conjugation.
FT CHAIN 1..578
FT /note="Protein phosphatase 1 regulatory subunit 15A"
FT /id="PRO_0000320519"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT INTRAMEM 22..39
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT TOPO_DOM 40..578
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT REPEAT 279..318
FT /note="1"
FT REPEAT 319..357
FT /note="2"
FT REPEAT 358..375
FT /note="3"
FT REGION 1..165
FT /note="Required for localization in the endoplasmic
FT reticulum"
FT /evidence="ECO:0000250"
FT REGION 101..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 158..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 279..375
FT /note="3 X approximate repeats"
FT REGION 319..417
FT /note="Interaction with SMAD7"
FT /evidence="ECO:0000250"
FT REGION 330..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 363..462
FT /note="Interaction with KMT2A/MLL1"
FT /evidence="ECO:0000250"
FT REGION 368..393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..490
FT /note="Interaction with SMARCB1"
FT /evidence="ECO:0000250"
FT REGION 532..578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..344
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 532..560
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 236
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT MOD_RES 365
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT MOD_RES 419
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT CONFLICT 347..348
FT /note="AS -> TA (in Ref. 3; AAH72513)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="D -> G (in Ref. 1; AAC24980)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 63570 MW; 923EC49921C0BC61 CRC64;
MAPSPRPQHV LHWKEAHSFY LLSPLMGFLS RAWSRLRGPE VSEAWLAETV AGANQIEADA
LLTPPPVSEN HLPLRETEGN GTPEWSKAAQ RLCLDVEAQS SPPKTWGLSD IDEHNGKPGQ
DGLREQEVEH TAGLPTLQPL HLQGADKKVG EVVAREEGVS ELAYPTSHWE GGPAEDEEDT
ETVKKAHQAS AASIAPGYKP STSVYCPGEA EHRATEEKGT DNKAEPSGSH SRVWEYHTRE
RPKQEGETKP EQHRAGQSHP CQNAEAEEGG PETSVCSGSA FLKAWVYRPG EDTEEEEDSD
LDSAEEDTAH TCTTPHTSAF LKAWVYRPGE DTEEEDDGDW DSAEEDASQS CTTPHTSAFL
KAWVYRPGED TEEEDDSENV APVDSETVDS CQSTQHCLPV EKTKGCGEAE PPPFQVAFYL
PGQKPAPPWA APKLPLRLQK RLRSFKAPAR NQDPEIPLKG RKVHFSEKVT VHFLAVWAGP
AQAARRGPWE QFARDRSRFA RRIAQAEEQL GPYLTPAFRA RAWTRLRNLP LPLSSSSLPL
PEPCSSTEAT PLSQDVTTPS PLPSEIPPPS LDLGGRRG
