ID PR15A_MOUSE Reviewed; 657 AA. AC P17564; Q3TJS6; Q3U3L5; Q8C579; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 13-NOV-2013, entry version 89. 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; GN Name=Ppp1r15a; Synonyms=Gadd34, Myd116; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=SL; RX PubMed=2339071; DOI=10.1093/nar/18.9.2823; RA Lord K.A., Hoffman-Liebermann B., Liebermann D.A.; RT "Sequence of MyD116 cDNA: a novel myeloid differentiation primary RT response gene induced by IL6."; RL Nucleic Acids Res. 18:2823-2823(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J, and NOD; TISSUE=Cerebellum, and Placenta; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP INDUCTION. RX PubMed=8139541; 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 [4] RP INTERACTION WITH PCNA. RX PubMed=9371605; RA Brown S.M., MacLean A.R., McKie E.A., Harland J.; RT "The herpes simplex virus virulence factor ICP34.5 and the cellular RT protein MyD116 complex with proliferating cell nuclear antigen through RT the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34."; RL J. Virol. 71:9442-9449(1997). RN [5] RP INTERACTION WITH PP1. RX PubMed=9023344; DOI=10.1073/pnas.94.3.843; RA He B., Gross M., Roizman B.; RT "The gamma(1)34.5 protein of herpes simplex virus 1 complexes with RT protein phosphatase 1alpha to dephosphorylate the alpha subunit of the RT eukaryotic translation initiation factor 2 and preclude the shutoff of RT protein synthesis by double-stranded RNA-activated protein kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 94:843-848(1997). RN [6] RP FUNCTION, INTERACTION WITH PP1, AND MUTAGENESIS OF VAL-549. RX PubMed=11381086; DOI=10.1083/jcb.153.5.1011; RA Novoa I., Zeng H., Harding H.P., Ron D.; RT "Feedback inhibition of the unfolded protein response by GADD34- RT mediated dephosphorylation of eIF2alpha."; RL J. Cell Biol. 153:1011-1022(2001). RN [7] RP INTERACTION WITH LYN. RX PubMed=11517336; DOI=10.1073/pnas.191130798; RA Grishin A.V., Azhipa O., Semenov I., Corey S.J.; RT "Interaction between growth arrest-DNA damage protein 34 and Src RT kinase Lyn negatively regulates genotoxic apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001). RN [8] RP INDUCTION, AND FUNCTION. RX PubMed=12606582; DOI=10.1093/emboj/cdg112; RA Novoa I., Zhang Y., Zeng H., Jungreis R., Harding H.P., Ron D.; RT "Stress-induced gene expression requires programmed recovery from RT translational repression."; RL EMBO J. 22:1180-1187(2003). RN [9] RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND RP DISRUPTION PHENOTYPE. RX PubMed=12824288; DOI=10.1096/fj.02-1184fje; RA Kojima E., Takeuchi A., Haneda M., Yagi A., Hasegawa T., Yamaki K., RA Takeda K., Akira S., Shimokata K., Isobe K.; RT "The function of GADD34 is a recovery from a shutoff of protein RT synthesis induced by ER stress: elucidation by GADD34-deficient RT mice."; RL FASEB J. 17:1573-1575(2003). RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=16478986; DOI=10.1128/MCB.26.5.1644-1653.2006; RA Patterson A.D., Hollander M.C., Miller G.F., Fornace A.J. Jr.; RT "Gadd34 requirement for normal hemoglobin synthesis."; RL Mol. Cell. Biol. 26:1644-1653(2006). RN [11] RP FUNCTION, AND INDUCTION. RX PubMed=17670836; DOI=10.1128/JVI.01063-07; RA Minami K., Tambe Y., Watanabe R., Isono T., Haneda M., Isobe K., RA Kobayashi T., Hino O., Okabe H., Chano T., Inoue H.; RT "Suppression of viral replication by stress-inducible GADD34 protein RT via the mammalian serine/threonine protein kinase mTOR pathway."; RL J. Virol. 81:11106-11115(2007). CC -!- FUNCTION: Recruits the serine/threonine-protein phosphatase PP1 to CC dephosphorylate the translation initiation factor eIF-2A/EIF2S1, CC thereby reversing the shut-off of protein synthesis initiated by CC stress-inducible kinases and facilitating recovery of cells from CC stress. Down-regulates the TGF-beta signaling pathway by promoting CC dephosphorylation of TGFB1 by PP1. May promote apoptosis by CC inducing TP53 phosphorylation on 'Ser-15'. In case of infection CC with vesicular stomatitis virus (VSV), impairs viral replication. CC -!- SUBUNIT: Interacts with KMT2A/MLL1. Interacts with SMARCB1. CC Interacts with SMAD7. Interacts with BAG1 (By similarity). CC Interacts with PCNA. Interacts with LYN. Interacts with PP1 and CC PPP1R1A. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P17564-1; Sequence=Displayed; CC Name=2; CC IsoId=P17564-2; Sequence=VSP_031651; CC -!- TISSUE SPECIFICITY: Expressed strongly in spleen and lung, CC moderately in thymus and muscle, and weakly in brain. CC -!- DEVELOPMENTAL STAGE: Expression starts at E8.5, and decreases to CC undetectable levels at E10.5 and E11.5. Expression is strongly up- CC regulated at E12.5, decreases at E16.5 and reappears at E18.5. At CC E12.5, ubiquitously expressed, with high levels in brain, spinal CC cord, tongue, lung and genital tubercle. CC -!- INDUCTION: By IL6 and various endoplasmic stresses such as methyl CC methanesulfonate. By infection with various viruses such as CC vesicular stomatitis virus (VSV). CC -!- PTM: Phosphorylated on tyrosine; which impairs its CC antiproliferative activity (By similarity). CC -!- DISRUPTION PHENOTYPE: Mice display abnormal erythrocytes and CC reduced hemoglobin content due to defects in hemoglobin synthesis. CC -!- SIMILARITY: Belongs to the PPP1R15 family. 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; X51829; CAA36128.1; -; mRNA. DR EMBL; AK079339; BAC37613.1; -; mRNA. DR EMBL; AK154697; BAE32770.1; -; mRNA. DR EMBL; AK167317; BAE39419.1; -; mRNA. DR IPI; IPI00110044; -. DR IPI; IPI00762368; -. DR PIR; S10001; S10001. DR RefSeq; NP_032680.1; NM_008654.2. DR UniGene; Mm.4048; -. DR ProteinModelPortal; P17564; -. DR STRING; 10090.ENSMUSP00000049488; -. DR PhosphoSite; P17564; -. DR PRIDE; P17564; -. DR Ensembl; ENSMUST00000042105; ENSMUSP00000049488; ENSMUSG00000040435. DR Ensembl; ENSMUST00000167273; ENSMUSP00000128497; ENSMUSG00000040435. DR GeneID; 17872; -. DR KEGG; mmu:17872; -. DR UCSC; uc009gvt.3; mouse. DR CTD; 23645; -. DR MGI; MGI:1927072; Ppp1r15a. DR eggNOG; NOG75356; -. DR GeneTree; ENSGT00510000049287; -. DR HOGENOM; HOG000060154; -. DR HOVERGEN; HBG052542; -. DR InParanoid; P17564; -. DR KO; K14019; -. DR OMA; WRDAHPF; -. DR OrthoDB; EOG75QR48; -. DR NextBio; 292649; -. DR PRO; PR:P17564; -. DR ArrayExpress; P17564; -. DR Bgee; P17564; -. DR CleanEx; MM_MYD116; -. DR Genevestigator; P17564; -. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:MGI. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR InterPro; IPR019523; Prot_Pase1_reg-su15A/B_C. DR Pfam; PF10488; PP1c_bdg; 1. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Complete proteome; KW Endoplasmic reticulum; Phosphoprotein; Reference proteome; Repeat; KW Stress response; Translation regulation. FT CHAIN 1 657 Protein phosphatase 1 regulatory subunit FT 15A. FT /FTId=PRO_0000096665. FT REPEAT 283 322 1. FT REPEAT 323 360 2. FT REPEAT 361 398 3. FT REPEAT 399 436 4. FT REPEAT 437 451 5; truncated. FT REGION 1 164 Required for localization in the FT endoplasmic reticulum (By similarity). FT REGION 283 451 4.5 X approximate repeats. FT REGION 323 503 Interaction with SMAD7 (By similarity). FT REGION 443 548 Interaction with KMT2A/MLL1 (By FT similarity). FT REGION 529 576 Interaction with SMARCB1 (By similarity). FT COMPBIAS 455 458 Poly-Glu. FT VAR_SEQ 284 360 Missing (in isoform 2). FT /FTId=VSP_031651. FT MUTAGEN 549 549 V->E: Abolishes interaction with PP1. FT CONFLICT 224 224 P -> H (in Ref. 2; BAE39419). FT CONFLICT 271 271 E -> G (in Ref. 2; BAE32770). FT CONFLICT 505 505 Y -> C (in Ref. 2; BAE32770). SQ SEQUENCE 657 AA; 71840 MW; 9B217001019C38A7 CRC64; MAPSPRPQHV LHWRDAHNFY LLSPLMGLLS RAWSRLRGPE VPEAWLAKTV TGADQIEAAA LLTPTPVSGN LLPHGETEES GSPEQSQAAQ RLCLVEAESS PPETWGLSNV DEYNAKPGQD DLREKEMERT AGKATLQPAG LQGADKRLGE VVAREEGVAE PAYPTSQLEG GPAENEEDGE TVKTYQASAA SIAPGYKPST PVPFLGEAEH QATEEKGTEN KADPSNSPSS GSHSRAWEYY SREKPKQEGE AKVEAHRAGQ GHPCRNAEAE EGGPETTFVC TGNAFLKAWV YRPGEDTEEE DNSDSDSAEE DTAQTGATPH TSAFLKAWVY RPGEDTEEED SDSDSAEEDT AQTGATPHTS AFLKAWVYRP GEDTEEENSD LDSAEEDTAQ TGATPHTSAF LKAWVYRPGE DTEEENSDLD SAEEDTAQTG ATPHTSPFLK AWVYRPGEDT EDDTEEEEDS ENVAPGDSET ADSSQSPCLQ PQRCLPGEKT KGRGEEPPLF QVAFYLPGEK PESPWAAPKL PLRLQRRLRL FKAPTRDQDP EIPLKARKVH FAEKVTVHFL AVWAGPAQAA RRGPWEQFAR DRSRFARRIA QAEEKLGPYL TPDSRARAWA RLRNPSLPQS EPRSSSEATP LTQDVTTPSP LPSETPSPSL YLGGRRG //