PR15A_CRILO
ID PR15A_CRILO Reviewed; 590 AA.
AC Q60465;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 50.
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;
GN Name=Ppp1r15a; Synonyms=Gadd34, Myd116;
OS Cricetulus longicaudatus (Long-tailed dwarf hamster) (Chinese hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10030;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP INTERACTION WITH PPP1CA.
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-mediated
RT dephosphorylation of eIF2alpha.";
RL J. Cell Biol. 153:1011-1022(2001).
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}.
CC -!- SUBUNIT: Interacts with PPP1CA (PubMed:11381086). Interacts with EIF2S1
CC (By similarity). Interacts with PCNA (By similarity). Interacts with
CC LYN and KMT2A/MLL1. Interacts with PPP1R1A and SMARCB1. Interacts with
CC SMAD7. Interacts with BAG1. Interacts with NOX4 (By similarity).
CC {ECO:0000250|UniProtKB:O75807, ECO:0000269|PubMed:11381086}.
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 -!- PTM: Phosphorylated at multiple Ser/Thr residues. Phosphorylated on
CC tyrosine by LYN; which impairs its antiproliferative activity.
CC Phosphorylation at Tyr-234 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}.
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DR EMBL; L28147; AAA36983.1; -; mRNA.
DR PIR; A56535; A56535.
DR AlphaFoldDB; Q60465; -.
DR SMR; Q60465; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0045936; P:negative regulation of phosphate metabolic process; IEA:UniProt.
DR GO; GO:0031400; P:negative regulation of protein modification process; IEA:UniProt.
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 Apoptosis; Endoplasmic reticulum; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Phosphoprotein; Repeat; Stress response;
KW Translation regulation; Ubl conjugation.
FT CHAIN 1..590
FT /note="Protein phosphatase 1 regulatory subunit 15A"
FT /id="PRO_0000320517"
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..590
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT REPEAT 278..317
FT /note="1"
FT REPEAT 318..357
FT /note="2"
FT REPEAT 358..397
FT /note="3"
FT REPEAT 398..415
FT /note="4; truncated"
FT REGION 1..60
FT /note="Required for localization in the endoplasmic
FT reticulum"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT REGION 57..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..460
FT /note="Interaction with SMAD7"
FT /evidence="ECO:0000250"
FT REGION 278..452
FT /note="3.5 X 39 AA approximate repeats"
FT REGION 286..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 422..441
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..505
FT /note="Interaction with KMT2A/MLL1"
FT /evidence="ECO:0000250"
FT REGION 486..533
FT /note="Interaction with SMARCB1"
FT /evidence="ECO:0000250"
FT COMPBIAS 218..232
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 234..248
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75807"
FT MOD_RES 234
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 462
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O75807"
SQ SEQUENCE 590 AA; 64527 MW; B3D879BDACBAE6D6 CRC64;
MAPSPRPQHI LLWRDAHSFH LLSPLMGFLS RAWSRLRVPE APEPWPAETV TGADQIEADA
HPAPPLVPEN HPPQGEAEES GTPEEGKAAQ GPCLDVQANS SPPETLGLSD DDKQGQDGPR
EQGRAHTAGL PILLSPGLQS ADKSLGEVVA GEEGVTELAY PTSHWEGCPS EEEEDGETVK
KAFRASADSP GHKSSTSVYC PGEAEHQATE EKQTENKADP PSSPSGSHSR AWEYCSKQEG
EADPEPHRAG KYQLCQNAEA EEEEEAKVSS LSVSSGNAFL KAWVYRPGED TEDDDDSDWG
SAEEEGKALS SPTSPEHDFL KAWVYRPGED TEDDDDSDWG SAEEEGKALS SPTSPEHDFL
KAWVYRPGED TEDDQDSDWG SAEKDGLAQT FATPHTSAFL KTWVCCPGED TEDDDCEVVV
PEDSEAADPD KSPSHEAQGC LPGEQTEGLV EAEHSLFQVA FYLPGEKPAP PWTAPKLPLR
LQRRLTLLRT PTQDQDPETP LRARKVHFSE NVTVHFLAVW AGPAQAARRG PWEQLARDRS
RFARRIAQAE EKLGPYLTPA FRARAWARLG NPSLPLALEP ICDHTFFPSQ
