PAWR_RAT
ID PAWR_RAT Reviewed; 332 AA.
AC Q62627;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 128.
DE RecName: Full=PRKC apoptosis WT1 regulator protein;
DE AltName: Full=Prostate apoptosis response 4 protein;
DE Short=Par-4;
DE AltName: Full=Transcriptional repressor Par-4-like protein PAWR;
GN Name=Pawr; Synonyms=Par4;
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], AND INDUCTION.
RC TISSUE=Prostate;
RX PubMed=8043520;
RA Sells S.F., Wood D.P. Jr., Joshi-Barve S.S., Muthukumar S., Jacob R.J.,
RA Crist S.A., Humphreys S., Rangnekar V.M.;
RT "Commonality of the gene programs induced by effectors of apoptosis in
RT androgen-dependent and -independent prostate cells.";
RL Cell Growth Differ. 5:457-466(1994).
RN [2]
RP DOMAIN SAC, MUTAGENESIS, AND SUBCELLULAR LOCATION.
RX PubMed=12897127; DOI=10.1128/mcb.23.16.5516-5525.2003;
RA El-Guendy N., Zhao Y., Gurumurthy S., Burikhanov R., Rangnekar V.M.;
RT "Identification of a unique core domain of par-4 sufficient for selective
RT apoptosis induction in cancer cells.";
RL Mol. Cell. Biol. 23:5516-5525(2003).
RN [3]
RP PHOSPHORYLATION AT THR-155 BY PKA.
RX PubMed=15657440; DOI=10.1128/mcb.25.3.1146-1161.2005;
RA Gurumurthy S., Goswami A., Vasudevan K.M., Rangnekar V.M.;
RT "Phosphorylation of Par-4 by protein kinase A is critical for apoptosis.";
RL Mol. Cell. Biol. 25:1146-1161(2005).
RN [4]
RP INTERACTION WITH ACTIN.
RX PubMed=15817164; DOI=10.1016/j.yexcr.2005.01.012;
RA Vetterkind S., Illenberger S., Kubicek J., Boosen M., Appel S., Naim H.Y.,
RA Scheidtmann K.H., Preuss U.;
RT "Binding of Par-4 to the actin cytoskeleton is essential for Par-4/Dlk-
RT mediated apoptosis.";
RL Exp. Cell Res. 305:392-408(2005).
CC -!- FUNCTION: Pro-apoptotic protein capable of selectively inducing
CC apoptosis in cancer cells, sensitizing the cells to diverse apoptotic
CC stimuli and causing regression of tumors in animal models. Induces
CC apoptosis in certain cancer cells by activation of the Fas prodeath
CC pathway and coparallel inhibition of NF-kappa-B transcriptional
CC activity. Inhibits the transcriptional activation and augments the
CC transcriptional repression mediated by WT1. Down-regulates the anti-
CC apoptotic protein BCL2 via its interaction with WT1. Seems also to be a
CC transcriptional repressor by itself. May be directly involved in
CC regulating the amyloid precursor protein (APP) cleavage activity of
CC BACE1 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homooligomer. Interacts (via the C-terminal region) with WT1.
CC Interacts with THAP1. Interacts with AATF. Interacts with BACE1.
CC Interacts with SPSB1 (via B30.2/SPRY domain); this interaction is
CC direct and occurs in association with the Elongin BC complex. Interacts
CC with SPSB2 (via B30.2/SPRY domain); this interaction occurs in
CC association with the Elongin BC complex. Interacts with SPSB4 (via
CC B30.2/SPRY domain); this interaction occurs in association with the
CC Elongin BC complex. Component of a ternary complex composed of SQSTM1
CC and PRKCZ (By similarity). Interacts with actin (PubMed:15817164).
CC {ECO:0000250|UniProtKB:Q925B0, ECO:0000250|UniProtKB:Q96IZ0,
CC ECO:0000269|PubMed:15817164}.
CC -!- INTERACTION:
CC Q62627; O88764: Dapk3; NbExp=5; IntAct=EBI-1187240, EBI-4404236;
CC Q62627; Q9JMG6: Tfpt; NbExp=8; IntAct=EBI-1187240, EBI-1767101;
CC Q62627; P11021: HSPA5; Xeno; NbExp=4; IntAct=EBI-1187240, EBI-354921;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Mainly cytoplasmic in absence of apoptosis signal and in normal
CC cells. Nuclear in most cancer cell lines. Nuclear entry seems to be
CC essential but not sufficient for apoptosis. Nuclear localization
CC includes nucleoplasm and PML nuclear bodies (By similarity).
CC {ECO:0000250}.
CC -!- INDUCTION: In ventral prostate following castration.
CC {ECO:0000269|PubMed:8043520}.
CC -!- DOMAIN: The leucine-zipper domain is not essential for apoptosis, but
CC is required for sensitization of cells to exogenous apoptotic insults
CC and for interaction with its partners. {ECO:0000250}.
CC -!- DOMAIN: The SAC domain is a death-inducing domain selective for
CC apoptosis induction in cancer cells. This domain is essential for
CC nuclear entry, Fas activation, inhibition of NF-kappa-B activity and
CC induction of apoptosis in cancer cells (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The B30.2/SPRY domain-binding motif mediates recognition by
CC proteins containing a B30.2/SPRY domain.
CC {ECO:0000250|UniProtKB:Q96IZ0}.
CC -!- PTM: Preferentially phosphorylated at the Thr-155 by PKC in cancer
CC cells. {ECO:0000269|PubMed:15657440}.
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DR EMBL; U05989; AAA16492.1; -; mRNA.
DR RefSeq; NP_277020.1; NM_033485.2.
DR PDB; 5FIY; X-ray; 3.00 A; A/B/C/D/E/F/G=240-332.
DR PDBsum; 5FIY; -.
DR AlphaFoldDB; Q62627; -.
DR SMR; Q62627; -.
DR BioGRID; 249098; 4.
DR IntAct; Q62627; 5.
DR STRING; 10116.ENSRNOP00000008222; -.
DR iPTMnet; Q62627; -.
DR PhosphoSitePlus; Q62627; -.
DR PaxDb; Q62627; -.
DR PRIDE; Q62627; -.
DR DNASU; 64513; -.
DR GeneID; 64513; -.
DR KEGG; rno:64513; -.
DR UCSC; RGD:69065; rat.
DR CTD; 5074; -.
DR RGD; 69065; Pawr.
DR eggNOG; ENOG502QVUF; Eukaryota.
DR InParanoid; Q62627; -.
DR OrthoDB; 1363165at2759; -.
DR PhylomeDB; Q62627; -.
DR PRO; PR:Q62627; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0043522; F:leucine zipper domain binding; ISO:RGD.
DR GO; GO:0005080; F:protein kinase C binding; IPI:RGD.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IPI:RGD.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IMP:RGD.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IDA:RGD.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071306; P:cellular response to vitamin E; IEP:RGD.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IDA:RGD.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IDA:RGD.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:RGD.
DR GO; GO:0090281; P:negative regulation of calcium ion import; IDA:RGD.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045760; P:positive regulation of action potential; IDA:RGD.
DR GO; GO:0042986; P:positive regulation of amyloid precursor protein biosynthetic process; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0060450; P:positive regulation of hindgut contraction; IDA:RGD.
DR GO; GO:1901300; P:positive regulation of hydrogen peroxide-mediated programmed cell death; ISO:RGD.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; IDA:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:1904457; P:positive regulation of neuronal action potential; IMP:RGD.
DR GO; GO:2000391; P:positive regulation of neutrophil extravasation; IDA:RGD.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IMP:RGD.
DR GO; GO:1901082; P:positive regulation of relaxation of smooth muscle; IDA:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0010040; P:response to iron(II) ion; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; IEP:RGD.
DR DisProt; DP00940; -.
DR InterPro; IPR026117; Par-4.
DR PANTHER; PTHR15093; PTHR15093; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Coiled coil; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..332
FT /note="PRKC apoptosis WT1 regulator protein"
FT /id="PRO_0000058238"
FT REGION 1..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..195
FT /note="Selective for apoptosis induction in cancer cells
FT (SAC)"
FT REGION 292..332
FT /note="Leucine-zipper"
FT COILED 176..198
FT /evidence="ECO:0000255"
FT MOTIF 61..65
FT /note="B30.2/SPRY domain-binding motif"
FT /evidence="ECO:0000250|UniProtKB:Q96IZ0"
FT MOTIF 137..153
FT /note="Nuclear localization signal"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..154
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 186..218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..244
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 155
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:15657440"
FT MOD_RES 223
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96IZ0"
FT HELIX 257..330
FT /evidence="ECO:0007829|PDB:5FIY"
SQ SEQUENCE 332 AA; 35866 MW; 2069B32DEFFF160F CRC64;
MATGGYRSSG STTDFLEEWK AKREKMRAKQ NPVGPGSSGG DPAAKSPAGP LAQTTAAGTS
ELNHGPAGAA APAAPGPGAL NCAHGSSALP RGAPGSRRPE DECPIAAGAA GAPASRGDEE
EPDSAPEKGR SSGPSARKGK GQIEKRKLRE KRRSTGVVNI PAAECLDEYE DDEAGQKERK
REDAITQQNT IQNEAASLPD PGTSYLPQDP SRTVPGRYKS TISAPEEEIL NRYPRTDRSG
FSRHNRDTSA PANFASSSTL EKRIEDLEKE VLRERQENLR LTRLMQDKEE MIGKLKEEID
LLNRDLDDME DENEQLKQEN KTLLKVVGQL TR
