PAWR_MOUSE
ID PAWR_MOUSE Reviewed; 333 AA.
AC Q925B0; Q0ZHI4; Q2HYJ1;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=PRKC apoptosis WT1 regulator protein;
DE AltName: Full=Prostate apoptosis response 4 protein;
DE Short=Par-4;
GN Name=Pawr; Synonyms=Par4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=129S4/SvJae;
RX PubMed=16520897; DOI=10.1007/s10495-006-3979-8;
RA Wang G., Silva J., Krishnamurthy K., Bieberich E.;
RT "A novel isoform of prostate apoptosis response 4 (PAR-4) that co-
RT distributes with F-actin and prevents apoptosis in neural stem cells.";
RL Apoptosis 11:315-325(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RA Han S.-S., Rangnekar V.M.;
RT "Mouse par-4 cDNA sequence.";
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 137-333 (ISOFORM 1).
RC STRAIN=Swiss Webster / NIH;
RA Hackett J.D.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION IN NEUROSYNAPTIC DEGENERATION.
RX PubMed=15606896; DOI=10.1111/j.1471-4159.2004.02834.x;
RA Xie J., Awad K.S., Guo Q.;
RT "RNAi knockdown of Par-4 inhibits neurosynaptic degeneration in ALS-linked
RT mice.";
RL J. Neurochem. 92:59-71(2005).
RN [5]
RP INTERACTION WITH SPSB1; SPSB2 AND SPSB4.
RX PubMed=16369487; DOI=10.1038/nsmb1034;
RA Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., Smith B.J.,
RA Babon J.J., Nicola N.A., Norton R.S., Nicholson S.E.;
RT "The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-
RT 4-binding residues.";
RL Nat. Struct. Mol. Biol. 13:77-84(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INTERACTION WITH SPSB1; SPSB2 AND SPSB4.
RX PubMed=20561531; DOI=10.1016/j.jmb.2010.06.017;
RA Filippakopoulos P., Low A., Sharpe T.D., Uppenberg J., Yao S., Kuang Z.,
RA Savitsky P., Lewis R.S., Nicholson S.E., Norton R.S., Bullock A.N.;
RT "Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-
RT containing proteins SPSB1, SPSB2, and SPSB4.";
RL J. Mol. Biol. 401:389-402(2010).
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, ECO:0000269|PubMed:15606896}.
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
CC (PubMed:16369487, PubMed:20561531). Interacts with SPSB2 (via
CC B30.2/SPRY domain); this interaction occurs in association with the
CC Elongin BC complex (PubMed:16369487, PubMed:20561531). Interacts with
CC SPSB4 (via B30.2/SPRY domain); this interaction occurs in association
CC with the Elongin BC complex (PubMed:16369487, PubMed:20561531).
CC Component of a ternary complex composed of SQSTM1 and PRKCZ (By
CC similarity). Interacts with actin (By similarity).
CC {ECO:0000250|UniProtKB:Q62627, ECO:0000250|UniProtKB:Q96IZ0}.
CC -!- INTERACTION:
CC Q925B0; O54784: Dapk3; NbExp=2; IntAct=EBI-77397, EBI-77359;
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q925B0-1; Sequence=Displayed;
CC Name=2; Synonyms=P33;
CC IsoId=Q925B0-2; Sequence=VSP_022018;
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-156 by PKC in cancer
CC cells. {ECO:0000250}.
CC -!- MISCELLANEOUS: The synapses are crucial cellular sites for the cell
CC death promoting actions of PAWR in motor neurons. Targeted inhibition
CC of PAWR by RNAi is neuroprotective.
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DR EMBL; DQ449073; ABE27591.1; -; mRNA.
DR EMBL; DQ449074; ABE27592.1; -; mRNA.
DR EMBL; DQ363525; ABC96645.1; -; mRNA.
DR EMBL; AF377871; AAK55414.1; -; mRNA.
DR CCDS; CCDS36053.1; -. [Q925B0-1]
DR RefSeq; NP_473397.1; NM_054056.2. [Q925B0-1]
DR AlphaFoldDB; Q925B0; -.
DR SMR; Q925B0; -.
DR BioGRID; 227870; 5.
DR IntAct; Q925B0; 3.
DR STRING; 10090.ENSMUSP00000092951; -.
DR iPTMnet; Q925B0; -.
DR PhosphoSitePlus; Q925B0; -.
DR MaxQB; Q925B0; -.
DR PaxDb; Q925B0; -.
DR PeptideAtlas; Q925B0; -.
DR PRIDE; Q925B0; -.
DR ProteomicsDB; 294388; -. [Q925B0-1]
DR ProteomicsDB; 294389; -. [Q925B0-2]
DR Antibodypedia; 1824; 395 antibodies from 40 providers.
DR DNASU; 114774; -.
DR Ensembl; ENSMUST00000095313; ENSMUSP00000092951; ENSMUSG00000035873. [Q925B0-1]
DR Ensembl; ENSMUST00000218332; ENSMUSP00000151457; ENSMUSG00000035873. [Q925B0-2]
DR GeneID; 114774; -.
DR KEGG; mmu:114774; -.
DR UCSC; uc007gzf.1; mouse. [Q925B0-1]
DR UCSC; uc011xnd.1; mouse. [Q925B0-2]
DR CTD; 5074; -.
DR MGI; MGI:2149961; Pawr.
DR VEuPathDB; HostDB:ENSMUSG00000035873; -.
DR eggNOG; ENOG502QVUF; Eukaryota.
DR GeneTree; ENSGT00390000000406; -.
DR HOGENOM; CLU_076619_0_0_1; -.
DR InParanoid; Q925B0; -.
DR OMA; RMYEREH; -.
DR OrthoDB; 1363165at2759; -.
DR PhylomeDB; Q925B0; -.
DR TreeFam; TF332824; -.
DR BioGRID-ORCS; 114774; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Pawr; mouse.
DR PRO; PR:Q925B0; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q925B0; protein.
DR Bgee; ENSMUSG00000035873; Expressed in ureter smooth muscle and 229 other tissues.
DR Genevisible; Q925B0; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0043522; F:leucine zipper domain binding; ISO:MGI.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0008157; F:protein phosphatase 1 binding; ISO:MGI.
DR GO; GO:0051017; P:actin filament bundle assembly; ISO:MGI.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:MGI.
DR GO; GO:0090281; P:negative regulation of calcium ion import; ISO:MGI.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; NAS:BHF-UCL.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045760; P:positive regulation of action potential; ISO:MGI.
DR GO; GO:0042986; P:positive regulation of amyloid precursor protein biosynthetic process; IDA:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:2000774; P:positive regulation of cellular senescence; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0060450; P:positive regulation of hindgut contraction; ISO:MGI.
DR GO; GO:1901300; P:positive regulation of hydrogen peroxide-mediated programmed cell death; IMP:BHF-UCL.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:1904457; P:positive regulation of neuronal action potential; ISO:MGI.
DR GO; GO:2000391; P:positive regulation of neutrophil extravasation; ISO:MGI.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; ISO:MGI.
DR GO; GO:1901082; P:positive regulation of relaxation of smooth muscle; ISO:MGI.
DR InterPro; IPR026117; Par-4.
DR PANTHER; PTHR15093; PTHR15093; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Coiled coil; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..333
FT /note="PRKC apoptosis WT1 regulator protein"
FT /id="PRO_0000058237"
FT REGION 1..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 138..196
FT /note="Selective for apoptosis induction in cancer cells
FT (SAC)"
FT REGION 293..333
FT /note="Leucine-zipper"
FT COILED 255..333
FT /evidence="ECO:0000255"
FT MOTIF 62..66
FT /note="B30.2/SPRY domain-binding motif"
FT /evidence="ECO:0000250|UniProtKB:Q96IZ0"
FT MOTIF 138..154
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 117..155
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 187..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 231..245
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 156
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q62627"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96IZ0"
FT VAR_SEQ 166..209
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16520897"
FT /id="VSP_022018"
SQ SEQUENCE 333 AA; 35908 MW; 80CD3DBA586C01F7 CRC64;
MATGGYRSGG STTTDFLEEW KAKREKMRAK QNPAGPGSSG GDPAAKSPAG SLTPTAVAGT
SELNHGPAGA AAPAAPAPGA LNCAHGSSTL PRAAPGSRRA EDECPSAAAA SGAPGSRGDE
EEPDSAREKG RSSGPSARKG KGQIEKRKLR EKRRSTGVVN IPAAECLDEY EDDEAGQKER
KREDAITQQN TIQNEAATLP DPGTSYLPQD PSRTVPGRYK STTSAPEDEI SNRYPRTDRS
GFSRHNRDAN APASFSSSST LEKRIEDLEK EVVRERQENL RLVRLMQDKE EMIGKLKEEI
DLLNRDLDDM EDENEQLKQE NKTLLKVVGQ LTR
