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Protein

PRKC apoptosis WT1 regulator protein

Gene

Pawr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Pro-apoptopic protein capable of selectively inducing apoptosis in cancer cells, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. Induces apoptosis in certain cancer cells by activation of the Fas prodeath pathway and coparallel inhibition of NF-kappa-B transcriptional activity. Inhibits the transcriptional activation and augments the transcriptional repression mediated by WT1. Down-regulates the anti-apoptotic protein BCL2 via its interaction with WT1. Seems also to be a transcriptional repressor by itself. May be directly involved in regulating the amyloid precursor protein (APP) cleavage activity of BACE1 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
PRKC apoptosis WT1 regulator protein
Alternative name(s):
Prostate apoptosis response 4 protein
Short name:
Par-4
Gene namesi
Name:Pawr
Synonyms:Par4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:2149961. Pawr.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Mainly cytoplasmic in absence of apoptosis signal and in normal cells. Nuclear in most cancer cell lines. Nuclear entry seems to be essential but not sufficient for apoptosis. Nuclear localization includes nucleoplasm and PML nuclear bodies (By similarity).By similarity

GO - Cellular componenti

  • actin cytoskeleton Source: MGI
  • actin filament Source: Ensembl
  • axon Source: Ensembl
  • cytoplasm Source: MGI
  • neuronal cell body Source: Ensembl
  • nuclear chromatin Source: BHF-UCL
  • nucleus Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 333333PRKC apoptosis WT1 regulator proteinPRO_0000058237Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei156 – 1561Phosphothreonine; by PKABy similarity

Post-translational modificationi

Preferentially phosphorylated at the Thr-156 by PKC in cancer cells.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ925B0.
MaxQBiQ925B0.
PaxDbiQ925B0.
PRIDEiQ925B0.

PTM databases

iPTMnetiQ925B0.
PhosphoSiteiQ925B0.

Expressioni

Gene expression databases

BgeeiQ925B0.
CleanExiMM_PAWR.
GenevisibleiQ925B0. MM.

Interactioni

Subunit structurei

Interacts with WT1, via the C-terminal region. Homooligomer. Interacts also with a wide variety of proteins, such as atypical PKCs, p62, DAPK3 kinase and THAP1. Interacts with actin, AATF, BACE1, SPSB1, SPSB2 AND SPSB4. Component of a ternary complex composed of SQSTM1 and PRKCZ.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Dapk3O547842EBI-77397,EBI-77359

GO - Molecular functioni

Protein-protein interaction databases

BioGridi227870. 5 interactions.
IntActiQ925B0. 1 interaction.
STRINGi10090.ENSMUSP00000092951.

Structurei

3D structure databases

ProteinModelPortaliQ925B0.
SMRiQ925B0. Positions 254-326.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni138 – 19659Selective for apoptosis induction in cancer cells (SAC)Add
BLAST
Regioni293 – 33341Leucine-zipperAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili255 – 33379Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi138 – 15417Nuclear localization signalBy similarityAdd
BLAST

Domaini

The leucine-zipper domain is not essential for apoptosis, but is required for sensitization of cells to exogenous apoptotic insults and for interaction with its partners.By similarity
The SAC domain is a death-inducing domain selective for apoptosis induction in cancer cells. This domain is essential for nuclear entry, Fas activation, inhibition of NF-kappa-B activity and induction of apoptosis in cancer cells (By similarity).By similarity

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IFBP. Eukaryota.
ENOG4111M3H. LUCA.
GeneTreeiENSGT00390000000406.
HOGENOMiHOG000115462.
HOVERGENiHBG058812.
InParanoidiQ925B0.
OMAiQDGVPEK.
OrthoDBiEOG7JQBP4.
PhylomeDBiQ925B0.
TreeFamiTF332824.

Family and domain databases

InterProiIPR026117. Par-4.
[Graphical view]
PANTHERiPTHR15093. PTHR15093. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q925B0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATGGYRSGG STTTDFLEEW KAKREKMRAK QNPAGPGSSG GDPAAKSPAG
60 70 80 90 100
SLTPTAVAGT SELNHGPAGA AAPAAPAPGA LNCAHGSSTL PRAAPGSRRA
110 120 130 140 150
EDECPSAAAA SGAPGSRGDE EEPDSAREKG RSSGPSARKG KGQIEKRKLR
160 170 180 190 200
EKRRSTGVVN IPAAECLDEY EDDEAGQKER KREDAITQQN TIQNEAATLP
210 220 230 240 250
DPGTSYLPQD PSRTVPGRYK STTSAPEDEI SNRYPRTDRS GFSRHNRDAN
260 270 280 290 300
APASFSSSST LEKRIEDLEK EVVRERQENL RLVRLMQDKE EMIGKLKEEI
310 320 330
DLLNRDLDDM EDENEQLKQE NKTLLKVVGQ LTR
Length:333
Mass (Da):35,908
Last modified:December 12, 2006 - v2
Checksum:i80CD3DBA586C01F7
GO
Isoform 2 (identifier: Q925B0-2) [UniParc]FASTAAdd to basket

Also known as: P33

The sequence of this isoform differs from the canonical sequence as follows:
     166-209: Missing.

Show »
Length:289
Mass (Da):30,944
Checksum:i3B729F993F35745F
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei166 – 20944Missing in isoform 2. 1 PublicationVSP_022018Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ449073 mRNA. Translation: ABE27591.1.
DQ449074 mRNA. Translation: ABE27592.1.
DQ363525 mRNA. Translation: ABC96645.1.
AF377871 mRNA. Translation: AAK55414.1.
CCDSiCCDS36053.1. [Q925B0-1]
RefSeqiNP_473397.1. NM_054056.2. [Q925B0-1]
UniGeneiMm.391419.

Genome annotation databases

EnsembliENSMUST00000095313; ENSMUSP00000092951; ENSMUSG00000035873. [Q925B0-1]
GeneIDi114774.
KEGGimmu:114774.
UCSCiuc007gzf.1. mouse. [Q925B0-1]
uc011xnd.1. mouse. [Q925B0-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ449073 mRNA. Translation: ABE27591.1.
DQ449074 mRNA. Translation: ABE27592.1.
DQ363525 mRNA. Translation: ABC96645.1.
AF377871 mRNA. Translation: AAK55414.1.
CCDSiCCDS36053.1. [Q925B0-1]
RefSeqiNP_473397.1. NM_054056.2. [Q925B0-1]
UniGeneiMm.391419.

3D structure databases

ProteinModelPortaliQ925B0.
SMRiQ925B0. Positions 254-326.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi227870. 5 interactions.
IntActiQ925B0. 1 interaction.
STRINGi10090.ENSMUSP00000092951.

PTM databases

iPTMnetiQ925B0.
PhosphoSiteiQ925B0.

Proteomic databases

EPDiQ925B0.
MaxQBiQ925B0.
PaxDbiQ925B0.
PRIDEiQ925B0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000095313; ENSMUSP00000092951; ENSMUSG00000035873. [Q925B0-1]
GeneIDi114774.
KEGGimmu:114774.
UCSCiuc007gzf.1. mouse. [Q925B0-1]
uc011xnd.1. mouse. [Q925B0-2]

Organism-specific databases

CTDi5074.
MGIiMGI:2149961. Pawr.

Phylogenomic databases

eggNOGiENOG410IFBP. Eukaryota.
ENOG4111M3H. LUCA.
GeneTreeiENSGT00390000000406.
HOGENOMiHOG000115462.
HOVERGENiHBG058812.
InParanoidiQ925B0.
OMAiQDGVPEK.
OrthoDBiEOG7JQBP4.
PhylomeDBiQ925B0.
TreeFamiTF332824.

Miscellaneous databases

NextBioi368825.
PROiQ925B0.
SOURCEiSearch...

Gene expression databases

BgeeiQ925B0.
CleanExiMM_PAWR.
GenevisibleiQ925B0. MM.

Family and domain databases

InterProiIPR026117. Par-4.
[Graphical view]
PANTHERiPTHR15093. PTHR15093. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel isoform of prostate apoptosis response 4 (PAR-4) that co-distributes with F-actin and prevents apoptosis in neural stem cells."
    Wang G., Silva J., Krishnamurthy K., Bieberich E.
    Apoptosis 11:315-325(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Strain: 129S4/SvJae.
  2. "Mouse par-4 cDNA sequence."
    Han S.-S., Rangnekar V.M.
    Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
  3. Hackett J.D.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 137-333 (ISOFORM 1).
    Strain: Swiss Webster / NIH.
  4. "RNAi knockdown of Par-4 inhibits neurosynaptic degeneration in ALS-linked mice."
    Xie J., Awad K.S., Guo Q.
    J. Neurochem. 92:59-71(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN NEUROSYNAPTIC DEGENERATION.
  5. "The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues."
    Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., Smith B.J., Babon J.J., Nicola N.A., Norton R.S., Nicholson S.E.
    Nat. Struct. Mol. Biol. 13:77-84(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SPSB1; SPSB2 AND SPSB4.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiPAWR_MOUSE
AccessioniPrimary (citable) accession number: Q925B0
Secondary accession number(s): Q0ZHI4, Q2HYJ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2005
Last sequence update: December 12, 2006
Last modified: May 11, 2016
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The synapses are crucial cellular sites for the cell death promoting actions of PAWR in motor neurons. Targeted inhibition of PAWR by RNAi is neuroprotective.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.