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Protein

PRKC apoptosis WT1 regulator protein

Gene

Pawr

Organism
Rattus norvegicus (Rat)
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 similarity

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • protein kinase C binding Source: RGD
  • protein phosphatase 1 binding Source: RGD

GO - Biological processi

  • actin filament bundle assembly Source: UniProtKB
  • activation of cysteine-type endopeptidase activity Source: RGD
  • apoptotic process Source: UniProtKB
  • calcium ion import into cell Source: RGD
  • cellular response to estradiol stimulus Source: RGD
  • cellular response to follicle-stimulating hormone stimulus Source: RGD
  • cellular response to interleukin-1 Source: RGD
  • cellular response to vitamin E Source: RGD
  • detection of mechanical stimulus involved in sensory perception of pain Source: RGD
  • detection of temperature stimulus involved in sensory perception of pain Source: RGD
  • negative regulation of calcium ion import Source: RGD
  • positive regulation of action potential Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of hindgut contraction Source: RGD
  • positive regulation of leukocyte tethering or rolling Source: RGD
  • positive regulation of neuronal action potential Source: RGD
  • positive regulation of neuron apoptotic process Source: RGD
  • positive regulation of neutrophil extravasation Source: RGD
  • positive regulation of phosphoprotein phosphatase activity Source: RGD
  • positive regulation of relaxation of smooth muscle Source: RGD
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to estradiol Source: RGD
  • response to iron(II) ion Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to wounding Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
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
Transcriptional repressor Par-4-like protein PAWR
Gene namesi
Name:Pawr
Synonyms:Par4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69065. 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

  • axon Source: RGD
  • cytoplasm Source: RGD
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 332332PRKC apoptosis WT1 regulator proteinPRO_0000058238Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei155 – 1551Phosphothreonine; by PKA1 Publication

Post-translational modificationi

Preferentially phosphorylated at the Thr-155 by PKC in cancer cells.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ62627.
PRIDEiQ62627.

PTM databases

iPTMnetiQ62627.
PhosphoSiteiQ62627.

Expressioni

Inductioni

In ventral prostate following castration.1 Publication

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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Dapk3O887645EBI-1187240,EBI-4404236
HSPA5P110214EBI-1187240,EBI-354921From a different organism.
TfptQ9JMG68EBI-1187240,EBI-1767101

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • protein kinase C binding Source: RGD
  • protein phosphatase 1 binding Source: RGD

Protein-protein interaction databases

BioGridi249098. 3 interactions.
IntActiQ62627. 5 interactions.
MINTiMINT-199814.
STRINGi10116.ENSRNOP00000008222.

Structurei

3D structure databases

ProteinModelPortaliQ62627.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni137 – 19559Selective for apoptosis induction in cancer cells (SAC)Add
BLAST
Regioni292 – 33241Leucine-zipperAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili176 – 19823Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi137 – 15317Nuclear localization signalAdd
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.
HOGENOMiHOG000115462.
HOVERGENiHBG058812.
InParanoidiQ62627.
PhylomeDBiQ62627.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q62627-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATGGYRSSG STTDFLEEWK AKREKMRAKQ NPVGPGSSGG DPAAKSPAGP
60 70 80 90 100
LAQTTAAGTS ELNHGPAGAA APAAPGPGAL NCAHGSSALP RGAPGSRRPE
110 120 130 140 150
DECPIAAGAA GAPASRGDEE EPDSAPEKGR SSGPSARKGK GQIEKRKLRE
160 170 180 190 200
KRRSTGVVNI PAAECLDEYE DDEAGQKERK REDAITQQNT IQNEAASLPD
210 220 230 240 250
PGTSYLPQDP SRTVPGRYKS TISAPEEEIL NRYPRTDRSG FSRHNRDTSA
260 270 280 290 300
PANFASSSTL EKRIEDLEKE VLRERQENLR LTRLMQDKEE MIGKLKEEID
310 320 330
LLNRDLDDME DENEQLKQEN KTLLKVVGQL TR
Length:332
Mass (Da):35,866
Last modified:November 1, 1996 - v1
Checksum:i2069B32DEFFF160F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05989 mRNA. Translation: AAA16492.1.
RefSeqiNP_277020.1. NM_033485.2.
UniGeneiRn.9127.

Genome annotation databases

GeneIDi64513.
KEGGirno:64513.
UCSCiRGD:69065. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05989 mRNA. Translation: AAA16492.1.
RefSeqiNP_277020.1. NM_033485.2.
UniGeneiRn.9127.

3D structure databases

ProteinModelPortaliQ62627.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249098. 3 interactions.
IntActiQ62627. 5 interactions.
MINTiMINT-199814.
STRINGi10116.ENSRNOP00000008222.

PTM databases

iPTMnetiQ62627.
PhosphoSiteiQ62627.

Proteomic databases

PaxDbiQ62627.
PRIDEiQ62627.

Protocols and materials databases

DNASUi64513.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi64513.
KEGGirno:64513.
UCSCiRGD:69065. rat.

Organism-specific databases

CTDi5074.
RGDi69065. Pawr.

Phylogenomic databases

eggNOGiENOG410IFBP. Eukaryota.
ENOG4111M3H. LUCA.
HOGENOMiHOG000115462.
HOVERGENiHBG058812.
InParanoidiQ62627.
PhylomeDBiQ62627.

Miscellaneous databases

PROiQ62627.

Family and domain databases

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

Publicationsi

  1. "Commonality of the gene programs induced by effectors of apoptosis in androgen-dependent and -independent prostate cells."
    Sells S.F., Wood D.P. Jr., Joshi-Barve S.S., Muthukumar S., Jacob R.J., Crist S.A., Humphreys S., Rangnekar V.M.
    Cell Growth Differ. 5:457-466(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
    Tissue: Prostate.
  2. "Identification of a unique core domain of par-4 sufficient for selective apoptosis induction in cancer cells."
    El-Guendy N., Zhao Y., Gurumurthy S., Burikhanov R., Rangnekar V.M.
    Mol. Cell. Biol. 23:5516-5525(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN SAC, MUTAGENESIS, SUBCELLULAR LOCATION.
  3. "Phosphorylation of Par-4 by protein kinase A is critical for apoptosis."
    Gurumurthy S., Goswami A., Vasudevan K.M., Rangnekar V.M.
    Mol. Cell. Biol. 25:1146-1161(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-155 BY PKA.
  4. "Binding of Par-4 to the actin cytoskeleton is essential for Par-4/Dlk-mediated apoptosis."
    Vetterkind S., Illenberger S., Kubicek J., Boosen M., Appel S., Naim H.Y., Scheidtmann K.H., Preuss U.
    Exp. Cell Res. 305:392-408(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ACTIN.

Entry informationi

Entry nameiPAWR_RAT
AccessioniPrimary (citable) accession number: Q62627
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2005
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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.