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Protein

PRKC apoptosis WT1 regulator protein

Gene

PAWR

Organism
Homo sapiens (Human)
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 BACE1.1 Publication

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • leucine zipper domain binding Source: UniProtKB
  • transcription corepressor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Enzyme and pathway databases

SIGNORiQ96IZ0.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:8614. PAWR.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • 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 (By similarity). Nuclear localization includes nucleoplasm and PML nuclear bodies.By similarity

GO - Cellular componenti

  • actin cytoskeleton Source: HPA
  • actin filament Source: GO_Central
  • cytoplasm Source: UniProtKB
  • nuclear chromatin Source: Ensembl
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi72N → A: Abolishes interaction with SPSB1-Elongin BC complex. 1 Publication1

Organism-specific databases

DisGeNETi5074.
OpenTargetsiENSG00000177425.
PharmGKBiPA32954.

Polymorphism and mutation databases

BioMutaiPAWR.
DMDMi66773935.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000582361 – 340PRKC apoptosis WT1 regulator proteinAdd BLAST340

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei108PhosphoserineCombined sources1
Modified residuei163Phosphothreonine; by PKABy similarity1
Modified residuei231PhosphoserineCombined sources1

Post-translational modificationi

Preferentially phosphorylated at the Thr-163 by PKC in cancer cells.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96IZ0.
MaxQBiQ96IZ0.
PaxDbiQ96IZ0.
PeptideAtlasiQ96IZ0.
PRIDEiQ96IZ0.
TopDownProteomicsiQ96IZ0.

PTM databases

iPTMnetiQ96IZ0.
PhosphoSitePlusiQ96IZ0.

Expressioni

Tissue specificityi

Widely expressed. Expression is elevated in various neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer, Parkinson and Huntington diseases and stroke. Down-regulated in several cancers.1 Publication

Inductioni

By apoptosis.

Gene expression databases

BgeeiENSG00000177425.
CleanExiHS_PAWR.
ExpressionAtlasiQ96IZ0. baseline and differential.
GenevisibleiQ96IZ0. HS.

Organism-specific databases

HPAiCAB020779.
HPA012640.

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.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HSPA5P110218EBI-595869,EBI-354921
SPSB1Q96BD62EBI-595869,EBI-2659201
Spsb2O888384EBI-595869,EBI-8820410From a different organism.
Spsb4Q8R5B62EBI-595869,EBI-8821982From a different organism.

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • leucine zipper domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111108. 46 interactors.
DIPiDIP-29003N.
IntActiQ96IZ0. 17 interactors.
MINTiMINT-1418971.
STRINGi9606.ENSP00000328088.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JK9X-ray1.79B67-81[»]
ProteinModelPortaliQ96IZ0.
SMRiQ96IZ0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96IZ0.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni145 – 203Selective for apoptosis induction in cancer cells (SAC)Add BLAST59
Regioni300 – 340Leucine-zipperAdd BLAST41

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili186 – 206Sequence analysisAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi145 – 161Nuclear localization signalBy similarityAdd BLAST17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi49 – 120Ala-richAdd BLAST72

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.
InParanoidiQ96IZ0.
OMAiNCAVGPA.
OrthoDBiEOG091G0JYK.
PhylomeDBiQ96IZ0.
TreeFamiTF332824.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q96IZ0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATGGYRTSS GLGGSTTDFL EEWKAKREKM RAKQNPPGPA PPGGGSSDAA
60 70 80 90 100
GKPPAGALGT PAAAAANELN NNLPGGAPAA PAVPGPGGVN CAVGSAMLTR
110 120 130 140 150
AAPGPRRSED EPPAASASAA PPPQRDEEEP DGVPEKGKSS GPSARKGKGQ
160 170 180 190 200
IEKRKLREKR RSTGVVNIPA AECLDEYEDD EAGQKERKRE DAITQQNTIQ
210 220 230 240 250
NEAVNLLDPG SSYLLQEPPR TVSGRYKSTT SVSEEDVSSR YSRTDRSGFP
260 270 280 290 300
RYNRDANVSG TLVSSSTLEK KIEDLEKEVV RERQENLRLV RLMQDKEEMI
310 320 330 340
GKLKEEIDLL NRDLDDIEDE NEQLKQENKT LLKVVGQLTR
Length:340
Mass (Da):36,568
Last modified:December 1, 2001 - v1
Checksum:i7E7515455402DBF8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti102 – 103AP → PPAR in AAC24947 (PubMed:8943350).Curated2
Sequence conflicti199I → M in CAG38786 (Ref. 2) Curated1
Sequence conflicti281R → T in AAC24947 (PubMed:8943350).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02246542P → L.1 PublicationCorresponds to variant rs8176804dbSNPEnsembl.1
Natural variantiVAR_02246678P → R.2 PublicationsCorresponds to variant rs8176805dbSNPEnsembl.1
Natural variantiVAR_022467137G → A.1 PublicationCorresponds to variant rs8176806dbSNPEnsembl.1
Natural variantiVAR_022468202E → A.1 PublicationCorresponds to variant rs8176870dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63809 mRNA. Translation: AAC24947.1.
CR536549 mRNA. Translation: CAG38786.1.
AY300794 Genomic DNA. Translation: AAP43693.1.
BC007018 mRNA. Translation: AAH07018.1.
AF503628 Genomic DNA. Translation: AAM27453.1.
CCDSiCCDS31863.1.
RefSeqiNP_002574.2. NM_002583.2.
XP_006719498.1. XM_006719435.2.
XP_016874866.1. XM_017019377.1.
UniGeneiHs.643130.
Hs.662065.

Genome annotation databases

EnsembliENST00000328827; ENSP00000328088; ENSG00000177425.
GeneIDi5074.
KEGGihsa:5074.
UCSCiuc001syx.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63809 mRNA. Translation: AAC24947.1.
CR536549 mRNA. Translation: CAG38786.1.
AY300794 Genomic DNA. Translation: AAP43693.1.
BC007018 mRNA. Translation: AAH07018.1.
AF503628 Genomic DNA. Translation: AAM27453.1.
CCDSiCCDS31863.1.
RefSeqiNP_002574.2. NM_002583.2.
XP_006719498.1. XM_006719435.2.
XP_016874866.1. XM_017019377.1.
UniGeneiHs.643130.
Hs.662065.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JK9X-ray1.79B67-81[»]
ProteinModelPortaliQ96IZ0.
SMRiQ96IZ0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111108. 46 interactors.
DIPiDIP-29003N.
IntActiQ96IZ0. 17 interactors.
MINTiMINT-1418971.
STRINGi9606.ENSP00000328088.

PTM databases

iPTMnetiQ96IZ0.
PhosphoSitePlusiQ96IZ0.

Polymorphism and mutation databases

BioMutaiPAWR.
DMDMi66773935.

Proteomic databases

EPDiQ96IZ0.
MaxQBiQ96IZ0.
PaxDbiQ96IZ0.
PeptideAtlasiQ96IZ0.
PRIDEiQ96IZ0.
TopDownProteomicsiQ96IZ0.

Protocols and materials databases

DNASUi5074.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328827; ENSP00000328088; ENSG00000177425.
GeneIDi5074.
KEGGihsa:5074.
UCSCiuc001syx.4. human.

Organism-specific databases

CTDi5074.
DisGeNETi5074.
GeneCardsiPAWR.
HGNCiHGNC:8614. PAWR.
HPAiCAB020779.
HPA012640.
MIMi601936. gene.
neXtProtiNX_Q96IZ0.
OpenTargetsiENSG00000177425.
PharmGKBiPA32954.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFBP. Eukaryota.
ENOG4111M3H. LUCA.
GeneTreeiENSGT00390000000406.
HOGENOMiHOG000115462.
HOVERGENiHBG058812.
InParanoidiQ96IZ0.
OMAiNCAVGPA.
OrthoDBiEOG091G0JYK.
PhylomeDBiQ96IZ0.
TreeFamiTF332824.

Enzyme and pathway databases

SIGNORiQ96IZ0.

Miscellaneous databases

ChiTaRSiPAWR. human.
EvolutionaryTraceiQ96IZ0.
GeneWikiiPAWR.
GenomeRNAii5074.
PROiQ96IZ0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177425.
CleanExiHS_PAWR.
ExpressionAtlasiQ96IZ0. baseline and differential.
GenevisibleiQ96IZ0. HS.

Family and domain databases

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

Entry informationi

Entry nameiPAWR_HUMAN
AccessioniPrimary (citable) accession number: Q96IZ0
Secondary accession number(s): O75796, Q6FHY9, Q8N700
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2005
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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.