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PRKC apoptosis WT1 regulator protein; prostate apoptosis response 4 protein; par-4 (PAWR PAR4)
Function:
1) pro-apoptopic protein
2) induces apoptosis in cancer cells
3) activation of Fas prodeath pathway
4) inhibition of NF-kappaB transcriptional activity
5) augments the transcriptional repression mediated by WT1
6) downregulates the anti-apoptotic protein BCL2 via interaction with WT
7) induction of aberrant amyloid A4 peptide production via BACE1-medicated amyloid precursor protein cleavage (putative) - inhibited by AATF
8) interacts with WT1, atypical PKCs, p62, DAPK3 kinase, THAP1, AATF, BACE1, SPSB1, SPSB2 AND SPSB4
9) component of SQSTM1/PRKCZ/PAR4 complex
Compartment:
- cytoplasm, nucleus
- mainly cytoplasmic, nuclear prior to apoptosis
Expression:
- widely expressed
Pathology:
- down-regulated in several cancers
- increased expression seen in prostate cancer cells undergoing apoptosis
- expression is elevated in neurodegenerative diseases
a) amyotrophic lateral sclerosis
b) Alzheimer's disease
- increased expression seen in vulnerable neurons in Alzheimer's disease.
c) Parkinson's disease
d) Huntington's disease
e) stroke
General
transcriptional silencer (transcriptional repressor)
Properties
SIZE: entity length = 342 aa
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: alanine-rich region {49-120}
MOTIF: alanine residue (SEVERAL)
death domain
NAME: death domain
SITE: 145-203
MOTIF: nuclear translocation signal {145-161}
Thr phosphorylation site {T163}
FOR-PHOSPHORYLATION-BY: protein kinase A
coiled coil {186-206}
leucine zipper
SITE: 300-340
FOR-BINDING-VIA: leucine zipper
Database Correlations
OMIM 601936
UniProt Q96IZ0
Entrez Gene 5074
Kegg hsa:5074
References
- Guo Q et al
Par-4 is a mediator of neuronal degeneration associated with
the pathogenesis of Alzheimer disease.
Nature Medicine 4:957-62, 1998
PMID: 9701251
- Mattson MP.
Apoptosis in neurodegenerative disorders.
Nature Reviews, Molecular Cell Biology 1:120-9, 2000
PMID: 11253364
- Entrez Gene :accession 5074
- UniProt :accession Q96IZ0
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/PAWRID41641ch12q21.html
- NIEHS-SNPs
http://egp.gs.washington.edu/data/pawr/