PAWR pro-apoptotic WT1 regulator [Homo sapiens (human)] - Gene

Summary

Official Symbol: PAWRprovided by HGNC
Official Full Name: pro-apoptotic WT1 regulatorprovided by HGNC
Primary source: HGNC:HGNC:8614
See related: Ensembl:ENSG00000177425 MIM:601936
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PAR4; Par-4
Summary: This gene encodes a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases. [provided by RefSeq, Aug 2017]
Expression: Ubiquitous expression in endometrium (RPKM 8.7), thyroid (RPKM 5.9) and 24 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12q21.2

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (79584879..79691097, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (79985745..80084877, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

These findings have identified an in vivo antileukemic role for Par-4 through an NF-kappaB-dependent mechanism in TCL1-mediated CLL-like disease progression.
Title: Par-4 overexpression impedes leukemogenesis in the Eµ-TCL1 leukemia model through downregulation of NF-κB signaling.
In further investigations into the functions and molecular mechanisms of PAR4 in ESCC.
Title: Quantitative Proteomics Identify the Possible Tumor Suppressive Role of Protease-Activated Receptor-4 in Esophageal Squamous Cell Carcinoma Cells.
These results identify Twist-induced epigenetic silencing of Par-4 as a targetable axis that promotes chemoresistance in recurrent breast cancer.
Title: Epigenetic silencing of tumor suppressor Par-4 promotes chemoresistance in recurrent breast cancer.
These results suggest that PtdIns 4-kinase II beta may be a novel regulator of Par-4 through protein-protein interactions.
Title: Silencing of type II phosphatidylinositol 4-kinase β stabilizes prostate apoptosis response-4 and induces apoptosis in cancer cells.
Results indicate that residual breast cancer tumor cell survival and recurrence requires circumventing Foxo-driven Par-4 upregulation and suggest that approaches to enforce Par-4 expression may prevent residual cell survival and recurrence.
Title: Foxo-dependent Par-4 Upregulation Prevents Long-term Survival of Residual Cells Following PI3K-Akt Inhibition.
Chronic lymphocytic leukemia (CLL) cells overexpress a well-defined tumor suppressor Par-4, which promotes malignant B-CLL growth and is regulated through B-cell receptor signaling.
Title: Novel role of prostate apoptosis response-4 tumor suppressor in B-cell chronic lymphocytic leukemia.
The results demonstrate pH-dependent folding of cl-Par-4, with high disorder and aggregation at neutral pH, but a largely folded, non-aggregated conformation at acidic pH.
Title: pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain.
siRNA-mediated silencing of endogenous Par-4 unveil reversal of mesenchymal-epithelial transition with diminished E-cadherin expression and invasive pancreatic cancer cells phenotypes.
Title: Dual role of Par-4 in abrogation of EMT and switching on Mesenchymal to Epithelial Transition (MET) in metastatic pancreatic cancer cells.
These results indicate PAR4-specific promotion of platelet granule release and platelet-leukocyte aggregate formation and suggest that pharmacological control of PAR4 activity could potentially attenuate platelet granule release or platelet-leukocyte interaction-mediated pathological processes.
Title: Protease-activated receptor 4 activity promotes platelet granule release and platelet-leukocyte interactions.
These findings suggest that PAR4 plays a potential tumor suppressor role in esophageal squamous cell carcinoma cells
Title: Activation of PAR4 Upregulates p16 through Inhibition of DNMT1 and HDAC2 Expression via MAPK Signals in Esophageal Squamous Cell Carcinoma Cells.

Submit: New GeneRIF Correction See all GeneRIFs (97)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Par-4 expression is upregulated by HIV-1 Tat in hippocampal neurons and participates at an early stage of Tat-induced neuronal apoptosis, suggesting Par-4 may be a mediator of neuronal apoptosis in HIV encephalitis	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH65933 (e-PCR)
- UniSTS:39173

SGC34094 (e-PCR)
- UniSTS:814

Homology

Orthologs from Annotation Pipeline: 320 organisms have orthologs with human gene PAWR
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
actin binding	ISS Inferred from Sequence or Structural Similarity more info
enzyme binding	IDA Inferred from Direct Assay more info	PubMed
leucine zipper domain binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
transcription corepressor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
actin filament bundle assembly	ISS Inferred from Sequence or Structural Similarity more info
apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of T cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
positive regulation of amyloid precursor protein biosynthetic process	IEA Inferred from Electronic Annotation more info
positive regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
positive regulation of cellular senescence	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
positive regulation of hydrogen peroxide-mediated programmed cell death	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
actin cytoskeleton	IDA Inferred from Direct Assay more info
colocalizes_with actin filament	ISS Inferred from Sequence or Structural Similarity more info
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
nuclear chromatin	IEA Inferred from Electronic Annotation more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: PRKC apoptosis WT1 regulator protein

Names: PRKC, apoptosis, WT1, regulator; WT1-interacting protein; prostate apoptosis response protein 4; prostate apoptosis response protein PAR-4; prostate apoptosis response-4; transcriptional repressor PAR4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001354732.2 → NP_001341661.1 PRKC apoptosis WT1 regulator protein isoform 1

Status: REVIEWED

Source sequence(s)

AC027288, AC073569, AC073595

Consensus CDS

CCDS31863.1

Conserved Domains (1) summary

pfam05911
Location:268 → 327

FPP; Filament-like plant protein, long coiled-coil
NM_001354733.2 → NP_001341662.1 PRKC apoptosis WT1 regulator protein isoform 2

Status: REVIEWED

Source sequence(s)

AC073569, AC073595
NM_002583.4 → NP_002574.2 PRKC apoptosis WT1 regulator protein isoform 1

See identical proteins and their annotated locations for NP_002574.2

Status: REVIEWED

Source sequence(s)

AC027288, BC007018, CN280333, U63809

Consensus CDS

CCDS31863.1

UniProtKB/Swiss-Prot

Q96IZ0

Related

ENSP00000328088.4, ENST00000328827.9

Conserved Domains (1) summary

pfam05911
Location:268 → 327

FPP; Filament-like plant protein, long coiled-coil

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p13 Primary Assembly

Range

79584879..79691097 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006719435.2 → XP_006719498.1 PRKC apoptosis WT1 regulator protein isoform X1

See identical proteins and their annotated locations for XP_006719498.1

UniProtKB/Swiss-Prot

Q96IZ0

Conserved Domains (1) summary

pfam05911
Location:268 → 327

FPP; Filament-like plant protein, long coiled-coil
XM_017019378.1 → XP_016874867.1 PRKC apoptosis WT1 regulator protein isoform X2
XM_017019379.1 → XP_016874868.1 PRKC apoptosis WT1 regulator protein isoform X3