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; Vega:OTTHUMG00000170080
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	current	GRCh38.p12 (GCF_000001405.38)	12	NC_000012.12 (79584874..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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

PAR4 is the target of mir-107 in colorectal cancer cells.
Title: miR-107 Promotes Proliferation and Inhibits Apoptosis of Colon Cancer Cells by Targeting Prostate Apoptosis Response-4 (Par4).
we confirmed that the RASSF2-PAR-4 axis was mainly responsible for miR-7 functions in CAFs using bioinformatics methods. Overexpression of miR-7 in CAFs led to down-regulation of RASSF2, which dramatically decreased the secretion of PAR-4 from CAFs and then enhanced the proliferation and migration of the co-cultured cancer cells.
Title: Cancer-associated fibroblasts promote cancer cell growth through a miR-7-RASSF2-PAR-4 axis in the tumor microenvironment.
we investigated in the present study the mechanisms regulating the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment in ovarian and endometrial cancer cell lines
Title: Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells.
Authors demonstrate that TRIM21 expression predicts survival in pancreatic cancer patients. This work highlights a novel mechanism of Par-4 regulation, and identifies a novel prognostic marker and potential therapeutic target for pancreatic cancer.
Title: TRIM21 is a novel regulator of Par-4 in colon and pancreatic cancer cells.
Data suggest that PAR4 and P2Y12 heterodimer internalization/endocytosis is required for beta-arrestin-2 recruitment to endosomes and up-regulation of Akt signaling; activation of PAR4 but not of P2Y12 drives internalization of the PAR4-P2Y12 heterodimer. (PAR4 = protease-activated receptor 4; P2Y12 = purinergic receptor P2Y, G-protein coupled, 12 protein; Akt = proto-oncogene protein c-akt)
Title: Protease-activated receptor-4 and purinergic receptor P2Y12 dimerize, co-internalize, and activate Akt signaling via endosomal recruitment of β-arrestin.
In this review, we will focus on the therapeutic perspective of Par-4 with a special reference to its (Par-4) virgin prospect of devastating metastasis control.
Title: A journey beyond apoptosis: new enigma of controlling metastasis by pro-apoptotic Par-4.
in vitro and in vivo upregulation of Par-4 expression is indispensable for the trafficking of GRP78 to the cell membrane and subsequent apoptosis of cancer cell
Title: Inhibitory effect of Par-4 combined with cisplatin on human Wilms' tumor cells.
Prostate apoptosis response 4 (PAR4) expression modulates WNT signaling pathways in MCF7 breast cancer cells: A possible mechanism underlying PAR4-mediated docetaxel chemosensitivity.
Title: Prostate apoptosis response 4 (PAR4) expression modulates WNT signaling pathways in MCF7 breast cancer cells: A possible mechanism underlying PAR4-mediated docetaxel chemosensitivity.
Decreased PAR4 expression in breast cancer is associated with shorter survival. PAR4 suppresses growth and invasiveness of breast cancer cells.
Title: Prostate Apoptosis Response-4 (PAR4) Suppresses Growth and Invasion of Breast Cancer Cells and Is Positively Associated with Patient Survival.
Authors determined that PAR-4 induces cell apoptosis in response to stimuli, in vitro, but is also involved in the relocation of GRP78 from endoplasmic reticulum to the cell surface of ovarian cancer cell line.
Title: Role of PAR-4 in ovarian cancer.

Submit: New GeneRIF Correction See all GeneRIFs (86)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

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

Pathways from BioSystems

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Ceramide signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
Ceramide signaling pathway, organism-specific biosystem
Ceramide signaling pathway
Coregulation of Androgen receptor activity, organism-specific biosystem (from Pathway Interaction Database)
Coregulation of Androgen receptor activity, organism-specific biosystem
Coregulation of Androgen receptor activity

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

Homologs of the PAWR gene: The PAWR gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 227 organisms have orthologs with human gene PAWR
The Hierarchical Catalog of 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
interleukin-2 biosynthetic process	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
transcription, DNA-templated	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
actin filament	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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

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_001354732.1 → 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_001354733.1 → NP_001341662.1 PRKC apoptosis WT1 regulator protein isoform 2

Status: REVIEWED

Source sequence(s)

AC073569, AC073595
NM_002583.3 → 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, HY035045, U63809

Consensus CDS

CCDS31863.1

UniProtKB/Swiss-Prot

Q96IZ0

Related

ENSP00000328088.4, OTTHUMP00000242764, ENST00000328827.8

Conserved Domains (1) summary

pfam05911
Location:268 → 327

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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p12 Primary Assembly

Range

79584874..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