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; AllianceGenome:HGNC:8614
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
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Genomic context

Location:: 12q21.2

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (79584879..79690964, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (79563553..79669620, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (79978659..80084744, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis.
Title: CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis.
PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells.
Title: PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells.
Determination of PAR4 numbers on the surface of human platelets: no effect of the single nucleotide polymorphism rs773902.
Title: Determination of PAR4 numbers on the surface of human platelets: no effect of the single nucleotide polymorphism rs773902.
Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Galpha in live cells.
Title: Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells.
Molecular mechanisms regulating Proteinase-Activated Receptors (PARs).
Title: Molecular mechanisms regulating Proteinase-Activated Receptors (PARs).
PAR4 activation involves extracellular loop 3 and transmembrane residue Thr153.
Title: PAR4 activation involves extracellular loop 3 and transmembrane residue Thr153.
Par-4 mediated Smad4 induction in PDAC cells restores canonical TGF-beta/ Smad4 axis driving the cells towards lethal EMT.
Title: Par-4 mediated Smad4 induction in PDAC cells restores canonical TGF-β/ Smad4 axis driving the cells towards lethal EMT.
A Platelet Function Modulator of Thrombin Activation Is Causally Linked to Cardiovascular Disease and Affects PAR4 Receptor Signaling.
Title: A Platelet Function Modulator of Thrombin Activation Is Causally Linked to Cardiovascular Disease and Affects PAR4 Receptor Signaling.
Par-4 regulates autophagic cell death in human cancer cells via upregulating p53 and BNIP3.
Title: Par-4 regulates autophagic cell death in human cancer cells via upregulating p53 and BNIP3.
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.

Submit: New GeneRIF Correction See all GeneRIFs (106)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

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

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

Gene Ontology Provided by GOA

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

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

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

UniProtKB/Swiss-Prot

O75796, Q6FHY9, Q8N700, Q96IZ0

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

O75796, Q6FHY9, Q8N700, 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: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

79584879..79690964 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047428916.1 → XP_047284872.1 PRKC apoptosis WT1 regulator protein isoform X1

UniProtKB/Swiss-Prot

O75796, Q6FHY9, Q8N700, Q96IZ0
XM_047428918.1 → XP_047284874.1 PRKC apoptosis WT1 regulator protein isoform X2
XM_047428917.1 → XP_047284873.1 PRKC apoptosis WT1 regulator protein isoform X2
XM_017019378.2 → XP_016874867.1 PRKC apoptosis WT1 regulator protein isoform X3
XM_047428919.1 → XP_047284875.1 PRKC apoptosis WT1 regulator protein isoform X3
XM_017019379.2 → XP_016874868.1 PRKC apoptosis WT1 regulator protein isoform X4

RNA

XR_944561.3 RNA Sequence
XR_944560.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

79563553..79669620 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054372151.1 → XP_054228126.1 PRKC apoptosis WT1 regulator protein isoform X1

UniProtKB/Swiss-Prot

O75796, Q6FHY9, Q8N700, Q96IZ0
XM_054372152.1 → XP_054228127.1 PRKC apoptosis WT1 regulator protein isoform X2
XM_054372153.1 → XP_054228128.1 PRKC apoptosis WT1 regulator protein isoform X3
XM_054372154.1 → XP_054228129.1 PRKC apoptosis WT1 regulator protein isoform X4