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FLASH GENE
Symbol PAWR contributors: mct - updated : 11-07-2018
HGNC name pro-apoptotic WT1 regulator
HGNC id 8614
Location 12q21.2      Physical location : 79.985.746 - 80.084.790
Synonym name
  • prostate apoptosis response protein 4
  • prostate apoptosis response protein PAR-4
  • transcriptional repressor PAR4
  • WT1-interacting protein
  • PRKC, apoptosis, WT1, regulator
  • Synonym symbol(s) PAR4, Par-4
    DNA
    TYPE functioning gene
    STRUCTURE 106.22 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • NFKB1-binding sites in PAWR promoter have previously been reported, and PAWR promoter region also contains SMAD4-binding site
  • MAPPING cloned Y linked N status provisional
    Physical map
    GLIPR1 12q21.1 GLI pathogenesis-related 1 (glioma) HRB2 12q21.1 HIV-1 rev binding protein 2 LOC390344 12 similar to 6-phosphogluconate dehydrogenase, decarboxylating LOC390345 12 similar to 60S ribosomal protein L10 (QM protein) (Tumor suppressor QM) (Laminin receptor homolog) PHLDA1 12q15 pleckstrin homology-like domain, family A, member 1 NAP1L1 12q15 nucleosome assembly protein 1-like 1 LOC121071 12q21.1 similar to NOGO-interacting mitochondrial protein FLJ23560 12q21.1 hypothetical protein FLJ23560 OSBPL8 12q14 oxysterol binding protein-like 8 LOC123031 12q21.1 similar to 60S ribosomal protein L21 HIP14 12q14-q15 similar to 60S ribosomal protein L21 CSRP2 12q21.1 cysteine and glycine-rich protein 2 LOC390346 12 similar to Ran-specific GTPase-activating protein (Ran binding protein 1) (RanBP1) E2F7 12q21.1 E2F transcription factor 7 NAV3 12q21.1 neuron navigator 3 MRPL11P3 12q21.2 neuron navigator 3 LOC390347 12 similar to ras related v-ral simian leukemia viral oncogene homolog A SYT1 12q15-q21 synaptotagmin I LOC338756 12q21.2 similar to hypothetical protein PAWR 12q21.2-q21.32 PRKC, apoptosis, WT1, regulator PPP1R12A 12q15-q21 protein phosphatase 1, regulatory (inhibitor) subunit 12A LOC120872 12q21.2 similar to ribosomal protein L7 LOC283308 12q21.2 similar to 60S ribosomal protein L26 FLJ90579 12q21.2 hypothetical protein FLJ90579 LOC387870 12 similar to protein tyrosine phosphatase, receptor type, Q isoform 1 precursor; glomerular mesangial cell receptor protein-tyrosine phosphatase PTPRQ 12q21.2 protein tyrosine phosphatase, receptor type, Q MYF6 12q21 myogenic factor 6 (herculin) MYF5 12q21 myogenic factor 5 LIN7A 12q21 lin-7 homolog A (C. elegans) FLJ21963 12q21.31 FLJ21963 protein PPFIA2 12q21.31 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 2 HSPC128 12q21.31 HSPC128 protein FLJ22789 12q21.31 hypothetical protein FLJ22789 DKFZp762A217 12q21.31 hypothetical protein DKFZp762A217 LOC390348 12 similar to 60S ribosomal protein L6 (TAX-responsive enhancer element binding protein 107) (TAXREB107) (Neoplasm-related protein C140)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 9129 - 340 - 2017 28652403
    5 - 1598 - 248 - 2017 28652403
    7 - 8928 - 340 - 2017 28652403
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
    Reproductivefemale systembreastmammary gland highly
    Visualeyeanterior segment  highly
     eyelens  highly
     eyeretina  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text stem cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a leucine-zipper domain, binding to the zinc finger domain of WT1
  • a SAC domain, selective apoptosis in cancer (SAC) cells
  • a 17-AAs long nuclear localization sequence encompassing between the 145th and the 161st AA
  • 41-AA long leucine zipper (LZ) domain, situated at the C-terminal end starting from the 300th to the last (340th) AA
  • HOMOLOGY
    interspecies homolog to murine Pawr
    Homologene
    FAMILY
    CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • co-localizes with PITX2 in nucleus
  • shuttling from the cytoplasm to the nucleus is essential for RASSF2 function
  • basic FUNCTION
  • PKC apoptosis WT1 regulator
  • transcriptional repressor activity
  • contributes to apoptotic neuronal cell death in Alzeihmer disease
  • regulated choline up-take via its interaction with CHT1
  • may be a mediator of neuronal apoptosis in HIV encephalitis
  • regulatory component in the dopamine signaling, constituting a molecular link between impaired dopamine signaling and depression
  • in addition to its proapoptotic function, acts as a novel transcription cofactor for AR to target CFLAR gene expression
  • proapoptotic protein with intracellular functions in the cytoplasm and nucleus
  • activates an extrinsic pathway involving cell surface HSPA5 for induction of apoptosis and is essential for its cell surface expression
  • PITX2-interacting protein that regulates PITX2 activity in ocular cells
  • unique proapoptotic protein that selectively induces apoptosis in cancer cells, sensitizes cells to the action of multiple apoptotic stimuli, and causes tumor regression through a region harboring 59-AAs starting from 145 to 203
  • act at multiple levels that include activating both the FAS- and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-controlled proapoptotic pathways, as well as inhibiting the NF-{kappa}B antiapoptotic pathway
  • implicated in the regulation of smooth muscle contraction
  • is expressed in trophoblastic cells and is involved in transport of HSPA5 to the cell surface and thus regulates invasive property of extravillous cytotrophoblastic cells (CTB)
  • is a novel and essential downstream target of TGFB1 signaling and acts as an important factor during TGFB1-induced EMT
  • importance of PAWR not only in preventing cancer development/recurrence but also as a promising anticancer therapeutic agent
  • intrinsically disordered pro-apoptotic protein with tumour suppressor function
  • induces cancer cell apoptosis through endoplasmic reticulum (ER) stress and mitochondrial dysfunction
  • novel role for PAWR/NFKB1 in islet beta cell apoptosis and type 2 diabetes
  • is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers
  • proapoptotic protein (PAWR/Par-4) negatively regulates residual cancer cell survival and recurrence
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    novel extrinsic pathway for apoptosis by PAWR acting via its SAC domain
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with numerous proteins such as WT1, atypical protein kinase C (aPKC)
  • interacting with THAP1 in primary endothelial cells and fibroblasts
  • interacting with CHT1
  • interacting with HIV-1 Tat
  • interacting directly with dopamine D2 receptor via the calmodulin bindig motif
  • cooperation between PAWR and PTEN as relevant for the development of prostate cancer and implicate the NF-kappaB pathway as a critical event in prostate tumorigenesis
  • PITX2-interacting protein that regulates PITX2 transcriptional activity in ocular cells (interaction between PITX2 and PAWR might have a role in apoptotic and/or neurodegeneration pathways involved in glaucoma)
  • is a novel substrate of CASP3 during apoptosis (the novel specific CASP3 cleavage site in PAWR, and the cleaved fragment of PAWR retains proapoptotic activity)
  • phosphorylation of PAWR at Thr155 disrupts its interaction with PPP1R12A, exposing the sites of phosphorylation in PPP1R12A and leading to myosin light chain phosphatase inhibition and contraction
  • role of X-linked inhibitor of apoptosis protein in the regulation of endogenous PAWR levels through inhibition of caspase-mediated cleavage
  • TNF-induced apoptosis leads to CASP8-dependent PAWR-cleavage followed by nuclear accumulation of the C-terminal PAWR (132-340) fragment, which then induces apoptosis
  • FBXO45 interacts with PAWR in the cytoplasm and mediates its ubiquitylation and proteasomal degradation
  • TRIM21 is a novel interacting partner of PAWR, and interact with PAWR endogenously and through its PRY-SPRY domain
  • FOXO3 directly binds to the PAWR promoter and activates its transcription following inhibition of the PI3K-AKT pathway
  • cell & other
    REGULATION
    induced by apoptotic insults
    1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP)
    HIV-1 Tat in hippocampal neurons
    inhibited by PRKCZ
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in a high percentage of prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss
    tumoral     --low  
    by promoter hypermethylation and silencing in endometrial cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    activation of PAWR by small activating RNAs may have a therapeutic benefit for prostate and other types of cancer
    cancermetastases 
    identification of an extracellular role for PAWR and its SAC domain significantly broadens their therapeutic potential for primary and metastatic tumors
    cancerreproductiveovary
    is likely a very interesting therapeutic target against ovarian carcinogenesis
    ANIMAL & CELL MODELS
    Par4(delta)LZ mice display significantly increased depression-like behaviors