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Q96IZ0

- PAWR_HUMAN

UniProt

Q96IZ0 - PAWR_HUMAN

Protein

PRKC apoptosis WT1 regulator protein

Gene

PAWR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Pro-apoptopic protein capable of selectively inducing apoptosis in cancer cells, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. Induces apoptosis in certain cancer cells by activation of the Fas prodeath pathway and coparallel inhibition of NF-kappa-B transcriptional activity. Inhibits the transcriptional activation and augments the transcriptional repression mediated by WT1. Down-regulates the anti-apoptotic protein BCL2 via its interaction with WT1. Seems also to be a transcriptional repressor by itself. May be directly involved in regulating the amyloid precursor protein (APP) cleavage activity of BACE1.1 Publication

    GO - Molecular functioni

    1. actin binding Source: UniProtKB
    2. enzyme binding Source: UniProtKB
    3. leucine zipper domain binding Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. transcription corepressor activity Source: ProtInc

    GO - Biological processi

    1. actin filament bundle assembly Source: UniProtKB
    2. apoptotic process Source: UniProtKB
    3. apoptotic signaling pathway Source: Ensembl
    4. interleukin-2 biosynthetic process Source: Ensembl
    5. negative regulation of B cell proliferation Source: Ensembl
    6. negative regulation of cell proliferation Source: ProtInc
    7. negative regulation of T cell proliferation Source: Ensembl
    8. negative regulation of T cell receptor signaling pathway Source: Ensembl
    9. negative regulation of transcription from RNA polymerase II promoter Source: ProtInc
    10. positive regulation of amyloid precursor protein biosynthetic process Source: Ensembl
    11. positive regulation of apoptotic process Source: UniProtKB
    12. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Biological processi

    Apoptosis, Transcription, Transcription regulation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    PRKC apoptosis WT1 regulator protein
    Alternative name(s):
    Prostate apoptosis response 4 protein
    Short name:
    Par-4
    Gene namesi
    Name:PAWR
    Synonyms:PAR4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:8614. PAWR.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Mainly cytoplasmic in absence of apoptosis signal and in normal cells. Nuclear in most cancer cell lines. Nuclear entry seems to be essential but not sufficient for apoptosis By similarity. Nuclear localization includes nucleoplasm and PML nuclear bodies.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi72 – 721N → A: Abolishes interaction with SPSB1-Elongin BC complex. 1 Publication

    Organism-specific databases

    PharmGKBiPA32954.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 340340PRKC apoptosis WT1 regulator proteinPRO_0000058236Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei163 – 1631Phosphothreonine; by PKABy similarity

    Post-translational modificationi

    Preferentially phosphorylated at the Thr-163 by PKC in cancer cells.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ96IZ0.
    PaxDbiQ96IZ0.
    PeptideAtlasiQ96IZ0.
    PRIDEiQ96IZ0.

    PTM databases

    PhosphoSiteiQ96IZ0.

    Expressioni

    Tissue specificityi

    Widely expressed. Expression is elevated in various neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer, Parkinson and Huntington diseases and stroke. Down-regulated in several cancers.1 Publication

    Inductioni

    By apoptosis.

    Gene expression databases

    ArrayExpressiQ96IZ0.
    BgeeiQ96IZ0.
    CleanExiHS_PAWR.
    GenevestigatoriQ96IZ0.

    Organism-specific databases

    HPAiCAB020779.
    HPA012640.

    Interactioni

    Subunit structurei

    Interacts with WT1, via the C-terminal region. Homooligomer. Interacts also with a wide variety of proteins, such as atypical PKCs, p62, DAPK3 kinase and THAP1. Interacts with actin, AATF, BACE1, SPSB1, SPSB2 AND SPSB4. Component of a ternary complex composed of SQSTM1 and PRKCZ.6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HSPA5P110218EBI-595869,EBI-354921
    SPSB1Q96BD62EBI-595869,EBI-2659201
    Spsb2O888384EBI-595869,EBI-8820410From a different organism.
    Spsb4Q8R5B62EBI-595869,EBI-8821982From a different organism.

    Protein-protein interaction databases

    BioGridi111108. 36 interactions.
    DIPiDIP-29003N.
    IntActiQ96IZ0. 13 interactions.
    MINTiMINT-1418971.
    STRINGi9606.ENSP00000328088.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2JK9X-ray1.79B67-81[»]
    ProteinModelPortaliQ96IZ0.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96IZ0.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni145 – 20359Selective for apoptosis induction in cancer cells (SAC)Add
    BLAST
    Regioni300 – 34041Leucine-zipperAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili186 – 20621Sequence AnalysisAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi145 – 16117Nuclear localization signalBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi49 – 12072Ala-richAdd
    BLAST

    Domaini

    The leucine-zipper domain is not essential for apoptosis, but is required for sensitization of cells to exogenous apoptotic insults and for interaction with its partners.By similarity
    The SAC domain is a death-inducing domain selective for apoptosis induction in cancer cells. This domain is essential for nuclear entry, Fas activation, inhibition of NF-kappa-B activity and induction of apoptosis in cancer cells By similarity.By similarity

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiNOG47166.
    HOGENOMiHOG000115462.
    HOVERGENiHBG058812.
    InParanoidiQ96IZ0.
    OMAiAKQNPPG.
    OrthoDBiEOG7JQBP4.
    PhylomeDBiQ96IZ0.
    TreeFamiTF332824.

    Family and domain databases

    InterProiIPR026117. Par-4.
    [Graphical view]
    PANTHERiPTHR15093. PTHR15093. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q96IZ0-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATGGYRTSS GLGGSTTDFL EEWKAKREKM RAKQNPPGPA PPGGGSSDAA    50
    GKPPAGALGT PAAAAANELN NNLPGGAPAA PAVPGPGGVN CAVGSAMLTR 100
    AAPGPRRSED EPPAASASAA PPPQRDEEEP DGVPEKGKSS GPSARKGKGQ 150
    IEKRKLREKR RSTGVVNIPA AECLDEYEDD EAGQKERKRE DAITQQNTIQ 200
    NEAVNLLDPG SSYLLQEPPR TVSGRYKSTT SVSEEDVSSR YSRTDRSGFP 250
    RYNRDANVSG TLVSSSTLEK KIEDLEKEVV RERQENLRLV RLMQDKEEMI 300
    GKLKEEIDLL NRDLDDIEDE NEQLKQENKT LLKVVGQLTR 340
    Length:340
    Mass (Da):36,568
    Last modified:December 1, 2001 - v1
    Checksum:i7E7515455402DBF8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti102 – 1032AP → PPAR in AAC24947. (PubMed:8943350)Curated
    Sequence conflicti199 – 1991I → M in CAG38786. 1 PublicationCurated
    Sequence conflicti281 – 2811R → T in AAC24947. (PubMed:8943350)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti42 – 421P → L.1 Publication
    Corresponds to variant rs8176804 [ dbSNP | Ensembl ].
    VAR_022465
    Natural varianti78 – 781P → R.2 Publications
    Corresponds to variant rs8176805 [ dbSNP | Ensembl ].
    VAR_022466
    Natural varianti137 – 1371G → A.1 Publication
    VAR_022467
    Natural varianti202 – 2021E → A.1 Publication
    Corresponds to variant rs8176870 [ dbSNP | Ensembl ].
    VAR_022468

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U63809 mRNA. Translation: AAC24947.1.
    CR536549 mRNA. Translation: CAG38786.1.
    AY300794 Genomic DNA. Translation: AAP43693.1.
    BC007018 mRNA. Translation: AAH07018.1.
    AF503628 Genomic DNA. Translation: AAM27453.1.
    CCDSiCCDS31863.1.
    RefSeqiNP_002574.2. NM_002583.2.
    XP_006719498.1. XM_006719435.1.
    UniGeneiHs.643130.

    Genome annotation databases

    EnsembliENST00000328827; ENSP00000328088; ENSG00000177425.
    GeneIDi5074.
    KEGGihsa:5074.
    UCSCiuc001syx.3. human.

    Polymorphism databases

    DMDMi66773935.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U63809 mRNA. Translation: AAC24947.1 .
    CR536549 mRNA. Translation: CAG38786.1 .
    AY300794 Genomic DNA. Translation: AAP43693.1 .
    BC007018 mRNA. Translation: AAH07018.1 .
    AF503628 Genomic DNA. Translation: AAM27453.1 .
    CCDSi CCDS31863.1.
    RefSeqi NP_002574.2. NM_002583.2.
    XP_006719498.1. XM_006719435.1.
    UniGenei Hs.643130.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2JK9 X-ray 1.79 B 67-81 [» ]
    ProteinModelPortali Q96IZ0.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111108. 36 interactions.
    DIPi DIP-29003N.
    IntActi Q96IZ0. 13 interactions.
    MINTi MINT-1418971.
    STRINGi 9606.ENSP00000328088.

    PTM databases

    PhosphoSitei Q96IZ0.

    Polymorphism databases

    DMDMi 66773935.

    Proteomic databases

    MaxQBi Q96IZ0.
    PaxDbi Q96IZ0.
    PeptideAtlasi Q96IZ0.
    PRIDEi Q96IZ0.

    Protocols and materials databases

    DNASUi 5074.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000328827 ; ENSP00000328088 ; ENSG00000177425 .
    GeneIDi 5074.
    KEGGi hsa:5074.
    UCSCi uc001syx.3. human.

    Organism-specific databases

    CTDi 5074.
    GeneCardsi GC12M079960.
    HGNCi HGNC:8614. PAWR.
    HPAi CAB020779.
    HPA012640.
    MIMi 601936. gene.
    neXtProti NX_Q96IZ0.
    PharmGKBi PA32954.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG47166.
    HOGENOMi HOG000115462.
    HOVERGENi HBG058812.
    InParanoidi Q96IZ0.
    OMAi AKQNPPG.
    OrthoDBi EOG7JQBP4.
    PhylomeDBi Q96IZ0.
    TreeFami TF332824.

    Miscellaneous databases

    ChiTaRSi PAWR. human.
    EvolutionaryTracei Q96IZ0.
    GeneWikii PAWR.
    GenomeRNAii 5074.
    NextBioi 19552.
    PROi Q96IZ0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96IZ0.
    Bgeei Q96IZ0.
    CleanExi HS_PAWR.
    Genevestigatori Q96IZ0.

    Family and domain databases

    InterProi IPR026117. Par-4.
    [Graphical view ]
    PANTHERi PTHR15093. PTHR15093. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1."
      Johnstone R.W., See R.H., Sells S.F., Wang J., Muthukkumar S., Englert C., Haber D.A., Licht J.D., Sugrue S.P., Roberts T., Rangnekar V.M., Shi Y.
      Mol. Cell. Biol. 16:6945-6956(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH WT1.
    2. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-78.
    3. NIEHS SNPs program
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-42; ARG-78; ALA-137 AND ALA-202.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Kidney.
    5. "Structural and functional characterization of the upstream regulatory region of the human gene encoding prostate apoptosis response factor-4."
      Hsu S.-C., Kirschenbaum F., Miller J., Cordell B., McCarthy J.V.
      Gene 295:109-116(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-64.
      Tissue: Blood.
    6. "Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression."
      Chakraborty M., Qiu S.G., Vasudevan K.M., Rangnekar V.M.
      Cancer Res. 61:7255-7263(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN APOPTOSIS AND TUMOR REGRESSION.
    7. "p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition."
      Chang S., Kim J.H., Shin J.
      FEBS Lett. 510:57-61(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SQSTM1 AND PRKCZ.
    8. "THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies."
      Roussigne M., Cayrol C., Clouaire T., Amalric F., Girard J.-P.
      Oncogene 22:2432-2442(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH THAP1.
    9. "AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4."
      Guo Q., Xie J.
      J. Biol. Chem. 279:4596-4603(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AATF.
    10. "PAR-4 is involved in regulation of beta-secretase cleavage of the Alzheimer amyloid precursor protein."
      Xie J., Guo Q.
      J. Biol. Chem. 280:13824-13832(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BACE1.
    11. "Structural basis for protein recognition by B30.2/SPRY domains."
      Woo J.S., Suh H.Y., Park S.Y., Oh B.H.
      Mol. Cell 24:967-976(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SPSB1 AND SPSB2, MUTAGENESIS OF ASN-72.
    12. "Apoptosis by Par-4 in cancer and neurodegenerative diseases."
      El-Guendy N., Rangnekar V.M.
      Exp. Cell Res. 283:51-66(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION IN APOPTOSIS AND NEURODEGENERATIVE DISEASES.
    13. "Par-4 inducible apoptosis in prostate cancer cells."
      Gurumurthy S., Rangnekar V.M.
      J. Cell. Biochem. 91:504-512(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    14. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    15. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    16. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiPAWR_HUMAN
    AccessioniPrimary (citable) accession number: Q96IZ0
    Secondary accession number(s): O75796, Q6FHY9, Q8N700
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 24, 2005
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 110 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references

    External Data

    Dasty 3