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Q96IZ0

- PAWR_HUMAN

UniProt

Q96IZ0 - PAWR_HUMAN

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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

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. 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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ96IZ0.
CleanExiHS_PAWR.
ExpressionAtlasiQ96IZ0. baseline and differential.
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. 37 interactions.
DIPiDIP-29003N.
IntActiQ96IZ0. 13 interactions.
MINTiMINT-1418971.
STRINGi9606.ENSP00000328088.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000000406.
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

        10         20         30         40         50
MATGGYRTSS GLGGSTTDFL EEWKAKREKM RAKQNPPGPA PPGGGSSDAA
60 70 80 90 100
GKPPAGALGT PAAAAANELN NNLPGGAPAA PAVPGPGGVN CAVGSAMLTR
110 120 130 140 150
AAPGPRRSED EPPAASASAA PPPQRDEEEP DGVPEKGKSS GPSARKGKGQ
160 170 180 190 200
IEKRKLREKR RSTGVVNIPA AECLDEYEDD EAGQKERKRE DAITQQNTIQ
210 220 230 240 250
NEAVNLLDPG SSYLLQEPPR TVSGRYKSTT SVSEEDVSSR YSRTDRSGFP
260 270 280 290 300
RYNRDANVSG TLVSSSTLEK KIEDLEKEVV RERQENLRLV RLMQDKEEMI
310 320 330 340
GKLKEEIDLL NRDLDDIEDE NEQLKQENKT LLKVVGQLTR
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:
EMBLi
GenBanki
DDBJi
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.
ENST00000552637; ENSP00000449928; 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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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. 37 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 .
ENST00000552637 ; ENSP00000449928 ; 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.
GeneTreei ENSGT00390000000406.
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

Bgeei Q96IZ0.
CleanExi HS_PAWR.
ExpressionAtlasi Q96IZ0. baseline and differential.
Genevestigatori Q96IZ0.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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 29, 2014
This is version 111 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