Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q96IZ0 (PAWR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
PRKC apoptosis WT1 regulator protein
Alternative name(s):
Prostate apoptosis response 4 protein
Short name=Par-4
Gene names
Name:PAWR
Synonyms:PAR4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length340 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Subunit structure

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. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subcellular location

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. Ref.1 Ref.8

Tissue specificity

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. Ref.1

Induction

By apoptosis.

Domain

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.

Post-translational modification

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

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainCoiled coil
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament bundle assembly

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

interleukin-2 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Traceable author statement Ref.1. Source: ProtInc

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

positive regulation of amyloid precursor protein biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Non-traceable author statement Ref.6. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

nucleus

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functionactin binding

Inferred from sequence or structural similarity. Source: UniProtKB

enzyme binding

Inferred from direct assay Ref.10. Source: UniProtKB

leucine zipper domain binding

Inferred from physical interaction Ref.9. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

transcription corepressor activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 340340PRKC apoptosis WT1 regulator protein
PRO_0000058236

Regions

Region145 – 20359Selective for apoptosis induction in cancer cells (SAC)
Region300 – 34041Leucine-zipper
Coiled coil186 – 20621 Potential
Motif145 – 16117Nuclear localization signal By similarity
Compositional bias49 – 12072Ala-rich

Amino acid modifications

Modified residue1631Phosphothreonine; by PKA By similarity

Natural variations

Natural variant421P → L. Ref.3
Corresponds to variant rs8176804 [ dbSNP | Ensembl ].
VAR_022465
Natural variant781P → R. Ref.2 Ref.3
Corresponds to variant rs8176805 [ dbSNP | Ensembl ].
VAR_022466
Natural variant1371G → A. Ref.3
VAR_022467
Natural variant2021E → A. Ref.3
Corresponds to variant rs8176870 [ dbSNP | Ensembl ].
VAR_022468

Experimental info

Mutagenesis721N → A: Abolishes interaction with SPSB1-Elongin BC complex. Ref.11
Sequence conflict102 – 1032AP → PPAR in AAC24947. Ref.1
Sequence conflict1991I → M in CAG38786. Ref.2
Sequence conflict2811R → T in AAC24947. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q96IZ0 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 7E7515455402DBF8

FASTA34036,568
        10         20         30         40         50         60 
MATGGYRTSS GLGGSTTDFL EEWKAKREKM RAKQNPPGPA PPGGGSSDAA GKPPAGALGT 

        70         80         90        100        110        120 
PAAAAANELN NNLPGGAPAA PAVPGPGGVN CAVGSAMLTR AAPGPRRSED EPPAASASAA 

       130        140        150        160        170        180 
PPPQRDEEEP DGVPEKGKSS GPSARKGKGQ IEKRKLREKR RSTGVVNIPA AECLDEYEDD 

       190        200        210        220        230        240 
EAGQKERKRE DAITQQNTIQ NEAVNLLDPG SSYLLQEPPR TVSGRYKSTT SVSEEDVSSR 

       250        260        270        280        290        300 
YSRTDRSGFP RYNRDANVSG TLVSSSTLEK KIEDLEKEVV RERQENLRLV RLMQDKEEMI 

       310        320        330        340 
GKLKEEIDLL NRDLDDIEDE NEQLKQENKT LLKVVGQLTR 

« Hide

References

« Hide 'large scale' references
[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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS31863.1.
RefSeqNP_002574.2. NM_002583.2.
XP_006719498.1. XM_006719435.1.
UniGeneHs.643130.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JK9X-ray1.79B67-81[»]
ProteinModelPortalQ96IZ0.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111108. 36 interactions.
DIPDIP-29003N.
IntActQ96IZ0. 13 interactions.
MINTMINT-1418971.
STRING9606.ENSP00000328088.

PTM databases

PhosphoSiteQ96IZ0.

Polymorphism databases

DMDM66773935.

Proteomic databases

MaxQBQ96IZ0.
PaxDbQ96IZ0.
PeptideAtlasQ96IZ0.
PRIDEQ96IZ0.

Protocols and materials databases

DNASU5074.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328827; ENSP00000328088; ENSG00000177425.
ENST00000552637; ENSP00000449928; ENSG00000177425.
GeneID5074.
KEGGhsa:5074.
UCSCuc001syx.3. human.

Organism-specific databases

CTD5074.
GeneCardsGC12M079960.
HGNCHGNC:8614. PAWR.
HPACAB020779.
HPA012640.
MIM601936. gene.
neXtProtNX_Q96IZ0.
PharmGKBPA32954.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47166.
HOGENOMHOG000115462.
HOVERGENHBG058812.
InParanoidQ96IZ0.
OMAAKQNPPG.
OrthoDBEOG7JQBP4.
PhylomeDBQ96IZ0.
TreeFamTF332824.

Gene expression databases

ArrayExpressQ96IZ0.
BgeeQ96IZ0.
CleanExHS_PAWR.
GenevestigatorQ96IZ0.

Family and domain databases

InterProIPR026117. Par-4.
[Graphical view]
PANTHERPTHR15093. PTHR15093. 1 hit.
ProtoNetSearch...

Other

ChiTaRSPAWR. human.
EvolutionaryTraceQ96IZ0.
GeneWikiPAWR.
GenomeRNAi5074.
NextBio19552.
PROQ96IZ0.
SOURCESearch...

Entry information

Entry namePAWR_HUMAN
AccessionPrimary (citable) accession number: Q96IZ0
Secondary accession number(s): O75796, Q6FHY9, Q8N700
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2005
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM