Reviewed, UniProtKB/Swiss-Prot Q96IZ0 (PAWR_HUMAN)

Names and origin

Protein names

Recommended name:
    PRKC apoptosis WT1 regulator protein
Alternative name(s):
    Prostate apoptosis response 4 protein
      Short name=Par-4

Gene names

Name:	PAWR
Synonyms:	PAR4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	340 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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
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.
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 process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	apoptosis Ref.1 Traceable author statement. Source: ProtInc negative regulation of transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc positive regulation of apoptosis Ref.6 Non-traceable author statement. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.1 Non-traceable author statement. Source: UniProtKB nucleus Ref.1 Non-traceable author statement. Source: UniProtKB
Molecular function	enzyme binding Ref.10 Inferred from direct assay. Source: UniProtKB transcription corepressor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAPK3	O43293	1	EBI-595869,EBI-77293

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 340	340	PRKC apoptosis WT1 regulator protein		PRO_0000058236
Regions
	Domain	300 – 340	41	Leucine-zipper
	Region	145 – 203	59	Selective for apoptosis induction in cancer cells (SAC)
	Coiled coil	186 – 206	21	Potential
	Motif	145 – 161	17	Nuclear localization signal By similarity
	Compositional bias	49 – 120	72	Ala-rich
Amino acid modifications
	Modified residue	163	1	Phosphothreonine; by PKA By similarity
	Modified residue	226	1	Phosphotyrosine Ref.13
	Modified residue	228	1	Phosphoserine Ref.13
	Modified residue	229	1	Phosphothreonine Ref.13
	Modified residue	231	1	Phosphoserine Ref.13
Natural variations
	Natural variant	42	1	P → L Ref.3		VAR_022465
	Natural variant	78	1	P → R: dbSNP rs8176805. Ref.3 Ref.2		VAR_022466
	Natural variant	137	1	G → A Ref.3		VAR_022467
	Natural variant	202	1	E → A: dbSNP rs8176870. Ref.3		VAR_022468
Experimental info
	Sequence conflict	102 – 103	2	AP → PPAR in AAC24947. Ref.1
	Sequence conflict	199	1	I → M in CAG38786. Ref.2
	Sequence conflict	281	1	R → T in AAC24947. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q96IZ0-1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 7E7515455402DBF8	FASTA	340	36,568
	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

References

	« Hide 'large scale' referencesShow '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: 8943350] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH WT1.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. 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: 15489334] [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: 12242017] [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: 11585763] [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: 11755531] [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: 12717420] [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: 14627703] [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: 15671026] [Abstract] Cited for: INTERACTION WITH BACE1.
[11]	"Apoptosis by Par-4 in cancer and neurodegenerative diseases." El-Guendy N., Rangnekar V.M. Exp. Cell Res. 283:51-66(2003) [PubMed: 12565819] [Abstract] Cited for: REVIEW ON FUNCTION IN APOPTOSIS AND NEURODEGENERATIVE DISEASES.
[12]	"Par-4 inducible apoptosis in prostate cancer cells." Gurumurthy S., Rangnekar V.M. J. Cell. Biochem. 91:504-512(2004) [PubMed: 14755681] [Abstract] Cited for: REVIEW.
[13]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-226; SER-228; THR-229 AND SER-231, MASS SPECTROMETRY.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00001871.

RefSeq

NP_002574.2.

UniGene

Hs.643130

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JK9	X-ray	1.79	B	67-81	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:29003N.

IntAct

Q96IZ0. 5 interactions.

PTM databases

PhosphoSite

Q96IZ0.

Proteomic databases

PeptideAtlas

Q96IZ0.

PRIDE

Q96IZ0.

Genome annotation databases

Ensembl

ENSG00000177425. Homo sapiens. [Contig view]

GeneID

5074.

KEGG

hsa:5074.

Organism-specific databases

GeneCards

GC12M078488.

H-InvDB

HIX0022199.

HGNC

HGNC:8614. PAWR.

HPA

HPA012640.

MIM

601936. gene.

PharmGKB

PA32954.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96IZ0.

HOVERGEN

Q96IZ0.

OMA

Q96IZ0. GGVNCAV.

Enzyme and pathway databases

Pathway_Interaction_DB

ceramidepathway. Ceramide signaling pathway.
ar_pathway. Coregulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

Q96IZ0.

Bgee

Q96IZ0.

CleanEx

HS_PAWR.

GermOnline

ENSG00000177425. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other Resources

NextBio

19552.

SOURCE

Search...

Entry information

Entry name

PAWR_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)