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PCLAF (PCNA clamp associated factor)

Written2011-05Shannon Joseph, Lingbo Hu, Fiona Simpson
University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)NS5ATP9
OEATC-1
p15(PAF)
PAF15
Other aliasKIAA0101
FLJ58702
OEATC1
PAF
p15PAF
HGNC (Hugo) PCLAF
LocusID (NCBI) 9768
Atlas_Id 41058
Location 15q22.31  [Link to chromosome band 15q22]
Location_base_pair Starts at 64365012 and ends at 64381510 bp from pter ( according to hg19-Feb_2009)  [Mapping PCLAF.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
HERC1 (15q22.31) / PCLAF (15q22.31)HERC2 (15q13.1) / PCLAF (15q22.31)HERC2P2 (15q11.2) / PCLAF (15q22.31)
PCLAF (15q22.31) / PCLAF (15q22.31)PCLAF (15q22.31) / TRIP4 (15q22.31)

DNA/RNA

Note Murine gene embryonic expression shows highly restricted expression of KIAA0101 in facial prominences, limbs, somites, brain, spinal cord and hair follicles. It has a suggested role in embryonic development (van Beuren et al., 2007).
 
  DNA diagram. KIAA0101 9768 chr: 62444265-62460755. One transcript, 4 exons.
Description The gene is composed of 4 exons.
Transcription One transcript. RNA was expressed as a 1.1 kb message in liver, pancreas and placenta at high levels (Yu et al., 2001). RNA profiling shows it is highly expressed in a number of tumors, specifically in esophageal tumors, anaplastic thyroid carcinomas, pancreatic cancer and non-small-cell lung cancer lines (Yu et al., 2001; Hosokawa et al., 2007). KIAA0101 was also reported to be down-regulated in colon cancer cells (Simpson et al., 2006) and human hepatocellular carcinoma (Guo et al., 2006). Nuclear protein NF-kappaB (p50) (Li et al., 2008), the Hepatitis C virus protein non-structural protein 5A (NS5A) (Shi et al., 2008) and ATF3 (Turchi et al., 2009) bind to the promoter region upstream of the KIAA0101 transcription initiation site promoting transcription in response to DNA damage.
Pseudogene None.

Protein

Note NS5ATP9, Hepatitis C virus NS5A-transactivated protein 9, HCV NS5A-transactivated protein 9, Overexpressed in anaplastic thyroid carcinoma-1, OEATC-1, OEATC1, p15(PAF), L5.
 
  Protein diagram. 111 aa in length, single transcript, mutation I-A at position 65 and mutation F-A at position 68 results in loss of PCNA binding.
Description The KIAA0101 gene encodes for a 111 amino acid 15 kDa protein. It contains a conserved proliferating cell nuclear antigen (PCNA)-binding motif (Yu et al., 2001).
Expression Predominant expression in liver, pancreas and brain. Not detected in heart or liver (Yu et al., 2001). The KIAA0101 protein was down-regulated in human hepatocellular carcinoma (Guo et al., 2006; Yuan et al., 2007). Increased protein levels have been detected in pancreatic cancer cells (Hosokawa et al., 2007).
Localisation Nucleus, mitochondrion (Yu et al., 2001; Guo et al., 2006; Simpson et al., 2006; Yuan et al., 2007).
Function The KIAA0101 protein binds to PCNA through a conserved PCNA binding domain. PCNA is required for DNA replication or repair as a supplementary factor for DNA polymerase (Paunesku et al., 2001). Proteins bound to PCNA can prevent its binding to DNA polymerase, in turn leading to inhibition of DNA synthesis, cell cycle progression and G1 cell cycle arrest (Yuan et al., 2007). PCNA binding proteins also interact with each other to modulate this regulation. For example, KIAA0101 also interacts in a complex with p33ING1 isoform 2, another PCNA binding protein which is a potential tumor suppressor and regulator of p53 (Simpson et al., 2006). UV irradiation caused increased association of KIAA0101 with PCNA suggesting that this association occurs in response to DNA damage. KIAA0101 also competes with p21WAF for binding to PCNA (Yu et al., 2001). KIAA0101 most recently been shown to act in concert with ATF3 to control genomic integrity after UV stress (Turchi et al., 2009). KIAA0101 expression levels are also regulated by NF-kappaB, this protein family having significant roles in apoptosis, cell cycle regulation and onocgenesis (Hosokawa et al., 2007; Li et al., 2008). Together this data suggests a likely role for KIAA0101 in DNA repair and in protection from UV-induced cell death.

Mutations

Note Experimentally mutation I-A at position 65 and F-A at position 68 result in loss of PCNA binding (Yu et al., 2001). No other mutations have been described. Screening of colon tumour samples identified a polymorphism in the intronic region just prior to the start of exon 2 (982-15delT) (Simpson et al., 2006).

Implicated in

Note
  
Entity Hepatocellular carcinoma
Disease KIAA0101 expression was proposed to promote growth advantage and hypoxic insult resistance and be associated with promoting cell proliferation (Yuan et al., 2007). KIAA0101 overexpression was associated with concomitant p53 mutation and vascular invasion (Yuan et al., 2007). This study suggested that high expression in hepatocellular carcinoma was indicative of tumour recurrence, metastatic potential and poor prognosis (Yuan et al., 2007). KIAA0101 was also reported to be downregulated in hepatocellular carcinoma (Guo et al., 2006). This study suggested that KIAA0101 had a growth inhibitory effect.
  
  
Entity Astrocytomas
Disease Grade IV (glioblastoma multiforme) astrocytomas had 5 times higher expression levels when compared to Grade I (pilocytic) astrocyomas suggesting that KIAA0101 abundance correlates with malignancy grade in human astrocytes (Marie et al., 2008).
  
  
Entity Pancreatic cancer
Disease Pancreatic cells overexpress KIAA0101 both at cDNA and protein level. Knock down of KIAA0101 by siRNA attenuated proliferation and DNA replication whereas overexpression enhanced cell growth in pancreatic cancer cell lines (Hosokawa et al., 2007).
  
  
Entity Anaplastic thyroid carcinoma
Disease Anaplastic thyroid carcinoma cell lines had significant overexpression of KIAA0101. Cell growth was inhibited by silencing KIAA0101 expression using siRNA. KIAA0101 may be oncogenic or cell growth-promoting but the mechanism for this is not understood (Mizutani et al., 2005).
  
  
Entity Follicular lymphoma
Disease High expression of KIAA0101 (along with CCNB1 (cyclin B1), CDC2, CDKN3A, CKS1B, ANP32E) was associated with better survival/response rate in a univariate analysis following CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) chemotherapy for follicular lymphoma treatment. Identification of these proteins aims to develop a follicular lymphoma international prognostic index to aid in informing a successful treatment strategy (Bjorck et al., 2005).
Oncogenesis This gene is thought to be oncogenic through modulation of DNA repair pathways via interaction with PCNA.
  

Bibliography

High expression of cyclin B1 predicts a favorable outcome in patients with follicular lymphoma.
Bjorck E, Ek S, Landgren O, Jerkeman M, Ehinger M, Bjorkholm M, Borrebaeck CA, Porwit-MacDonald A, Nordenskjold M.
Blood. 2005 Apr 1;105(7):2908-15. Epub 2004 Dec 2.
PMID 15576476
 
Genomic profiling of circulating plasma RNA for the analysis of cancer.
Collado M, Garcia V, Garcia JM, Alonso I, Lombardia L, Diaz-Uriarte R, Fernandez LA, Zaballos A, Bonilla F, Serrano M.
Clin Chem. 2007 Oct;53(10):1860-3. Epub 2007 Aug 23.
PMID 17717129
 
KIAA0101 (OEACT-1), an expressionally down-regulated and growth-inhibitory gene in human hepatocellular carcinoma.
Guo M, Li J, Wan D, Gu J.
BMC Cancer. 2006 Apr 29;6:109.
PMID 16646990
 
Oncogenic role of KIAA0101 interacting with proliferating cell nuclear antigen in pancreatic cancer.
Hosokawa M, Takehara A, Matsuda K, Eguchi H, Ohigashi H, Ishikawa O, Shinomura Y, Imai K, Nakamura Y, Nakagawa H.
Cancer Res. 2007 Mar 15;67(6):2568-76.
PMID 17363575
 
NS5ATP9 gene regulated by NF-kappaB signal pathway.
Li K, Ma Q, Shi L, Dang C, Hong Y, Wang Q, Li Y, Fan W, Zhang L, Cheng J.
Arch Biochem Biophys. 2008 Nov 1;479(1):15-9. Epub 2008 Aug 14.
PMID 18727915
 
Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas.
Marie SK, Okamoto OK, Uno M, Hasegawa AP, Oba-Shinjo SM, Cohen T, Camargo AA, Kosoy A, Carlotti CG Jr, Toledo S, Moreira-Filho CA, Zago MA, Simpson AJ, Caballero OL.
Int J Cancer. 2008 Feb 15;122(4):807-15.
PMID 17960622
 
Changes in expression of oestrogen regulated and proliferation genes with neoadjuvant treatment highlight heterogeneity of clinical resistance to the aromatase inhibitor, letrozole.
Miller WR, Larionov A.
Breast Cancer Res. 2010;12(4):R52. Epub 2010 Jul 20.
PMID 20646288
 
Overexpressed in anaplastic thyroid carcinoma-1 (OEATC-1) as a novel gene responsible for anaplastic thyroid carcinoma.
Mizutani K, Onda M, Asaka S, Akaishi J, Miyamoto S, Yoshida A, Nagahama M, Ito K, Emi M.
Cancer. 2005 May 1;103(9):1785-90.
PMID 15789362
 
Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1.
Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H, et al.
DNA Res. 1995;2(1):37-43.
PMID 7788527
 
Proliferating cell nuclear antigen (PCNA): ringmaster of the genome.
Paunesku T, Mittal S, Protic M, Oryhon J, Korolev SV, Joachimiak A, Woloschak GE.
Int J Radiat Biol. 2001 Oct;77(10):1007-21. (REVIEW)
PMID 11682006
 
NS5ATP9, a gene up-regulated by HCV NS5A protein.
Shi L, Zhang SL, Li K, Hong Y, Wang Q, Li Y, Guo J, Fan WH, Zhang L, Cheng J.
Cancer Lett. 2008 Feb 8;259(2):192-7.
PMID 18068894
 
The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b.
Simpson F, Lammerts van Bueren K, Butterfield N, Bennetts JS, Bowles J, Adolphe C, Simms LA, Young J, Walsh MD, Leggett B, Fowles LF, Wicking C.
Exp Cell Res. 2006 Jan 1;312(1):73-85. Epub 2005 Nov 8.
PMID 16288740
 
ATF3 and p15PAF are novel gatekeepers of genomic integrity upon UV stress.
Turchi L, Fareh M, Aberdam E, Kitajima S, Simpson F, Wicking C, Aberdam D, Virolle T.
Cell Death Differ. 2009 May;16(5):728-37. Epub 2009 Feb 13.
PMID 19219066
 
p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues.
Yu P, Huang B, Shen M, Lau C, Chan E, Michel J, Xiong Y, Payan DG, Luo Y.
Oncogene. 2001 Jan 25;20(4):484-9.
PMID 11313979
 
Overexpression of KIAA0101 predicts high stage, early tumor recurrence, and poor prognosis of hepatocellular carcinoma.
Yuan RH, Jeng YM, Pan HW, Hu FC, Lai PL, Lee PH, Hsu HC.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5368-76.
PMID 17875765
 
Murine embryonic expression of the gene for the UV-responsive protein p15(PAF).
van Bueren KL, Bennetts JS, Fowles LF, Berkman JL, Simpson F, Wicking C.
Gene Expr Patterns. 2007 Jan;7(1-2):47-50. Epub 2006 May 25.
PMID 16815099
 

Citation

This paper should be referenced as such :
Joseph, S ; Hu, L ; Simpson, F
KIAA0101 (KIAA0101)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(11):965-967.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/KIAA0101ID41058ch15q22.html


External links

Nomenclature
HGNC (Hugo)PCLAF   28961
Cards
AtlasKIAA0101ID41058ch15q22
Entrez_Gene (NCBI)PCLAF  9768  PCNA clamp associated factor
AliasesKIAA0101; L5; NS5ATP9; OEATC; 
OEATC-1; OEATC1; PAF; PAF15; p15(PAF); p15/PAF; p15PAF
GeneCards (Weizmann)PCLAF
Ensembl hg19 (Hinxton)ENSG00000166803 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000166803 [Gene_View]  chr15:64365012-64381510 [Contig_View]  PCLAF [Vega]
ICGC DataPortalENSG00000166803
TCGA cBioPortalPCLAF
AceView (NCBI)PCLAF
Genatlas (Paris)PCLAF
WikiGenes9768
SOURCE (Princeton)PCLAF
Genetics Home Reference (NIH)PCLAF
Genomic and cartography
GoldenPath hg38 (UCSC)PCLAF  -     chr15:64365012-64381510 -  15q22.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PCLAF  -     15q22.31   [Description]    (hg19-Feb_2009)
EnsemblPCLAF - 15q22.31 [CytoView hg19]  PCLAF - 15q22.31 [CytoView hg38]
Mapping of homologs : NCBIPCLAF [Mapview hg19]  PCLAF [Mapview hg38]
OMIM610696   
Gene and transcription
Genbank (Entrez)AF529370 AK290748 AV757440 AY598324 BC005832
RefSeq transcript (Entrez)NM_001029989 NM_014736
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PCLAF
Cluster EST : UnigeneHs.81892 [ NCBI ]
CGAP (NCI)Hs.81892
Alternative Splicing GalleryENSG00000166803
Gene ExpressionPCLAF [ NCBI-GEO ]   PCLAF [ EBI - ARRAY_EXPRESS ]   PCLAF [ SEEK ]   PCLAF [ MEM ]
Gene Expression Viewer (FireBrowse)PCLAF [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9768
GTEX Portal (Tissue expression)PCLAF
Human Protein AtlasENSG00000166803-PCLAF [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15004   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ15004  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15004
Splice isoforms : SwissVarQ15004
PhosPhoSitePlusQ15004
Domains : Interpro (EBI)PCNA-AF   
Domain families : Pfam (Sanger)PAF (PF15715)   
Domain families : Pfam (NCBI)pfam15715   
Conserved Domain (NCBI)PCLAF
DMDM Disease mutations9768
Blocks (Seattle)PCLAF
PDB (SRS)4D2G   
PDB (PDBSum)4D2G   
PDB (IMB)4D2G   
PDB (RSDB)4D2G   
Structural Biology KnowledgeBase4D2G   
SCOP (Structural Classification of Proteins)4D2G   
CATH (Classification of proteins structures)4D2G   
SuperfamilyQ15004
Human Protein Atlas [tissue]ENSG00000166803-PCLAF [tissue]
Peptide AtlasQ15004
HPRD13778
IPIIPI00014147   IPI00645835   
Protein Interaction databases
DIP (DOE-UCLA)Q15004
IntAct (EBI)Q15004
FunCoupENSG00000166803
BioGRIDPCLAF
STRING (EMBL)PCLAF
ZODIACPCLAF
Ontologies - Pathways
QuickGOQ15004
Ontology : AmiGOchromatin binding  protein binding  nucleus  nucleoplasm  centrosome  DNA replication  cellular response to DNA damage stimulus  centrosome cycle  response to UV  translesion synthesis  translesion synthesis  perinuclear region of cytoplasm  regulation of cell cycle  
Ontology : EGO-EBIchromatin binding  protein binding  nucleus  nucleoplasm  centrosome  DNA replication  cellular response to DNA damage stimulus  centrosome cycle  response to UV  translesion synthesis  translesion synthesis  perinuclear region of cytoplasm  regulation of cell cycle  
NDEx NetworkPCLAF
Atlas of Cancer Signalling NetworkPCLAF
Wikipedia pathwaysPCLAF
Orthology - Evolution
OrthoDB9768
GeneTree (enSembl)ENSG00000166803
Phylogenetic Trees/Animal Genes : TreeFamPCLAF
HOVERGENQ15004
HOGENOMQ15004
Homologs : HomoloGenePCLAF
Homology/Alignments : Family Browser (UCSC)PCLAF
Gene fusions - Rearrangements
Fusion : MitelmanHERC1/KIAA0101 [15q22.31/15q22.31]  [t(15;15)(q22;q22)]  
Fusion : MitelmanKIAA0101/TRIP4 [15q22.31/15q22.31]  [t(15;15)(q22;q22)]  
Fusion: TCGA_MDACCHERC1 15q22.31 KIAA0101 15q22.31 BRCA
Fusion: TCGA_MDACCKIAA0101 15q22.31 TRIP4 15q22.31 BRCA
Tumor Fusion PortalPCLAF
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPCLAF [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PCLAF
dbVarPCLAF
ClinVarPCLAF
1000_GenomesPCLAF 
Exome Variant ServerPCLAF
ExAC (Exome Aggregation Consortium)ENSG00000166803
GNOMAD BrowserENSG00000166803
Genetic variants : HAPMAP9768
Genomic Variants (DGV)PCLAF [DGVbeta]
DECIPHERPCLAF [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPCLAF 
Mutations
ICGC Data PortalPCLAF 
TCGA Data PortalPCLAF 
Broad Tumor PortalPCLAF
OASIS PortalPCLAF [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDPCLAF
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PCLAF
DgiDB (Drug Gene Interaction Database)PCLAF
DoCM (Curated mutations)PCLAF (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PCLAF (select a term)
intoGenPCLAF
NCG5 (London)PCLAF
Cancer3DPCLAF(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM610696   
Orphanet
DisGeNETPCLAF
MedgenPCLAF
Genetic Testing Registry PCLAF
NextProtQ15004 [Medical]
TSGene9768
GENETestsPCLAF
Target ValidationPCLAF
Huge Navigator PCLAF [HugePedia]
snp3D : Map Gene to Disease9768
BioCentury BCIQPCLAF
ClinGenPCLAF
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9768
Chemical/Pharm GKB GenePA134974023
Clinical trialPCLAF
Miscellaneous
canSAR (ICR)PCLAF (select the gene name)
Probes
Litterature
PubMed46 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePCLAF
EVEXPCLAF
GoPubMedPCLAF
iHOPPCLAF
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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