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PAF1 (Paf1, RNA polymerase II associated factor, homolog (S. cerevisiae))

Written2008-09Shonali Deb, Moorthy P Ponnusamy, Surinder K Batra
Department of Biochemistry, Molecular Biology University of Nebraska Medical Center 985870 Nebraska Medical Center Durham Research center 7005 Omaha, NE 68198-5870, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPaf1
Alias_symbol (synonym)PD2
F23149_1
FLJ11123
Other aliashPAF1
HGNC (Hugo) PAF1
LocusID (NCBI) 54623
Atlas_Id 44202
Location 19q13.2  [Link to chromosome band 19q13]
Location_base_pair Starts at 39385630 and ends at 39391195 bp from pter ( according to hg19-Feb_2009)  [Mapping PAF1.png]
Fusion genes
(updated 2016)
ASNA1 (19p13.2) / PAF1 (19q13.2)PAF1 (19q13.2) / ASNA1 (19p13.2)
Note Paf1 is a member of the hPAF complex and is dysregulated in cancer. The RNA polymerase II-associated factor (PAF) complex was initially reported in yeast (yPAF), and comprises five subunits in humans, Paf1, Ctr9, Leo1, Cdc73 and Ski8. yPAF is associated with both the promoter and coding regions of transcriptionally active genes and plays a role in transcription elongation.

DNA/RNA

 
  Shows the genomic organization of Paf1 gene.
Description The Paf1 gene is located on chromosome 19 in the q13.2 (loc126275) region, oriented from centromere to telomere, between the IgG binding protein gene (FcGBP) and the zinc-finger protein 36 gene (ZFP36). The Paf1 gene is 5178-bp long and contains 14 exons of sizes ranging from 30 to 551 bp. The first exon contains the 50-untranslated region, the translation start site, and the first 16 amino-acid residues. The last exon contains sequences that code for a domain rich in serine and aspartic acid residues and the 30-untranslated region. Introns range in size from 78 to 1539 bp. The sequences at the exon/intron boundaries are highly conserved with respect to canonical acceptor/donor site (AG/GT). The sequence of this gene is defined by 540 GenBank accessions from 506 cDNA clones, some from pancreas (seen 68 times), brain (51), ductal carcinoma, cell line (32), testis (23), lung (22), epithelioid carcinoma (20), placenta (20) and 151 other tissues.
Transcription The complete PD2 cDNA sequence is present in the GenBankt/EBI Data Bank under the accession number, AJ401156. This sequence contains a 50-untranslated region of 156 bp upstream of the ATG translation initiation codon, and is flanked by a Kozak consensus sequence and a 30-untranslated region of 138 bp. The noncoding 30 region contains the polyadenylation signal, AATAAA. An open reading frame, from bp 157 to 1752, yields a predicted translation product of 59.9 kDa. Paf1 is overexpressed in the poorly differentiated pancreatic cancer cell line, Panc1. This gene is expressed at a very high level, 4.7 times the average gene in this release.

Protein

 
  Schematic representation of protein structure and its organization. RRM, RNA recognition motif; RCC, regulator of chromosome condensation.
Description There is a high degree of similarity between PD2 and the functional domains of DNA- and RNA-binding proteins. Paf1 protein possesses four myc-type helix-loop-helix, a leucine zipper, a DEAD-box subfamily ATP-dependent helicase domain, one eukaryotic RNA recognition motif (RRM) RNP-1 region signature, and a regulator of chromosome condensation (RCC1) signature. Two specific domains were also positioned toward the carboxyl-terminus: a glutamic acid rich domain, from amino acid 358 to 452, and a serine/aspartic acid-rich domain, from amino acid 402 to 531.
Expression Paf1 is expressed at high levels in head, neck, liver, ovary and testis and at a low level in several other tissues including kidney.
Localisation Paf1 is localized in the nucleus.
Function It has been determined that hPaf1 is a subunit of the human PAF protein complex which was first identified during characterization of proteins associated with parafibromin. The hPAF complex interacts with the non-phosphorylated and Ser2- and Ser5-phosphorylated forms of the RNAP II large subunit, indicating its involvement in both transcription initiation and elongation. It has been shown that the establishment of H2B monoubiquitination is dependent on hPAF, the histone chaperone FACT and transcription. Further, the RNF20 / RNF40 UBCH6-PAF complex is required for transcription of the HOX genes in the following cascade: PAF - histone H2B ubiquitination - histone H3-K4 and H3-K79 methylation - HOX gene expression. Immunoprecipitation analysis has demonstrated that, found that RNA polymerase II associates with PAF1. Overexpression of hPaf1 in NIH3T3 cells results in enhanced growth rates in vitro and tumor formation in vivo.
Homology There is a high degree of similarity between Paf1 and sequences from mouse (AK017762, AB041615, BC010317), Drosophila melanogaster (AY070561.1, AC008139, and AE003605), Caenorhabditis elegans (NP-505925, NM-073524 and CAB02869.1), Schizosaccharomyces pombe (CAB65804), and Saccharomyces cerevisiae (P38351). The human Paf1 shows 98% and 50% similarity to its rodent and Drosophila counterparts, respectively. The S. cerevisiae homologue corresponds to the widely investigated Paf1 protein, which shows 22% identity with the human sequence, and 44% similarity for a segment of 333 amino-acid residues that excluded the carboxyl terminus. Altogether, 22 amino acids are totally conserved among human, rodent, Drosophila, and S. cerevisiae, including two tyrosine residues. The least conserved domain is found in the carboxyl-terminal region. This domain is very rich in serine and aspartic acid residues.

Implicated in

Note
  
Entity Various cancers
Disease The hPaf1 overexpression is associated with various cancers as given below in the section of Oncogenesis. Although there is no direct association of Paf1 with any other disease, parafibromin, which is part of the hPAF complex, is encoded by the HRPT2 gene and is implicated in suppression of the hyperparathyroidism-jaw tumor (HPT-JT) syndrome . The HRPT2 gene is mutated in the germ line of HPT-JT patients.
Oncogenesis The oncogenic property of hPaf1 has been reported. Overexpression of hPaf1 in NIH3T3 cells results in enhanced growth rates in vitro and tumor formation in vivo. Further, hPaf1 overexpression is associated with different cancers, including leukemia, lung, myeloma and fallopian tube and testicular carcinoma. In cell lines, hPaf1 is overexpressed due to gene amplification in the poorly differentiated pancreatic cancer cell line, Panc1.
  

Bibliography

Facts about FACT and transcript elongation through chromatin.
Belotserkovskaya R, Reinberg D.
Curr Opin Genet Dev. 2004 Apr;14(2):139-46.
PMID 15196460
 
Human RNA polymerase II-associated factor complex: dysregulation in cancer.
Chaudhary K, Deb S, Moniaux N, Ponnusamy MP, Batra SK.
Oncogene. 2007 Nov 29;26(54):7499-507.(REVIEW)
PMID 17599057
 
Human PAF Complexes in Endocrine Tumors and Pancreatic Cancer.
Deb S, Ponnusamy MP, Senapati S, Dey P, Batra SK.
Expert Rev Endocrinol Metab. 2008 Sep 3(5), 557-565.
 
The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis.
Moniaux N, Nemos C, Schmied BM, Chauhan SC, Deb S, Morikane K, Choudhury A, Vanlith M, Sutherlin M, Sikela JM, Hollingsworth MA, Batra SK.
Oncogene. 2006 Jun 1;25(23):3247-57.
PMID 16491129
 
From transcription to mRNA: PAF provides a new path.
Rosonina E, Manley JL.
Mol Cell. 2005 Oct 28;20(2):167-8.
PMID 16246718
 
The parafibromin tumor suppressor protein is part of a human Paf1 complex.
Rozenblatt-Rosen O, Hughes CM, Nannepaga SJ, Shanmugam KS, Copeland TD, Guszczynski T, Resau JH, Meyerson M.
Mol Cell Biol. 2005 Jan;25(2):612-20.
PMID 15632063
 
The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II.
Yart A, Gstaiger M, Wirbelauer C, Pecnik M, Anastasiou D, Hess D, Krek W.
Mol Cell Biol. 2005 Jun;25(12):5052-60.
PMID 15923622
 
The human PAF complex coordinates transcription with events downstream of RNA synthesis.
Zhu B, Mandal SS, Pham AD, Zheng Y, Erdjument-Bromage H, Batra SK, Tempst P, Reinberg D.
Genes Dev. 2005 Jul 15;19(14):1668-73.
PMID 16024656
 
Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation.
Zhu B, Zheng Y, Pham AD, Mandal SS, Erdjument-Bromage H, Tempst P, Reinberg D.
Mol Cell. 2005 Nov 23;20(4):601-11.
PMID 16307923
 

Citation

This paper should be referenced as such :
Deb, S ; Ponnusamy, MP ; Batra, SK. PAF1 (Paf1, RNA polymerase II associated factor, homolog (S
cerevisiae))
Atlas Genet Cytogenet Oncol Haematol. 2009;13(8):570-572.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PAF1ID44202ch19q13.html


External links

Nomenclature
HGNC (Hugo)PAF1   25459
Cards
AtlasPAF1ID44202ch19q13
Entrez_Gene (NCBI)PAF1  54623  PAF1 homolog, Paf1/RNA polymerase II complex component
AliasesF23149_1; PD2
GeneCards (Weizmann)PAF1
Ensembl hg19 (Hinxton)ENSG00000006712 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000006712 [Gene_View]  chr19:39385630-39391195 [Contig_View]  PAF1 [Vega]
ICGC DataPortalENSG00000006712
TCGA cBioPortalPAF1
AceView (NCBI)PAF1
Genatlas (Paris)PAF1
WikiGenes54623
SOURCE (Princeton)PAF1
Genetics Home Reference (NIH)PAF1
Genomic and cartography
GoldenPath hg38 (UCSC)PAF1  -     chr19:39385630-39391195 -  19q13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PAF1  -     19q13.2   [Description]    (hg19-Feb_2009)
EnsemblPAF1 - 19q13.2 [CytoView hg19]  PAF1 - 19q13.2 [CytoView hg38]
Mapping of homologs : NCBIPAF1 [Mapview hg19]  PAF1 [Mapview hg38]
OMIM610506   
Gene and transcription
Genbank (Entrez)AF086555 AJ401156 AK001985 AK098423 AK294625
RefSeq transcript (Entrez)NM_001256826 NM_019088
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PAF1
Cluster EST : UnigeneHs.466714 [ NCBI ]
CGAP (NCI)Hs.466714
Alternative Splicing GalleryENSG00000006712
Gene ExpressionPAF1 [ NCBI-GEO ]   PAF1 [ EBI - ARRAY_EXPRESS ]   PAF1 [ SEEK ]   PAF1 [ MEM ]
Gene Expression Viewer (FireBrowse)PAF1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)54623
GTEX Portal (Tissue expression)PAF1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8N7H5   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8N7H5  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8N7H5
Splice isoforms : SwissVarQ8N7H5
PhosPhoSitePlusQ8N7H5
Domains : Interpro (EBI)RNA_pol_II-assoc_Paf1   
Domain families : Pfam (Sanger)Paf1 (PF03985)   
Domain families : Pfam (NCBI)pfam03985   
Conserved Domain (NCBI)PAF1
DMDM Disease mutations54623
Blocks (Seattle)PAF1
PDB (SRS)4M6T   
PDB (PDBSum)4M6T   
PDB (IMB)4M6T   
PDB (RSDB)4M6T   
Structural Biology KnowledgeBase4M6T   
SCOP (Structural Classification of Proteins)4M6T   
CATH (Classification of proteins structures)4M6T   
SuperfamilyQ8N7H5
Human Protein AtlasENSG00000006712
Peptide AtlasQ8N7H5
HPRD10140
IPIIPI00300333   IPI00384593   IPI00908865   IPI01025379   
Protein Interaction databases
DIP (DOE-UCLA)Q8N7H5
IntAct (EBI)Q8N7H5
FunCoupENSG00000006712
BioGRIDPAF1
STRING (EMBL)PAF1
ZODIACPAF1
Ontologies - Pathways
QuickGOQ8N7H5
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core binding  endodermal cell fate commitment  chromatin binding  protein binding  nucleoplasm  nucleoplasm  cytoplasm  transcription from RNA polymerase II promoter  transcription elongation from RNA polymerase II promoter  mRNA polyadenylation  histone monoubiquitination  membrane  Wnt signaling pathway  protein ubiquitination  nucleosome positioning  Cdc73/Paf1 complex  stem cell population maintenance  cell junction  positive regulation of histone methylation  positive regulation of mRNA 3'-end processing  positive regulation of transcription elongation from RNA polymerase II promoter  histone H2B ubiquitination  protein localization to nucleus  negative regulation of myeloid cell differentiation  positive regulation of transcription from RNA polymerase II promoter  cellular response to lipopolysaccharide  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core binding  endodermal cell fate commitment  chromatin binding  protein binding  nucleoplasm  nucleoplasm  cytoplasm  transcription from RNA polymerase II promoter  transcription elongation from RNA polymerase II promoter  mRNA polyadenylation  histone monoubiquitination  membrane  Wnt signaling pathway  protein ubiquitination  nucleosome positioning  Cdc73/Paf1 complex  stem cell population maintenance  cell junction  positive regulation of histone methylation  positive regulation of mRNA 3'-end processing  positive regulation of transcription elongation from RNA polymerase II promoter  histone H2B ubiquitination  protein localization to nucleus  negative regulation of myeloid cell differentiation  positive regulation of transcription from RNA polymerase II promoter  cellular response to lipopolysaccharide  
REACTOMEQ8N7H5 [protein]
REACTOME PathwaysR-HSA-8866654 [pathway]   
NDEx NetworkPAF1
Atlas of Cancer Signalling NetworkPAF1
Wikipedia pathwaysPAF1
Orthology - Evolution
OrthoDB54623
GeneTree (enSembl)ENSG00000006712
Phylogenetic Trees/Animal Genes : TreeFamPAF1
HOVERGENQ8N7H5
HOGENOMQ8N7H5
Homologs : HomoloGenePAF1
Homology/Alignments : Family Browser (UCSC)PAF1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPAF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PAF1
dbVarPAF1
ClinVarPAF1
1000_GenomesPAF1 
Exome Variant ServerPAF1
ExAC (Exome Aggregation Consortium)PAF1 (select the gene name)
Genetic variants : HAPMAP54623
Genomic Variants (DGV)PAF1 [DGVbeta]
DECIPHERPAF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPAF1 
Mutations
ICGC Data PortalPAF1 
TCGA Data PortalPAF1 
Broad Tumor PortalPAF1
OASIS PortalPAF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPAF1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPAF1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PAF1
DgiDB (Drug Gene Interaction Database)PAF1
DoCM (Curated mutations)PAF1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PAF1 (select a term)
intoGenPAF1
NCG5 (London)PAF1
Cancer3DPAF1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM610506   
Orphanet
MedgenPAF1
Genetic Testing Registry PAF1
NextProtQ8N7H5 [Medical]
TSGene54623
GENETestsPAF1
Target ValidationPAF1
Huge Navigator PAF1 [HugePedia]
snp3D : Map Gene to Disease54623
BioCentury BCIQPAF1
ClinGenPAF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD54623
Chemical/Pharm GKB GenePA142671206
Clinical trialPAF1
Miscellaneous
canSAR (ICR)PAF1 (select the gene name)
Probes
Litterature
PubMed66 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePAF1
EVEXPAF1
GoPubMedPAF1
iHOPPAF1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Aug 1 17:33:17 CEST 2017

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