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

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PAF1 (Paf1, RNA polymerase II associated factor,
homolog (S. cerevisiae))
Shonali Deb, Moorthy P Ponnusamy, Surinder K Batra
Department of Biochemistry and Molecular Biology University of Nebraska Medical Center 985870
Nebraska Medical Center Durham Research center 7005 Omaha, NE 68198-5870, USA (SD, MPP, SKB)
Published in Atlas Database: September 2008
Online updated version: http://AtlasGeneticsOncology.org/Genes/PAF1ID44202ch19q13.html
DOI: 10.4267/2042/44536
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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.
Identity
Other names: F23149_1; FLJ11123; hPAF1; PD2
HGNC (Hugo): PAF1
Location: 19q13.1
Note: Paf1 is a member of the hPAF complex and is
dysregulated in cancer. The RNA polymerase IIassociated 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.
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.
DNA/RNA
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
Shows the genomic organization of Paf1 gene.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(8)
570
PAF1 (Paf1, RNA polymerase II associated factor, homolog (S. cerevisiae))
Deb S, et al.
Schematic representation of protein structure and its organization. RRM, RNA recognition motif; RCC, regulator of chromosome
condensation.
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.
Protein
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 helixloop-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.
Implicated in
Various cancers
Localisation
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 hyperparathyroidismjaw 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.
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.
References
Homology
Belotserkovskaya R, Reinberg D. Facts about FACT and
transcript elongation through chromatin. Curr Opin Genet Dev.
2004 Apr;14(2):139-46
There is a high degree of similarity between Paf1 and
sequences from mouse (AK017762, AB041615,
Rosonina E, Manley JL. From transcription to mRNA: PAF
provides a new path. Mol Cell. 2005 Oct 28;20(2):167-8
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(8)
571
PAF1 (Paf1, RNA polymerase II associated factor, homolog (S. cerevisiae))
Rozenblatt-Rosen O, Hughes CM, Nannepaga SJ,
Shanmugam KS, Copeland TD, Guszczynski T, Resau JH,
Meyerson M. The parafibromin tumor suppressor protein is
part of a human Paf1 complex. Mol Cell Biol. 2005
Jan;25(2):612-20
Moniaux N, Nemos C, Schmied BM, Chauhan SC, Deb S,
Morikane K, Choudhury A, Vanlith M, Sutherlin M, Sikela JM,
Hollingsworth MA, Batra SK. The human homologue of the
RNA polymerase II-associated factor 1 (hPaf1), localized on
the 19q13 amplicon, is associated with tumorigenesis.
Oncogene. 2006 Jun 1;25(23):3247-57
Yart A, Gstaiger M, Wirbelauer C, Pecnik M, Anastasiou D,
Hess D, Krek W. The HRPT2 tumor suppressor gene product
parafibromin associates with human PAF1 and RNA
polymerase II. Mol Cell Biol. 2005 Jun;25(12):5052-60
Chaudhary K, Deb S, Moniaux N, Ponnusamy MP, Batra SK.
Human RNA polymerase II-associated factor complex:
dysregulation in cancer. Oncogene. 2007 Nov 29;26(54):7499507
Zhu B, Mandal SS, Pham AD, Zheng Y, Erdjument-Bromage
H, Batra SK, Tempst P, Reinberg D. The human PAF complex
coordinates transcription with events downstream of RNA
synthesis. Genes Dev. 2005 Jul 15;19(14):1668-73
Deb S, Ponnusamy MP, Senapati S, Dey P, Batra SK.. Human
PAF Complexes in Endocrine Tumors and Pancreatic Cancer.
Expert Rev Endocrinol Metab. 2008 Sep 3(5), 557-565.
Zhu B, Zheng Y, Pham AD, Mandal SS, Erdjument-Bromage
H, Tempst P, Reinberg D. Monoubiquitination of human
histone H2B: the factors involved and their roles in HOX gene
regulation. Mol Cell. 2005 Nov 23;20(4):601-11
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(8)
Deb S, et al.
This article 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.
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