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

	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.

	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.

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