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).

The gene is composed of 4 exons.

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.

None.

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.

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).

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).

Nucleus, mitochondrion (Yu et al., 2001; Guo et al., 2006; Simpson et al., 2006; Yuan et al., 2007).

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.

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).