The human HTATIP2 gene has 6 exons that span more than 2.5 kb of genomic sequence located on chromosome 11p15.1.

HTATIP2 has four types of transcripts with 1.5 kb, 1.4 kb, 1.7 kb and 1.4 kb and they encode the same protein, 242aa, as a result of alternative splicing. And a small type of HTATIP2 isoform is 0.78 kb composed of 2 exons coding a 133aa protein.

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HTATIP2 includes isoform a and isoform b, both of which contain 242aa, and isoform c, 131aa. HTATIP2 can interact with the N-terminal trans-activation domain of HIV-tat directly as 30kDa Tat-interacting protein, to activate the HIV-1 promoter (Xiao et al., 1998), and with an ERa-interacting coactivator CIA to repress the expression of c-myc (Jiang et al., 2004). It is a member of the short-chain dehydrogenases/reductases (SDR) family (Baker et al., 2000) and have a cavity of NADPH binding site in its structure (El Omari et al., 2005). HTATIP2 has Ser/Thr protein kinase activity, which can undergo autophosphorylation, and phosphorylates the heptapeptide repeats of the C-terminal domain of the largest RNA polymerase II subunit in a tat-dependent manner. HTATIP2 binds directly to the karyopherins of the importin beta family in a RanGTP-insensitive manner and associates with nucleoporins in vivo (King and Shtivelman, 2004).

HTATIP2 is an evolutionary conserved gene that is expressed ubiquitously in human tissues, while it is down-expressed in many tumors tissues, such as prostate, colon, liver, lung and breast cancers (Hewitt et al., 2000; Jiang et al., 2007; Lee et al., 2004; Varambally et al., 2002).

HTATIP2 protein was found predominantly in the membrane and nuclear fractions but not in the particulate free cytoplasmic fraction (Whitman et al., 2000).

The HTATIP2 gene is a tumor susceptibility gene, which is associated with the suppression of metastasis in small cell lung cancer (SCLC) (Shtivelman, 1997), hepatocarcinoma (Ito et al., 2003). HTATIP2 interacts with an Estrogen Receptor alpha-interacting coactivator CIA (coactivator independent of AF-2 function), to repress the expression of c-myc gene, and also associated with ets-1 to inhibit osteopontin transcription in human hepatocellular carcinoma (Zhao et al., 2008b). HTATIP2 forms a RanGTP-resistant complex with importins to inhibit nuclear import and induce apoptosis (King and Shtivelman, 2004). HTATIP2 also induces apoptosis under oxidative stress through stabilization of p53 mRNA (Zhao et al., 2008a).

HTATIP2 encodes a protein whose sequence is highly conserved in evolution, with homologous genes being present in Caenorhabditis elegans, Saccharomyces cerevisiae, Escherichia coli (Whitman et al., 2000), Branchiostoma belcheri (Wang et al., 2008), and Mus musculus.

HTATIP2 mutant derived from hepatocellular carcinoma specimens promotes growth of HepG2 cells (Jiang et al., 2007).

There are two types of HTATIP2 mutation, G134V and R106H, in hepatocellular carcinoma specimens (Jiang et al., 2007).