User:Brittany Allen/Sandbox 1

From Proteopedia

Revision as of 02:40, 4 December 2017

General Background Information

TIP30, also known as both CC3Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title is a tat-interacting protein that functions as a tumor suppressor involved in cell growth, apoptosis, metastasis, DNA repair, metabolism and angiogenesis of tumor cells^[1]. TIP30 acts as a transcription cofactor that can regulate gene expression^[2] and has both pro-apoptotic and anti-metastatic properties^[3]. When the promoter of TIP30 is methylated, TIP30 becomes downregulated and associated with tumor prognosis^[4]. It is thought that the tumor suppressor effect is the result of the inhibition of nuclear transport through binding with importin βs or by regulating transcription through interaction as a complex with a co-activator independent of AF-2 function and the c-myc gene^[5]. Several studies have found that TIP30 may be linked to esophageal carcinoma, laryngeal carcinoma, glioma, pancreatic ductal adenocarcinoma, breast cancer, gastric cancer, gallbladder adenocarcinoma, lung cancer, and hepatocellular carcinoma^[6].

Structure

TIP30 is an evolutionary conserved gene located on human chromosome 11^[7] . TIP30 has a molecular mass of 30 kd^[8] and is composed of 242 amino acids^[9]. TIP30 is composed of alpha helices, beta sheets, and loops (Movie). Through sequence analysis studies, it is thought that TIP30 may be a member of the SDR (substrate determining residue) family which contain a characteristic motif at their catalytic start sites^[10]. The carboxyl terminus of TIP30 binds to the SDR substrate, while the amino terminus of TIP30 is the nucleotide cofactor-binding domain which has a characteristic Gly-X-X-Gly- X-X-Gly motif (where X can be any amino acid)^[11]. Since SDR families have binding specificity for NADPH^[12] and TIP30 contains a dehydrogenase reductase fold that contains binding specificity for NADPH^[13]., the binding of NADPH may be important for the biological activity of TIP30 including interactions with importins as well as the c-myc system^[14].

Figure 1. The binding sites of TIP30 as identified using PYMOL.

TIP30 is known to bind 4 ligands: NDP (NADPH Dihydro-nicotinamide-adenine-dinucleotide-phosphate), PE8 (3,6,9,12,15,18,21 heptatricosane-1,2,3-diol), GOL (glycerol), and SO4 (sulfate ion)^[15]. The location these residues bind can be seen in ________. According to uniprot, TIP30 contains a nucleotide binding region between residues 19-52, as shown in ________, and a binding site at residue 131, as shown in______. When comparing _____ and ________, it can be observed that the ligands bind in the active regions and interact with the residues. Uniprot also noted that TIP30 can contain a mutagenic site at positions 28-31 (______), if this site is present there is a loss of proapoptotic and metastasis-inhibiting effects.

Figure 2. TIP30 displayed showing residues 19-52.

Figure 3. Mutagenesis

Function

TIP30 Tumor Suppressive Functions

TIP30 regulates apoptosis

TIP30 regulates proliferation

TIP30 regulates metastasis

TIP30 regulates angiogenesis

TIP30 controls gene expression

TIP30 regulates tumor cell metabolism

TIP30 regulates DNA damage responses

Role in Disease

Evolutionary Conservation

References

1. ↑ 3,4,5
2. ↑ 6
3. ↑ 7
4. ↑ 2
5. ↑ 8
6. ↑ 1
7. ↑ 1
8. ↑ 6
9. ↑ 1
10. ↑ 1
11. ↑ 1
12. ↑ 8
13. ↑ 1
14. ↑ 8
15. ↑ 9