oxidoreductase HTATIP2 (HIV-1 TAT-interactive protein 2, 30 kD HIV-1 TAT-interacting protein, HTATIP2, CC3, TIP30)

Function: 1) oxidoreductase required for tumor suppression 2) NAPDH-bound form inhibits nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors 3) may act as a redox sensor linked to transcription through regulation of nuclear import 4) isoform 1 is a metastasis suppressor with proapoptotic & antiangiogenic properties 5) isoform 2 has an antiapoptotic effect 6) binds nuclear transport receptors XPO₄, RANBP5/IPO5, IPO7, IPO9, KPNB1 7) binds GCN1L1/GCN1 & LRPPRC probably via HEAT repeats 8) binds NCOA5/CIA 9) isoform 2 binds proteasome subunit PSMD4/s5a through its N-terminus Structure: - monomer - unique C-terminus confers high proteasome-dependent instability to isoform 2. Compartment: cytoplasm, nuclear envelope Alternative splicing: named isoforms=2 Expression: - ubiquitous - expressed in liver > lung, skeletal muscle, pancreas, placenta > heart, kidney > brain Pathology: - binds activation domain of HIV TAT protein - Not expressed (or low levels) in variant small cell lung carcinomas 33% of hepatocellular carcinomas neuroblastomas - defects in HTATIP2 are a cause of aggressive metastatic proliferation in variant small cell lung carcinomas - lack of HTATIP2 renders tumor cells resistant to apoptotic signals

Properties

SIZE: MW = 27 kD entity length = 242 aa COMPARTMENT: cytoplasm nuclear membrane MOTIF: cofactor-binding site [19-52] COFACTOR-BOUND: NAD binding site SITE: 131-131 FOR-BINDING-OF: Substrate (Probable) tyrosine residue {Y143} lysine residue {K147}

Database Correlations

OMIM 605628 UniProt Q9BUP3

References

UniProt :accession Q9BUP3