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

Function

• oxidoreductase required for tumor suppression
• NAPDH-bound form inhibits nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors
• may act as a redox sensor linked to transcription through regulation of nuclear import
• isoform 1 is a metastasis suppressor with proapoptotic & antiangiogenic properties
• isoform 2 has an antiapoptotic effect
• binds nuclear transport receptors XPO4, RANBP5/IPO5, IPO7, IPO9, KPNB1
• binds GCN1L1/GCN1 & LRPPRC probably via HEAT repeats
• binds NCOA5/CIA
• 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

More general terms

• oxidoreductase

Database

• OMIM: https://mirror.omim.org/entry/605628
• UniProt: http://www.uniprot.org/uniprot/Q9BUP3.html