30 exons spanning 47 kb of genomic DNA. Exons 1 to 14 are derived from the TBC1D3 (PRC17), and exons 15 to 30 are derived from the USP32 (NY-REN-60).

The gene is transcribed from telomere to centromere. The coding region starts on exon 2 but many splicing variants have been identified in the untranslated exon 1. There are at least two major transcripts with an approximate lenght of 8 kb.

USP6 encodes for a 1406 aminoacid protein containing two major domains: TBC (from TRE2-Bub2-Cdc16), which encodes a GTPase-activating protein of the Rab family of GTPases, and a UBP domain with a ubiquitin specific protease activity. A USP6 splicing variant, also known as onco-TRE17 or TRE17-onco, encodes a 786 aminoacid protein with a truncated UBP domain. See figure 1.

Among normal tissues, USP6 seems to primarily expressed in testes.

Cytoplasmic protein.

USP6 function is still poorly understood but recent evidence has shown that USP6 is involved in endocytic trafficking. USP6 seems to operate in the same pathway controlled by Arf6 GTPase, which has been linked to mitogenic signaling and invasive behavior.

While the N-terminal portion of USP6 is highly homologous to PRC17 (89% identity), the C-terminal end is highly homologous to USP32 (97% identity).