USP6 (ubiquitin specific protease 6 (Tre-2 oncogene))

2005-04-01   Andre M Oliveira , Margaret Chou 

Department of Pathology, Laboratory Medicine, Mayo Clinic, Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA

Identity

HGNC
LOCATION
17p13.2
LOCUSID
ALIAS
HRP1,TRE17,TRE2,TRESMCR,Tre-2,USP6-short
FUSION GENES

DNA/RNA

Description

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).

Transcription

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.

Proteins

Atlas Image

Description

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.

Expression

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

Localisation

Cytoplasmic protein.

Function

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.

Homology

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).

Implicated in

Disease
Aneurysmal Bone Cyst or Aneurysmal Bone Tumor
Cytogenetics
Rearrangements of 17p13 with different partner chromosomes.
Hybrid gene
USP6 fusion genes are formed by juxtaposition of USP6 coding sequences to the promoter regions of several partner genes, which lead to USP6 transcriptional upregulation. There is no fusion protein.
  • COL1A1 -USP6 in t(17;17)(q12;p13)
  • Atlas Image

    Breakpoints

    Atlas Image

    Bibliography

    Pubmed IDLast YearTitleAuthors
    32740851988A rearranged transforming gene, tre, is made up of human sequences derived from chromosome regions 5q, 17q and 18q.Huebner K et al
    155097802004The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6.Martinu L et al
    123994752002Endocytosis of epidermal growth factor receptor regulated by Grb2-mediated recruitment of the Rab5 GTPase-activating protein RN-tre.Martinu L et al
    126120852003The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling.Masuda-Robens JM et al
    15654681992A novel transcriptional unit of the tre oncogene widely expressed in human cancer cells.Nakamura T et al
    157356892005Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes.Oliveira AM et al
    126047962003The Tre2 (USP6) oncogene is a hominoid-specific gene.Paulding CA et al

    Other Information

    Locus ID:

    NCBI: 9098
    MIM: 604334
    HGNC: 12629
    Ensembl: ENSG00000129204

    Variants:

    dbSNP: 9098
    ClinVar: 9098
    TCGA: ENSG00000129204
    COSMIC: USP6

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000129204ENST00000250066P35125
    ENSG00000129204ENST00000572949P35125
    ENSG00000129204ENST00000574788P35125
    ENSG00000129204ENST00000575709Q15635

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30
    35

    References

    Pubmed IDYearTitleCitations
    155095452004USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts.49
    150263242004USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst.44
    204189052010TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB.31
    155097802004The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6.28
    237694222014USP6-induced neoplasms: the biologic spectrum of aneurysmal bone cyst and nodular fasciitis.22
    271623532016USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds.22
    161271722005Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific protease TRE17/USP6.21
    126120852003The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling.20
    220810692012Atypical mechanism of NF-κB activation by TRE17/ubiquitin-specific protease 6 (USP6) oncogene and its requirement in tumorigenesis.16
    247428292014USP6 gene rearrangements occur preferentially in giant cell reparative granulomas of the hands and feet but not in gnathic location.10

    Citation

    Andre M Oliveira ; Margaret Chou

    USP6 (ubiquitin specific protease 6 (Tre-2 oncogene))

    Atlas Genet Cytogenet Oncol Haematol. 2005-04-01

    Online version: http://atlasgeneticsoncology.org/gene/530/usp6