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Gene Review

VPS52  -  vacuolar protein sorting 52 homolog (S....

Homo sapiens

Synonyms: ARE1, SAC2, SAC2 suppressor of actin mutations 2-like protein, SACM2L, Vacuolar protein sorting-associated protein 52 homolog, ...
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Disease relevance of VPS52

  • Linkage between polymorphisms in the prostate specific antigen ARE1 gene region, prostate cancer risk, and circulating tumor cells [1].
  • The recently described B cell-related ARE-1 activity is important for promoter III activation in the melanoma cells [2].

High impact information on VPS52

  • The differential banding pattern in in vivo genomic footprinting and transcription factor binding at the ARE-1 and site C between T cells and B cells probably reflects differences in CIITA-PIII activation pathways employed by these cell types [3].
  • In Jurkat T cells, both ARE-1 and ARE-2 are crucial for CIITA-PIII activity, similar to Raji B cells [3].
  • Thus, we investigated the frequency of polymorphism of the adenine- and thymine-rich element (ARE-1 and its variant ARE-2) in 426 Japanese type 2 diabetic and 380 nondiabetic subjects using a polymerase chain reaction (PCR)-restriction enzyme fragment length polymorphism (RFLP) method [4].
  • BNF and tBHQ activated a human ARE (hARE) reporter gene in RAW264.7 cells [5].
  • Interestingly, bacterial lipopolysaccharide also induced hARE/chloramphenicol acetyltransferase activity [5].

Biological context of VPS52

  • This analysis revealed that the gene order from VPS52 to SRPK1 is conserved between human and swine and that comparison with the human sequence identified a rearrangement in the swine genome at the proximal end of VPS52 [6].
  • It includes two novel human genes (BING4 and SACM2L) and a thus far unnoticed human leucocyte antigen (HLA) class II pseudogene, termed HLA-DPA3 [7].
  • The deduced amino acid sequence of the rat Sacm2l gene shows a putative coiled-coil region and significant homology to a putative Caenorhabditis elegans protein and the yeast SAC2 protein [8].
  • Mutations in the human NQO1 gene ARE (hARE) revealed the requirement for two TRE or TRE-like elements arranged in inverse orientation at the interval of three base pairs and a GC box for optimal expression and beta-naphthoflavone induction of the NQO1 gene [9].
  • The 5'-most ARE (ARE-1, 5'-TGTCCT-3') resembles a half-site of the palindromic consensus hormone response element, recognized by several steroid receptors, including AR, and the 3'-sequence (ARE-2, 5'-AGTACTCC-3') is identical to a portion of an androgen-responsive region found in the rat probasin gene promoter [10].

Anatomical context of VPS52

  • UV-induced RNA cross-linking assays revealed that untreated HL-60 cell extracts contain approximately eight proteins, ranging in size from 32 to 100 kDa, that bind to ARE 1 RNA [11].

Associations of VPS52 with chemical compounds

  • Both 5'- and 3'-deletion mapping of the PB 5'-flanking DNA revealed that ARE-1 and ARE-2 were required for androgen regulation [12].
  • In addition, ARE-1/1 subjects had significantly lower serum concentrations of dehydroepiandrosterone sulfate compared with ARE-2/2 subjects (4.2 +/- 0.3 vs. 6.6 +/- 0.7 micromol/liter) and a trend toward lower levels of free testosterone (78.8 +/- 6.5 vs. 114.1 +/- 30.8 pmol/liter) [13].
  • The PPP1R3 gene encoding the G-subunit of protein phosphatase-1 has three polymorphisms in linkage disequilibrium in the Pima Indians: an mRNA-destabilizing element in the 3'-untranslated region (ARE1/ARE2 alleles), Arg883Ser, and Asp905Tyr substitutions [14].

Other interactions of VPS52


Analytical, diagnostic and therapeutic context of VPS52

  • Gel shift analyses and mutational studies showed that maximal androgen regulation and AR binding were dependent on the integrity of four AREs (ARE-1, ARE-1A, IVSARE, and ARE-2) [17].


  1. Linkage between polymorphisms in the prostate specific antigen ARE1 gene region, prostate cancer risk, and circulating tumor cells. Medeiros, R., Morais, A., Vasconcelos, A., Costa, S., Pinto, D., Oliveira, J., Carvalho, R., Lopes, C. Prostate (2002) [Pubmed]
  2. Varying functions of specific major histocompatibility class II transactivator promoter III and IV elements in melanoma cell lines. Goodwin, B.L., Xi, H., Tejiram, R., Eason, D.D., Ghosh, N., Wright, K.L., Nagarajan, U., Boss, J.M., Blanck, G. Cell Growth Differ. (2001) [Pubmed]
  3. Activated human T cells accomplish MHC class II expression through T cell-specific occupation of class II transactivator promoter III. Holling, T.M., van der Stoep, N., Quinten, E., van den Elsen, P.J. J. Immunol. (2002) [Pubmed]
  4. The 3'-untranslated region polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 in the type 2 diabetic Japanese population. Maegawa, H., Shi, K., Hidaka, H., Iwai, N., Nishio, Y., Egawa, K., Kojima, H., Haneda, M., Yasuda, H., Nakamura, Y., Kinoshita, M., Kikkawa, R., Kashiwagi, A. Diabetes (1999) [Pubmed]
  5. Macrophage activation by polycyclic aromatic hydrocarbons: evidence for the involvement of stress-activated protein kinases, activator protein-1, and antioxidant response elements. Ng, D., Kokot, N., Hiura, T., Faris, M., Saxon, A., Nel, A. J. Immunol. (1998) [Pubmed]
  6. Genomic structure and gene order of swine chromosome 7q1.1-->q1.2. Tanaka, M., Suzuki, K., Morozumi, T., Kobayashi, E., Matsumoto, T., Domukai, M., Eguchi-Ogawa, T., Shinkai, H., Awata, T., Uenishi, H. Anim. Genet. (2006) [Pubmed]
  7. Gene organisation, sequence variation and isochore structure at the centromeric boundary of the human MHC. Stephens, R., Horton, R., Humphray, S., Rowen, L., Trowsdale, J., Beck, S. J. Mol. Biol. (1999) [Pubmed]
  8. Identification of a novel highly conserved gene in the centromeric part of the major histocompatibility complex. Walter, L., Günther, E. Genomics (1998) [Pubmed]
  9. ARE- and TRE-mediated regulation of gene expression. Response to xenobiotics and antioxidants. Xie, T., Belinsky, M., Xu, Y., Jaiswal, A.K. J. Biol. Chem. (1995) [Pubmed]
  10. Two androgen response elements in the androgen receptor coding region are required for cell-specific up-regulation of receptor messenger RNA. Dai, J.L., Burnstein, K.L. Mol. Endocrinol. (1996) [Pubmed]
  11. Taxol- and okadaic acid-induced destabilization of bcl-2 mRNA is associated with decreased binding of proteins to a bcl-2 instability element. Bandyopadhyay, S., Sengupta, T.K., Fernandes, D.J., Spicer, E.K. Biochem. Pharmacol. (2003) [Pubmed]
  12. Characterization of two cis-acting DNA elements involved in the androgen regulation of the probasin gene. Rennie, P.S., Bruchovsky, N., Leco, K.J., Sheppard, P.C., McQueen, S.A., Cheng, H., Snoek, R., Hamel, A., Bock, M.E., MacDonald, B.S. Mol. Endocrinol. (1993) [Pubmed]
  13. Association of the (AU)AT-rich element polymorphism in PPP1R3 with hormonal and metabolic features of polycystic ovary syndrome. Alcoser, S.Y., Hara, M., Bell, G.I., Ehrmann, D.A. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  14. Functional analyses of amino acid substitutions Arg883Ser and Asp905Tyr of protein phosphatase-1 G-subunit. Permana, P.A., Kahn, B.B., Huppertz, C., Mott, D.M. Mol. Genet. Metab. (2000) [Pubmed]
  15. Comparative and evolutionary analysis of the rhesus macaque extended MHC class II region. Sudbrak, R., Reinhardt, R., Hennig, S., Lehrach, H., Günther, E., Walter, L. Immunogenetics (2003) [Pubmed]
  16. Genotyping of AR and PSA polymorphisms in a patient with Klinefelter syndrome, non-Hodgkin lymphoma, and adenocarcinoma of the prostate. Mattos Dos Santos, R., Aparecida Rainho, C., Carlos Souza Trindade, J., Carlos Souza Trindade Filho, J., Lauro Viana De Camargo, J., Regina Rogatto, S. Cancer Genet. Cytogenet. (2004) [Pubmed]
  17. Multiple androgen response elements and a Myc consensus site in the androgen receptor (AR) coding region are involved in androgen-mediated up-regulation of AR messenger RNA. Grad, J.M., Dai, J.L., Wu, S., Burnstein, K.L. Mol. Endocrinol. (1999) [Pubmed]
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