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Gene Review

RNF139  -  ring finger protein 139

Homo sapiens

Synonyms: E3 ubiquitin-protein ligase RNF139, HRCA1, RCA1, RING finger protein 139, TRC8, ...
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Disease relevance of RNF139

  • In a series of sporadic renal carcinomas, an acquired TRC8 mutation was identified [1].
  • We now show that the 8q24.1 breakpoint region encodes a 664-aa multiple membrane spanning protein, TRC8, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched [1].
  • The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8 [1].
  • The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway [2].
  • Binding by lectins from Ricinus communis (RCA-1), Limax flavus (LFA), Lotus tetragonolobus (LTA) and Ulex europaeus (UEA-1) appeared unaltered in secondary Sjögren's syndrome, suggesting no obvious change in N-glycosylation of parotid glycoproteins [3].

High impact information on RNF139

  • Several otherwise-unrelated RING finger proteins, including BRCA1, Siah-1, TRC8, NF-X1, kf-1, and Praja1, were assessed for their ability to facilitate E2-dependent ubiquitination [4].
  • In the 3;8 translocation, TRC8 is fused to FHIT and is disrupted within the sterol-sensing domain [1].
  • By analogy to patched, TRC8 might function as a signaling receptor and other pathway members, to be defined, are mutation candidates in malignant diseases involving the kidney and thyroid [1].
  • RT-in situ PCR experiments also demonstrated the presence of iNOS mRNA in the cytoplasm of cells that also expressed the ligand recognized by the Ricinus communis agglutinin 1 (RCA-1), a monocyte/macrophage lineage marker [5].
  • In healing oral wounds from eight humans and three monkeys, RCA1 receptors were demonstrated both in normal epithelium adjacent to the wounds and in the epithelial outgrowth from the wound margin [6].

Chemical compound and disease context of RNF139


Biological context of RNF139

  • The deduced amino acid sequences of RCA1, RCA2, RCA3, and RCA3' (a subform of RCA3) have agreement with average molecular masses from electrospray mass spectrometry of 4537, 4543, 4532, and 4560 kD, respectively [8].
  • We have shown that primary dissociated cultures from human embryos as young as 10 weeks gestation contain RCA-1+ cells [9].
  • While Ricinus communis agglutinin 1 (RCA-1) can be used as a specific marker to study the development and differentiation of microglial cells in human embryogenesis, little is known about the structural heterogeneity and nature of RCA-1+ cells [9].
  • As early as in the 8th week of gestational age RCA-1 positive cells were detected, mainly in form of amoeboid microglial cells [10].
  • The correlation between RCA-1 reactivity and cellular proliferative potential was investigated in 10 high-grade gliomas using a combined staining technique: the silver colloid method for nucleolar organizer regions (Ag-NORs) and histochemistry with RCA-1 [11].

Anatomical context of RNF139

  • Human and Drosophila TRC8 proteins localize to the endoplasmic reticulum [2].
  • Biopsies from 15 human oral carcinomas and adjacent normal mucosa showed RCA1 receptors at the cell membranes in the basal and spinous layer of the normal epithelium, whereas receptors could not be demonstrated in invading islands of the tumors [6].
  • Results of double-immunostaining revealed that gp41-positive cells of all morphologic types, including cells with bipolar or multipolar processes, were double-labeled with RCA-1, but not with markers for astrocytes, neurons, or endothelia [12].
  • Cell-type specific markers for double-labeling included: Ricinus communis agglutinin-1 (RCA-1) for macrophages and microglia; Ulex europaeus agglutinin-1 for endothelium; anti-glial fibrillary acidic protein (GFAP) for astrocytes; anti-amyloid precursor protein for neurons; and anti-leukocyte common antigen for leukocytes [12].
  • Therefore, we studied the relationship between microglia and diffuse plaques in the cerebral cortex of four patients with HCHWA-D using a panel of macrophage/microglia markers (mAbs LCA, LeuM5, LeuM3, LN3, KP1, OKIa, CLB54, Mac1, Ki-M6, AMC30 and the lectin RCA-1) [13].

Associations of RNF139 with chemical compounds


Analytical, diagnostic and therapeutic context of RNF139

  • Lectins (RCA1 and WGA) upon immobilization on liposomes retained saccharide specificity and the ability to agglutinate red blood cells [19].
  • (1) RCA-1 heavily stains blood vessels, while anti-ferritin does not, hence the microglial cells are more readily visualized with ferritin immunohistochemistry [16].
  • The pattern of lectin binding in normal human labial mucosa was examined by light and electron microscopy using eight different lectins (ConA, LCA, WGA, UEA-1, RCA-1, SBA, DBA and PNA) and compared with the patterns in normal human skin and oesophageal mucosa [20].
  • We used a group of lectins (Con-A, WGA, SBA, DBA, RCA-1, UEA-1), enzymes (neuraminidase digestion) and conventional histochemical techniques (periodic acid-Schiff reaction and reduction-saponification-Schiff reaction) in order to detect the presence of glycoproteins rich in sialic and neuraminic acids in the human eccrine sweat glands [21].
  • Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of perchloric acid extracts of RCA-1 tumor, followed by immunoblotting with the above-mentioned anti-CEA reagents, revealed that rat CEA activity resided in components with a molecular weight of approximately 350 kD [22].


  1. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Gemmill, R.M., West, J.D., Boldog, F., Tanaka, N., Robinson, L.J., Smith, D.I., Li, F., Drabkin, H.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway. Gemmill, R.M., Bemis, L.T., Lee, J.P., Sozen, M.A., Baron, A., Zeng, C., Erickson, P.F., Hooper, J.E., Drabkin, H.A. Oncogene (2002) [Pubmed]
  3. Lectin binding studies of parotid salivary glycoproteins in Sjögren's syndrome. Carpenter, G.H., Pankhurst, C.L., Proctor, G.B. Electrophoresis (1999) [Pubmed]
  4. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Lorick, K.L., Jensen, J.P., Fang, S., Ong, A.M., Hatakeyama, S., Weissman, A.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Bagasra, O., Michaels, F.H., Zheng, Y.M., Bobroski, L.E., Spitsin, S.V., Fu, Z.F., Tawadros, R., Koprowski, H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  6. Expression of Ricinus communis receptors on epithelial cells in oral carcinomas and oral wounds. Dabelsteen, E., Mackenzie, I.C. Cancer Res. (1978) [Pubmed]
  7. Lectin histochemistry of human gliomas. Wang, X.C., Kochi, N., Tani, E., Kaba, K., Matsumoto, T., Shindo, H. Acta Neuropathol. (1989) [Pubmed]
  8. Purification and sequencing of radish seed calmodulin antagonists phosphorylated by calcium-dependent protein kinase. Polya, G.M., Chandra, S., Condron, R. Plant Physiol. (1993) [Pubmed]
  9. Ultrastructural identification of Ricinus communis agglutinin-1 positive cells in primary dissociated cell cultures of human embryonic brain. Bobryshev, Y., Ashwell, K. Arch. Histol. Cytol. (1994) [Pubmed]
  10. Morphological study of microglia in human mesencephalon during the development and aging. Wierzba-Bobrowicz, T., Gwiazda, E., Poszwińska, Z. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. (1995) [Pubmed]
  11. Relationship between Ricinus communis agglutinin-1 binding and nucleolar organizer regions in human gliomas. Niikawa, S., Hara, A., Shirakami, S., Zhang, W., Sakai, N., Yamada, H., Shimokawa, K. Neurol. Med. Chir. (Tokyo) (1993) [Pubmed]
  12. Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemical method. Kure, K., Lyman, W.D., Weidenheim, K.M., Dickson, D.W. Am. J. Pathol. (1990) [Pubmed]
  13. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study. Maat-Schieman, M.L., Rozemuller, A.J., van Duinen, S.G., Haan, J., Eikelenboom, P., Roos, R.A. J. Neuropathol. Exp. Neurol. (1994) [Pubmed]
  14. Fraction A of armadillo submandibular glycoprotein and its desialylated product as sialyl-Tn and Tn receptors for lectins. Wu, A.M., Shen, F., Herp, A., Song, S.C., Wu, J.H. FEBS Lett. (1995) [Pubmed]
  15. Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases. Raghavan, D., Brandes, L.J., Klapp, K., Snyder, T., Styles, E., Tsao-Wei, D., Lieskovsky, G., Quinn, D.I., Ramsey, E.W. J. Urol. (2005) [Pubmed]
  16. Ferritin immunohistochemistry as a marker for microglia. Kaneko, Y., Kitamoto, T., Tateishi, J., Yamaguchi, K. Acta Neuropathol. (1989) [Pubmed]
  17. Interaction of lectins with human IgE: IgE-binding property and histamine-releasing activity of twelve plant lectins. Shibasaki, M., Sumazaki, R., Isoyama, S., Takita, H. Int. Arch. Allergy Immunol. (1992) [Pubmed]
  18. RING-dependent tumor suppression and G2/M arrest induced by the TRC8 hereditary kidney cancer gene. Brauweiler, A., Lorick, K.L., Lee, J.P., Tsai, Y.C., Chan, D., Weissman, A.M., Drabkin, H.A., Gemmill, R.M. Oncogene (2007) [Pubmed]
  19. Protein immobilization on the surface of liposomes via carbodiimide activation in the presence of N-hydroxysulfosuccinimide. Bogdanov, A.A., Klibanov, A.L., Torchilin, V.P. FEBS Lett. (1988) [Pubmed]
  20. Lectin binding pattern in normal human labial mucosa. Mizukawa, Y., Takata, K., Ookusa, Y., Nagashima, M., Hirano, H. Histochem. J. (1994) [Pubmed]
  21. Study of the distribution of glycosidic residues in eccrine sweat glands, with special reference to the content of sialic acid. Illana, M., Prada, A., Verástegui, C., González Macías, M.C., Fernández-Trujillo, F.J. European journal of histochemistry : EJH. (1997) [Pubmed]
  22. Isolation and characterization of rat carcinoembryonic antigen. Kim, J.G., Abeyounis, C.J. Int. Arch. Allergy Appl. Immunol. (1990) [Pubmed]
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