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Gene Review

UBE2D1  -  ubiquitin-conjugating enzyme E2D 1

Homo sapiens

Synonyms: E2(17)KB1, SFT, Stimulator of Fe transport, UBC4/5, UBC4/5 homolog, ...
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Disease relevance of UBE2D1

  • Additionally, the accumulation of high levels of certain Ub-conjugating enzymes (UbcH1, UbcH2, and UbcH5), was specific to breast cancer, as no change in abundance was detected in primary colon cancer tissue extracts [1].
  • The unexpected observation that SFT transcript levels are up-regulated in hemochromatosis patients therefore suggests that enhanced SFT expression contributes to the etiology of this iron overload disorder [2].
  • SFT Thijsen et al. Hypersensitivity of bcr-abl progenitors to hyperthermia in patients with chronic myeloid leukemia. Leukemia 1997; 11: 1762-1768 [3].
  • We report six cases of a neoplasm that arose in the upper respiratory tract and had a histological appearance indistinguishable from that of solitary fibrous tumor of the pleura (SFT, so-called fibrous mesothelioma) [4].
  • The resulting mutant SFT, designated as [S170A]SFT, was expressed in Streptomyces lividans and purified to homogeneity [5].

Psychiatry related information on UBE2D1

  • The results are discussed in terms of the SFT (Warrington & Shallice, 1984) and individual differences (Lambon-Ralph et al., 2003) accounts of category-specificity in SD [6].
  • Hearing results, when compared between the two groups, show a statistically significant advantage for the SFT patients in postoperative high frequency threshold sensitivity and speech discrimination scores [7].
  • Cases were classified into predominant maltreatment types according to three different schemes: Hierarchical regression analyses examined whether the HT, SFT, and EHT type classifications contributed to prediction of child behavior problems, trauma symptoms and adaptive functioning [8].

High impact information on UBE2D1

  • A UbcH5/ubiquitin noncovalent complex is required for processive BRCA1-directed ubiquitination [9].
  • However, as presented herein, the UbcH5 family of E2s can also bind Ub noncovalently on a surface well removed from the E2 active site [9].
  • The 3' untranslated region of SFT contains a translation inhibitory element and inhibition of SFT expression in Xenopus oocytes was found to be relieved by coinjection of transcripts from other defined cDNAs that are also described in this report [10].
  • We present evidence that the effector OspG is a protein kinase that binds various ubiquitinylated ubiquitin-conjugating enzymes, including UbcH5, which belongs to the stem cell factor SCF(beta-TrCP) complex promoting ubiquitination of phosphorylated inhibitor of NF-kappaB type alpha (phospho-IkappaBalpha) [11].
  • Further mRNA expression studies using a sequence-specific reverse transcriptase-polymerase chain reaction (RT-PCR) assay showed that UbcH5A is significantly up-regulated in the liver of iron-overloaded patients with hereditary hemochromatosis, as previously published for SFT [12].

Chemical compound and disease context of UBE2D1


Biological context of UBE2D1


Anatomical context of UBE2D1

  • The significantly elevated levels of SFT/UbcH5A mRNA in the neonatal mouse and its localization to choroid plexus, a major site of brain iron acquisition, suggest that this factor may contribute to the rapid rate of brain iron uptake that occurs in the early postnatal period [17].
  • A stimulator of Fe transport (SFT) was identified by functional expression cloning in Xenopus oocytes [10].
  • OBJECTIVE: The objective of this study was to investigate whether absorption and transepithelial movement of iron correlated with gene expression of DMT1, HFE, and SFT in an experimental model of human absorptive enterocytes [15].
  • Assimilation of nontransferrin-bound Fe by HeLa cells stably expressing SFT was time- and temperature-dependent; both the rate and extent of uptake was enhanced relative to the activity of control nontransfected cells [18].
  • The cumulative data of 13 cases (comprised of the seven present cases and the six previously reported) suggest a benign clinical behavior for thyroid SFT [19].

Associations of UBE2D1 with chemical compounds

  • SFT, a stimulator of iron (Fe) transport, has been described as a transmembrane protein that facilitates the uptake of ferrous and ferric iron in mammalian cells [12].
  • SFT (Stimulator of Iron Transport) is postulated to facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be important in transfer of iron from enterocytes into the plasma [20].
  • Curiously, we also find that depletion of intracellular iron by desferrioxamine impairs SFT transport and iron-binding functions [21].
  • Transport mediated by SFT was inhibitable by diethylenetriaminepentaacetic acid and ferrozine, Fe3+- and Fe2+-specific chelators [18].
  • SFT (stimulator of Fe transport) is a novel transport protein that has been found to facilitate uptake of iron presented to cells as either Fe(II) or Fe(III) [2].

Other interactions of UBE2D1

  • To characterize better the potential mechanisms for iron transport into and within the brain, we have analyzed expression patterns of two factors: divalent metal transporter 1 (DMT1) and stimulator of Fe transport (SFT) [17].
  • Of the E2s tested only UbcH5A, -B, and -C and E2-25K support Mdm2-mediated ubiquitination of p53 [22].
  • UbcH6 is a novel member of an evolutionally conserved subfamily of E2s that includes UbcH5 and Saccharomyces cerevisiae UBC4 [23].
  • Analysis of the enzymatic cascade involved in the conjugation process reveals that the ubiquitin-carrier protein E2-F1 and its human homolog UbcH5, which target the tumor suppressor p53 for degradation, are also involved in c-Fos recognition [24].
  • Characterization of human hect domain family members and their interaction with UbcH5 and UbcH7 [25].

Analytical, diagnostic and therapeutic context of UBE2D1

  • Here we report the molecular cloning and characterization of the human gene for SFT [16].
  • PCR analysis indicates 1000 nucleotides of intervening intron sequence near the 3' end of the coding region for SFT [16].
  • Immunohistochemistry was performed on duodenal biopsy specimens with anti-TfR and anti-SFT antibodies which recognize a putative stimulator of Fe transport of ~80 kilodaltons [26].
  • Northern blot analysis of transferrin receptor messenger RNA (mRNA) levels showed variations similar to those observed for IRPs, but both NO donors increased L-ferritin mRNA levels and had no effect on the stimulator of Fe transport (SFT) mRNA [27].
  • Of the 1,001 Dermacentor variabilis examined by the hemolymph test, 59 (5.9%) contained rickettsia-like organisms; direct immunofluorescence tests verified the presence of SFT rickettsiae in 14 specimens [28].


  1. Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Chen, L., Madura, K. Cancer Res. (2005) [Pubmed]
  2. Expression of SFT (stimulator of Fe transport) is enhanced by iron chelation in HeLa cells and by hemochromatosis in liver. Yu, J., Yu, Z.K., Wessling-Resnick, M. J. Biol. Chem. (1998) [Pubmed]
  3. SFT Thijsen et al. Hypersensitivity of bcr-abl progenitors to hyperthermia in patients with chronic myeloid leukemia. Leukemia 1997; 11: 1762-1768. Baccarani, M. Leukemia (1998) [Pubmed]
  4. Solitary fibrous tumor of the upper respiratory tract. A report of six cases. Witkin, G.B., Rosai, J. Am. J. Surg. Pathol. (1991) [Pubmed]
  5. A mutant trypsin-like enzyme from Streptomyces fradiae, created by site-directed mutagenesis, improves affinity chromatography for protein trypsin inhibitors. Katoh, T., Kikuchi, N., Nagata, K., Yoshida, N. Appl. Microbiol. Biotechnol. (1996) [Pubmed]
  6. Knowledge of living, nonliving and "sensory quality" categories in semantic dementia. Carroll, E., Garrard, P. Neurocase : case studies in neuropsychology, neuropsychiatry, and behavioural neurology. (2005) [Pubmed]
  7. Small fenestra stapedectomy. A preliminary report. Bailey, H.A., Pappas, J.J., Graham, S.S. Laryngoscope (1981) [Pubmed]
  8. What's in a name? A comparison of methods for classifying predominant type of maltreatment. Lau, A.S., Leeb, R.T., English, D., Graham, J.C., Briggs, E.C., Brody, K.E., Marshall, J.M. Child abuse & neglect. (2005) [Pubmed]
  9. A UbcH5/ubiquitin noncovalent complex is required for processive BRCA1-directed ubiquitination. Brzovic, P.S., Lissounov, A., Christensen, D.E., Hoyt, D.W., Klevit, R.E. Mol. Cell (2006) [Pubmed]
  10. Functional expression cloning and characterization of SFT, a stimulator of Fe transport. Gutierrez, J.A., Yu, J., Rivera, S., Wessling-Resnick, M. J. Cell Biol. (1997) [Pubmed]
  11. The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Kim, D.W., Lenzen, G., Page, A.L., Legrain, P., Sansonetti, P.J., Parsot, C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is closely related to SFT, a stimulator of iron transport, and is up-regulated in hereditary hemochromatosis. Gehrke, S.G., Riedel, H.D., Herrmann, T., Hadaschik, B., Bents, K., Veltkamp, C., Stremmel, W. Blood (2003) [Pubmed]
  13. Assignment of UBE2D1 to human chromosome bands 10q11.2-->q21 by in situ hybridization. Robinson, P.A., Leek, J.P., Ardley, H.C., Thompson, J., Rose, S.A., Markham, A.F. Cytogenet. Cell Genet. (1998) [Pubmed]
  14. Identification of a family of closely related human ubiquitin conjugating enzymes. Jensen, J.P., Bates, P.W., Yang, M., Vierstra, R.D., Weissman, A.M. J. Biol. Chem. (1995) [Pubmed]
  15. Functional and molecular responses of human intestinal Caco-2 cells to iron treatment. Tallkvist, J., Bowlus, C.L., Lönnerdal, B. Am. J. Clin. Nutr. (2000) [Pubmed]
  16. Characterization and chromosomal mapping of the human gene for SFT, a stimulator of Fe transport. Gutierrez, J.A., Yu, J., Wessling-Resnick, M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Developmental, regional, and cellular expression of SFT/UbcH5A and DMT1 mRNA in brain. Knutson, M., Menzies, S., Connor, J., Wessling-Resnick, M. J. Neurosci. Res. (2004) [Pubmed]
  18. Influence of copper depletion on iron uptake mediated by SFT, a stimulator of Fe transport. Yu, J., Wessling-Resnick, M. J. Biol. Chem. (1998) [Pubmed]
  19. Solitary fibrous tumor of the thyroid gland: report of seven cases. Rodriguez, I., Ayala, E., Caballero, C., De Miguel, C., Matias-Guiu, X., Cubilla, A.L., Rosai, J. Am. J. Surg. Pathol. (2001) [Pubmed]
  20. Iron absorption and transport-an update. Conrad, M.E., Umbreit, J.N. Am. J. Hematol. (2000) [Pubmed]
  21. Structural and functional analysis of SFT, a stimulator of Fe Transport. Yu, J., Wessling-Resnick, M. J. Biol. Chem. (1998) [Pubmed]
  22. Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. Saville, M.K., Sparks, A., Xirodimas, D.P., Wardrop, J., Stevenson, L.F., Bourdon, J.C., Woods, Y.L., Lane, D.P. J. Biol. Chem. (2004) [Pubmed]
  23. Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5. Nuber, U., Schwarz, S., Kaiser, P., Schneider, R., Scheffner, M. J. Biol. Chem. (1996) [Pubmed]
  24. Degradation of the proto-oncogene product c-Fos by the ubiquitin proteolytic system in vivo and in vitro: identification and characterization of the conjugating enzymes. Stancovski, I., Gonen, H., Orian, A., Schwartz, A.L., Ciechanover, A. Mol. Cell. Biol. (1995) [Pubmed]
  25. Characterization of human hect domain family members and their interaction with UbcH5 and UbcH7. Schwarz, S.E., Rosa, J.L., Scheffner, M. J. Biol. Chem. (1998) [Pubmed]
  26. Duodenal expression of a putative stimulator of Fe transport and transferrin receptor in anemia and hemochromatosis. Barisani, D., Parafioriti, A., Armiraglio, E., Meneveri, R., Conte, D. Gastroenterology (2001) [Pubmed]
  27. Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells. Barisani, D., Cairo, G., Ginelli, E., Marozzi, A., Conte, D. Hepatology (1999) [Pubmed]
  28. Endemicity of spotted fever group rickettsiae in Connecticut. Magnarelli, L.A., Anderson, J.F., Philip, R.N., Burgdorfer, W., Casper, E.A. Am. J. Trop. Med. Hyg. (1981) [Pubmed]
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