F
IPR045194

E3 ubiquitin-protein ligase MGRN1/RNF157-like

InterPro entry
Short nameMGRN1/RNF157-like

Description

This entry represents a group of confirmed and predicted E3 ubiquitin ligases, including MGRN1/RNF157 from humans and LOG2/LUL1-4 from Arabidopsis.

MGRN1 is a cytosolic E3 ubiquitin-protein ligase that inhibits signalling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes
[6]
. It suppresses chaperone-associated misfolded protein aggregation and toxicity
[3]
. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration
[7]
. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus
[6]
. Furthermore, MGRN1 interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration
[5, 2]
.

RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in brain. In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis
[1]
. Both MGRN1 and RNF157 contain a modified C3HC5-type RING-HC finger, and a functionally uncharacterized region, known as domain associated with RING2 (DAR2), N-terminal to the RING finger.

In Arabidopsis, LOG2 is a predicted E3 ubiquitin ligase that interact with GDU1 and is involved in the regulation of amino acid export from plant cells
[4]
.

References

1.Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157. Matz A, Lee SJ, Schwedhelm-Domeyer N, Zanini D, Holubowska A, Kannan M, Farnworth M, Jahn O, Gopfert MC, Stegmuller J. Cell Death Differ 22, 626-42, (2015). PMID: 25342469

2.Abnormal regulation of TSG101 in mice with spongiform neurodegeneration. Jiao J, Sun K, Walker WP, Bagher P, Cota CD, Gunn TM. Biochim Biophys Acta 1792, 1027-35, (2009). PMID: 19703557

3.Mahogunin ring finger-1 (MGRN1) suppresses chaperone-associated misfolded protein aggregation and toxicity. Chhangani D, Mishra A. Sci Rep 3, 1972, (2013). PMID: 23756845

4.The ubiquitin E3 ligase LOSS OF GDU2 is required for GLUTAMINE DUMPER1-induced amino acid secretion in Arabidopsis. Pratelli R, Guerra DD, Yu S, Wogulis M, Kraft E, Frommer WB, Callis J, Pilot G. Plant Physiol. 158, 1628-42, (2012). View articlePMID: 22291198

5.Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates TSG101 and regulates endosomal trafficking. Kim BY, Olzmann JA, Barsh GS, Chin LS, Li L. Mol Biol Cell 18, 1129-42, (2007). PMID: 17229889

6.Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling from melanocortin receptor by competition with Galphas. Perez-Oliva AB, Olivares C, Jimenez-Cervantes C, Garcia-Borron JC. J Biol Chem 284, 31714-25, (2009). PMID: 19737927

7.MGRN1-mediated ubiquitination of α-tubulin regulates microtubule dynamics and intracellular transport. Mukherjee R, Majumder P, Chakrabarti O. Traffic 18, 791-807, (2017). PMID: 28902452

GO terms

biological process

  • None

cellular component

  • None

Cross References

Contributing Member Database Entry
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.