Urm1: A Non-Canonical UBL
Urm1 (ubiquitin related modifier 1) is a molecular fossil in the class of ubiquitin-like proteins (UBLs). It encompasses characteristics of classical UBLs, such as ubiquitin or SUMO (small ubiquitin-related modifier), but also of bacterial sulfur-carrier proteins (SCP). Since its main function is to...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/2/139 |
| _version_ | 1797408509088759808 |
|---|---|
| author | Martin Termathe Sebastian A. Leidel |
| author_facet | Martin Termathe Sebastian A. Leidel |
| author_sort | Martin Termathe |
| collection | DOAJ |
| description | Urm1 (ubiquitin related modifier 1) is a molecular fossil in the class of ubiquitin-like proteins (UBLs). It encompasses characteristics of classical UBLs, such as ubiquitin or SUMO (small ubiquitin-related modifier), but also of bacterial sulfur-carrier proteins (SCP). Since its main function is to modify tRNA, Urm1 acts in a non-canonical manner. Uba4, the activating enzyme of Urm1, contains two domains: a classical E1-like domain (AD), which activates Urm1, and a rhodanese homology domain (RHD). This sulfurtransferase domain catalyzes the formation of a C-terminal thiocarboxylate on Urm1. Thiocarboxylated Urm1 is the sulfur donor for 5-methoxycarbonylmethyl-2-thiouridine (mcm<sup>5</sup>s<sup>2</sup>U), a chemical nucleotide modification at the wobble position in tRNA. This thio-modification is conserved in all domains of life and optimizes translation. The absence of Urm1 increases stress sensitivity in yeast triggered by defects in protein homeostasis, a hallmark of neurological defects in higher organisms. In contrast, elevated levels of tRNA modifying enzymes promote the appearance of certain types of cancer and the formation of metastasis. Here, we summarize recent findings on the unique features that place Urm1 at the intersection of UBL and SCP and make Urm1 an excellent model for studying the evolution of protein conjugation and sulfur-carrier systems. |
| first_indexed | 2024-03-09T04:00:30Z |
| format | Article |
| id | doaj.art-79fb53bacc2d4751ab0245d139b8e9bf |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T04:00:30Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-79fb53bacc2d4751ab0245d139b8e9bf2023-12-03T14:14:22ZengMDPI AGBiomolecules2218-273X2021-01-0111213910.3390/biom11020139Urm1: A Non-Canonical UBLMartin Termathe0Sebastian A. Leidel1Institute of Biochemistry, Protein Biochemistry and Photobiocatalysis, University of Greifswald, Felix-Hausdorff-Strasse 4, 17489 Greifswald, GermanyDepartment of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, SwitzerlandUrm1 (ubiquitin related modifier 1) is a molecular fossil in the class of ubiquitin-like proteins (UBLs). It encompasses characteristics of classical UBLs, such as ubiquitin or SUMO (small ubiquitin-related modifier), but also of bacterial sulfur-carrier proteins (SCP). Since its main function is to modify tRNA, Urm1 acts in a non-canonical manner. Uba4, the activating enzyme of Urm1, contains two domains: a classical E1-like domain (AD), which activates Urm1, and a rhodanese homology domain (RHD). This sulfurtransferase domain catalyzes the formation of a C-terminal thiocarboxylate on Urm1. Thiocarboxylated Urm1 is the sulfur donor for 5-methoxycarbonylmethyl-2-thiouridine (mcm<sup>5</sup>s<sup>2</sup>U), a chemical nucleotide modification at the wobble position in tRNA. This thio-modification is conserved in all domains of life and optimizes translation. The absence of Urm1 increases stress sensitivity in yeast triggered by defects in protein homeostasis, a hallmark of neurological defects in higher organisms. In contrast, elevated levels of tRNA modifying enzymes promote the appearance of certain types of cancer and the formation of metastasis. Here, we summarize recent findings on the unique features that place Urm1 at the intersection of UBL and SCP and make Urm1 an excellent model for studying the evolution of protein conjugation and sulfur-carrier systems.https://www.mdpi.com/2218-273X/11/2/1392-thiolationtRNA modificationthiocarboxylaterhodanesesulfur-carrier proteinnon-canonical UBL |
| spellingShingle | Martin Termathe Sebastian A. Leidel Urm1: A Non-Canonical UBL Biomolecules 2-thiolation tRNA modification thiocarboxylate rhodanese sulfur-carrier protein non-canonical UBL |
| title | Urm1: A Non-Canonical UBL |
| title_full | Urm1: A Non-Canonical UBL |
| title_fullStr | Urm1: A Non-Canonical UBL |
| title_full_unstemmed | Urm1: A Non-Canonical UBL |
| title_short | Urm1: A Non-Canonical UBL |
| title_sort | urm1 a non canonical ubl |
| topic | 2-thiolation tRNA modification thiocarboxylate rhodanese sulfur-carrier protein non-canonical UBL |
| url | https://www.mdpi.com/2218-273X/11/2/139 |
| work_keys_str_mv | AT martintermathe urm1anoncanonicalubl AT sebastianaleidel urm1anoncanonicalubl |