Structural highlightsDisease[SBDS_HUMAN] Idiopathic aplastic anemia;Shwachman-Diamond syndrome. The disease is caused by mutations affecting the gene represented in this entry.[1] [2]
Function[ETUD1_HUMAN] Involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with SBDS, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Has low intrinsic GTPase activity. GTPase activity is increased by contact with 60S ribosome subunits.[3] [RLA0_DICDI] Ribosomal protein P0 is the functional equivalent of E.coli protein L10. [IF6_DICDI] Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. May also be involved in ribosome biogenesis. [RL40_DICDI] Ubiquitin: exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-48-linked is involved in protein degradation via the proteasome. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). 60S ribosomal protein L40: component of the 60S subunit of the ribosome. [RL3_DICDI] The L3 protein is a component of the large subunit of cytoplasmic ribosomes. [SBDS_HUMAN] Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFTUD1, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Required for normal levels of protein synthesis. May play a role in cellular stress resistance. May play a role in cellular response to DNA damage. May play a role in cell proliferation.[4] [5] [6] [7]
References
- ↑ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732 doi:10.1101/gad.623011
- ↑ Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet. 2003 Jan;33(1):97-101. Epub 2002 Dec 23. PMID:12496757 doi:http://dx.doi.org/10.1038/ng1062
- ↑ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732 doi:10.1101/gad.623011
- ↑ Hesling C, Oliveira CC, Castilho BA, Zanchin NI. The Shwachman-Bodian-Diamond syndrome associated protein interacts with HsNip7 and its down-regulation affects gene expression at the transcriptional and translational levels. Exp Cell Res. 2007 Dec 10;313(20):4180-95. Epub 2007 Jul 10. PMID:17643419 doi:10.1016/j.yexcr.2007.06.024
- ↑ Ball HL, Zhang B, Riches JJ, Gandhi R, Li J, Rommens JM, Myers JS. Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in cellular stress responses. Hum Mol Genet. 2009 Oct 1;18(19):3684-95. doi: 10.1093/hmg/ddp316. Epub 2009 Jul , 14. PMID:19602484 doi:http://dx.doi.org/10.1093/hmg/ddp316
- ↑ Orelio C, Verkuijlen P, Geissler J, van den Berg TK, Kuijpers TW. SBDS expression and localization at the mitotic spindle in human myeloid progenitors. PLoS One. 2009 Sep 17;4(9):e7084. doi: 10.1371/journal.pone.0007084. PMID:19759903 doi:http://dx.doi.org/10.1371/journal.pone.0007084
- ↑ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732 doi:10.1101/gad.623011
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