8b9x: Difference between revisions
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The entry | ==Chimeric protein of human UFM1 E3 ligase, UFL1, and DDRGK1== | ||
<StructureSection load='8b9x' size='340' side='right'caption='[[8b9x]], [[Resolution|resolution]] 3.07Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8b9x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B9X FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.066Å</td></tr> | |||
[[Category: | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8b9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b9x OCA], [https://pdbe.org/8b9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b9x RCSB], [https://www.ebi.ac.uk/pdbsum/8b9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b9x ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/DDRGK_HUMAN DDRGK_HUMAN] Spondyloepimetaphyseal dysplasia, Shohat type. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/UFL1_HUMAN UFL1_HUMAN] E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498, PubMed:32160526). In response to endoplasmic reticulum stress, recruited to the endoplasmic reticulum membrane by DDRGK1, and mediates ufmylation of proteins such as RPN1 and RPL26/uL24, thereby promoting reticulophagy of endoplasmic reticulum sheets (PubMed:32160526). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha (PubMed:23152784, PubMed:32160526). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (PubMed:32050156). Regulates inflammation in response to endoplasmic reticulum stress by promoting reticulophagy, leading to inhibit the activity of the NF-kappa-B transcription factor (By similarity). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain whether ufmylation of these proteins is a collateral effect or is required for ufmylation (PubMed:20531390, PubMed:20018847). Catalyzes ufmylation of various subunits of the ribosomal complex or associated components, such as RPS3/uS3, RPS20/uS10, RPL10/uL16, RPL26/uL24 and EIF6 (By similarity). Anchors CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus which allows expression of the CCND1 cyclin and progression of cells through the G1/S transition (PubMed:20531390). Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 (PubMed:30886146). Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription (PubMed:25219498). Required for hematopoietic stem cell function and hematopoiesis (By similarity). Required for cardiac homeostasis (By similarity).[UniProtKB:A1A4I9][UniProtKB:Q8CCJ3]<ref>PMID:20018847</ref> <ref>PMID:20164180</ref> <ref>PMID:20228063</ref> <ref>PMID:20531390</ref> <ref>PMID:23152784</ref> <ref>PMID:25219498</ref> <ref>PMID:30886146</ref> <ref>PMID:32050156</ref> <ref>PMID:32160526</ref> [https://www.uniprot.org/uniprot/DDRGK_HUMAN DDRGK_HUMAN] Substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, which plays a key role in reticulophagy (also called ER-phagy) (PubMed:32160526). In response to endoplasmic reticulum stress, promotes recruitment of the E3 UFM1-protein ligase UFL1 to the endoplasmic reticulum membrane: in turn, UFL1 mediates ufmylation of proteins such as RPN1 and RPL26/uL24, promoting reticulophagy of endoplasmic reticulum sheets (PubMed:32160526). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability (PubMed:28128204, PubMed:32160526). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis or inflammatory response (By similarity). Required for TRIP4 ufmylation, thereby regulating nuclear receptors-mediated. transcription (PubMed:25219498). May play a role in NF-kappa-B-mediated transcription through regulation of the phosphorylation and the degradation of NFKBIA, the inhibitor of NF-kappa-B (PubMed:23675531). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186).[UniProtKB:Q80WW9]<ref>PMID:23675531</ref> <ref>PMID:25219498</ref> <ref>PMID:28128204</ref> <ref>PMID:28263186</ref> <ref>PMID:32160526</ref> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Isupov M]] | |||
[[Category: Wiener R]] | |||
[[Category: Banerjee S]] | |||