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7pyv

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Current revision

Crystal structure of human UBA6 in complex with the ubiquitin-like modifier FAT10

Structural highlights

7pyv is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.27Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

UBA1_HUMAN X-linked distal arthrogryposis multiplex congenita. The disease is caused by mutations affecting the gene represented in this entry.

Function

UBA1_HUMAN Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.^[1] UBA6_HUMAN Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility.^[2] ^[3] ^[4]

Publication Abstract from PubMed

The covalent modification of target proteins with ubiquitin or ubiquitin-like modifiers is initiated by E1 activating enzymes, which typically transfer a single modifier onto cognate conjugating enzymes. UBA6 is an unusual E1 since it activates two highly distinct modifiers, ubiquitin and FAT10. Here, we report crystal structures of UBA6 in complex with either ATP or FAT10. In the UBA6-FAT10 complex, the C-terminal domain of FAT10 binds to where ubiquitin resides in the UBA1-ubiquitin complex, however, a switch element ensures the alternate recruitment of either modifier. Simultaneously, the N-terminal domain of FAT10 interacts with the 3-helix bundle of UBA6. Site-directed mutagenesis identifies residues permitting the selective activation of either ubiquitin or FAT10. These results pave the way for studies investigating the activation of either modifier by UBA6 in physiological and pathophysiological settings.

Structures of UBA6 explain its dual specificity for ubiquitin and FAT10.,Truongvan N, Li S, Misra M, Kuhn M, Schindelin H Nat Commun. 2022 Aug 15;13(1):4789. doi: 10.1038/s41467-022-32040-6. PMID:35970836^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Moudry P, Lukas C, Macurek L, Hanzlikova H, Hodny Z, Lukas J, Bartek J. Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage. Cell Cycle. 2012 Apr 15;11(8):1573-82. doi: 10.4161/cc.19978. Epub 2012 Apr 15. PMID:22456334 doi:http://dx.doi.org/10.4161/cc.19978
↑ Zhu H, Zhou ZM, Huo R, Huang XY, Lu L, Lin M, Wang LR, Zhou YD, Li JM, Sha JH. Identification and characteristics of a novel E1 like gene nUBE1L in human testis. Acta Biochim Biophys Sin (Shanghai). 2004 Mar;36(3):227-34. doi:, 10.1093/abbs/36.3.227. PMID:15202508 doi:http://dx.doi.org/10.1093/abbs/36.3.227
↑ Jin J, Li X, Gygi SP, Harper JW. Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging. Nature. 2007 Jun 28;447(7148):1135-8. PMID:17597759 doi:http://dx.doi.org/nature05902
↑ Chiu YH, Sun Q, Chen ZJ. E1-L2 activates both ubiquitin and FAT10. Mol Cell. 2007 Sep 21;27(6):1014-23. PMID:17889673 doi:http://dx.doi.org/10.1016/j.molcel.2007.08.020
↑ Truongvan N, Li S, Misra M, Kuhn M, Schindelin H. Structures of UBA6 explain its dual specificity for ubiquitin and FAT10. Nat Commun. 2022 Aug 15;13(1):4789. doi: 10.1038/s41467-022-32040-6. PMID:35970836 doi:http://dx.doi.org/10.1038/s41467-022-32040-6

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7pyv"

Categories: Homo sapiens | Large Structures | Li S | Schindelin H | Truongvan N

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7pyv]] is a 3 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=7PYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PYV FirstGlance]. <br>
-</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=7pyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pyv OCA], [https://pdbe.org/7pyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pyv RCSB], [https://www.ebi.ac.uk/pdbsum/7pyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pyv ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.27&#8491;</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=7pyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pyv OCA], [https://pdbe.org/7pyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pyv RCSB], [https://www.ebi.ac.uk/pdbsum/7pyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pyv ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/UBA1_HUMAN UBA1_HUMAN]] X-linked distal arthrogryposis multiplex congenita. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/UBA1_HUMAN UBA1_HUMAN] X-linked distal arthrogryposis multiplex congenita. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[https://www.uniprot.org/uniprot/UBA1_HUMAN UBA1_HUMAN]] Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.<ref>PMID:22456334</ref> [[https://www.uniprot.org/uniprot/UBA6_HUMAN UBA6_HUMAN]] Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility.<ref>PMID:15202508</ref> <ref>PMID:17597759</ref> <ref>PMID:17889673</ref>
+[https://www.uniprot.org/uniprot/UBA1_HUMAN UBA1_HUMAN] Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.<ref>PMID:22456334</ref> [https://www.uniprot.org/uniprot/UBA6_HUMAN UBA6_HUMAN] Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility.<ref>PMID:15202508</ref> <ref>PMID:17597759</ref> <ref>PMID:17889673</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

7pyv

From Proteopedia

Current revision

Crystal structure of human UBA6 in complex with the ubiquitin-like modifier FAT10

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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