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2hlw

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Revision as of 18:30, 25 December 2014

Solution Structure of the Human Ubiquitin-conjugating Enzyme Variant Uev1a

Structural highlights

2hlw is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2a4d, 2c2v
Gene:	UEV1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[UB2V1_HUMAN] Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Lys(63)-linked polyubiquitination of TRAF2 or TRAF6 is an essential step within the signal transduction cascade responsible for activation of p38, c-Jun N-terminal kinase, and the transcription factor NF-kappaB. Attachment of ubiquitin (Ub) to a TRAF, and conjugation of Ub molecules to form a polyUb chain, is catalyzed by a heterodimer composed of a catalytically active E2 (hUbc13), involved in covalent bond transfer, and hUev1a, an E2-like protein involved in substrate Ub binding. Given the key biochemical processes in which hUev1a is involved, it is important to determine the molecular basis of the catalytic mechanism for Lys(63)-linked protein ubiquitination. Nuclear magnetic resonance (NMR) spectroscopy was used to determine the structure of hUev1a and its interactions with Ub and hUbc13. A structural model for the Ub-hUev1a-hUbc13-Ub tetramer was developed to gain chemical insight into the synthesis of Lys(63)-linked Ub chains. We propose that a network of hydrogen bonds involving hUbc13-Asp(81) and Ub-Glu(64) positions Ub-Lys(63) proximal to the active site. Interestingly, restrained molecular dynamics simulations in implicit solvent indicate that deprotonation of Ub-Lys(63) does not involve a general Asp or Glu base and may occur when the amino group approaches the thioester carbonyl carbon near the Burgi-Dunitz trajectory.

Structure and interactions of the ubiquitin-conjugating enzyme variant human Uev1a: implications for enzymatic synthesis of polyubiquitin chains.,Hau DD, Lewis MJ, Saltibus LF, Pastushok L, Xiao W, Spyracopoulos L Biochemistry. 2006 Aug 15;45(32):9866-77. PMID:16893187^[8]

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

References

↑ Rothofsky ML, Lin SL. CROC-1 encodes a protein which mediates transcriptional activation of the human FOS promoter. Gene. 1997 Aug 22;195(2):141-9. PMID:9305758
↑ Sancho E, Vila MR, Sanchez-Pulido L, Lozano JJ, Paciucci R, Nadal M, Fox M, Harvey C, Bercovich B, Loukili N, Ciechanover A, Lin SL, Sanz F, Estivill X, Valencia A, Thomson TM. Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. Mol Cell Biol. 1998 Jan;18(1):576-89. PMID:9418904
↑ Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000 Oct 13;103(2):351-61. PMID:11057907
↑ Thomson TM, Khalid H, Lozano JJ, Sancho E, Arino J. Role of UEV-1A, a homologue of the tumor suppressor protein TSG101, in protection from DNA damage. FEBS Lett. 1998 Feb 13;423(1):49-52. PMID:9580084
↑ Xiao W, Lin SL, Broomfield S, Chow BL, Wei YF. The products of the yeast MMS2 and two human homologs (hMMS2 and CROC-1) define a structurally and functionally conserved Ubc-like protein family. Nucleic Acids Res. 1998 Sep 1;26(17):3908-14. PMID:9705497
↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
↑ Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grutter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21;472(7343):361-5. doi: 10.1038/nature09976. PMID:21512573 doi:10.1038/nature09976
↑ Hau DD, Lewis MJ, Saltibus LF, Pastushok L, Xiao W, Spyracopoulos L. Structure and interactions of the ubiquitin-conjugating enzyme variant human Uev1a: implications for enzymatic synthesis of polyubiquitin chains. Biochemistry. 2006 Aug 15;45(32):9866-77. PMID:16893187 doi:10.1021/bi060631r

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hlw"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2hlw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HLW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HLW FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a4d|2a4d]], [[2c2v|2c2v]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a4d|2a4d]], [[2c2v|2c2v]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UEV1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UEV1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hlw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hlw RCSB], [http://www.ebi.ac.uk/pdbsum/2hlw PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hlw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hlw RCSB], [http://www.ebi.ac.uk/pdbsum/2hlw PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/UB2V1_HUMAN UB2V1_HUMAN]] Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes.<ref>PMID:9305758</ref> <ref>PMID:9418904</ref> <ref>PMID:11057907</ref> <ref>PMID:9580084</ref> <ref>PMID:9705497</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Hau, D D.]]
+[[Category: Hau, D D]]
-[[Category: Lewis, M J.]]
+[[Category: Lewis, M J]]
-[[Category: Pastushok, L.]]
+[[Category: Pastushok, L]]
-[[Category: Saltibus, L F.]]
+[[Category: Saltibus, L F]]
-[[Category: Spyracopoulos, L.]]
+[[Category: Spyracopoulos, L]]
-[[Category: Xiao, W.]]
+[[Category: Xiao, W]]
 [[Category: E2]]
 [[Category: Hubc13]]

2hlw

From Proteopedia

Revision as of 18:30, 25 December 2014

Solution Structure of the Human Ubiquitin-conjugating Enzyme Variant Uev1a

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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