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Information on EC 2.3.2.26 - HECT-type E3 ubiquitin transferase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P19812
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EC Tree
2.3.2.26 HECT-type E3 ubiquitin transferaseIUBMB Comments
In the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the epsilon-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
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Word Map
- 2.3.2.26
- ligases
- proteasome
- smads
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polyubiquitination
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ubiquitin-proteasome
- adaptor
- tumorigenesis
- lysosomal
- osteoblast
- pten
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ubiquitin-dependent
- endosomal
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itch
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ubiquitin-mediated
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morphogenetic
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endocytosis
- factor-beta
- rhoa
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osteogenic
- rsp5
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deubiquitinating
- oncoproteins
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angelman
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cell-expressed
- tgf-beta
- papillomavirus
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e6-associated
- runx2
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tensin
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deubiquitinase
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e3-ubiquitin
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escrt
- ebola
- ehrlichiae
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liddle
-
4-like
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ubiquitin-binding
- chaffeensis
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monoubiquitination
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virus-like
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proteasome-mediated
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amiloride-sensitive
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k63-linked
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ubiquitin-conjugating
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autoubiquitination
- analysis
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ubiquitin-activating
- synthesis
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ubiquitin-ligase
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ubiquitination-mediated
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smad1/5
- medicine
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receptor-regulated
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
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=
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine
+
[acceptor protein]-L-lysine
=
[E2 ubiquitin-conjugating enzyme]-L-cysteine
+
[acceptor protein]-N6-ubiquitinyl-L-lysine
Synonyms
nedd4, smurf1, smurf2, huwe1, nedd4l, nedd4-1, e6-ap, ube3c, trp120, trip12, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
RSP5
PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming)
In the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the epsilon-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [Spo12]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Spo12]-N6-ubiquitinyl-L-lysine
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[Rsp-ubiquitin-conjugating enzyme UbcH5B]-S-ubiquitin-L-cysteine + [Sna3 cytoplasmic domain]-L-lysine
[Rsp5-ubiquitin-conjugating enzyme UbcH5B]-L-cysteine + [Sna3 cytoplasmic domain]-N6-ubiquitinyl-L-lysine
a specific HECT domain architecture may be important for ubiquitin ligation to Sna3 cytoplasmic domain, which involves both the catalytic C-lobe and the distal N-lobe packing differently from the arrangement promoting ubiquitin transfer from E2 enzyme to E3-ubiquitin intermediate
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additional information
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the type-1/2 substrate-binding sites of isoform UBR1, are located in the first 700 residues of the 1950-residue enzyme. Type-1 site is specific for basic N-terminal residues Arg, Lys, and His. The type-2 site is specific for bulky hydrophobic N-terminal residues Trp, Phe, Tyr, Leu, and Ile. Isoform UBR1 binds, with a Kd of about 1microM to either type-1 or type-2 N-terminal residues of reporter peptides but does not bind to a stabilizing N-terminal residue such as Gly
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additional information
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UBR1 and CUP9, a transcriptional repressor of peptide import, interact nonspecifically and specific binding which involves, in particular, the binding by cognate dipeptides to theUBR1 type-1/2 substrate-binding sites, can be restored either by a chaperone such as EF1A or through macromolecular crowding
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additional information
?
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isoform Rsp5 is loaded with ubiquitin by E2 enzyme UbcH5. A region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with RSP5
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additional information
?
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isoform Rsp5 is loaded with ubiquitin by E2 enzyme UbcH5. A region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with RSP5
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additional information
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ubiquitin ligases HECT E3 use a two-step mechanism to ligate ubiquitin to target proteins. The second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. There exist three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3-ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize targets lysines for ubiquitination
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
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deletion of isoform Rsp5 or mutation of its ligase activity, blocks the nuclear export of mRNAs. Affected messenger RNAs include both total poly(A)+ mRNA and heat-shock mRNAs. Mutation of Rsp5 does not affect nuclear protein import or export. Deletion of RSP5 blocks mRNA export, even under conditions where its essential role in unsaturated fatty acids biosynthesis is bypassed. The ligase activity is required for proper mRNA export
physiological function
in a temperature-sensitive mutant strain of isoform Rsp5, ubiquitin is limiting. Reduced synthesis of ubiquitin appears to contribute to ubiquitin depletion. In a wildtype strain upon heat-shock, transient inhibition of general protein synthesis is observed. Wildtype cells quickly recover from this transient arrest, the Rsp5 mutant cells remain arrested
physiological function
ubiquitin ligase Tom1 contributes to the turnover of Spo12, a component of the Cdc14 early anaphase release network, in G2/M phase. Tom1 and Spo12 interact. Overexpression of Spo12 is cytotoxic in the absence of Tom1. In S phase, Spo12 is degraded even in the absence of Tom1 and Cdh1
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of a trapped complex of ubiquitin ligase Rsp5 with ubiquitin and substrate Sna3 cytoplasmic domain as a proxy for the catalytic intermediate. The covalent linkage between ubiquitin and the HECT domain is oriented by ubiquitin interactions with the HECT domain N- and C-lobes that stabilize HECT domain conformation. The HECT domain architecture of the ligase primed for ligation prioritizes potential target lysines by their placement relative to a composite catalytic center for ubiquitination
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nuber, U.; Scheffner, M.
Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction
J. Biol. Chem.
274
7576-7582
1999
Saccharomyces cerevisiae (P39940), Saccharomyces cerevisiae, Homo sapiens (Q05086), Homo sapiens, Saccharomyces cerevisiae ATCC 204508 (P39940)
Xia, Z.; Webster, A.; Du, F.; Piatkov, K.; Ghislain, M.; Varshavsky, A.
Substrate-binding sites of UBR1, the ubiquitin ligase of the N-end rule pathway
J. Biol. Chem.
283
24011-24028
2008
Saccharomyces cerevisiae (P19812), Saccharomyces cerevisiae ATCC 204508 (P19812)
Kamadurai, H.B.; Qiu, Y.; Deng, A.; Harrison, J.S.; Macdonald, C.; Actis, M.; Rodrigues, P.; Miller, D.J.; Souphron, J.; Lewis, S.M.; Kurinov, I.; Fujii, N.; Hammel, M.; Piper, R.; Kuhlman, B.; Schulman, B.A.
Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3
eLife
2
e00828
2013
Saccharomyces cerevisiae (P39940), Saccharomyces cerevisiae ATCC 204508 (P39940)
Krsmanovic, T.; Koelling, R.
The HECT E3 ubiquitin ligase Rsp5 is important for ubiquitin homeostasis in yeast
FEBS Lett.
577
215-219
2004
Saccharomyces cerevisiae (P39940), Saccharomyces cerevisiae
Rodriguez, M.S.; Gwizdek, C.; Haguenauer-Tsapis, R.; Dargemont, C.
The HECT ubiquitin ligase Rsp5p is required for proper nuclear export of mRNA in Saccharomyces cerevisiae
Traffic
4
566-575
2003
Saccharomyces cerevisiae
EXTERNAL LINKS (specific for EC-Number 2.3.2.26)
Transporter Classification Database (TCDB): 8.A.30.1.5, 8.A.30.1.2, 3.A.31.1.1, 8.A.30.1.4, 8.A.30.1.1, 3.A.25.1.1
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