Ubc9 is the sole SUMO (Smt3) conjugating enzyme (E2) of Saccharomyces cerevisiae. It is an essential 157-residue UBC-fold protein. Ubc9 accepts Smt3 from the Aos1-Uba2 (Sua1-Uba2) E1 onto its active-site Cys93 as a thioester, and transfers it to lysines on target proteins, either directly or helped by SP-RING E3s such as Siz1/Siz2. Characterised substrates include the septins and PCNA. Ubc9 is mainly nuclear and associates with chromosomes, including meiotic chromosomes, where sumoylation promotes synaptonemal complex formation. A small fraction of Ubc9 is itself sumoylated at Lys153. This form loses classical E2 activity and instead acts as a cofactor for SUMO chain assembly through non-covalent backside SUMO binding. Loss of Ubc9 arrests the cell cycle at G2/M, a consequence of the loss of essential sumoylation. Sumoylation by Ubc9 and Smt3 is needed for efficient APC/C-mediated degradation of securin Pds1 and the mitotic cyclins, which explains the original observation that S- and M-phase cyclins are stabilized when Ubc9 is lost.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000022 mitotic spindle elongation | IMP PMID:7800043 Role of a ubiquitin-conjugating enzyme in degradation of S- ... | MARK AS OVER ANNOTATED | Summary: Depleting UBC9 arrests cells at G2/early M with a short spindle. The annotation reads this arrest phenotype as participation in mitotic spindle elongation. Reason: In the 1995 study the short spindle is one feature of a terminal G2/M arrest after UBC9 repression. At the time UBC9 was thought to be a ubiquitin E2 for cyclin degradation. Ubc9 was later shown to be the SUMO E2, with no detectable ubiquitin thioester (PMID:9341106). The spindle defect is a pleiotropic consequence of losing essential sumoylation and cell-cycle progression. It does not show that Ubc9 does any of the work of spindle elongation. The phenotype is real, so the annotation is not wrong, but it over-reaches as a process claim. Supporting Evidence: PMID:7800043 Repression of UBC9 synthesis prevents cell cycle progression at the G2 or early M phase, causing the accumulation of large budded cells with a single nucleus, a short spindle and replicated DNA PMID:9341106 While we were unable to detect formation of a Ub approximately Ubc9p thioester |
| GO:0000794 condensed nuclear chromosome | IDA PMID:16782016 A Role for SUMO in meiotic chromosome synapsis. | KEEP AS NON CORE | Summary: Immunolocalisation in meiotic prophase shows Ubc9 on meiotic chromosomes, coinciding with SUMO in synapsed regions. Reason: The meiotic IDA directly supports chromosome localisation of Ubc9 in meiosis, and the term is as precise as the abstract allows. The paper does not resolve Ubc9 to the synaptonemal complex itself. This is a stage-specific location, not the core site of action. Supporting Evidence: PMID:16782016 The Ubc9 protein localizes to meiotic chromosomes, coincident with SUMO staining |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | REMOVE | Summary: High-throughput interaction study (two-hybrid or complex purification) reporting Ubc9 binding to Smt3 (Q12306). Reason: Bare protein binding carries no functional information. The Ubc9-Smt3 interaction is genuine, but its functional content is captured by SUMO conjugating enzyme activity (the E2 thioester relay; PMID:9341106, PMID:9435231) and by the NEW non-covalent SUMO binding row (PMID:23644018). These large-scale datasets cannot say which of these interactions they detected, so they do not support a more specific MF. Removing the row does not mean the interaction is false. Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway |
| GO:0005515 protein binding | IPI PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast pro... | REMOVE | Summary: High-throughput interaction study (two-hybrid or complex purification) reporting Ubc9 binding to Smt3 (Q12306). Reason: Bare protein binding carries no functional information. The Ubc9-Smt3 interaction is genuine, but its functional content is captured by SUMO conjugating enzyme activity (the E2 thioester relay; PMID:9341106, PMID:9435231) and by the NEW non-covalent SUMO binding row (PMID:23644018). These large-scale datasets cannot say which of these interactions they detected, so they do not support a more specific MF. Removing the row does not mean the interaction is false. Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | REMOVE | Summary: High-throughput interaction study (two-hybrid or complex purification) reporting Ubc9 binding to Smt3 (Q12306). Reason: Bare protein binding carries no functional information. The Ubc9-Smt3 interaction is genuine, but its functional content is captured by SUMO conjugating enzyme activity (the E2 thioester relay; PMID:9341106, PMID:9435231) and by the NEW non-covalent SUMO binding row (PMID:23644018). These large-scale datasets cannot say which of these interactions they detected, so they do not support a more specific MF. Removing the row does not mean the interaction is false. Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: High-throughput interaction study (two-hybrid or complex purification) reporting Ubc9 binding to Smt3 (Q12306). Reason: Bare protein binding carries no functional information. The Ubc9-Smt3 interaction is genuine, but its functional content is captured by SUMO conjugating enzyme activity (the E2 thioester relay; PMID:9341106, PMID:9435231) and by the NEW non-covalent SUMO binding row (PMID:23644018). These large-scale datasets cannot say which of these interactions they detected, so they do not support a more specific MF. Removing the row does not mean the interaction is false. Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT IBD on the Ubc9 node PTN000629675 places the eukaryotic Ubc9 clade in the nucleus. This gene is one of the seeds. Reason: P50623 is a descendant of PTN000629675 (PTHR24067:SF248) and keeps the catalytic Cys93. Its own nuclear localisation is experimentally supported (PMID:7800043; UniProt nucleus from the global GFP survey PMID:14562095). Its appearance among the WITH/FROM seeds is the expected experimental grounding, not circularity. Supporting Evidence: file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md S. cerevisiae Ubc9 P50623 is placed in PANTHER subfamily PTHR24067:SF248, together with S. pombe hus5 P40984 and Neurospora NCU04302 Q1K772; human UBE2I P63279 is in PTHR24067:SF280. file:yeast/UBC9/UBC9-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095} |
| GO:0005634 nucleus | IDA PMID:7800043 Role of a ubiquitin-conjugating enzyme in degradation of S- ... | ACCEPT | Summary: The original UBC9 characterisation describes it as an essential nuclear enzyme. Reason: Nuclear localisation agrees with the nuclear substrates of Ubc9 (PCNA, chromosomal proteins) and with the global GFP localisation recorded in UniProt. Supporting Evidence: PMID:7800043 B-type-cyclin degradation in yeast involves an essential nuclear ubiquitin-conjugating enzyme, UBC9 file:yeast/UBC9/UBC9-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095} |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic nucleus annotation from the UniProt subcellular location (combined IEA). Reason: This agrees with the experimental IDA and the IBA. The UniProt subcellular location is curated from the GFP localisation survey. Supporting Evidence: file:yeast/UBC9/UBC9-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095} |
| GO:0005694 chromosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA-derived electronic annotation to chromosome. Reason: This is supported independently of ARBA. Ubc9 localises to meiotic chromosomes (PMID:16782016) and sumoylates the chromatin-bound sliding clamp PCNA in mitotic cells (PMID:12226657). The broad term is appropriate because chromosome association is not limited to the condensed meiotic state. Chromosome is a site of action rather than the core function. Supporting Evidence: PMID:16782016 The Ubc9 protein localizes to meiotic chromosomes, coincident with SUMO staining PMID:12226657 is conjugated to SUMO by UBC9 |
| GO:0016925 protein sumoylation | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBD of protein sumoylation at the eukaryotic Ubc9 node PTN000629675, seeded in part by this gene's own experimental annotations. Reason: This is the core process. P50623 lies within the Ubc9 clade (PTHR24067:SF248, under PTN000629675) and has direct yeast evidence that it is the sole Smt3 E2. Supporting Evidence: file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md S. cerevisiae Ubc9 P50623 is placed in PANTHER subfamily PTHR24067:SF248, together with S. pombe hus5 P40984 and Neurospora NCU04302 Q1K772; human UBE2I P63279 is in PTHR24067:SF280. PMID:9341106 Ubc9p is required for attachment of Smt3p to other proteins in vitro, suggesting that it is the only such enzyme in S. cerevisiae |
| GO:0016925 protein sumoylation | IDA PMID:9341106 Ubc9p is the conjugating enzyme for the ubiquitin-like prote... | ACCEPT | Summary: Smt3 affinity chromatography identified Ubc9p as the Smt3 E2. Ubc9p forms a Smt3 thioester and is required for Smt3 conjugation in vitro. Reason: Ubc9 catalyses the E2 step of Smt3 conjugation, so it does the work of protein sumoylation. This is the core process, with direct biochemical evidence in S. cerevisiae. Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway PMID:9341106 Ubc9p is required for attachment of Smt3p to other proteins in vitro, suggesting that it is the only such enzyme in S. cerevisiae |
| GO:0016925 protein sumoylation | IDA PMID:9435231 The ubiquitin-like proteins SMT3 and SUMO-1 are conjugated b... | ACCEPT | Summary: UBC9 is required for SMT3 conjugation in vivo, and recombinant yeast UBC9 forms SMT3 thioesters. Reason: Direct in vivo and in vitro evidence in S. cerevisiae establishes Ubc9 as the catalytic E2 of the sumoylation pathway. Later substrate studies (septins with Siz1, PCNA) confirm it. Supporting Evidence: PMID:9435231 UBC9, one of the 13 different E2 enzymes from yeast, is required for SMT3 conjugation in vivo PMID:9435231 recombinant yeast and mammalian UBC9 enzymes were found to form thioester complexes with SMT3 and SUMO-1, respectively PMID:12226657 is conjugated to SUMO by UBC9 PMID:11577116 Ull1 is additionally required as well as E1 (Sua1.Uba2 complex), E2 (Ubc9), and ATP |
| GO:0016925 protein sumoylation | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic annotation (UniPathway UPA00886 / ARBA) to protein sumoylation. Reason: This agrees with the experimental yeast evidence that Ubc9 is required for Smt3 conjugation in vivo and in vitro. Supporting Evidence: PMID:9435231 UBC9, one of the 13 different E2 enzymes from yeast, is required for SMT3 conjugation in vivo |
| GO:0016925 protein sumoylation | IMP PMID:9341106 Ubc9p is the conjugating enzyme for the ubiquitin-like prote... | ACCEPT | Summary: Smt3 affinity chromatography identified Ubc9p as the Smt3 E2. Ubc9p forms a Smt3 thioester and is required for Smt3 conjugation in vitro. Reason: Ubc9 catalyses the E2 step of Smt3 conjugation, so it does the work of protein sumoylation. This is the core process, with direct biochemical evidence in S. cerevisiae. Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway PMID:9341106 Ubc9p is required for attachment of Smt3p to other proteins in vitro, suggesting that it is the only such enzyme in S. cerevisiae |
| GO:0016925 protein sumoylation | IMP PMID:9435231 The ubiquitin-like proteins SMT3 and SUMO-1 are conjugated b... | ACCEPT | Summary: UBC9 is required for SMT3 conjugation in vivo, and recombinant yeast UBC9 forms SMT3 thioesters. Reason: Direct in vivo and in vitro evidence in S. cerevisiae establishes Ubc9 as the catalytic E2 of the sumoylation pathway. Later substrate studies (septins with Siz1, PCNA) confirm it. Supporting Evidence: PMID:9435231 UBC9, one of the 13 different E2 enzymes from yeast, is required for SMT3 conjugation in vivo PMID:9435231 recombinant yeast and mammalian UBC9 enzymes were found to form thioester complexes with SMT3 and SUMO-1, respectively PMID:12226657 is conjugated to SUMO by UBC9 PMID:11577116 Ull1 is additionally required as well as E1 (Sua1.Uba2 complex), E2 (Ubc9), and ATP |
| GO:0019789 SUMO transferase activity | IDA PMID:9341106 Ubc9p is the conjugating enzyme for the ubiquitin-like prote... | MODIFY | Summary: Yeast Ubc9 forms a thioester with Smt3 and is required for Smt3 conjugation, the hallmark of a SUMO E2. Reason: The activity is correct but more general than the evidence supports. The yeast data show the E2 thioester relay: Ubc9 accepts Smt3 from the E1 on Cys93 as a thioester and passes it to substrate lysines. This is GO:0061656 SUMO conjugating enzyme activity, an is_a child of GO:0019789 (OLS hierarchy) that the gene already carries by IBA. The replacement is that existing, more specific term. Yeast Ubc9 also has E3-independent transfer to substrates in vitro, which is still the E2 activity. Proposed replacements: SUMO conjugating enzyme activity Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway PMID:9435231 recombinant yeast and mammalian UBC9 enzymes were found to form thioester complexes with SMT3 and SUMO-1, respectively file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md The yeast catalytic cysteine Cys93 (UniProt ACT_SITE, glycyl thioester intermediate) aligns to a cysteine in all three other proteins. |
| GO:0019789 SUMO transferase activity | IDA PMID:9435231 The ubiquitin-like proteins SMT3 and SUMO-1 are conjugated b... | MODIFY | Summary: Yeast Ubc9 forms a thioester with Smt3 and is required for Smt3 conjugation, the hallmark of a SUMO E2. Reason: The activity is correct but more general than the evidence supports. The yeast data show the E2 thioester relay: Ubc9 accepts Smt3 from the E1 on Cys93 as a thioester and passes it to substrate lysines. This is GO:0061656 SUMO conjugating enzyme activity, an is_a child of GO:0019789 (OLS hierarchy) that the gene already carries by IBA. The replacement is that existing, more specific term. Yeast Ubc9 also has E3-independent transfer to substrates in vitro, which is still the E2 activity. Proposed replacements: SUMO conjugating enzyme activity Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway PMID:9435231 recombinant yeast and mammalian UBC9 enzymes were found to form thioester complexes with SMT3 and SUMO-1, respectively file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md The yeast catalytic cysteine Cys93 (UniProt ACT_SITE, glycyl thioester intermediate) aligns to a cysteine in all three other proteins. |
| GO:0019789 SUMO transferase activity | IEA GO_REF:0000117 | MODIFY | Summary: Electronic (ARBA) annotation to the generic SUMO transferase activity. Reason: The activity is correct but more general than the evidence supports. The yeast data show the E2 thioester relay: Ubc9 accepts Smt3 from the E1 on Cys93 as a thioester and passes it to substrate lysines. This is GO:0061656 SUMO conjugating enzyme activity, an is_a child of GO:0019789 (OLS hierarchy) that the gene already carries by IBA. The replacement is that existing, more specific term. Yeast Ubc9 also has E3-independent transfer to substrates in vitro, which is still the E2 activity. Proposed replacements: SUMO conjugating enzyme activity Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md The yeast catalytic cysteine Cys93 (UniProt ACT_SITE, glycyl thioester intermediate) aligns to a cysteine in all three other proteins. |
| GO:0019789 SUMO transferase activity | IMP PMID:9435231 The ubiquitin-like proteins SMT3 and SUMO-1 are conjugated b... | MODIFY | Summary: Yeast Ubc9 forms a thioester with Smt3 and is required for Smt3 conjugation, the hallmark of a SUMO E2. Reason: The activity is correct but more general than the evidence supports. The yeast data show the E2 thioester relay: Ubc9 accepts Smt3 from the E1 on Cys93 as a thioester and passes it to substrate lysines. This is GO:0061656 SUMO conjugating enzyme activity, an is_a child of GO:0019789 (OLS hierarchy) that the gene already carries by IBA. The replacement is that existing, more specific term. Yeast Ubc9 also has E3-independent transfer to substrates in vitro, which is still the E2 activity. Proposed replacements: SUMO conjugating enzyme activity Supporting Evidence: PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway PMID:9435231 recombinant yeast and mammalian UBC9 enzymes were found to form thioester complexes with SMT3 and SUMO-1, respectively file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md The yeast catalytic cysteine Cys93 (UniProt ACT_SITE, glycyl thioester intermediate) aligns to a cysteine in all three other proteins. |
| GO:0061656 SUMO conjugating enzyme activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBD of SUMO conjugating enzyme activity at the eukaryotic Ubc9 node PTN000629675. Reason: This is the core activity. P50623 belongs to SF248 under PTN000629675 and keeps the catalytic Cys93, and the activity is experimentally demonstrated in yeast itself (Smt3 thioester formation and Smt3 conjugation). SGD is not among the seeds for this node term because SGD curated the parent term SUMO transferase activity. The yeast experiments nonetheless establish this specific E2 activity directly. Supporting Evidence: file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md S. cerevisiae Ubc9 P50623 is placed in PANTHER subfamily PTHR24067:SF248, together with S. pombe hus5 P40984 and Neurospora NCU04302 Q1K772; human UBE2I P63279 is in PTHR24067:SF280. file:yeast/UBC9/UBC9-bioinformatics/RESULTS.md The yeast catalytic cysteine Cys93 (UniProt ACT_SITE, glycyl thioester intermediate) aligns to a cysteine in all three other proteins. PMID:9341106 Ubc9p was found to form a thioester with Smt3p, indicating that Ubc9p is the functional analog of E2s in the Smt3p pathway PMID:9435231 recombinant yeast and mammalian UBC9 enzymes were found to form thioester complexes with SMT3 and SUMO-1, respectively |
| GO:0032183 SUMO binding | IDA PMID:23644018 Ubc9 sumoylation controls SUMO chain formation and meiotic s... | NEW | Summary: Sumoylated yeast Ubc9 (Ubc9*SUMO, Lys153) cooperates with charged Ubc9~SUMO through non-covalent backside SUMO binding to promote SUMO chain assembly. Reason: This is a non-covalent SUMO-binding activity distinct from the covalent thioester. It is demonstrated biochemically for the yeast protein and underlies the regulatory, non-catalytic role of Ubc9*SUMO in chain formation and meiotic synapsis. It is non-core relative to the E2 activity. It also gives a functional reading of the many reported Ubc9-Smt3 interactions. Supporting Evidence: PMID:23644018 Ubc9(*)SUMO cooperates with charged Ubc9 (Ubc9~SUMO) by noncovalent backside SUMO binding and by positioning the donor SUMO for optimal transfer |
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Download this section (compressed HTML)Q: Do the Ubc9 subfamilies SF248 (fungal) and SF280 (vertebrate) differ in any functional property, such as E3-independent substrate selection or backside-binding regulation, or does the PANTHER split only reflect taxonomy?
Q: Should GO represent the non-catalytic cofactor role of sumoylated Ubc9 in SUMO chain assembly separately from SUMO binding?
Experiment: Complement a yeast ubc9 shuffle strain with Neurospora NCU04302 and S. pombe hus5, including the K153-equivalent mutants, to test whether the E2 and chain-assembly cofactor functions are conserved across SF248.
Type: genetic complementation
SUMO-conjugating enzyme involved in the Smt3p conjugation pathway; nuclear protein required for S- and M-phase cyclin degradation and mitotic control; involved in proteolysis mediated by the anaphase-promoting complex cyclosome (APCC); auto-sumoylates on K153 and K157
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