Affinage

UBE2V2

Ubiquitin-conjugating enzyme E2 variant 2 · UniProt Q15819

Length
145 aa
Mass
16.4 kDa
Annotated
2026-06-10
37 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2V2 (Mms2) is a catalytically inactive ubiquitin-conjugating enzyme variant (UEV) that functions as the specificity-determining partner of the E2 enzyme Ubc13/UBE2N in the assembly of Lys63-linked polyubiquitin chains used as non-proteolytic DNA repair signals (PMID:10089880, PMID:9576943). UBE2V2 forms an obligate, specific heterodimer with Ubc13: a single key Mms2 residue inserts into a complementary Ubc13 pocket to enforce pairing exclusivity, and disrupting this interface abolishes heterodimer formation, ubiquitin conjugation, and DNA repair function (PMID:15749714, PMID:11440714). Within the complex UBE2V2 binds an acceptor ubiquitin non-covalently while Ubc13 carries the donor ubiquitin as a thioester, orienting acceptor Lys63 at the Ubc13 active site to dictate strict K63 linkage; this geometry was resolved through NMR and crystal structures of the heterodimer and its covalent UEV-E2-Ub intermediate, and the Mms2-Ile57/ubiquitin-Ile44 contact is a critical determinant of acceptor binding and chain synthesis (PMID:12569095, PMID:16980971, PMID:15772086, PMID:16518696). The Ubc13-Mms2 complex operates in the error-free branch of postreplication repair, where it acts with the E3 ligases SHPRH and Rad5 to catalyze K63-linked polyubiquitylation of PCNA, promoting template-switch DNA synthesis during replication stress (PMID:17108083, PMID:11884624, PMID:15507115), and at DNA double-strand breaks it pairs with the dimeric E3 RNF8 to generate K63 chains (PMID:22589545). UEV partner choice routes Ubc13 to distinct outcomes: Mms2/UBE2V2 supports DNA repair but not NF-κB activation, the reverse of its paralog Uev1A/UBE2V1 (PMID:16129784). A privileged sensor cysteine on UBE2V2 can be covalently modified by reactive electrophiles to allosterically hyperactivate Ubc13 and stimulate H2AX-dependent DNA damage signaling (PMID:29532025).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 High

    Established that MMS2 is a Ubc-like protein lacking E2 activity that acts specifically in the error-free postreplication repair branch, distinguishing it from mutagenic lesion bypass.

    Evidence Complementation cloning and genetic epistasis (hypostatic to rad6/rad18, synergistic with rev3) with UV mutagenesis assays in yeast

    PMID:9576943

    Open questions at the time
    • Did not define the molecular partner or biochemical activity of Mms2
    • No chain-linkage information
  2. 1999 High

    Identified that Mms2 acts through a heteromeric complex with Ubc13 to assemble K63-linked chains, linking the genetic repair phenotype to a specific biochemical activity.

    Evidence Reconstituted in vitro chain assembly with purified components plus yeast genetic epistasis (ubc13/mms2/ubiK63R) and UV sensitivity phenotyping

    PMID:10089880

    Open questions at the time
    • Structural basis of K63 specificity not yet known
    • E3 ligase partners and physiological substrates unidentified
  3. 1998 Medium

    Showed human MMS2 functionally conserves yeast Mms2 repair activity, extending the pathway to mammals.

    Evidence Cross-species functional complementation of yeast mms2 with DNA damage/mutagenesis assays and a c-fos–CAT reporter in Rat-1 cells

    PMID:9705497

    Open questions at the time
    • c-fos transactivation link is correlative and mechanistically undefined
    • Single lab
  4. 2001 High

    Resolved the heterodimer architecture and demonstrated the intact interface is required for repair, and that the human complex builds K63-specific diubiquitin by orienting acceptor ubiquitin.

    Evidence X-ray crystallography of Mms2/Ubc13 with interface mutagenesis and UV assays; in vitro chain assembly and NMR mapping of human Mms2/Ubc13/ubiquitin surfaces

    PMID:11440714 PMID:11504715

    Open questions at the time
    • Donor-ubiquitin positioning during catalysis not yet visualized
    • E3 partners still unidentified
  5. 2002 High

    Placed Rad5 together with Mms2-Ubc13 in the same error-free gap-filling pathway, connecting the complex to repair of replication discontinuities.

    Evidence Yeast genetics and alkaline sucrose gradient detection of DNA discontinuities in rad5Δ/mms2Δ strains

    PMID:11884624

    Open questions at the time
    • Direct biochemical demonstration of Rad5 as the E3 not shown here
    • PCNA as substrate not yet established in this study
  6. 2003 High

    Provided a complete structural model of how acceptor and donor ubiquitin are jointly positioned to enforce K63 linkage, defining the catalytic logic of the complex.

    Evidence NMR chemical-shift mapping and restraint-driven computational docking of the Ubc13·Mms2 complex with both ubiquitins

    PMID:12569095

    Open questions at the time
    • Model from docking restraints rather than a single crystallized ternary intermediate
    • Catalytic transition state not captured
  7. 2003 Medium

    Identified Chfr as an E3 that uses Ubc13-Mms2 to build non-degradative K63 chains, broadening the complex's role to mitotic stress signaling.

    Evidence In vitro ubiquitin ligase assay with chain-linkage characterization

    PMID:14562038

    Open questions at the time
    • Single method for linkage determination
    • Physiological mitotic substrate not defined
  8. 2004 Medium

    Connected Mms2-dependent PCNA polyubiquitination to template-switch DNA synthesis under replication stress.

    Evidence Yeast genetics with PCNA-K164R and mms2Δ/rad5Δ/rad18Δ epistasis in replication-defective backgrounds

    PMID:15507115

    Open questions at the time
    • No direct biochemical confirmation of the template-switch mechanism
    • Single lab
  9. 2005 High

    Defined the molecular determinants of acceptor-ubiquitin recognition and interface specificity, explaining both K63 fidelity and exclusive Ubc13 pairing.

    Evidence Site-directed mutagenesis (Mms2-Ile57/Ub-Ile44; the 'key' interface residue) with in vitro chain assembly, SPR/Y2H/pulldown binding, and yeast complementation

    PMID:15749714 PMID:15772086

    Open questions at the time
    • Single-lab mutagenesis studies
    • Quantitative kinetics of chain elongation not fully resolved
  10. 2005 High

    Established that UEV partner identity (Mms2 vs Uev1A) routes Ubc13 to distinct cellular pathways, separating DNA repair from NF-κB activation.

    Evidence In vitro chain-length assays plus siRNA knockdown with UV/DNA-repair and NF-κB reporter readouts

    PMID:16129784

    Open questions at the time
    • Mechanism by which partner choice alters chain length not defined
    • Mammalian E3 specificity for each pathway not detailed here
  11. 2006 High

    Captured the catalytic intermediate by crystallography and an NMR Mms2-ubiquitin structure, confirming how acceptor Lys63 is positioned at the active site during elongation.

    Evidence X-ray structure of covalent Mms2-Ubc13-ubiquitin intermediate; solution NMR structure of Mms2-ubiquitin

    PMID:16518696 PMID:16980971

    Open questions at the time
    • Acceptor positioning inferred from adjacent crystal complex
    • Dynamics of processive elongation not addressed
  12. 2006 High

    Identified SHPRH as the human E3 partner of Mms2-Ubc13 for K63-linked PCNA polyubiquitylation, completing the mammalian error-free PRR enzyme set.

    Evidence Co-IP, in vitro ubiquitylation reconstitution, and SHPRH siRNA knockdown with PCNA ubiquitylation readout

    PMID:17108083

    Open questions at the time
    • Relative contributions of SHPRH versus other E3s in cells not quantified
    • Downstream polymerase-switch step not directly reconstituted
  13. 2006 Medium

    Linked UBE2V2 to neuronal AT2 receptor signaling, where induced MMS2 promotes Id1 proteolysis, DNA repair, and neurite/synapse formation.

    Evidence siRNA knockdown of MMS2 with neurite/synapse phenotyping, Co-IP of the ATIP-SHP-1 complex, nuclear fractionation, and RT-PCR

    PMID:17068200

    Open questions at the time
    • Functional link between MMS2 and the neuronal phenotype is indirect
    • Single lab
  14. 2007 High

    Demonstrated cooperative two-residue ubiquitin binding by Mms2 is essential, where the double mutant abolishes chain formation and yeast function.

    Evidence Site-directed mutagenesis with in vitro chain assembly, binding assays, and yeast complementation

    PMID:17964296

    Open questions at the time
    • Single-lab study
    • Energetic basis of cooperativity not dissected
  15. 2007 Medium

    Distinguished Ubc13/Mms2-dependent ubiquitination as a separate functional subset from Ubc4-mediated turnover in Chfr-homolog cell-cycle control.

    Evidence Yeast genetics, in vitro ubiquitination reconstitution, tandem-MS linkage analysis, and site-directed mutagenesis

    PMID:18202552

    Open questions at the time
    • Single lab
    • Direct cell-cycle substrates of the K63 chains not identified
  16. 2011 Medium

    Extended the complex to vertebrate p53-mediated DNA damage signaling, showing Mms2 (not Uev1) restrains p53 effector expression.

    Evidence Zebrafish morpholino knockdown with RT-PCR of p21/mdm2, in vitro K63 chain assembly, and GST pulldown of Ubc13-p53

    PMID:22055568

    Open questions at the time
    • Mechanistic link between K63 chains and p53 effector regulation undefined
    • Single vertebrate model
  17. 2012 High

    Defined RNF8 as a dimeric E3 partner that engages Ubc13/Mms2 to build K63 chains at double-strand breaks, contrasting with monomeric RNF168.

    Evidence Crystal structure of the RNF8/Ubc13/Mms2 ternary complex with mutagenesis and in vitro ubiquitylation

    PMID:22589545

    Open questions at the time
    • Single lab
    • In-cell choreography of RNF8 versus other E3s not resolved structurally
  18. 2018 Medium

    Revealed a privileged sensor cysteine on Ube2V2 that, when electrophile-modified, allosterically hyperactivates Ubc13 and amplifies H2AX-dependent DNA damage signaling.

    Evidence G-REX in vivo cysteine profiling, mass spectrometry, in vitro K63 ubiquitination, and γH2AX DDR readout

    PMID:29532025

    Open questions at the time
    • Single lab
    • Physiological electrophile(s) and in vivo significance not established
  19. 2020 Medium

    Uncovered a non-repair role for Ubc13-Mms2 in K63-dependent membrane protein sorting via the MVB pathway with FYVE-RING E3 partners.

    Evidence Yeast deletion/epistasis genetics, fluorescence trafficking microscopy, and genetic E3-partner identification (Pib1)

    PMID:32265276

    Open questions at the time
    • No in vitro reconstitution of the trafficking pathway
    • Conservation in mammals untested here
  20. 2023 Medium

    Showed Mms2 abundance drives Ubc13-independent, Ubc4/Rsp5/Not4-dependent mutagenesis and modulates Polδ catalytic subunit levels, revealing dosage-dependent functions beyond the canonical complex.

    Evidence Yeast genetic epistasis with ubc13Δ/ubc4Δ/rsp5/not4/rev3Δ/rev1Δ/pcna-K164R, Western blotting for Pol3, and spontaneous mutagenesis assays

    PMID:36934633

    Open questions at the time
    • Ubc4-dependent pathway not reconstituted in vitro
    • Mechanism controlling Pol3 levels undefined
  21. 2025 Low

    Proposed a tumor-relevant role in which the UBE2V2 ortholog cooperates with APC/C to degrade Cyclin A and counteract oncogenic Ras-driven division stress.

    Evidence Drosophila genetic screen with Ras, knockdown/overexpression, and human colorectal xenografts in nude mice (preprint)

    Open questions at the time
    • Preprint; biochemical APC/C-Cyclin A degradation not reconstituted
    • Direct human UBE2V2 mechanism in this pathway not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UBE2V2's dosage-dependent, Ubc13-independent activities and its electrophile sensor cysteine are regulated and integrated with canonical K63 repair signaling in mammalian cells remains unresolved.
  • No mammalian reconstitution of the Ubc4/Rsp5-dependent or APC/C-linked activities
  • Physiological electrophile triggers of the sensor cysteine unknown
  • Quantitative partitioning of UBE2V2 among PRR, DSB, trafficking, and cell-cycle roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-69306 DNA Replication 2
Partners
CHFRRAD5RNF8SHPRHTP53UBE2N
Complex memberships
RNF8/Ubc13/Mms2 ternary complexUbc13-Mms2 (UBE2N-UBE2V2) heterodimer

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Mms2p (yeast ortholog of UBE2V2) forms a specific heteromeric complex with Ubc13p (E2) and is required for Ubc13p-dependent assembly of Lys63-linked polyubiquitin chains. A ubc13 strain is UV sensitive, and single, double, and triple mutants of UBC13, MMS2, and ubiquitin ubiK63R display comparable UV sensitivity, establishing the Mms2p/Ubc13p complex as essential for assembling K63-linked polyubiquitin chains used in DNA repair signaling. In vitro ubiquitin chain assembly assay with purified components; yeast genetics (epistasis with ubc13, mms2, ubiK63R mutants); UV sensitivity phenotyping Cell High 10089880
1998 MMS2 encodes a Ubc-like protein that lacks E2 (ubiquitin-conjugating) activity but functions specifically in the error-free postreplication repair (PRR) pathway in yeast. Genetic analysis showed mms2 is hypostatic to rad6 and rad18, synergistic with rev3, and proficient in UV mutagenesis, placing MMS2 in the error-free branch of the RAD6 pathway parallel to the REV3 mutagenesis pathway. Functional complementation cloning; genetic epistasis analysis (double/triple mutant UV sensitivity); UV-induced mutagenesis assays Proceedings of the National Academy of Sciences of the United States of America High 9576943
2001 Crystal structure of the Mms2/Ubc13 heterodimer reveals the Ubc13 active site at the intersection of two channels that are potential binding sites for two substrate ubiquitins. Mutations destabilizing the heterodimer interface confer marked UV sensitivity, demonstrating the intact heterodimer is necessary for DNA repair. X-ray crystallography; site-directed mutagenesis of heterodimer interface; yeast UV sensitivity assays Cell High 11440714
2001 Human Mms2 and Ubc13 form a stable heterodimer capable of transferring ubiquitin specifically to Lys63 of an untethered ubiquitin, producing diubiquitin. NMR mapping identified a surface of the acceptor ubiquitin that interacts with Mms2 in both monomeric and heterodimeric forms, with the C-terminal tail of ubiquitin not participating, supporting the model that Mms2 orients acceptor ubiquitin to position Lys63 proximal to the Ubc13 active site. In vitro ubiquitin chain assembly with purified human Mms2 and Ubc13; 1H-15N HSQC NMR mapping of ubiquitin-Mms2 and ubiquitin-Ubc13 interaction surfaces The Journal of biological chemistry High 11504715
2003 NMR-based structural model of the human Ubc13·Mms2 heterodimer bound to acceptor and donor ubiquitin reveals the molecular basis of K63-specific chain synthesis: Mms2 binds acceptor ubiquitin non-covalently while Ubc13 carries donor ubiquitin as a thioester, positioning Lys63 of acceptor ubiquitin at the Ubc13 active site. 2D 1H-15N NMR chemical shift mapping of subunit-subunit and subunit-ubiquitin interactions; unbiased computational docking using NMR-derived restraints The Journal of biological chemistry High 12569095
2005 Mms2-Ile57 and ubiquitin-Ile44 are critical molecular determinants of the Mms2–acceptor ubiquitin interaction. Mutating either side chain to alanine causes 10–20-fold inhibition of K63-linked chain synthesis in vitro by compromising acceptor ubiquitin binding to Mms2, and abolishes error-free lesion bypass in vivo in yeast. Site-directed mutagenesis; in vitro K63-linked chain assembly assay; yeast error-free bypass assay (DNA damage sensitivity) The Journal of biological chemistry High 15772086
2005 A single 'key' residue of Mms2 inserts into a complementary pocket of Ubc13 to determine interface specificity. Structure-based mutagenesis identified critical residues at the Ubc13–Mms2 interface; disrupting these contacts abrogates heterodimer formation, ubiquitin conjugation, and functional complementation of DNA repair, explaining why Mms2 forms a specific complex with Ubc13 but not other E2s. Structure-based mutagenesis; yeast two-hybrid; GST pulldown; surface plasmon resonance; functional complementation of yeast mms2 mutant; in vitro ubiquitin conjugation assay The Journal of biological chemistry High 15749714
2005 The two mammalian UEV proteins, Mms2 and Uev1A, differentially modulate the length of Ubc13-mediated K63-linked polyubiquitin chains. Ubc13–Mms2 is required for DNA damage repair but not NF-κB activation, whereas Ubc13–Uev1A is involved in NF-κB activation but not DNA repair, demonstrating that alternative UEV pairing directs Ubc13 to distinct cellular processes. Structural comparison; in vitro ubiquitin chain length assays; siRNA knockdown with functional assays (UV sensitivity/DNA repair; NF-κB reporter assays) The Journal of cell biology High 16129784
2006 Crystal structure of Mms2–Ubc13 covalently linked to donor ubiquitin (UEV-E2-Ub intermediate) reveals that an acceptor-ubiquitin binding site on Mms2 (from an adjacent complex in the crystal) positions Lys63 of acceptor ubiquitin at the Ubc13 active site, providing the structural basis for K63 linkage specificity in polyubiquitin chain elongation. X-ray crystallography of covalent Mms2–Ubc13–ubiquitin intermediate Nature structural & molecular biology High 16980971
2006 Human SHPRH physically interacts with the Mms2–Ubc13 complex and acts as the E3 ubiquitin ligase indispensable for Mms2–Ubc13-dependent K63-linked polyubiquitylation of PCNA, placing SHPRH as the E3 partner of Mms2–Ubc13 in human error-free PRR. Co-immunoprecipitation; in vitro ubiquitylation assay with purified components; siRNA knockdown of SHPRH with PCNA ubiquitylation readout Proceedings of the National Academy of Sciences of the United States of America High 17108083
2006 NMR solution structure of human Mms2 bound to ubiquitin reveals the molecular basis for the non-covalent Mms2–ubiquitin interaction that positions acceptor ubiquitin for K63-linked chain synthesis. Solution-state NMR spectroscopy (structure determination of Mms2–ubiquitin complex) Journal of biomolecular NMR High 16518696
2006 AT2 receptor signaling in neurons induces MMS2 (UBE2V2) expression via the ATIP–SHP-1 cascade. ATIP and SHP-1 translocate to the nucleus after forming a complex upon AT2 receptor stimulation; increased MMS2 expression mediates inhibitor of DNA binding 1 (Id1) proteolysis and promotes DNA repair, and siRNA knockdown of MMS2 abolishes neurite outgrowth and synapse formation. siRNA knockdown of MMS2; overexpression and dominant-negative SHP-1; co-immunoprecipitation of ATIP–SHP-1 complex; nuclear fractionation; RT-PCR of MMS2 expression; neurite outgrowth assay; synapse formation assay Molecular endocrinology Medium 17068200
2003 Chfr ubiquitin ligase catalyzes formation of non-canonical K63-linked polyubiquitin chains using Ubc13–Mms2 as the ubiquitin-conjugating enzyme, rather than targeting proteins for proteasomal degradation; this activity is proposed to signal mitotic stress. In vitro ubiquitin ligase assay; ubiquitin chain linkage characterization Oncogene Medium 14562038
2007 Two residues of human Mms2 cooperatively interact with ubiquitin to promote Ubc13-mediated K63-linked polyubiquitin chain formation: each single mutation reduces binding affinity, but the double mutation severely reduces ubiquitin binding and abolishes polyubiquitin chain formation in vitro and in vivo (yeast double mutant shows complete loss of MMS2 function). Site-directed mutagenesis; in vitro polyubiquitin chain assembly assay; binding assays; yeast functional complementation FEBS letters High 17964296
2012 RNF8 dimerizes and binds to Ubc13/Mms2, stimulating K63-linked ubiquitin chain formation at DNA double-strand breaks; the crystal structure of the RNF8/Ubc13/Mms2 ternary complex reveals that an RNF8 coiled-coil mediates dimerization and that disrupting RNF8/Ubc13 binding surfaces or truncating the coiled-coil reduces ubiquitylation. In contrast, RNF168 RING domain is monomeric and does not catalyze K63 polyubiquitylation with Ubc13/Mms2. X-ray crystallography of RNF8/Ubc13/Mms2 ternary complex; site-directed mutagenesis; in vitro ubiquitylation assays The Journal of biological chemistry High 22589545
2018 Ube2V2 contains a functionally privileged sensor cysteine that can be modified by reactive electrophiles in a non-enzyme-catalyzed manner. This modification allosterically hyperactivates Ube2V2's binding partner Ube2N (Ubc13), promoting K63-linked client ubiquitination and stimulating H2AX-dependent DNA damage response. G-REX electrophile-release technology for in vivo cysteine identification; mass spectrometry; in vitro K63-linked ubiquitination assays; γH2AX DNA damage response readout ACS central science Medium 29532025
2002 Rad5 protein and the Mms2–Ubc13 ubiquitin-conjugating enzyme complex are both required for postreplication repair of UV-damaged DNA in yeast: discontinuities in newly synthesized DNA strands from UV-damaged templates are not repaired in rad5Δ or mms2Δ mutants, indicating these components act in the same pathway for error-free gap filling. Yeast genetic analysis; alkaline sucrose gradient sedimentation to detect DNA discontinuities in rad5Δ and mms2Δ strains Molecular and cellular biology High 11884624
2004 The Rad18/Rad5/Mms2 polyubiquitination pathway is important for replication completion in yeast: PCNA-K164R (blocking ubiquitination) and mms2Δ/rad5Δ mutations impair replication in rfc5-1 mutants, indicating Mms2-dependent PCNA polyubiquitination promotes a template-switch type of DNA synthesis during replication stress. Yeast genetics; PCNA mutant (K164R) analysis; epistasis analysis combining mms2Δ, rad5Δ, siz1Δ, rad18Δ mutations with replication-defective alleles; growth assays Genes to cells Medium 15507115
1998 Human MMS2 (hMMS2/UBE2V2) and its close paralog CROC-1 functionally complement yeast mms2 mutations for DNA damage sensitivity and spontaneous mutagenesis, demonstrating conservation of Mms2 function. Both yeast MMS2 and human hMMS2 also transactivate a c-fos–CAT reporter gene in Rat-1 cells. Functional complementation of yeast mms2 mutant; DNA damage sensitivity assays; mutagenesis assays; transient co-transfection reporter assay (c-fos–CAT) Nucleic acids research Medium 9705497
2007 Yeast Chfr homologs Chf1/Chf2 require Ubc13/Mms2 for G2 cell-cycle delay but not for Chf protein turnover; Ubc4 mediates G1 delay and Chf protein turnover. Reconstituted in vitro ubiquitination and tandem MS characterization of ubiquitin chain linkages showed that Ubc13/Mms2-dependent modifications are a distinct subset of those catalyzed by Ubc4, with site-specific mutagenesis confirming different functional consequences. Genetic analysis in yeast; in vitro ubiquitination reconstitution with purified components; tandem mass spectrometry linkage analysis; site-directed mutagenesis of ubiquitination sites Cell cycle Medium 18202552
2011 Zebrafish Mms2 (DrMms2) forms a stable complex with DrUbc13 and promotes K63-linked polyubiquitination in vitro. Morpholino knockdown of DrMms2 (but not DrUev1) enhances spontaneous and DNA-damage-induced expression of p53 effectors p21 and mdm2 in zebrafish embryos. Additionally, DrUbc13 specifically binds p53 in vitro, linking the Mms2–Ubc13 complex to the p53-mediated DNA damage response. Zebrafish morpholino knockdown; in vitro K63-linked polyubiquitination assay; in vitro GST pulldown (DrUbc13–p53 binding); RT-PCR of p53 target genes (p21, mdm2) DNA repair Medium 22055568
2020 Ubc13–Mms2 contributes to K63-linked polyubiquitylation in membrane protein sorting to the yeast vacuole via the multivesicular body (MVB) pathway. Genetic analysis identified FYVE-RING finger E3 proteins (including Pib1) as cognate E3 partners for Ubc13–Mms2 in membrane trafficking, revealing a role for Ubc13–Mms2 in membrane protein sorting beyond DNA repair. Yeast genetics (deletion analysis, epistasis); fluorescence microscopy of membrane protein trafficking; identification of E3 partners by genetic interaction screening Journal of cell science Medium 32265276
2023 Mms2 overproduction in yeast causes a spontaneous mutator effect that is independent of Ubc13 but requires Ubc4, the HECT E3 Rsp5, and RING E3 Not4, as well as error-prone polymerases ζ and Rev1 and PCNA K164 ubiquitination. Mms2 abundance also influences Pol3 (Polδ catalytic subunit) cellular levels: loss of Mms2 increases Pol3 abundance, while Mms2 overproduction decreases Pol3 levels. Yeast genetics; Western blotting for Pol3 levels; epistasis analysis with ubc13Δ, ubc4Δ, rsp5, not4, rev3Δ, rev1Δ, and pcna-K164R mutants; spontaneous mutagenesis assays DNA repair Medium 36934633
2025 In Drosophila, Uev1A (ortholog of UBE2V2) collaborates with the E3 APC/C complex to mediate proteasomal degradation of Cyclin A, thereby protecting polyploid cells from aberrant division stress induced by oncogenic Ras. Overexpression of human UBE2V2 mitigates oncogenic Ras-induced nurse cell death, and UBE2V2 counteracts oncogenic Ras-driven tumorigenesis in human colorectal tumor xenografts in nude mice. Drosophila genome-wide genetic screen; Drosophila knockdown/overexpression with oncogenic Ras; human colorectal tumor xenograft in nude mice; Cyclin A degradation assay (Uev1A + APC/C reconstitution implied by genetic and xenograft evidence) bioRxivpreprint Low

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 673 10089880
2006 Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. Nature structural & molecular biology 290 16980971
2001 Molecular insights into polyubiquitin chain assembly: crystal structure of the Mms2/Ubc13 heterodimer. Cell 270 11440714
1998 MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway. Proceedings of the National Academy of Sciences of the United States of America 224 9576943
2006 Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Proceedings of the National Academy of Sciences of the United States of America 200 17108083
2005 Distinct regulation of Ubc13 functions by the two ubiquitin-conjugating enzyme variants Mms2 and Uev1A. The Journal of cell biology 151 16129784
2002 Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Molecular and cellular biology 144 11884624
2001 Noncovalent interaction between ubiquitin and the human DNA repair protein Mms2 is required for Ubc13-mediated polyubiquitination. The Journal of biological chemistry 115 11504715
2006 Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae. Molecular and cellular biology 93 16908531
1998 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 research 90 9705497
2003 An NMR-based model of the ubiquitin-bound human ubiquitin conjugation complex Mms2.Ubc13. The structural basis for lysine 63 chain catalysis. The Journal of biological chemistry 85 12569095
2003 The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Oncogene 79 14562038
2006 Angiotensin II-induced neural differentiation via angiotensin II type 2 (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor-interacting protein and Src homology 2 domain-containing protein-tyrosine phosphatase 1. Molecular endocrinology (Baltimore, Md.) 75 17068200
2012 Molecular insights into the function of RING finger (RNF)-containing proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation. The Journal of biological chemistry 64 22589545
2018 Ube2V2 Is a Rosetta Stone Bridging Redox and Ubiquitin Codes, Coordinating DNA Damage Responses. ACS central science 53 29532025
2001 The srs2 suppressor of UV sensitivity acts specifically on the RAD5- and MMS2-dependent branch of the RAD6 pathway. Nucleic acids research 52 11522817
2006 Structural basis for non-covalent interaction between ubiquitin and the ubiquitin conjugating enzyme variant human MMS2. Journal of biomolecular NMR 44 16518696
2004 Rad18/Rad5/Mms2-mediated polyubiquitination of PCNA is implicated in replication completion during replication stress. Genes to cells : devoted to molecular & cellular mechanisms 42 15507115
2005 A single Mms2 "key" residue insertion into a Ubc13 pocket determines the interface specificity of a human Lys63 ubiquitin conjugation complex. The Journal of biological chemistry 41 15749714
2010 Rad8Rad5/Mms2-Ubc13 ubiquitin ligase complex controls translesion synthesis in fission yeast. The EMBO journal 35 20453833
2006 Mgs1 and Rad18/Rad5/Mms2 are required for survival of Saccharomyces cerevisiae mutants with novel temperature/cold sensitive alleles of the DNA polymerase delta subunit, Pol31. DNA repair 26 16949354
2005 Ubiquitin binding site of the ubiquitin E2 variant (UEV) protein Mms2 is required for DNA damage tolerance in the yeast RAD6 pathway. The Journal of biological chemistry 26 15772086
2007 Yeast Chfr homologs retard cell cycle at G1 and G2/M via Ubc4 and Ubc13/Mms2-dependent ubiquitination. Cell cycle (Georgetown, Tex.) 25 18202552
2007 Two Mms2 residues cooperatively interact with ubiquitin and are critical for Lys63 polyubiquitination in vitro and in vivo. FEBS letters 18 17964296
2005 UBE2V2 (MMS2) is not required for effective immunoglobulin gene conversion or DNA damage tolerance in DT40. DNA repair 17 15725630
2011 The roles of PCNA SUMOylation, Mms2-Ubc13 and Rad5 in translesion DNA synthesis in Saccharomyces cerevisiae. Molecular microbiology 16 21362066
2020 Ubc13-Mms2 cooperates with a family of RING E3 proteins in budding yeast membrane protein sorting. Journal of cell science 15 32265276
2005 Main chain and side chain dynamics of the ubiquitin conjugating enzyme variant human Mms2 in the free and ubiquitin-bound States. Biochemistry 14 15952783
2021 miR-499a inhibits the proliferation and apoptosis of prostate cancer via targeting UBE2V2. World journal of surgical oncology 13 34429120
2011 Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53-mediated DNA-damage response. DNA repair 13 22055568
1997 Molecular cloning of a 1alpha,25-dihydroxyvitamin D3-inducible transcript (DDVit 1) in human blood monocytes. Biochemical and biophysical research communications 11 9199207
2021 UBE2V2 Positively Correlates With PD-L1 Expression and Confers Poor Patient Survival in Lung Adenocarcinoma. Applied immunohistochemistry & molecular morphology : AIMM 9 33734107
2011 Mutation screening of the RNF8, UBC13 and MMS2 genes in Northern Finnish breast cancer families. BMC medical genetics 4 21774837
2005 Purification and properties of the ubiquitin-conjugating enzymes Cdc34 and Ubc13.Mms2. Methods in enzymology 2 16275318
2023 A novel role for Mms2 in the control of spontaneous mutagenesis and Pol3 abundance. DNA repair 1 36934633
2022 Molecular cloning and functional characterization of UBC13 and MMS2 from Candida albicans. Gene 1 34995738
2009 The available SRL3 deletion strain of Saccharomyces cerevisiae contains a truncation of DNA damage tolerance protein Mms2: Implications for Srl3 and Mms2 functions. The Internet journal of microbiology 1 24795789

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