Affinage

SEM1

26S proteasome complex subunit SEM1 · UniProt P60896

Round 2 corrected
Length
70 aa
Mass
8.3 kDa
Annotated
2026-04-28
130 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SEM1 (DSS1) is a small, intrinsically disordered, highly acidic protein that serves as a shared structural and regulatory subunit of three functionally distinct multiprotein complexes: the 26S proteasome lid, the BRCA2 homologous recombination machinery, and the TREX-2 mRNA export complex. Within the 26S proteasome, SEM1 bridges the PCI domains of RPN3 and RPN7, acting as a molecular tether during lid biogenesis and functioning as an intrinsic ubiquitin receptor for K48- and K63-linked polyubiquitin chains (PMID:24412063, PMID:25306921, PMID:15572408). As an obligate partner of BRCA2, SEM1 stabilizes BRCA2 against degradation, allosterically regulates BRCA2 DNA-binding competence through controlled dissociation, and acts as a DNA mimic to attenuate RPA–ssDNA affinity, thereby enabling RPA-to-RAD51 exchange during homologous recombination (PMID:16205630, PMID:26145171, PMID:23094644). In the TREX-2 complex, SEM1 stabilizes the Sac3–Thp1 PCI-domain scaffold at the nuclear pore, coupling transcription with mRNP export and preventing transcription-associated genomic instability (PMID:22343721, PMID:19289793).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Identification of DSS1 as a novel highly acidic gene within the SHFM1 split-hand/foot malformation locus established the gene's existence and its developmental expression pattern, but left its molecular function unknown.

    Evidence YAC contig mapping and RNA in situ hybridization in human and mouse embryos

    PMID:8733122

    Open questions at the time
    • No protein-level function assigned
    • Causal role in SHFM1 not demonstrated
    • No interacting partners identified
  2. 1999 High

    Discovery that DSS1 physically interacts with the DNA-binding domain of BRCA2 provided the first molecular partner and linked this small acidic protein to the breast cancer susceptibility pathway, though the functional consequence was undefined.

    Evidence Yeast two-hybrid, mammalian two-hybrid, and co-immunoprecipitation of endogenous proteins in MCF7 cells

    PMID:10373512

    Open questions at the time
    • Functional role of the interaction unknown
    • Whether DSS1 participates in DNA repair not tested
    • Structural basis of interaction unresolved
  3. 2002 High

    The crystal structure of the BRCA2 DBD–DSS1 complex revealed that DSS1 binds within the OB-fold region of BRCA2 and is required for BRCA2-stimulated RAD51-mediated recombination, establishing a structural and functional basis for DSS1 in homologous recombination.

    Evidence X-ray crystallography at 3.1 Å resolution plus in vitro recombination assay

    PMID:12228710

    Open questions at the time
    • Mechanism by which DSS1 activates recombination unknown
    • Whether DSS1 stabilizes BRCA2 in vivo untested
    • No in vivo HR assay performed
  4. 2004 High

    Independent studies in S. cerevisiae and human cells simultaneously established SEM1/DSS1 as a bona fide subunit of the 26S proteasome lid and showed it is required for ubiquitin-dependent proteolysis and DNA double-strand break repair, revealing its dual complex membership.

    Evidence Affinity purification of proteasome in yeast and human cells, in vivo/in vitro proteolysis assays, synthetic lethality with proteasome mutations, ChIP at HO-induced DSBs, RAD51 focus formation assays after RNAi

    PMID:15117943 PMID:15359272 PMID:15572408 PMID:15610744

    Open questions at the time
    • Structural position within the proteasome lid unknown
    • Whether proteasome and HR functions are separable not resolved
    • Mechanism of proteasome recruitment to DSBs unclear
  5. 2006 High

    DSS1 depletion was shown to cause BRCA2 protein degradation, demonstrating that DSS1 is an obligate stabilizer of BRCA2 in vivo — not merely a cofactor — and that essentially all cellular BRCA2 is DSS1-bound.

    Evidence RNAi knockdown with pulse-chase degradation assay and DNA damage sensitivity in human cells

    PMID:16205630

    Open questions at the time
    • Degradation pathway for DSS1-free BRCA2 not identified
    • Whether stabilization is proteasome-dependent not clarified
    • Stoichiometry of the complex in different tissues unknown
  6. 2008 High

    Genetic interaction mapping and mRNA export assays revealed SEM1 as a third-complex component of TREX-2 (Sac3–Thp1), establishing a proteasome-independent nuclear function in coupling transcription to mRNA export at the nuclear pore.

    Evidence Quantitative E-MAP epistasis screen, biochemical fractionation, mRNA export assays in yeast

    PMID:19061648

    Open questions at the time
    • Structural role of Sem1 in TREX-2 unknown
    • Whether mammalian DSS1 participates in TREX-2 not yet shown
    • Mechanism of NPC targeting unclear
  7. 2009 High

    Biochemical reconstitution demonstrated that DSS1 allosterically attenuates BRCA2 DNA binding — not by direct competition — and that DNA promotes DSS1 dissociation, revealing a regulated handoff mechanism controlling BRCA2 activation.

    Evidence In vitro DNA binding assays with U. maydis Brh2–Dss1 reconstituted complexes and domain truncations

    PMID:19919104

    Open questions at the time
    • Whether the allosteric mechanism operates identically for human BRCA2 not confirmed
    • Kinetics of Dss1 release at replication forks unknown
    • Relationship to RPA displacement not yet addressed
  8. 2012 High

    Crystal structures of both the TREX-2 Sac3–Thp1–Sem1 complex and the cryo-EM localization of Sem1 bridging Rpn3–Rpn7 in the proteasome lid revealed a common architectural principle: SEM1 uses its acidic disordered segments to stabilize PCI-domain heterodimers across distinct complexes.

    Evidence X-ray crystallography of TREX-2 with structure-guided mutagenesis; cryo-EM and cross-linking of 26S proteasome

    PMID:22343721 PMID:23643786

    Open questions at the time
    • Whether the binding mode is truly analogous at atomic level across complexes not resolved
    • Dynamic transitions between complexes not characterized
  9. 2014 High

    Two mechanistic breakthroughs showed SEM1 acts as a chaperone-like tether during proteasome lid assembly (dispensable once the larger lid forms) and as an intrinsic ubiquitin receptor recognizing K48- and K63-linked chains via its acidic residues, defining dual functions within a single complex.

    Evidence TEV-cleavage engineering of Sem1 for assembly assays; ubiquitin-binding assays with atomic resolution structural data and mutagenesis

    PMID:24412063 PMID:25306921

    Open questions at the time
    • Whether ubiquitin-receptor and assembly functions compete or are temporally separated unknown
    • Contribution relative to established ubiquitin receptors Rpn10/Rpn13 not quantified
  10. 2015 High

    DSS1 was shown to function as a DNA mimic: its acidic domain attenuates RPA–ssDNA affinity, enabling the BRCA2–DSS1 complex to physically engage RPA and promote RPA-to-RAD51 exchange, providing a unified mechanism for DSS1 function in homologous recombination.

    Evidence Biochemical reconstitution, structural analysis, in vivo HR assay, and site-directed mutagenesis of the DSS1 acidic domain

    PMID:26145171

    Open questions at the time
    • Whether DSS1 directly contacts RPA in vivo not confirmed
    • Structural basis of the DSS1–RPA interface not resolved
    • Whether other acidic IDPs can substitute unknown
  11. 2022 High

    A mouse knock-in mutation disrupting BRCA2–DSS1 interaction showed that this interaction is essential for somatic HR and viability but dispensable for meiotic RAD51 loading, revealing context-dependent requirements for DSS1 in recombination.

    Evidence BRCA2 L2431P knock-in mice with RAD51 focus formation, HR efficiency, and meiosis analysis

    PMID:35365640

    Open questions at the time
    • Mechanism enabling DSS1-independent RAD51 loading during meiosis unclear
    • Whether other factors compensate in meiosis not identified
    • Long-term genomic instability consequences in surviving animals not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SEM1/DSS1 partitions among its three major complexes (proteasome, BRCA2, TREX-2) in different cellular contexts, whether its ubiquitin-receptor function is coordinated with its HR role, and the structural basis of the full-length human BRCA2–DSS1 complex remain major open questions.
  • No quantitative measurement of SEM1 allocation among complexes in vivo
  • Full-length BRCA2–DSS1 structure not determined
  • Regulatory signals controlling complex-specific engagement unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 7 R-HSA-392499 Metabolism of proteins 6 R-HSA-8953854 Metabolism of RNA 3
Partners
BRCA2PCID2PSMD3PSMD6RAD52RPASAC3THP1
Complex memberships
26S proteasome (19S lid)BRCA2-DSS1 complexTREX-2 (Sac3-Thp1-Sem1)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 DSS1 (SEM1 human ortholog) was identified as a novel gene within the SHFM1 locus at 7q21.3-q22.1, predicted to encode a highly acidic polypeptide with 100% amino acid identity to its murine homolog (Dss1), and expressed specifically in limb bud, craniofacial primordia, and skin during development. YAC contig mapping, RNA in situ hybridization, sequence analysis Human molecular genetics High 8733122
1999 Human DSS1 physically interacts with the C-terminal region (amino acids 2472–2957) of BRCA2, as demonstrated by yeast two-hybrid, mammalian two-hybrid, and coimmunoprecipitation of endogenous proteins in MCF7 cells. Yeast strains deleted for DSS1-like genes showed temperature-sensitive growth defects linked to cell cycle completion. Yeast two-hybrid, mammalian two-hybrid, coimmunoprecipitation of endogenous proteins Molecular and cellular biology High 10373512
1999 Yeast SEM1 (DSS1 ortholog) multicopy-suppresses exocyst mutants (sec3-2, sec8-9, sec10-2, sec15-1) and its deletion triggers pseudohyphal growth in diploid yeast; Sem1p cosediments with the exocyst component Sec8p, indicating a role in polarized secretion and cellular differentiation. Genetic suppression, cell fractionation, sucrose gradient cosedimentation, phenotypic analysis Proceedings of the National Academy of Sciences of the United States of America Medium 9927667
2002 The crystal structure of a ~90 kDa BRCA2 domain bound to DSS1 was solved at 3.1 Å, revealing that DSS1 binds within the DNA-binding domain of BRCA2 which contains three OB folds and a helix-turn-helix motif. DSS1 binding is required for BRCA2 to stimulate RAD51-mediated recombination in vitro. X-ray crystallography (3.1 Å and 3.5 Å structures), in vitro recombination assay Science (New York, N.Y.) High 12228710
2002 Mouse Dss1 is induced by TPA in keratinocyte progenitor cells and skin papillomas; ectopic overexpression of Dss1 in JB6 preneoplastic cells strongly increased focus formation and neoplastic transformation in soft agar. cDNA microarray, Northern blot, ectopic overexpression functional assay (focus formation, soft agar) The Journal of biological chemistry Medium 12419822
2003 The U. maydis DSS1 ortholog associates with Brh2 (BRCA2-related protein) and is essential for radiation resistance, recombinational repair, meiosis, and genome stability, phenocopying Brh2 and Rad51 mutants, establishing Dss1 as a core component of the BRCA2-dependent recombinational repair pathway. Gene deletion, gamma-radiation sensitivity assay, recombination assay, meiosis analysis Molecular cell High 14580353
2004 Sem1 is a component of the lid subcomplex of the 19S regulatory particle (RP) of the 26S proteasome in S. cerevisiae; loss of Sem1 impairs 26S proteasome stability and ubiquitin-dependent proteolysis, and sem1 is synthetically lethal with proteasome subunit mutations. Rpn10 functions with Sem1 to maintain lid-base association. Affinity purification, genetic interaction (synthetic lethality), proteasome stability assays, in vivo proteolysis assays Journal of cell science High 15572408
2004 Sem1p was identified as a novel subunit of the 26S proteasome lid in S. cerevisiae by affinity purification; Sem1-deficient proteasomes are impaired in degradation of polyubiquitinated proteins in vivo and in vitro, and human DSS1 can functionally complement yeast Sem1 and interact with the human 26S proteasome. Affinity purification, in vitro and in vivo ubiquitin-dependent proteolysis assays, genetic complementation The Journal of biological chemistry High 15117943
2004 DSS1 depletion in mammalian cells impairs DNA damage-induced RAD51 focus formation and genomic stability but does not affect BRCA2 or RAD51 protein levels or their mutual interaction, suggesting DSS1 is required for the BRCA2-RAD51 complex to associate with DNA damage sites. RNAi knockdown, immunofluorescence (RAD51 foci), Western blot, genomic instability assay EMBO reports High 15359272
2004 Affinity purification of the yeast 19S proteasome identified Sem1 as a subunit; human DSS1 likewise copurified with the human 19S proteasome. Sem1 deletion impairs efficient repair of HO-generated DSBs by both HR and NHEJ, and chromatin immunoprecipitation showed Sem1 is recruited with the 19S and 20S proteasomes to a DSB in vivo. Affinity purification, chromatin immunoprecipitation, HO endonuclease DSB repair assay, genetic interaction analysis Molecular cell High 15610744
2005 In U. maydis, Dss1 is not required for Brh2 stability or Brh2-Rad51 association but is required for GFP-Rad51 focus formation after DNA damage. Brh2 variants lacking the C-terminal Dss1-binding domain but retaining the N-terminal Rad51-interacting BRC element can partially bypass Dss1 requirement, revealing that Dss1 activates the Brh2-Rad51 complex and balances recombinational repair. Genetic suppressor screen, GFP-Rad51 live imaging, domain deletion analysis, survival assays Molecular and cellular biology High 15767662
2006 RNAi knockdown of DSS1 in human cell lines leads to dramatic loss of BRCA2 protein through increased degradation, dependent on the DSS1-binding domain of BRCA2. Essentially all BRCA2 in human cells is associated with DSS1. DSS1 depletion also causes hypersensitivity to DNA damage, phenocopying BRCA2 depletion. RNAi, Western blot (modified protocol for endogenous DSS1), DNA damage sensitivity assay, pulse-chase degradation assay Oncogene High 16205630
2006 S. pombe Dss1 associates with the 19S regulatory particle of the 26S proteasome; dss1 mutants accumulate poly-ubiquitylated proteins and show canavanine sensitivity, and genetic interactions with other proteasome subunit mutations confirm an evolutionarily conserved role in proteasome function. Affinity purification, genetic interaction analysis, ubiquitin accumulation assay, drug sensitivity assay The Biochemical journal High 16149916
2007 In U. maydis, Dss1 dissociates Brh2 complexes from at least dimeric to monomeric form; the intermolecular complementation between separate BRC and CRE domains of Brh2 depends on the presence of Dss1, indicating that Dss1-provoked dissociation of Brh2 oligomers is requisite for Brh2 function in recombinational repair. Biochemical fractionation, in vivo intermolecular complementation assay, protein interaction analysis Molecular and cellular biology Medium 17261595
2008 Human DSS1 associates with the 26S proteasome via the RPN3/S3 subunit of the 19S regulatory particle through an N-terminal RPN3/S3-interacting motif (R3IM, residues 15–21) whose negative charges are required for proteasome interaction. DSS1 depletion by siRNA reduces p53 ubiquitination and degradation via the gankyrin-MDM2/HDM2 pathway. Co-immunoprecipitation, siRNA knockdown, domain mutagenesis, ubiquitination assays Journal of molecular biology Medium 18775730
2008 In C. elegans, dss-1 is essential for oogenesis, embryogenesis, and larval growth; DSS-1::GFP localizes primarily to the nucleus; C. elegans dss-1 rescues the temperature-sensitive growth and polyubiquitin accumulation of yeast sem1 deletion mutants, demonstrating functional conservation across metazoans. Loss-of-function mutant and RNAi, GFP localization, yeast complementation, ubiquitin accumulation assay BMC developmental biology High 18471277
2008 Genetic interaction mapping (E-MAP) revealed that Sem1/Dss1 functions as a component of the Sac3-Thp1 (TREX-2) complex involved in mRNA export, independent of the proteasome. Sem1 also interacts with Csn12 (COP9 signalosome component), and Csn12 plays a role in pre-mRNA splicing. Quantitative genetic interaction mapping (E-MAP), biochemical fractionation, mRNA export assay Molecular cell High 19061648
2007 Mass spectrometric characterization of affinity-purified human 26S proteasome identified DSS1 as a bona fide subunit of the human 19S regulatory particle. Affinity purification, LC-MS/MS proteomic analysis Biochemistry Medium 17323924
2009 Yeast Sem1 is a functional component of the TREX-2 complex at the nuclear pore; sem1 mutants show impaired mRNA export, transcription elongation defects, and transcription-associated hyper-recombination. Sem1 is required for proper targeting of TREX-2 component Thp1 to the nuclear pore complex, independent of its role in the proteasome. mRNA export assay, genetic analysis, biochemical fractionation, co-enrichment with TREX-2/NPC components The Journal of cell biology High 19289793
2009 Dss1 regulates Brh2 (BRCA2 ortholog) interaction with DNA: full-length Brh2 complexed with Dss1 binds DNA slowly, while Dss1-free N-terminal Brh2 binds quickly. Dss1 addition attenuates DNA binding allosterically (not by direct competition), and DNA presence promotes Dss1 dissociation from Brh2, suggesting Dss1 governs DNA access via allosteric regulation. In vitro DNA binding assays, biochemical reconstitution, competition assays Biochemistry High 19919104
2010 RNAi depletion of DSS1 in human cells reduces homologous recombinational repair (HRR) efficiency to small fractions of normal, with residual HRR correlating with residual DSS1 levels. Proteasome inhibition only partially reproduces the HRR defect, indicating DSS1's role in HRR extends beyond proteasomal function. RNAi, HRR reporter assay, proteasome inhibitor treatment Mutation research High 20817001
2012 Dss1 association with Brh2 (via C-terminal domain) attenuates the DNA binding potential of full-length Brh2; the N-terminal domain of Brh2 helps evict Dss1 from its C-terminal binding surface, providing a mechanism by which Dss1 release activates DNA binding competence in Brh2. In vitro DNA binding assays with Brh2 fusions and truncations, biochemical reconstitution Biochemistry High 23094644
2012 The crystal structure of the Sac3-Thp1-Sem1 segment of yeast TREX-2 was solved; Sem1 stabilizes this PCI-domain complex by bridging Sac3 and Thp1, forming a platform that mediates nucleic acid binding. Structure-guided mutations support the role of the Thp1-Sac3 interaction in mRNA binding and coupling of transcription to mRNP assembly and export. X-ray crystallography, structure-guided mutagenesis, nucleic acid binding assays Nature structural & molecular biology High 22343721
2012 Mammalian TREX-2 consists of GANP, ENY2, PCID2, and centrins; depletion of any component inhibits mRNA export. Crystal structure of GANP:ENY2 shows two ENY2 chains interact with GANP in orientations different from yeast Sac3. GANP recruits ENY2 to nuclear pore complexes and associates with RNA Pol II, linking transcription to mRNA export. Crystal structure, RNAi depletion, mRNA export assay, co-immunoprecipitation Nucleic acids research High 22307388
2013 Cryo-EM single-particle reconstruction localized the C-terminal helix of Sem1 to the PCI domain of Rpn7 in the 26S proteasome; site-specific cross-linking data positioned the N-terminal region of Sem1 bridging the cleft between Rpn7 and Rpn3, functioning as molecular glue stabilizing the Rpn3/Rpn7 heterodimer. Cryo-electron microscopy, site-specific cross-linking Biochemical and biophysical research communications High 23643786
2013 Sem1 (as a TREX-2 subunit) is required for activation of SAGA-regulated genes (ARG1, GAL1); Sem1 influences proper recruitment of SAGA subunits to the GAL1 promoter and modulates SAGA-dependent histone H2B deubiquitylation both in vivo and in vitro. Chromatin immunoprecipitation, in vivo and in vitro H2B deubiquitylation assays, gene induction assays Nucleic acids research Medium 23599000
2014 Dss1 (Sem1) functions as a 26S proteasome ubiquitin receptor that binds K63- and K48-linked ubiquitin chains. Atomic resolution data show Dss1 is intrinsically disordered and binds ubiquitin via acidic and hydrophobic residues; the complementary ubiquitin surface involves a hydrophobic patch (I13, I44, L69) flanked by basic regions. Mutations in the ubiquitin-binding site cause growth defects and accumulation of ubiquitylated proteins. Ubiquitin-binding assays, atomic resolution structural data, site-directed mutagenesis, in vivo ubiquitin accumulation assay Molecular cell High 25306921
2014 Sem1 acts as a molecular tether during proteasome lid biogenesis by using conserved acidic segments separated by a flexible linker to simultaneously grasp Rpn3 and Rpn7, enforcing ordered subunit incorporation. TEV protease cleavage of engineered sites in Sem1 showed this tethering is essential for Rpn3-Sem1-Rpn7 ternary complex formation but becomes dispensable once the complex incorporates into larger lid precursors, revealing a chaperone-like function in early assembly. TEV protease cleavage engineering, biochemical assembly assays, domain mutagenesis Molecular cell High 24412063
2015 DSS1 is required for efficient RPA-to-RAD51 exchange during homologous recombination by acting as a DNA mimic: DSS1's solvent-exposed acidic domain attenuates RPA affinity for ssDNA, allowing the BRCA2-DSS1 complex to physically and functionally interact with RPA. A mutation in the acidic domain of DSS1 compromises RPA-RAD51 exchange. Biochemical reconstitution, structural analysis, in vivo HR assays, site-directed mutagenesis, RPA interaction assays Molecular cell High 26145171
2018 In Aspergillus nidulans, Sem1 is required for stabilization of the Rpn11 deubiquitinating enzyme, incorporation of ubiquitin receptor Rpn10 into the 19S regulatory particle, and efficient 26S proteasome assembly. sem1 deletion leads to elevated 20S proteasome levels with increased ATP-independent catalytic activity and impairs multicellular development; Sem1 also maintains high NADH levels and mitochondria integrity during stress. Gene deletion, proteasome purification, enzymatic activity assays, developmental phenotype analysis PLoS genetics Medium 29401458
2018 The interactome of S. pombe Dss1 was expanded to include eIF3, the COP9 signalosome, and mitotic septins. Within its intrinsically disordered ensemble, Dss1 forms a transiently populated C-terminal helix that dynamically shields a central binding region; this helix inhibits interaction with ATP-citrate lyase but is required for septin binding, and dss1 deletion reduces ATP-citrate lyase solubility and increases septin ring persistence. Affinity purification/mass spectrometry, NMR, in vivo phenotypic analysis Cell reports Medium 30355493
2019 DSS1 interacts with and stimulates RAD52; DSS1 binding changes RAD52 oligomeric conformation, modulates its DNA binding properties, stimulates single-strand annealing (SSA) activity, and promotes strand invasion, establishing RAD52 as a novel DSS1 binding partner in DSB repair. Co-immunoprecipitation, oligomerization assays, in vitro SSA and strand invasion assays, DNA binding assays Nucleic acids research Medium 31799622
2020 DSS1 and ssDNA counteract BRCA2 multimerization; three self-interacting regions and two types of self-association (N-to-C terminal and N-to-N terminal) were identified. The N-to-C terminal self-interaction is sensitive to DSS1 and ssDNA, defining a novel role for DSS1 in regulating BRCA2 monomer/oligomer equilibrium independent of RPA. Biochemical assays, electron microscopy imaging, domain mapping Nucleic acids research Medium 32609828
2021 DSS1 and PCID2 (TREX-2 components) depletion in breast cancer cells increases chemosensitivity via BRCA2-independent DNA damage; DSS1 overexpression confers chemoresistance while depletion increases sensitivity to chemotherapy, demonstrating a BRCA2-independent function of DSS1 in DNA damage response. RNAi knockdown/overexpression, propidium iodide staining, comet assay, clonogenic survival assay Laboratory investigation Medium 34031538
2022 A BRCA2 L2431P mutation that disrupts the BRCA2-DSS1 interaction causes embryonic lethality in most mice but surviving homozygous mutants are fertile with normal RAD51 recruitment during meiosis, despite loss of radiation-induced RAD51 foci and severe HR defect in somatic cells. This demonstrates that BRCA2-DSS1 interaction is dispensable for RAD51 loading when homologous DNA is in close proximity. Mouse knock-in model, RAD51 focus formation assay, HR efficiency assay, meiosis analysis Nature communications High 35365640
2023 SEM1 knockout in glioma cells (U251, LN229) inhibits proliferation, invasion, and migration and promotes apoptosis; weighted gene co-expression network analysis identified the PI3K-Akt pathway as the principal mediator of SEM1-driven malignant behavior, suggesting SEM1 activates AKT signaling to promote glioblastoma progression. CRISPR knockout, MTT assay, flow cytometry, Transwell assay, organoid assay, WGCNA Cancer letters Low 37652287

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annual review of biochemistry 1398 19489727
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2012 Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature genetics 958 22504420
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2002 BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science (New York, N.Y.) 574 12228710
2009 Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nature genetics 552 19801982
2005 Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 443 16239144
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2010 Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 322 20732625
2017 BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing. Nature 305 28976962
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2007 Mass spectrometric characterization of the affinity-purified human 26S proteasome complex. Biochemistry 220 17323924
2008 A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing. Molecular cell 218 19061648
2003 The DNA sequence of human chromosome 7. Nature 188 12853948
2004 Proteasome involvement in the repair of DNA double-strand breaks. Molecular cell 186 15610744
1996 Characterization of the split hand/split foot malformation locus SHFM1 at 7q21.3-q22.1 and analysis of a candidate gene for its expression during limb development. Human molecular genetics 170 8733122
2006 Top-down ESI-ECD-FT-ICR mass spectrometry localizes noncovalent protein-ligand binding sites. Journal of the American Chemical Society 168 17090006
2002 Properties of the hybrid form of the 26S proteasome containing both 19S and PA28 complexes. The EMBO journal 168 12032076
2013 Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD: a new pathomechanism in CADASIL. Brain : a journal of neurology 163 23649698
1999 Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals. Molecular and cellular biology 161 10373512
2003 Human chromosome 7: DNA sequence and biology. Science (New York, N.Y.) 154 12690205
2010 Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus. PLoS genetics 153 20808887
2015 Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry. Molecular cell 143 26145171
2014 Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of ubiquitin conjugates. The EMBO journal 139 24811749
2013 Multistage genome-wide association meta-analyses identified two new loci for bone mineral density. Human molecular genetics 123 24249740
2012 Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export. Nucleic acids research 119 22307388
2010 Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nature genetics 118 20694011
2004 Sem1p is a novel subunit of the 26 S proteasome from Saccharomyces cerevisiae. The Journal of biological chemistry 115 15117943
2022 8-oxoguanine and 8-oxodeoxyguanosine Biomarkers of Oxidative DNA Damage: A Review on HPLC-ECD Determination. Molecules (Basel, Switzerland) 108 35268721
2006 DSS1 is required for the stability of BRCA2. Oncogene 104 16205630
2003 The BRCA2-interacting protein DSS1 is vital for DNA repair, recombination, and genome stability in Ustilago maydis. Molecular cell 101 14580353
2012 Structural basis for the assembly and nucleic acid binding of the TREX-2 transcription-export complex. Nature structural & molecular biology 97 22343721
2004 DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells. EMBO reports 94 15359272
2009 Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery. The Journal of cell biology 89 19289793
2004 Sem1, the yeast ortholog of a human BRCA2-binding protein, is a component of the proteasome regulatory particle that enhances proteasome stability. Journal of cell science 85 15572408
2014 Dss1 is a 26S proteasome ubiquitin receptor. Molecular cell 77 25306921
2015 ACK1 promotes gastric cancer epithelial-mesenchymal transition and metastasis through AKT-POU2F1-ECD signalling. The Journal of pathology 70 25678401
2006 Interaction between Arabidopsis Brca2 and its partners Rad51, Dmc1, and Dss1. Plant physiology 66 16415210
2014 The intrinsically disordered Sem1 protein functions as a molecular tether during proteasome lid biogenesis. Molecular cell 62 24412063
1998 The yeast nuclear gene DSS1, which codes for a putative RNase II, is necessary for the function of the mitochondrial degradosome in processing and turnover of RNA. Molecular & general genetics : MGG 61 9829834
2006 Quantification of Parkinson's disease-related network expression with ECD SPECT. European journal of nuclear medicine and molecular imaging 57 17096095
2005 Brh2-Dss1 interplay enables properly controlled recombination in Ustilago maydis. Molecular and cellular biology 56 15767662
1995 The novel nuclear gene DSS-1 of Saccharomyces cerevisiae is necessary for mitochondrial biogenesis. Current genetics 56 8590460
2016 Cutaneous manifestations of Erdheim-Chester disease (ECD): Clinical, pathological, and molecular features in a monocentric series of 40 patients. Journal of the American Academy of Dermatology 55 26785805
2014 Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD. Talanta 54 25127638
1996 Cellular basis of ECD brain retention. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 54 8862314
2014 Sequestration of latent TGF-β binding protein 1 into CADASIL-related Notch3-ECD deposits. Acta neuropathologica communications 53 25190493
2006 Selective inhibition of ADAM metalloproteases blocks HER-2 extracellular domain (ECD) cleavage and potentiates the anti-tumor effects of trastuzumab. Cancer biology & therapy 53 16627988
2012 Challenges in the clinical utility of the serum test for HER2 ECD. Biochimica et biophysica acta 52 22521738
1999 Jararhagin ECD-containing disintegrin domain: expression in escherichia coli and inhibition of the platelet-collagen interaction. Archives of biochemistry and biophysics 52 10486149
1999 SEM1, a homologue of the split hand/split foot malformation candidate gene Dss1, regulates exocytosis and pseudohyphal differentiation in yeast. Proceedings of the National Academy of Sciences of the United States of America 49 9927667
2008 Probing the gas-phase folding kinetics of peptide ions by IR activated DR-ECD. Journal of the American Society for Mass Spectrometry 47 18400512
1996 Loss of human E-cadherin (ECD) correlated with invasiveness of transitional cell cancer in the renal pelvis, ureter and urinary bladder. Cancer letters 44 8616803
1995 8-hydroxydeoxyguanosine levels in DNA of human breast cancer are not significantly different from those of non-cancerous breast tissues by the HPLC-ECD method. Cancer letters 43 7736451
2007 Dss1 interaction with Brh2 as a regulatory mechanism for recombinational repair. Molecular and cellular biology 42 17261595
1984 Ecdysteroids during the third larval instar in 1(3)ecd-1ts, a temperature-sensitive mutant of Drosophila melanogaster. General and comparative endocrinology 42 6427061
2016 DSS1/Sem1, a Multifunctional and Intrinsically Disordered Protein. Trends in biochemical sciences 41 26944332
2008 Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation. Journal of molecular biology 40 18775730
2018 Notch3ECD immunotherapy improves cerebrovascular responses in CADASIL mice. Annals of neurology 37 30014602
2012 Two-dimensional ECD FT-ICR mass spectrometry of peptides and glycopeptides. Analytical chemistry 37 22762261
2008 Activated Ion Electron Capture Dissociation (AI ECD) of proteins: synchronization of infrared and electron irradiation with ion magnetron motion. Journal of the American Society for Mass Spectrometry 36 19200749
2022 A high-performance electrochemical aptasensor based on graphene-decorated rhodium nanoparticles to detect HER2-ECD oncomarker in liquid biopsy. Scientific reports 35 35228597
2010 Depletion of DSS1 protein disables homologous recombinational repair in human cells. Mutation research 34 20817001
2006 Fission yeast Dss1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis. The Biochemical journal 34 16149916
2018 ECD promotes gastric cancer metastasis by blocking E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation. Cell death & disease 33 29706618
2014 Conformational changes of ubiquitin during electrospray ionization as determined by in-ESI source H/D exchange combined with high-resolution MS and ECD fragmentation. Journal of mass spectrometry : JMS 33 25303388
2008 C. elegans dss-1 is functionally conserved and required for oogenesis and larval growth. BMC developmental biology 33 18471277
2002 Identification of Dss1 as a 12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in keratinocyte progenitor cells, with possible involvement in early skin tumorigenesis. The Journal of biological chemistry 32 12419822
2020 Immunomagnetic bead-based bioassay for the voltammetric analysis of the breast cancer biomarker HER2-ECD and tumour cells using quantum dots as detection labels. Mikrochimica acta 31 32088788
2007 Liquid chromatography electron capture dissociation tandem mass spectrometry (LC-ECD-MS/MS) versus liquid chromatography collision-induced dissociation tandem mass spectrometry (LC-CID-MS/MS) for the identification of proteins. Journal of the American Society for Mass Spectrometry 31 17350280
2020 DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs. Nucleic acids research 29 31799622
2020 DSS1 and ssDNA regulate oligomerization of BRCA2. Nucleic acids research 28 32609828
2017 Amplification of ACK1 promotes gastric tumorigenesis via ECD-dependent p53 ubiquitination degradation. Oncotarget 28 26498357
2004 Serum levels of HER2 ECD can determine the response rate to low dose oral cyclophosphamide and methotrexate in patients with advanced stage breast carcinoma. Anticancer research 28 15154657
2013 Localization of the regulatory particle subunit Sem1 in the 26S proteasome. Biochemical and biophysical research communications 27 23643786
2019 Modulation of PTH1R signaling by an ECD binding antibody results in inhibition of β-arrestin 2 coupling. Scientific reports 26 31594997
2010 Acurhagin-C, an ECD disintegrin, inhibits integrin alphavbeta3-mediated human endothelial cell functions by inducing apoptosis via caspase-3 activation. British journal of pharmacology 26 20590625
1993 Developmental requirements for the ecdysoneless (ecd) locus in Drosophila melanogaster. Developmental genetics 26 8293578
2022 MPLA-Adjuvanted Liposomes Encapsulating S-Trimer or RBD or S1, but Not S-ECD, Elicit Robust Neutralization Against SARS-CoV-2 and Variants of Concern. Journal of medicinal chemistry 24 35108485
2016 Native MS and ECD Characterization of a Fab-Antigen Complex May Facilitate Crystallization for X-ray Diffraction. Journal of the American Society for Mass Spectrometry 24 27103115
2013 Analysis of human blood plasma and hen egg white by chiroptical spectroscopic methods (ECD, VCD, ROA). Analytical and bioanalytical chemistry 24 23657444
2011 Lapatinib, a dual HER1/HER2 tyrosine kinase inhibitor, augments basal cleavage of HER2 extracellular domain (ECD) to inhibit HER2-driven cancer cell growth. Journal of cellular physiology 24 20658522
2010 The use of experimental design in the development of an HPLC-ECD method for the analysis of captopril. Talanta 24 21147355
1991 Further characterization of the in vitro hydrolysis of [Leu]- and [Met]enkephalin in rat plasma: HPLC-ECD measurement of substrate and metabolite concentrations. Regulatory peptides 24 1678195
2008 Trastuzumab plus paclitaxel or docetaxel in HER-2-negative/HER-2 ECD-positive anthracycline- and taxane-refractory advanced breast cancer. The oncologist 23 18448549
2017 Complementarity of DFT Calculations, NMR Anisotropy, and ECD for the Configurational Analysis of Brevipolides K-O from Hyptis brevipes. Journal of natural products 22 28099005
2014 Evaluation of serum HER2-ECD levels in patients with gastric cancer. Journal of gastroenterology 22 24557054
2014 ECD of tyrosine phosphorylation in a triple quadrupole mass spectrometer with a radio-frequency-free electromagnetostatic cell. Journal of the American Society for Mass Spectrometry 21 25037842
2008 GC x GC-ECD: a promising method for the determination of dioxins and dioxin-like PCBs in food and feed. Analytical and bioanalytical chemistry 21 18256808
2011 Identification of GABA A receptor modulators in Kadsura longipedunculata and assignment of absolute configurations by quantum-chemical ECD calculations. Phytochemistry 20 21889177
1998 Yeast nuclear PET127 gene can suppress deletions of the SUV3 or DSS1 genes: an indication of a functional interaction between 3' and 5' ends of mitochondrial mRNAs. Acta biochimica Polonica 20 10397341
2022 BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks. Nature communications 19 35365640
2013 Inhibition of integrins αv/α5-dependent functions in melanoma cells by an ECD-disintegrin acurhagin-C. Matrix biology : journal of the International Society for Matrix Biology 19 23333557
2009 Dss1 regulates interaction of Brh2 with DNA. Biochemistry 19 19919104
2016 [Erdheim-Chester disease (ECD), an inflammatory myeloid neoplasia]. Presse medicale (Paris, France : 1983) 18 27234902
2013 Oligomerization of DDR1 ECD affects receptor-ligand binding. Journal of structural biology 18 23810922
2012 Linear and conformational B cell epitope prediction of the HER 2 ECD-subdomain III by in silico methods. Asian Pacific journal of cancer prevention : APJCP 18 22994709
2018 Dramatic efficacy of dabrafenib in Erdheim-Chester disease (ECD): a pediatric patient with multiple large intracranial ECD lesions hidden by refractory Langerhans cell histiocytosis. Journal of neurosurgery. Pediatrics 16 30265230
2017 Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray, ECD, NMR J-based configurational analysis and HSQC overlay experiments. Biochimica et biophysica acta. General subjects 16 28919469
2009 Absolute configurations of DNA lesions determined by comparisons of experimental ECD and ORD spectra with DFT calculations. Chirality 16 19937959
2020 QTL Mapping and Inheritance of Clubroot Resistance Genes Derived From Brassica rapa subsp. rapifera (ECD 02) Reveals Resistance Loci and Distorted Segregation Ratios in Two F 2 Populations of Different Crosses. Frontiers in plant science 15 32719696
2019 Investigation of ECD conformational transition mechanism of GLP-1R by molecular dynamics simulations and Markov state model. Physical chemistry chemical physics : PCCP 15 30957116
2004 Serum HER-2 extracellular domain (ECD) before the first metastasis in 128 breast cancer patients. Clinical laboratory 15 15074470
2021 Ecd promotes U5 snRNP maturation and Prp8 stability. Nucleic acids research 14 33444449
2021 Effective discrimination of gas-phase peptide conformers using TIMS-ECD-ToF MS/MS. Analytical methods : advancing methods and applications 14 34698320
2021 Urinary p75ECD levels in patients with amyotrophic lateral sclerosis: a meta-analysis. Amyotrophic lateral sclerosis & frontotemporal degeneration 14 34726989
2016 Erdheim-Chester disease (ECD): Case report, clinical and basic investigations, and review of literature. Medicine 14 27759649
2018 Sem1 links proteasome stability and specificity to multicellular development. PLoS genetics 13 29401458
2018 Expanded Interactome of the Intrinsically Disordered Protein Dss1. Cell reports 13 30355493
2014 A common progenitor cell in LCH and ECD. Blood 13 25124781
1996 Compilation of DNA sequences of Escherichia coli K12 (ECD and ECDC; update 1995). Nucleic acids research 13 8594594
2014 Structural characterization of semen coagulum-derived SEM1(86-107) amyloid fibrils that enhance HIV-1 infection. Biochemistry 12 24811874
2014 Does electron capture dissociation (ECD) provide quantitative information on the chemical modification of lysine side chains in proteins? The glycation of ubiquitin. Analytical chemistry 12 25029396
1999 Drug release from diffusion pellets coated with the aqueous ethyl cellulose dispersion Aquacoat ECD-30 and 20% dibutyl sebacate as plasticizer: partition mechanism and pore diffusion. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 12 10234524
2021 Increased chemosensitivity via BRCA2-independent DNA damage in DSS1- and PCID2-depleted breast carcinomas. Laboratory investigation; a journal of technical methods and pathology 11 34031538
2016 Meaningful interpretation of serum HER2 ECD levels requires clear patient clinical background, and serves several functions in the efficient management of breast cancer patients. Clinica chimica acta; international journal of clinical chemistry 11 27109901
2013 A novel role for Sem1 and TREX-2 in transcription involves their impact on recruitment and H2B deubiquitylation activity of SAGA. Nucleic acids research 11 23599000
2010 Sem1: a versatile "molecular glue"? Nucleus (Austin, Tex.) 11 21327099
2008 Determination of Bisphenol A (BPA) in Plasma of Hemodialysis Patients Using Three Methods: LC/ECD, LC/MS, and ELISA. Toxicology mechanisms and methods 11 20020932
2007 Disposition of protein-bound 3-nitrotyrosine in rat plasma analysed by a novel protocol for HPLC-ECD. Journal of biochemistry 11 17261543
1997 Compilation of DNA sequences of Escherichia coli K12: description of the interactive databases ECD and ECDC (update 1996). Nucleic acids research 11 9016501
2023 SEM1 promotes tumor progression of glioblastoma via activating the akt signaling pathway. Cancer letters 10 37652287
2012 Dss1 release activates DNA binding potential in Brh2. Biochemistry 10 23094644