SHLD2 is the DNA-binding scaffold of the shieldin complex. It connects the SHLD3–REV7 module to SHLD1 and helps protect DNA ends from excessive resection, favoring non-homologous end joining over homologous recombination. Shieldin accumulates at nuclear DNA breaks and supports immunoglobulin class switching and end joining at damaged telomeres.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | NAS PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 is recruited to damaged chromatin. Reason: The shieldin complex acts at chromosomal DNA breaks. Chromatin/chromosome localization agrees with the recruitment experiments and does not imply a constitutive chromosome-wide distribution. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0002208 somatic diversification of immunoglobulins involved in immune response | NAS PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: Shieldin supports immunoglobulin diversification by class switching. Reason: The experimentally supported mechanism is end joining of class-switch breaks. The broad diversification term is retained as a specialized immune context of the DNA-repair machinery, rather than implying every form of antibody diversification. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: The interaction is part of shieldin complex assembly. Reason: PMID:29656893 identifies the shieldin subunits and their interactions. Retain this partner-specific experimental interaction, while the generic protein-binding term adds little functional specificity beyond the DNA-binding scaffold activity. Supporting Evidence: file:human/SHLD2/SHLD2-uniprot.txt SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 CC subcomplex via its N-terminus, and with SHLD1 via its C-terminus |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: The interaction is part of shieldin complex assembly. Reason: PMID:29656893 identifies the shieldin subunits and their interactions. Retain this partner-specific experimental interaction, while the generic protein-binding term adds little functional specificity beyond the DNA-binding scaffold activity. Supporting Evidence: file:human/SHLD2/SHLD2-uniprot.txt SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 CC subcomplex via its N-terminus, and with SHLD1 via its C-terminus |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: The interaction is part of shieldin complex assembly. Reason: PMID:29656893 identifies the shieldin subunits and their interactions. Retain this partner-specific experimental interaction, while the generic protein-binding term adds little functional specificity beyond the DNA-binding scaffold activity. Supporting Evidence: file:human/SHLD2/SHLD2-uniprot.txt SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 CC subcomplex via its N-terminus, and with SHLD1 via its C-terminus |
| GO:0005515 protein binding | IPI PMID:29789392 FAM35A associates with REV7 and modulates DNA damage respons... | KEEP AS NON CORE | Summary: FAM35A associates with REV7, RIF1 and 53BP1 in the DNA-repair pathway. Reason: The full-text reciprocal immunoprecipitation experiments support the recorded interaction. Association alone does not establish a separate core molecular activity or direct contact for every recovered partner. Supporting Evidence: PMID:29789392 DNA repair proteins associating with FAM35A included REV7, RIF1, BLM, and TOP3A |
| GO:0005515 protein binding | IPI PMID:29789392 FAM35A associates with REV7 and modulates DNA damage respons... | KEEP AS NON CORE | Summary: FAM35A associates with REV7, RIF1 and 53BP1 in the DNA-repair pathway. Reason: The full-text reciprocal immunoprecipitation experiments support the recorded interaction. Association alone does not establish a separate core molecular activity or direct contact for every recovered partner. Supporting Evidence: PMID:29789392 DNA repair proteins associating with FAM35A included REV7, RIF1, BLM, and TOP3A |
| GO:0005515 protein binding | IPI PMID:29789392 FAM35A associates with REV7 and modulates DNA damage respons... | KEEP AS NON CORE | Summary: FAM35A associates with REV7, RIF1 and 53BP1 in the DNA-repair pathway. Reason: The full-text reciprocal immunoprecipitation experiments support the recorded interaction. Association alone does not establish a separate core molecular activity or direct contact for every recovered partner. Supporting Evidence: PMID:29789392 DNA repair proteins associating with FAM35A included REV7, RIF1, BLM, and TOP3A |
| GO:0005515 protein binding | IPI PMID:34354233 ASTE1 promotes shieldin-complex-mediated DNA repair by atten... | KEEP AS NON CORE | Summary: ASTE1 is a shieldin-associated DNA-repair factor. Reason: The original study places ASTE1 downstream of shieldin. Retain the curated physical interaction without treating generic binding as a separate core function; the cached abstract does not by itself establish the detailed contact geometry. Supporting Evidence: PMID:34354233 The SHLD2 subunit binds to single-stranded DNA ends and blocks end resection through OB-fold domains. |
| GO:0005634 nucleus | EXP PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 functions in the nucleus during DNA repair. Reason: Nuclear localization is supported by FAM35A imaging and the independently characterized shieldin recruitment mechanism. The IBA and vocabulary-derived rows agree with this experimentally grounded function. Supporting Evidence: PMID:29789392 FAM35A re-localized in damaged cell nuclei PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: SHLD2 functions in the nucleus during DNA repair. Reason: Nuclear localization is supported by FAM35A imaging and the independently characterized shieldin recruitment mechanism. The IBA and vocabulary-derived rows agree with this experimentally grounded function. Supporting Evidence: PMID:29789392 FAM35A re-localized in damaged cell nuclei PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0005634 nucleus | IDA PMID:29789392 FAM35A associates with REV7 and modulates DNA damage respons... | ACCEPT | Summary: SHLD2 functions in the nucleus during DNA repair. Reason: Nuclear localization is supported by FAM35A imaging and the independently characterized shieldin recruitment mechanism. The IBA and vocabulary-derived rows agree with this experimentally grounded function. Supporting Evidence: PMID:29789392 FAM35A re-localized in damaged cell nuclei PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: SHLD2 functions in the nucleus during DNA repair. Reason: Nuclear localization is supported by FAM35A imaging and the independently characterized shieldin recruitment mechanism. The IBA and vocabulary-derived rows agree with this experimentally grounded function. Supporting Evidence: PMID:29789392 FAM35A re-localized in damaged cell nuclei PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasmic localization agrees with nuclear SHLD2 function. Reason: The HPA immunofluorescence record lists nucleoplasm as the main location with supported reliability, consistent with the DNA-damage localization studies. Supporting Evidence: file:human/SHLD2/SHLD2-hpa.xml Mainly localized to the nucleoplasm. In addition localized to the actin filaments. PMID:29789392 FAM35A re-localized in damaged cell nuclei |
| GO:0005694 chromosome | IDA PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 is recruited to damaged chromatin. Reason: The shieldin complex acts at chromosomal DNA breaks. Chromatin/chromosome localization agrees with the recruitment experiments and does not imply a constitutive chromosome-wide distribution. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: SHLD2 is recruited to damaged chromatin. Reason: The shieldin complex acts at chromosomal DNA breaks. Chromatin/chromosome localization agrees with the recruitment experiments and does not imply a constitutive chromosome-wide distribution. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0010569 regulation of double-strand break repair via homologous recombination | IBA GO_REF:0000033 | MODIFY | Summary: SHLD2 restrains homologous recombination through end protection. Reason: The broad regulation term is correct but the loss-of-function evidence establishes negative regulation: depletion permits resection and RAD51 focus formation in BRCA1-deficient cells. The gene-level judgment does not assert equivalent activity of all isoforms: PMID:30022168 reports an OB-fold-disrupting short splice form that retains recruitment but fails to suppress HR. Proposed replacements: negative regulation of double-strand break repair via homologous recombination Supporting Evidence: PMID:29789392 However, the BRCA1‐mutant cells formed damage‐dependent nuclear RAD51 foci following FAM35A depletion, suggesting that 5′ end resection was more active in the absence of FAM35A (Fig 5B). PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. |
| GO:0035861 site of double-strand break | IBA GO_REF:0000033 | ACCEPT | Summary: SHLD2 is recruited to DNA double-strand breaks. Reason: Shieldin recruitment downstream of the ATM–53BP1–RIF1 pathway directly supports this location. This is the site at which the complex protects DNA ends. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0035861 site of double-strand break | IDA PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 is recruited to DNA double-strand breaks. Reason: Shieldin recruitment downstream of the ATM–53BP1–RIF1 pathway directly supports this location. This is the site at which the complex protects DNA ends. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0035861 site of double-strand break | NAS PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 is recruited to DNA double-strand breaks. Reason: Shieldin recruitment downstream of the ATM–53BP1–RIF1 pathway directly supports this location. This is the site at which the complex protects DNA ends. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0043247 telomere maintenance in response to DNA damage | NAS PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: Shieldin promotes joining of deprotected telomeres. Reason: The reported telomere phenotype concerns end joining of unprotected chromosome ends. Retain this specialized damage-response context without implying routine telomerase-mediated telomere lengthening. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:0045830 positive regulation of isotype switching | IDA PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: Shieldin promotes immunoglobulin class-switch recombination. Reason: Class switching is a specific physiological use of shieldin-mediated end joining. The underlying work includes mammalian B-cell experiments; this is distinct from a constitutive immune-specific identity for SHLD2. Supporting Evidence: PMID:29656893 Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. |
| GO:2000042 negative regulation of double-strand break repair via homologous recombination | IDA PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 suppresses resection-dependent homologous recombination. Reason: Loss of FAM35A restores damage-induced RAD51 foci in BRCA1-deficient cells, consistent with shieldin restricting resection and homologous repair. The gene-level judgment does not assert equivalent activity of all isoforms: PMID:30022168 reports an OB-fold-disrupting short splice form that retains recruitment but fails to suppress HR. Supporting Evidence: PMID:29789392 However, the BRCA1‐mutant cells formed damage‐dependent nuclear RAD51 foci following FAM35A depletion, suggesting that 5′ end resection was more active in the absence of FAM35A (Fig 5B). PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. |
| GO:2001034 positive regulation of double-strand break repair via nonhomologous end joining | IDA PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 promotes non-homologous end joining. Reason: Independent shieldin identification and FAM35A depletion/rescue studies establish the direction of repair-pathway regulation. The gene supports end joining as a scaffold and DNA-end protector, rather than catalyzing ligation. The gene-level judgment does not assert equivalent activity of all isoforms: PMID:30022168 reports an OB-fold-disrupting short splice form that retains recruitment but fails to suppress HR. Supporting Evidence: PMID:29656893 We propose that 53BP1-RIF1 act upstream to facilitate the recruitment of the shieldin complex, which we postulate shields DSBs against resection and thereby promotes NHEJ. PMID:29789392 Expression of FAM35A isoform 1 in 293T cells (Fig 4D) restored NHEJ to normal levels (Fig 4E). PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. |
| GO:2001034 positive regulation of double-strand break repair via nonhomologous end joining | IDA PMID:29789392 FAM35A associates with REV7 and modulates DNA damage respons... | ACCEPT | Summary: SHLD2 promotes non-homologous end joining. Reason: Independent shieldin identification and FAM35A depletion/rescue studies establish the direction of repair-pathway regulation. The gene supports end joining as a scaffold and DNA-end protector, rather than catalyzing ligation. The gene-level judgment does not assert equivalent activity of all isoforms: PMID:30022168 reports an OB-fold-disrupting short splice form that retains recruitment but fails to suppress HR. Supporting Evidence: PMID:29656893 We propose that 53BP1-RIF1 act upstream to facilitate the recruitment of the shieldin complex, which we postulate shields DSBs against resection and thereby promotes NHEJ. PMID:29789392 Expression of FAM35A isoform 1 in 293T cells (Fig 4D) restored NHEJ to normal levels (Fig 4E). PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. |
| GO:2001034 positive regulation of double-strand break repair via nonhomologous end joining | NAS PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | ACCEPT | Summary: SHLD2 promotes non-homologous end joining. Reason: Independent shieldin identification and FAM35A depletion/rescue studies establish the direction of repair-pathway regulation. The gene supports end joining as a scaffold and DNA-end protector, rather than catalyzing ligation. The gene-level judgment does not assert equivalent activity of all isoforms: PMID:30022168 reports an OB-fold-disrupting short splice form that retains recruitment but fails to suppress HR. Supporting Evidence: PMID:29656893 We propose that 53BP1-RIF1 act upstream to facilitate the recruitment of the shieldin complex, which we postulate shields DSBs against resection and thereby promotes NHEJ. PMID:29789392 Expression of FAM35A isoform 1 in 293T cells (Fig 4D) restored NHEJ to normal levels (Fig 4E). PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. PMID:30022168 Importantly, both mutants localized to DSB sites (ED Fig 10cd) and interacted with the other members of the Shieldin complex (ED Fig 10e). Therefore, the SHLD2-m1 and SHLD2S mutants are defective in suppressing HR. |
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