SHLD3 Gene

Name shieldin complex subunit 3
Description Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in nucleolus; nucleoplasm; and site of double-strand break. [provided by Alliance of Genome Resources, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nShieldin complex subunit 3 (SHLD3) serves as the apical subunit of the shieldin complex, playing a pivotal role in DNA double-strand break repair by mediating interactions with key repair proteins. Structural studies revealed that SHLD3 contains a ladle‐shaped REV7-binding domain (RBD) composed of a conserved N-terminal loop and a less-conserved C-terminal α-helix. Crystallographic analyses at 2.2–2.3 Å resolution showed that the N-terminal loop adopts a structure similar to that found in other REV7-binding proteins, while the α-helix region uses a distinct interaction mode to bind REV7 (“safety belt” region), which is critical for retarding the dissociation of the complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vitro and in vivo binding assays underscored that both the N-terminal loop and the α-helix are indispensable for achieving high-affinity (low-nanomolar) binding of SHLD3 to REV7. This dual-region interaction underpins the functional role of SHLD3 in organizing the shieldin complex and facilitating efficient DNA repair through regulated REV7 engagement."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yaxin Dai, Fan Zhang, Longge Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for shieldin complex subunit 3-mediated recruitment of the checkpoint protein REV7 during DNA double-strand break repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.011464"}], "href": "https://doi.org/10.1074/jbc.RA119.011464"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31796627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31796627"}]}]}]}
NCBI Gene ID 112441434
API
Download Associations
Predicted Functions View SHLD3's ARCHS4 Predicted Functions.
Co-expressed Genes View SHLD3's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View SHLD3's ARCHS4 Predicted Functions.

Functional Associations

SHLD3 has 697 functional associations with biological entities spanning 5 categories (functional term, phrase or reference, disease, phenotype or trait, chemical, cell line, cell type or tissue, gene, protein or microRNA) extracted from 20 datasets.

Click the + buttons to view associations for SHLD3 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of SHLD3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing SHLD3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with SHLD3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with SHLD3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with SHLD3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
GO Biological Process Annotations 2025 biological processes involving SHLD3 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2025 cellular components containing SHLD3 protein from the curated GO Cellular Component Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of SHLD3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of SHLD3 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with SHLD3 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of SHLD3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of SHLD3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of SHLD3 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
PFOCR Pathway Figure Associations 2024 pathways involving SHLD3 protein from the Wikipathways PFOCR 2024 dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of SHLD3 gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of SHLD3 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of SHLD3 gene from the RummaGEO Gene Perturbation Signatures dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of SHLD3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with SHLD3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2024 pathways involving SHLD3 protein from the WikiPathways Pathways 2024 dataset.