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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ASCC2
activating signal cointegrator 1 complex subunit 2
Chromosome 22 · 22q12.2
NCBI Gene: 84164Ensembl: ENSG00000100325.16HGNC: HGNC:24103UniProt: Q9H1I8
74PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingregulation of DNA-templated transcriptionribosome disassemblyrescue of stalled cytosolic ribosomeneurodegenerative diseasetype 2 diabetes mellitustype 1 diabetes mellitusneurofibromatosis
✦AI Summary

ASCC2 is a ubiquitin-binding protein that functions as a critical component of the ASCC complex, with dual roles in DNA repair and ribosome quality control. In DNA repair, ASCC2 recognizes K63-linked polyubiquitin chains through its CUE domain and recruits the ASCC complex to sites of alkylation damage, specifically binding polyubiquitinated PCNA at stalled replication forks 12. This recruitment is essential for proper alkylation adduct repair kinetics; cells lacking functional ASCC2 show increased sensitivity to alkylating agents 1. In the ribosome quality control pathway, ASCC2 forms the human RQT complex alongside ASCC3 and TRIP4 34. Here, ASCC2 recognizes K63-linked polyubiquitin chains on ribosomal uS10 protein that are deposited by ZNF598 during ribosomal collision, promoting recruitment of the RQT complex and enabling ASCC3-mediated disassembly of stalled ribosomes 4. The ubiquitin-binding and ATPase activities of ASCC2 and ASCC3 are both crucial for triggering ribosome quality control 3. Additionally, ASCC2 participates in transcriptional regulation as part of the ASC-1 complex 5. Cancer-associated mutations in ASCC2 reduce its interaction affinity with ASCC3, potentially compromising both DNA repair and quality control functions 6.

Sources cited
1
ASCC2 recognizes K63-linked polyubiquitin chains via its CUE domain and recruits ASCC to alkylation damage sites; loss of ASCC2 impedes alkylation adduct repair and increases sensitivity to alkylating agents
PMID: 29144457
2
ASCC2 recruits ASCC3 to stalled replication forks in a ubiquitin binding-dependent manner through recognition of PCNA polyubiquitylation
PMID: 40777259
3
ASCC2 is a component of the human RQT complex and its ubiquitin-binding activity is crucial for triggering ribosome-associated quality control
PMID: 32099016
4
ASCC2 recognizes K63-linked polyubiquitin chains on ribosomal uS10 and promotes hRQT-mediated subunit dissociation of collided ribosomes
PMID: 36302773
5
ASCC2 is part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation
PMID: 12077347
6
Cancer-associated somatic mutations in ASCC2-ASCC3 interaction interfaces reduce binding affinity
PMID: 33139697
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.29Weak
type 1 diabetes mellitusOpen Targets
0.28Weak
neurofibromatosisOpen Targets
0.27Weak
Benign Brain NeoplasmOpen Targets
0.27Weak
Central Nervous System NeoplasmOpen Targets
0.27Weak
ulcerative colitisOpen Targets
0.25Weak
neurocutaneous syndromeOpen Targets
0.25Weak
response to mineral dust exposureOpen Targets
0.25Weak
migraine disorderOpen Targets
0.21Weak
denturesOpen Targets
0.21Weak
Abruptio PlacentaeOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.08Suggestive
Abnormality of refractionOpen Targets
0.08Suggestive
lung cancerOpen Targets
0.07Suggestive
irritable bowel syndromeOpen Targets
0.07Suggestive
thyroiditisOpen Targets
0.07Suggestive
hypothyroidismOpen Targets
0.07Suggestive
urinary bladder carcinomaOpen Targets
0.06Suggestive
mathematical abilityOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ALKBH3Protein interaction93%ASCC3Protein interaction90%TRIP4Protein interaction79%PPIL2Protein interaction73%ASCC1Protein interaction66%ZNF598Protein interaction63%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
86%
Lung
74%
Ovary
50%
Heart
49%
Brain
28%
Gene Interaction Network
Click a node to explore
ASCC2ALKBH3ASCC3TRIP4PPIL2ASCC1ZNF598
PROTEIN STRUCTURE
Preparing viewer…
PDB6YXQ · 2.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.46 [0.35–0.59]
RankingsWhere ASCC2 stands among ~20K protein-coding genes
  • #6,378of 20,598
    Most Researched74
  • #4,031of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedASCC2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair.
PMID: 29144457
Nature · 2017
1.00
2
The ASC-1 Complex Disassembles Collided Ribosomes.
PMID: 32579943
Mol Cell · 2020
0.90
3
The Ski2 helicase ASCC3 unwinds DNA upon fork stalling to control replication stress responses.
PMID: 40777259
bioRxiv · 2025
0.80
4
The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations.
PMID: 33139697
Nat Commun · 2020
0.70
5
Aberrant RNA methylation triggers recruitment of an alkylation repair complex.
PMID: 34686315
Mol Cell · 2021
0.60