protein
E3 ubiquitin-protein ligase ARIH1
Gene
ARIH1
Organism
Homo sapiens(9606)
Length
557 aa
Mass
64,118 Da
ARIH1 (E3 ubiquitin-protein ligase ARIH1) is an atypical E3 ubiquitin ligase that catalyzes ubiquitination of target proteins in conjunction with ubiquitin-conjugating enzyme UBE2L3 (UniProt: Q9Y4X5). It functions within cullin-RING ubiquitin ligase (CRL) complexes to initiate ubiquitination of CRL substrates, with the initial ubiquitin subsequently elongated by CDC34 and UBE2R. ARIH1 is activated upon binding to neddylated CRL complexes and also regulates protein translation in response to DNA damage through ubiquitination of EIF4E2.
ARIH1 participates in cellular protein quality control and nuclear organization pathways. The protein mediates ubiquitination of SUN2, a linker of nucleoskeleton and cytoskeleton (LINC) complex member, influencing nuclear localization and morphology. No disease associations are documented in UniProt for ARIH1.
In Alzheimer's disease brain tissue, ARIH1 shows ambiguous regulation across subcellular fractions in post-mortem AD compared to age-matched controls (Chaparral AD proteomics). Analysis of human brain tissue by tandem mass tag proteomics across four subcellular fractions yielded a mean log2 fold-change of −0.55, indicating modest overall reduction, though directionality varies by cellular compartment. This suggests potential compartment-specific dysregulation in AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
⚠ Ambiguous — detected in AD samples, direction unclear across fractionsP3
not detected
P2
+0.273
S2
-1.370
S3
not detected
Mean log₂FC across detected fractions: -0.5485 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:23707686, PubMed:24076655, PubMed:27565346). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets (PubMed:27565346). The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346). Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear (PubMed:25624349). According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report EIF4E2 ubiquitination leads to its subsequent degradation (PubMed:14623119). Acts as the ligase involved in ISGylation of EIF4E2 (PubMed:17289916). In vitro, controls the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may therefore have a role in the formation and localization of the LINC complex, and as a consequence, nuclear subcellular localization and nuclear morphology (PubMed:29689197)
Sources
Last updated 5/8/2026, 6:30:00 AM