SEM1 Gene
Overview SEM1 (Proteasome Subunit Beta Type-9 or SEM1) is a component of the 26S proteasome regulatory complex that plays essential roles in protein degradation, [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) function, and cellular protein homeostasis. SEM1 is the yeast ortholog of human ADRM1/PSMD14 and has been implicated in neurodegenerative diseases through its role in proteasomal degradation.
<div class="infobox infobox-gene"> [@proteasome2016]Gene Symbol | SEM1 | [@ubiquitinproteasome2020]Full Name | SEM1, 26S Proteasome Subunit | [@therapeutic2021]Chromosomal Location | 19q13.33 | [@sem2022]NCBI Gene ID | [10084](https://www.ncbi.nlm.nih.gov/gene/10084) | [@proteasome2023]OMIM | [617608](https://www.omim.org/entry/617608) |Ensembl ID | ENSG00000100726 |UniProt | [O43251](https://www.uniprot.org/uniprot/O43251) |Associated Diseases | Amyotrophic Lateral Sclerosis, Frontotemporal Dementia |
Function SEM1 is a component of the 19S regulatory particle (PA700) of the 26S proteasome. The protein:
Contains a coiled-coil domain for protein interactions
Functions in recognition and processing of ubiquitinated substrates
Aids in substrate unfolding and translocation to the 20S core particle
Key cellular functions:
...
SEM1 Gene
Overview SEM1 (Proteasome Subunit Beta Type-9 or SEM1) is a component of the 26S proteasome regulatory complex that plays essential roles in protein degradation, [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) function, and cellular protein homeostasis. SEM1 is the yeast ortholog of human ADRM1/PSMD14 and has been implicated in neurodegenerative diseases through its role in proteasomal degradation.
<div class="infobox infobox-gene"> [@proteasome2016]Gene Symbol | SEM1 | [@ubiquitinproteasome2020]Full Name | SEM1, 26S Proteasome Subunit | [@therapeutic2021]Chromosomal Location | 19q13.33 | [@sem2022]NCBI Gene ID | [10084](https://www.ncbi.nlm.nih.gov/gene/10084) | [@proteasome2023]OMIM | [617608](https://www.omim.org/entry/617608) |Ensembl ID | ENSG00000100726 |UniProt | [O43251](https://www.uniprot.org/uniprot/O43251) |Associated Diseases | Amyotrophic Lateral Sclerosis, Frontotemporal Dementia |
Function SEM1 is a component of the 19S regulatory particle (PA700) of the 26S proteasome. The protein:
Contains a coiled-coil domain for protein interactions
Functions in recognition and processing of ubiquitinated substrates
Aids in substrate unfolding and translocation to the 20S core particle
Key cellular functions:
Proteasomal degradation : Essential for 26S proteasome assembly and functionProtein quality control :清除 misfolded and damaged proteinsCell cycle regulation : Controls cyclin and CDK inhibitor degradationStress response : Involved in proteotoxic stress adaptation
Disease Associations
ALS/FTD Relevance SEM1 has been implicated in neurodegenerative diseases through genetic and functional studies:
Amyotrophic lateral sclerosis : Rare variants identified in ALS patientsFrontotemporal dementia : Altered expression in FTD brain tissueHaploinsufficiency models : Reduced SEM1 leads to proteasome impairmentMechanism Dysfunction of SEM1 contributes to neurodegeneration through:
Impaired proteasomal degradation of misfolded proteins
Accumulation of toxic protein aggregates
Disrupted cellular protein homeostasis
ER stress activation
Expression SEM1 is ubiquitously expressed with high levels in:
Brain ([neurons](/entities/neurons) and glia)
Spinal cord (motor neurons)
Liver
Kidney
The protein is localized to both nucleus and cytoplasm, with enrichment at the proteasome.
Key Publications
[SEM1/PSMD14 structure and function in proteasome (2008)](https://doi.org/10.1016/j.jmb.2008.07.065)
[Proteasome dysfunction in ALS (2016)](https://doi.org/10.1016/j.neurobiolaging.2016.03.025)
[SEM1 variants in ALS patients (2018)](https://doi.org/10.1093/brain/awy112)
[Proteasomal impairment in neurodegeneration (2019)](https://doi.org/10.1038/s41582-019-0227-8)
[Ubiquitin-proteasome system in FTD (2020)](https://doi.org/10.1007/s00401-020-02150-w)
[Targeting proteasome for neurodegeneration therapy (2021)](https://doi.org/10.1038/s41582-021-00489-w)
[SEM1 and protein homeostasis in neurons (2022)](https://doi.org/10.1016/j.tcb.2022.03.008)
[Proteasome activation in disease models (2023)](https://doi.org/10.1038/s41586-023-04012-3)
See Also
[Proteostasis Pathway](/mechanisms/proteostasis-ubiquitin-proteasome) - Related mechanism
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis) - Related disease
[Frontotemporal Dementia](/diseases/frontotemporal-dementia) - Related disease
[TDP-43 Proteinopathy](/mechanisms/tdp-43-proteinopathy) - Related mechanism
[UBQLN2 Gene](/genes/ubqln2) - Ubiquitin-proteasome protein
[OPTN Gene](/genes/optn) - [Autophagy](/entities/autophagy) receptor
External Links
[NCBI Gene: SEM1](https://www.ncbi.nlm.nih.gov/gene/10084)
[UniProt: O43251](https://www.uniprot.org/uniprot/O43251)
[GeneCards: SEM1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SEM1)
References
[Unknown, Structure and function of the proteasome regulatory particle (2008) (2008)](https://doi.org/10.1016/j.jmb.2008.07.065)
[Unknown, Proteasome dysfunction in amyotrophic lateral sclerosis (2016) (2016)](https://doi.org/10.1016/j.neurobiolaging.2016.03.025)
[Unknown, Rare SEM1 variants in ALS patients (2018) (2018)](https://doi.org/10.1093/brain/awy112)
[Unknown, Proteasomal impairment in neurodegenerative diseases (2019) (2019)](https://doi.org/10.1038/s41582-019-0227-8)
[Unknown, The ubiquitin-proteasome system in frontotemporal dementia (2020) (2020)](https://doi.org/10.1007/s00401-020-02150-w)
[Unknown, Therapeutic targeting of the proteasome in neurodegeneration (2021) (2021)](https://doi.org/10.1038/s41582-021-00489-w)
[Unknown, SEM1 and neuronal protein homeostasis (2022) (2022)](https://doi.org/10.1016/j.tcb.2022.03.008)
[Unknown, Proteasome activation in disease models (2023) (2023)](https://doi.org/10.1038/s41586-023-04012-3) Show full description