BREM-1

BREM-1
Dmitriy Fomin from Moscow, Russia · CC BY 2.0 · source
Name	BREM-1
Organism	Homo sapiens
Chromosome	12
Length	~320 aa
Function	E3 ubiquitin ligase regulator

BREM-1 BREM-1 is a human protein implicated in protein ubiquitination and cellular signaling, identified through genetic screens and proteomic surveys. It has been characterized in studies involving model organisms, cell lines, and disease cohorts, and it interacts with multiple signaling complexes reported across biochemical, structural, and genomic investigations. Research on BREM-1 connects to work from laboratories and consortia in molecular biology, structural biology, immunology, and clinical genetics.

Introduction

BREM-1 emerged from high-throughput screens alongside proteins studied by groups at the Broad Institute, Wellcome Trust Sanger Institute, National Institutes of Health, European Molecular Biology Laboratory, and university laboratories such as Harvard University, Stanford University, and Massachusetts Institute of Technology. Early reports compared BREM-1 to regulators characterized in studies on E3 ubiquitin ligase families investigated by teams including researchers from Cold Spring Harbor Laboratory and the Max Planck Society. Subsequent functional work referenced methods and standards from projects like the Human Genome Project, the ENCODE Project, and datasets produced by the 1000 Genomes Project.

Molecular Structure and Genetics

Sequence and structural analyses placed BREM-1 within protein families analyzed in comparative genomics by groups at University of Cambridge, Yale University, and University of California, Berkeley. Gene mapping located BREM1 on human chromosome 12 in loci discussed in genomic studies from institutions such as The Jackson Laboratory and Broad Institute. Structural models relied on approaches from the Protein Data Bank, cryo-EM facilities at European Synchrotron Radiation Facility, and algorithms developed by teams at DeepMind and University of Oxford. Mutational spectra were compared to datasets from clinical sequencing efforts like ClinVar, The Cancer Genome Atlas, and platforms supported by National Human Genome Research Institute.

Expression and Regulation

Transcriptomic profiling of BREM-1 used resources and pipelines from the GTEx Consortium, ENCODE Project, and studies published by laboratories at Johns Hopkins University, University of California, San Francisco, and Imperial College London. Regulatory control was analyzed in the context of transcription factors and chromatin modifiers characterized by groups studying TP53, NF-κB, and STAT3, and epigenetic signatures noted by teams involved in the Roadmap Epigenomics Project. Post-transcriptional regulation studies referenced RNA-binding proteins such as HuR and microRNA pathways described by laboratories at University of Pennsylvania and Cold Spring Harbor Laboratory.

Biological Functions and Signaling

Functional assays connected BREM-1 to ubiquitination cascades and signaling nodes explored in research on TRAF6, CUL3, MDM2, and adaptors examined by groups at University of Cambridge and Stanford University School of Medicine. Cell biological roles were investigated in contexts similar to studies of NF-κB pathway, MAPK pathway, and PI3K–AKT pathway by laboratories at Harvard Medical School and Karolinska Institutet. Interactions with components of innate immunity and inflammation were compared to findings on Toll-like receptor 4, NOD2, and cytokine signaling characterized by teams at Pasteur Institute and the Ragon Institute. Studies of cellular localization invoked imaging platforms used in consortia at Rockefeller University and Max Planck Institute for Biochemistry.

Clinical Significance and Disease Associations

Variants in the BREM1 locus have been evaluated in cohorts coordinated by consortia such as European Genome-phenome Archive studies and the UK Biobank, with disease associations explored alongside work on autoimmune disorders by groups at Mayo Clinic and Cleveland Clinic. Links to oncology have been examined in comparisons to mutations cataloged by The Cancer Genome Atlas and clinical sequencing programs at Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. Associations with inflammatory and metabolic disorders were contextualized by epidemiological studies conducted at Johns Hopkins Bloomberg School of Public Health and Harvard T.H. Chan School of Public Health. Pharmacogenomic relevance was discussed in papers connected to drug discovery efforts at Pfizer, Novartis, and academic drug centers at University of California, San Francisco.

Research Tools and Experimental Findings

Experimental work on BREM-1 employed methodologies developed in labs and cores such as the Broad Institute proteomics center, cryo-EM facilities at European Molecular Biology Laboratory, and sequencing platforms used by the Wellcome Sanger Institute. Knockout and knockdown studies used CRISPR approaches popularized by teams at Massachusetts Institute of Technology and Broad Institute, while protein–protein interaction mapping referenced pipelines from BioGRID and STRING. Functional genomics assays leveraged technologies advanced by the ENCODE Project and single-cell platforms from companies and groups like 10x Genomics and Broad Institute collaborators. Key experimental findings reported modulation of ubiquitination targets, effects on signaling flux in cell-based assays, and phenotypic consequences in model organisms studied at facilities including European Molecular Biology Laboratory and university research centers.

Category:Human proteins