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FLASH GENE
Symbol BRMS1 contributors: mct/npt - updated : 12-06-2013
HGNC name breast cancer metastasis-suppressor 1
HGNC id 17262
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunetonsils   highly
Nervousbrain    
Respiratoryrespiratory tractlarynx  highly
Visualeyeuveachoroid  
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier/liningretinal pigment epithelium (RPE)  
Lymphoid    
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • both nuclear import and export signals enabling its nucleo-cytoplasmic shuttling
  • two predicted nuclear localization sequences (NLS) that are located near the C-terminus (amino acids 198-205 and 238-244, NLS1 and NLS2 respectively, with an important role for NLS2 in the cytoplasm that is critical for metastasis suppression and is distinct from nuclear localization
  • HOMOLOGY
    Homologene
    FAMILY
  • BRMS1 family
  • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • predominantly nuclear protein that suppresses metastasis in multiple human and murine carcinoma cell lines
  • cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion
  • basic FUNCTION
  • may be a mediator of metastasis suppression in breast carcinoma
  • inhibits metastases in multiple organs by blocking several steps in the metastatic cascade
  • regulate the expression of multiple metastasis-associated microRNAs (miR-10b, -373, -520C, -146a, -146b, and -335) in breast carcinoma cells
  • suppresses metastasis without affecting primary tumorigenesis
  • potential role of BRMS1 in regulating Hepatocellular carcinoma apoptosis and metastasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • member of mSin3-HDAC transcription co-repressor complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting wth SPP1 (regulates SPP1 transcription by abrogating NF-kappaB activation)
  • recruits HDAC1 to the NF-kappaB binding site of the PLAU promoter, modulates histone acetylation of RELA on the PLAU promoter, leading to reduced NF-kappaB binding activity on its consensus sequence, and reduced transactivation of PLAU expression
  • association of SNX6 with breast cancer metastasis suppressor 1 (BRMS1) protein
  • ING4 is a downstream target of BRMS1 in regulating tumor angiogenesis
  • inhibits the activity of NFKB1, a well-known transcription factor that plays significant roles in tumor progression. Moreover, and coordinately regulates the expression of metastasis-associated microRNA known as metastamir (
  • CUL3, a component of E3 ubiquitin ligase, is a new binding partner of BRMS1 and the interaction between BRMS1 and CUL3 is mediated by the SPOP adaptor protein
  • suppresses osteopontin (SPP1) expression in Hepatocellular carcinoma cells (HCC) and there is a negative correlation between BRMS1 and SPP1 mRNA expression in HCC tissues
  • induces polyubiquitination of EP300, resulting in its proteasome-mediated degradation
  • cell & other
    REGULATION
    Other ubiquitination-dependent degradation by the CUL3–SPOP complex is a novel regulatory mechanism of BRMS1 and this regulation is important for breast cancer progression
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in oral squamous cell carcinoma
    tumoral   deletion    
    in cervical carcinoma
    tumoral   LOH    
    in prostatic cancer
    tumoral   deletion    
    in isolated familial somatotropinoma
    tumoral     --low  
    in breast cancer brain metastasis
    tumoral     --low  
    in metastatic melanoma compared with primary melanoma or dysplastic nevi
    tumoral     --low  
    in hepatocellular carcinoma cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerskin 
    may serve an therapeutic target for melanoma patients
    cancerreproductivebreast
    CUL3–SPOP-mediated degradation of BRMS1 could be a new therapeutic target for improving the treatment efficiency of breast cancer
    ANIMAL & CELL MODELS