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LYRIC protein ; 3D3/LYRIC; astrocyte elevated gene-1 protein; AEG-1; lysine-rich CEACAM1 co-isolated protein; metadherin; metastasis adhesion protein (MTDH, AEG1, LYRIC)
Function:
- downregulates SLC1A2/EAAT2 promoter activity when expressed ectopically
- activates the nuclear factor kappa-B (NF-kappa-B) transcription factor
- promotes anchorage-independent growth of immortalized melanocytes & astrocytes
- promotes lung metastasis
- also has an effect on bone & brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium
- induces chemoresistance
- interacts with BCIPP, CREBBP/CBP & RELA/p65
Compartment:
- endoplasmic reticulum membrane
- nuclear membrane
- cell junction, tight junction
- single pass membrane protein
- nucleus, nucleolus (putative)
- cytoplasm, perinuclear region
- in epithelial cells, recruited to tight junctions during maturation of tight junction complexes
- nucleolar staining may be due to nuclear targeting of an isoform lacking the transmembrane domain
- TNF-alpha causes translocation from the cytoplasm to the nucleus
Expression:
- widely expressed
- highest levels in muscle-dominating organs such as skeletal muscle, heart, tongue & small intestine & in endocrine glands such as thyroid & adrenal gland
- induced by TNF (at protein level)
- induced in primary fetal astrocytesby HIV-1 infection
- knockdown (inhibition of ecpression) significantly reduces the adhesion of cancer cells to lung microvascular endothelial cells & the reciprocal effect is observed following overexpression
Pathology:
- overexpressed in various cancers including breast cancer, prostate carcinoma, melanoma & glioblastoma multiforme
- possibly mediates breast cancer metastasis to lung
Notes:
- originally thought to be a type 2 membrane protein
Related
metastasis
General
membrane protein
phosphoprotein
Properties
SIZE: entity length = 582 aa
MW = 64 kD
COMPARTMENT: cytoplasm
cell nucleus
endoplasmic reticulum
MOTIF: domain {1-71}
MOTIF: transmembrane domain {49-69}
BCCIP interaction {72-169}
RELA interaction {101-205}
MOTIF: Ser phosphorylation site {S111}
Thr phosphorylation site {T143}
Ser phosphorylation site {S295}
Ser phosphorylation site {S298}
Ser phosphorylation site {S308}
Ser phosphorylation site {S311}
Ser phosphorylation site {S344}
Ser phosphorylation site {S369}
Lung-homing {381-443}
MOTIF: Ser phosphorylation site {S415}
Ser phosphorylation site {S426}
lysine-rich region {441-451}
MOTIF: lysine residue (SEVERAL)
Thr phosphorylation site {T458}
Ser phosphorylation site {S568}
lysine-rich region {573-577}
MOTIF: lysine residue (SEVERAL)
Database Correlations
OMIM 610323
UniProt Q86UE4
Entrez Gene 92140
Kegg hsa:92140
References
- UniProt :accession Q86UE4
- Pubmed: 15093543