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FLASH GENE
Symbol AMER1 contributors: mct/npt/pgu - updated : 29-08-2014
HGNC name APC membrane recruitment protein 1
HGNC id 26837
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 splicing 8443 150 1135 - 2009 19416806
2 splicing - - 858 in kidneys, brain, and spleen 2009 19416806
  • produced by an internal splicing event that removes amino acids 50–326 (Rivera 2009)
  • also called WTX-S
  • 2 - - - 804 - 2009 19416806
  • predicted to arise from a shorter second exon (785 aa) and an additional third exon that have not been confirmed endogenously
  • also called WTX-PRED
  • 2 - - 190 - - 2009 19416806
  • full-length nonspliceable transcript with a single nucleotide change that ablates the donor splice site while maintaining the same amino acid sequence
  • also called WTX-NS
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinelarge intestinecolon  
    Endocrinepancreas    
     thyroid    
    Lymphoid/Immunespleen    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus possesses phospholipid binding activity (localized to within residues 2–209, multiple phosphatidylinositol (4, 5)-bisphosphate binding sites that appear to mediate its localization to the plasma membrane
  • N-terminal clusters of lysines termed K1 and K2 conserved between AMER2 and AMER1
  • a domain that interacts with ß-catenin (CTNNB)
  • an acidic domain
  • three APC binding domains (APCBD1-3)
  • the binding domain for beta-catenin lies C terminal to residue Gly368, with a putative tumor suppressor motif within the C terminus
  • HOMOLOGY
    Homologene
    FAMILY
  • FAM123 family
  • CATEGORY unknown/unspecified
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • shuttles to the nucleus
  • present in distinct subnuclear structures and co-localizes with the paraspeckle marker NONO, suggesting a role in transcriptional regulation
  • basic FUNCTION
  • negatively regulating WNT signaling by promoting ß-catenin (CTNNB) ubiquitination
  • repressor of canonical WNT signaling, mediating repressive effects on the ossification of bones that develop both by a cartilage scaffold (for example, long bones) and by direct differentiation from mesenchymal precursors (for example, calvaria)
  • implicated in WNT signaling through enhancement of cytoplasmic beta-catenin (CTNNB1) degradation
  • critical for differentiation of mesenchymal progenitor cells
  • AMER1, AMER2, AMER3 have conserved and divergent cellular roles
  • may be playing a role in nuclear pathways implicated in the transcriptional regulation of cellular differentiation programs
  • may be directly involved in the transcriptional regulation of cellular differentiation programs through interactions with WT1 and potentially other transcription factors in the kidney and in other tissues
  • exerts its negative regulatory role in Wnt signaling by acting as a scaffold protein for the CTNNB destruction complex and promoting stabilization of Axin at the plasma membrane
  • tumor suppressor, frequently inactivated in Wilms tumor
  • nuclear fraction of AMER1 plays likely a role in epigenetic silencing, an effect that may contribute to its function as a regulator of cellular differentiation and tumorigenesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the CTNNB destruction complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds WT1, another Wilms tumor suppressor and stem cell marker that encodes a zinc-finger transcription factor, and enhances WT1-mediated transcription of Amphiregulin, an endogenous target gene
  • fusion of FAM123B to the cytoplasmic domain of LRP6 induces LRP6 phosphorylation and stimulates robust Wnt/beta catenin signalling
  • binds to the tumor suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing CTNNB degradation
  • can directly interact with CTNNB1 via repeats of the amino acid sequence REA
  • stabilizes Axin and counteracts Wnt-induced degradation of Axin, which requires membrane localization of FAM123B
  • AMER1 and NFE2L2 compete for binding to KEAP1, and thus loss of AMER1 leads to rapid ubiquitination and degradation of NFE2L2 and a reduced response to cytotoxic insult
  • modulates TP53 function, in part through regulation of its activator EP300
  • AMER1, PALB2, and SQSTM1 bind KEAP1 to activate NFE2L2
  • TRIM28 is the major binding partner for nuclear AMER1(AMER1 interacted with the coiled coil domain of TRIM28 required for its binding to Krüppel-associated box domains of transcription factors)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) OSCS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    inactivated in approximately one-third of Wilms tumors (15 of 51 tumors).
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS