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    TLE5 TLE family member 5, transcriptional modulator [ Homo sapiens (human) ]

    Gene ID: 166, updated on 25-Apr-2024

    Summary

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    Official Symbol
    TLE5provided by HGNC
    Official Full Name
    TLE family member 5, transcriptional modulatorprovided by HGNC
    Primary source
    HGNC:HGNC:307
    See related
    Ensembl:ENSG00000104964 MIM:600188; AllianceGenome:HGNC:307
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AES; GRG; ESP1; GRG5; AES-1; AES-2; Grg-5
    Summary
    The protein encoded by this gene is similar in sequence to the amino terminus of Drosophila enhancer of split groucho, a protein involved in neurogenesis during embryonic development. The encoded protein, which belongs to the groucho/TLE family of proteins, can function as a homooligomer or as a heteroologimer with other family members to dominantly repress the expression of other family member genes. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in heart (RPKM 135.6), spleen (RPKM 116.8) and 25 other tissues See more
    Orthologs
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    Genomic context

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    Location:
    19p13.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (3052910..3062966, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (3026363..3036419, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (3052908..3062964, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9819 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2982456-2982974 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2982975-2983491 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr19:2984010-2984526 Neighboring gene TLE family member 6, subcortical maternal complex member Neighboring gene ReSE screen-validated silencer GRCh37_chr19:3003179-3003325 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3006113-3007047 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:3007156-3007353 Neighboring gene TLE family member 2, transcriptional corepressor Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13724 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9820 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9821 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:3041680-3041803 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:3054606-3055171 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3057431-3057995 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3057996-3058560 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:3059514-3059717 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9822 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9823 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9824 Neighboring gene uncharacterized LOC105372242 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:3066867-3067075 Neighboring gene Sharpr-MPRA regulatory region 11171 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:3076432-3076689 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3094165-3095152 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3095153-3096138 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:3096139-3097126 Neighboring gene Sharpr-MPRA regulatory region 3290 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9829 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9830 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:3107873-3108374 Neighboring gene G protein subunit alpha 11

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Amino-terminal enhancer of split (AES) interacts with the oncoprotein NUP98-HOXA9 and enhances its transforming ability. Sarma NJ, et al. J Biol Chem, 2011 Nov 11. PMID 21937451, Free PMC Article
    2. Structural and functional analysis of amino-terminal enhancer of split in androgen-receptor-driven transcription. Zhang Y, et al. Biochem J, 2010 Apr 14. PMID 20163360
    3. Ovarian and breast cytotoxic T lymphocytes can recognize peptides from the amino enhancer of split protein of the Notch complex. Babcock B, et al. Mol Immunol, 1998 Dec. PMID 10395201
    4. Genomic organization and chromosome localization to band 19p13.3 of the human AES gene: gene product exhibits strong similarity to the N-terminal domain of Drosophila enhancer of Split Groucho protein. Hou EW, et al. DNA Cell Biol, 1998 Oct. PMID 9809752
    5. Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES). Han EH, et al. Biochem Biophys Res Commun, 2015 Dec 4-11. PMID 26549228

    See all (78) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Unrevealed roles of extracellular enolase-1 (ENO1) in promoting glycolysis and pro-cancer activities in multiple myeloma via hypoxia-inducible factor 1alpha.
      Title: Unrevealed roles of extracellular enolase‑1 (ENO1) in promoting glycolysis and pro‑cancer activities in multiple myeloma via hypoxia‑inducible factor 1α.
    2. The CK1delta/epsilon-AES axis regulates tumorigenesis and metastasis in colorectal cancer.
      Title: The CK1δ/ε-AES axis regulates tumorigenesis and metastasis in colorectal cancer.
    3. Results suggest that amino enhancer of split protein (AES) plays an important role in controlling tumor growth and metastasis of prostate cancer (PCa) by regulating both androgen receptor (AR) and Notch signaling pathway.
      Title: Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer.
    4. results indicate that Aes may belong to a novel family of metastasis suppressors with a CpG-island promoter enhancer, and it is regulated transcriptionally
      Title: Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2.
    5. heat shock cognate 70 (HSC70) is an essential component of Aes foci in colorectal cancer cells.
      Title: Characterization of Aes nuclear foci in colorectal cancer cells.
    6. AES is a transcriptional repressor for HNF-1-alpha in pancreatic beta-cell.
      Title: Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES).
    7. AES binds to PROP1 and represses its expression; PROP1 mutation is a likely cause of combined pituitary hormone deficiency.
      Title: A PROP1-binding factor, AES cloned by yeast two-hybrid assay represses PROP1-induced Pit-1 gene expression.
    8. GRG5/AES interacts with TCF4 and represses Wnt-mediated transcription both in human cells and zebrafish embryos.
      Title: GRG5/AES interacts with T-cell factor 4 (TCF4) and downregulates Wnt signaling in human cells and zebrafish embryos.
    9. alteration of the malignant behavior of cancer cells by AES is related to RND3 regulation.
      Title: Suppression of RND3 activity by AES downregulation promotes cancer cell proliferation and invasion.
    10. In the presence of NUP98-HOXA9, AES caused an increase in long-term proliferation of primary human CD34+ cells with a marked increase in the numbers of primitive cells.
      Title: Amino-terminal enhancer of split (AES) interacts with the oncoprotein NUP98-HOXA9 and enhances its transforming ability.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of amino-terminal enhancer of split (AES) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed
    Knockdown of amino-terminal enhancer of split (AES) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription corepressor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription corepressor activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of response to cytokine stimulus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of anoikis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to interleukin-1 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in skeletal system development IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    TLE family member 5
    Names
    amino-terminal enhancer of split
    gp130-associated protein GAM
    groucho-related protein 5

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029870.1 RefSeqGene

      Range
      5472..15057
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001130.6 → NP_001121.2  TLE family member 5 isoform b

      See identical proteins and their annotated locations for NP_001121.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (b) is shorter and has a distinct N-terminus compared to isoform a.
      Source sequence(s)
      AC005944, AF269289, AK094591, BM550097, BM908356
      Consensus CDS
      CCDS12102.1
      UniProtKB/Swiss-Prot
      B2RBL0, Q08117, Q12808, Q14CJ1, Q96TG9, Q9UDY9
      Related
      ENSP00000317537.4, ENST00000327141.9
      Conserved Domains (1) summary
      pfam03920
      Location:11 → 132
      TLE_N; Groucho/TLE N-terminal Q-rich domain

    2. NM_198969.1 → NP_945320.1  TLE family member 5 isoform a

      See identical proteins and their annotated locations for NP_945320.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AF269289, AK094591, BG913049, N23852
      Consensus CDS
      CCDS12101.1
      UniProtKB/Swiss-Prot
      Q08117
      UniProtKB/TrEMBL
      Q8WY48
      Related
      ENSP00000221561.7, ENST00000221561.12
      Conserved Domains (1) summary
      pfam03920
      Location:72 → 199
      TLE_N; Groucho/TLE N-terminal Q-rich domain

    3. NM_198970.2 → NP_945321.1  TLE family member 5 isoform c

      See identical proteins and their annotated locations for NP_945321.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (c) is shorter, has a distinct N-terminus, and lacks 1 aa in the C-terminus compared to isoform a.
      Source sequence(s)
      AC005944, AF269289, AK094591, BG696926, BM908356
      UniProtKB/Swiss-Prot
      Q08117
      UniProtKB/TrEMBL
      Q8WY48
      Conserved Domains (1) summary
      pfam03920
      Location:11 → 131
      TLE_N; Groucho/TLE N-terminal Q-rich domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      3052910..3062966 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006722664.2 → XP_006722727.1  TLE family member 5 isoform X1

      Conserved Domains (1) summary
      pfam03920
      Location:72 → 198
      TLE_N; Groucho/TLE N-terminal Q-rich domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      3026363..3036419 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054320108.1 → XP_054176083.1  TLE family member 5 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q08117.4 GenPept UniProtKB/Swiss-Prot:Q08117

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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