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

Gene ID: 166, updated on 7-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 cellular response to extracellular stimulus 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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