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    EPS15 epidermal growth factor receptor pathway substrate 15 [ Homo sapiens (human) ]

    Gene ID: 2060, updated on 27-Nov-2024

    Summary

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    Official Symbol
    EPS15provided by HGNC
    Official Full Name
    epidermal growth factor receptor pathway substrate 15provided by HGNC
    Primary source
    HGNC:HGNC:3419
    See related
    Ensembl:ENSG00000085832 MIM:600051; AllianceGenome:HGNC:3419
    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
    AF1P; AF-1P; MLLT5
    Summary
    This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]
    Expression
    Ubiquitous expression in brain (RPKM 29.8), testis (RPKM 29.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See EPS15 in Genome Data Viewer
    Location:
    1p32.3
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (51354263..51519266, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (51234162..51399178, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (51819935..51984938, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904177 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:51763453-51764095 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 874 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:51777239-51777740 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:51777741-51778240 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:51778629-51779444 Neighboring gene tetratricopeptide repeat domain 39A Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 875 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1019 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1020 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1021 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1022 Neighboring gene TTC39A antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 876 Neighboring gene proteasome 26S subunit, non-ATPase 7 pseudogene Neighboring gene RNA, U6 small nuclear 877, pseudogene Neighboring gene MPRA-validated peak220 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1024 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:51984193-51985121 Neighboring gene EPS15 antisense RNA 1 Neighboring gene RNA, U6 small nuclear 1281, pseudogene Neighboring gene oxysterol binding protein like 9 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1026 Neighboring gene calreticulin 4, pseudogene

    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. Modified iPOND revealed the role of mutant p53 in promoting helicase function and telomere maintenance. Wang Q, et al. Aging (Albany NY), 2023 Oct 12. PMID 37827695, Free PMC Article
    2. A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Bernard OA, et al. Oncogene, 1994 Apr. PMID 8134107
    3. UIM domain-dependent recruitment of the endocytic adaptor protein Eps15 to ubiquitin-enriched endosomes. Gucwa AL, et al. BMC Cell Biol, 2014 Sep 27. PMID 25260758, Free PMC Article
    4. The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32. Wong WT, et al. Oncogene, 1994 Jun. PMID 8183552
    5. Over-expression of EPS15 is a favorable prognostic factor in breast cancer. Dai X, et al. Mol Biosyst, 2015 Nov. PMID 26289382

    See all (195) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Modified iPOND revealed the role of mutant p53 in promoting helicase function and telomere maintenance.
      Title: Modified iPOND revealed the role of mutant p53 in promoting helicase function and telomere maintenance.
    2. EPS15-NTRK1: a novel NTRK1 oncogenic fusion in patient with lung adenocarcinoma.
      Title: EPS15-NTRK1: a novel NTRK1 oncogenic fusion in patient with lung adenocarcinoma.
    3. Fcho1/2Eps15/RAP-2 ternary complexes to facilitate conformational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement.
      Title: Transient Fcho1/2⋅Eps15/R⋅AP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding.
    4. An interaction of Eps15 and pS227-FIP2 at the appropriate time and location in polarizing cells is necessary for proper establishment of epithelial polarity.
      Title: Interaction of phosphorylated Rab11-FIP2 with Eps15 regulates apical junction composition.
    5. RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.
      Title: Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.
    6. Together, the data indicate that a CUL3-SPOPL E3 ubiquitin ligase complex regulates endocytic trafficking and formation of multivesicular bodies by ubiquitinating and degrading EPS15 at endosomes.
      Title: A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes.
    7. identify USP9X as a novel regulator of EGFR endocytosis
      Title: USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15.
    8. over-expression of EPS15 is a potential favorable prognostic marker in breast cancer.
      Title: Over-expression of EPS15 is a favorable prognostic factor in breast cancer.
    9. MLL-EPS15 translocation and individual genomic copy number alterations in monozygotic infant twins are associated with acute lymphoblastic leukemia.
      Title: Molecular characterization of identical, novel MLL-EPS15 translocation and individual genomic copy number alterations in monozygotic infant twins with acute lymphoblastic leukemia.
    10. Ubiquitin is sufficient for Eps15 recruitment to endosomes.
      Title: UIM domain-dependent recruitment of the endocytic adaptor protein Eps15 to ubiquitin-enriched endosomes.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    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

    EBI GWAS Catalog

    Description
    A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of EPS15 by shRNA significantly inhibits HIV-1 replication in CD4+ T-cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef Genome-wide shRNA screening identifies EPS15, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells PubMed
    Pr55(Gag) gag Inhibition of endocytosis by siRNA-mediated depletion of EPS15, STX7, RAB7, and VAMP7 restores Gag/p24 expression in the presence of APOL1 PubMed
    capsid gag Inhibition of endocytosis by siRNA-mediated depletion of EPS15, STX7, RAB7, and VAMP7 restores Gag/p24 expression in the presence of APOL1 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 SH3 domain binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cadherin binding HDA PubMed 
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables polyubiquitin modification-dependent protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Golgi to endosome transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in clathrin coat assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in endocytic recycling IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in endocytosis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in endosomal transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of receptor recycling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in postsynaptic neurotransmitter receptor internalization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in receptor-mediated endocytosis of virus by host cell IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in symbiont entry into host cell IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in vesicle organization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in aggresome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in apical plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in basal plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of clathrin coat of coated pit IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in clathrin-coated pit TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in early endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in membrane HDA PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in postsynaptic endocytic zone IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    epidermal growth factor receptor substrate 15
    Names
    ALL1 fused gene from chromosome 1
    protein AF-1p

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_001159969.2 → NP_001153441.1  epidermal growth factor receptor substrate 15 isoform B

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks multiple exons at the 5' end and has a distinct 5' UTR and start codon, compared to variant 1. These differences result in a protein (isoform B) with a shorter and distinct N-terminus, compared to isoform A. Isoform B localizes to early endosome membranes.
      Source sequence(s)
      AA789139, AK294297, AW949896, BM681433, BX647676, DA801048, U07707
      Consensus CDS
      CCDS90955.1
      UniProtKB/TrEMBL
      B3KR37
      Related
      ENSP00000516332.1, ENST00000493793.2
      Conserved Domains (4) summary
      pfam07926
      Location:89 → 195
      TPR_MLP1_2; TPR/MLP1/MLP2-like protein
      pfam10211
      Location:39 → 121
      Ax_dynein_light; Axonemal dynein light chain
      pfam12329
      Location:82 → 151
      TMF_DNA_bd; TATA element modulatory factor 1 DNA binding
      pfam15898
      Location:129 → 195
      PRKG1_interact; cGMP-dependent protein kinase interacting domain

    2. NM_001410796.1 → NP_001397725.1  epidermal growth factor receptor substrate 15 isoform C

      Status: REVIEWED

      Source sequence(s)
      AC104170, AL671986
      Consensus CDS
      CCDS90956.1
      UniProtKB/TrEMBL
      A0A994J5J3
      Related
      ENSP00000516334.1, ENST00000706288.1

    3. NM_001410797.1 → NP_001397726.1  epidermal growth factor receptor substrate 15 isoform D

      Status: REVIEWED

      Source sequence(s)
      AC104170, AL671986
      Consensus CDS
      CCDS90957.1
      UniProtKB/TrEMBL
      A0A994J5A3
      Related
      ENSP00000516336.1, ENST00000706292.1

    4. NM_001981.3 → NP_001972.1  epidermal growth factor receptor substrate 15 isoform A

      See identical proteins and their annotated locations for NP_001972.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (A). Isoform A mainly localizes to clathrin-coated pits at the plasma membrane.
      Source sequence(s)
      AL671986, CD657119, Z29064
      Consensus CDS
      CCDS557.1
      UniProtKB/Swiss-Prot
      B2R8J7, D3DPJ2, P42566, Q5SRH4
      UniProtKB/TrEMBL
      B1AUU8
      Related
      ENSP00000360798.3, ENST00000371733.8
      Conserved Domains (5) summary
      smart00027
      Location:121 → 215
      EH; Eps15 homology domain
      cd00052
      Location:228 → 293
      EH; Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A ...
      pfam03528
      Location:332 → 750
      Rabaptin; Rabaptin
      pfam12329
      Location:396 → 465
      TMF_DNA_bd; TATA element modulatory factor 1 DNA binding
      pfam16043
      Location:335 → 501
      DUF4795; Domain of unknown function (DUF4795)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      51354263..51519266 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017000618.3 → XP_016856107.1  epidermal growth factor receptor substrate 15 isoform X3

      UniProtKB/TrEMBL
      B1AUU8

    2. XM_017000617.3 → XP_016856106.1  epidermal growth factor receptor substrate 15 isoform X2

      UniProtKB/TrEMBL
      B1AUU8
      Related
      ENSP00000360795.2, ENST00000371730.6

    3. XM_017000616.3 → XP_016856105.1  epidermal growth factor receptor substrate 15 isoform X1

      UniProtKB/TrEMBL
      B1AUU8

    4. XM_047449243.1 → XP_047305199.1  epidermal growth factor receptor substrate 15 isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      51234162..51399178 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054335061.1 → XP_054191036.1  epidermal growth factor receptor substrate 15 isoform X3

    2. XM_054335060.1 → XP_054191035.1  epidermal growth factor receptor substrate 15 isoform X2

    3. XM_054335059.1 → XP_054191034.1  epidermal growth factor receptor substrate 15 isoform X1

    4. XM_054335062.1 → XP_054191037.1  epidermal growth factor receptor substrate 15 isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P42566.2 GenPept UniProtKB/Swiss-Prot:P42566

    Gene LinkOut

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

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