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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
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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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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

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Chemical Information
Molecular Biology Databases
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