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Aliases for EPS15 Gene

Aliases for EPS15 Gene

  • Epidermal Growth Factor Receptor Pathway Substrate 15 2 3 5
  • Protein AF-1p 3 4
  • AF1P 3 4
  • Epidermal Growth Factor Receptor Substrate 15 3
  • ALL1 Fused Gene From Chromosome 1 3
  • Protein Eps15 4
  • AF-1P 3
  • MLLT5 3

External Ids for EPS15 Gene

Previous GeneCards Identifiers for EPS15 Gene

  • GC01M050709
  • GC01M051179
  • GC01M051190
  • GC01M051532
  • GC01M051819
  • GC01M049937

Summaries for EPS15 Gene

Entrez Gene Summary for EPS15 Gene

  • 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]

GeneCards Summary for EPS15 Gene

EPS15 (Epidermal Growth Factor Receptor Pathway Substrate 15) is a Protein Coding gene. Diseases associated with EPS15 include Vaccinia and Spastic Paraplegia 20, Autosomal Recessive. Among its related pathways are EGF/EGFR Signaling Pathway and wtCFTR and delta508-CFTR traffic / Generic schema (norm and CF). Gene Ontology (GO) annotations related to this gene include calcium ion binding and SH3 domain binding. An important paralog of this gene is EPS15L1.

UniProtKB/Swiss-Prot for EPS15 Gene

  • Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.

Gene Wiki entry for EPS15 Gene

Additional gene information for EPS15 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EPS15 Gene

Genomics for EPS15 Gene

GeneHancer (GH) Regulatory Elements for EPS15 Gene

Promoters and enhancers for EPS15 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J051513 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 657.8 +1.6 1556 7.7 DMAP1 YY1 ZNF213 E2F8 ZNF416 SP3 ZNF610 GLIS1 RCOR2 NBN FAF1 EPS15 ENSG00000227070 LOC105378720 OSBPL9 ENSG00000266993 PRPF38A KTI12 LOC100190934 ORC1
GH01J051433 Enhancer 1 Ensembl ENCODE 16.8 +85.4 85353 1.2 CHAMP1 ETV6 RUNX3 SMARCA5 CEBPB ELF1 ZNF592 NR2F2 SP1 MAFF EPS15 ENSG00000227070 ENSG00000238140 RNU6-877P GC01M051448 GC01M051449 GC01P051412
GH01J051563 Enhancer 1.4 Ensembl ENCODE dbSUPER 11.1 -48.7 -48664 9.3 HNRNPUL1 ATF1 PKNOX1 NEUROD1 SIN3A ATF7 FOS RUNX3 JUNB REST NRDC RNU6-1281P ENSG00000266993 CDKN2C EPS15 ENSG00000227070 RNU6-877P CALR4P OSBPL9 GC01P051545
GH01J051621 Enhancer 1.2 Ensembl ENCODE 10.7 -103.2 -103202 1.8 HDGF PKNOX1 ATF1 SIN3A FEZF1 YY1 TCF12 ATF7 FOS RXRA LOC105378719 EPS15 ENSG00000227070 CALR4P OSBPL9
GH01J051423 Enhancer 1.1 Ensembl ENCODE 11.5 +96.2 96196 1.7 HDAC1 HDGF PKNOX1 ATF1 TAF9B ARNT BMI1 RFX5 CHAMP1 ZNF335 ENSG00000238140 EPS15 RNU6-877P ENSG00000227070 TTC39A GC01P051412 GC01M051448 GC01M051449
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around EPS15 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the EPS15 gene promoter:
  • AP-2alphaA
  • AP-2alpha isoform 4
  • AP-2alpha isoform 3
  • AP-2alpha isoform 2
  • AP-2alpha
  • AP-1
  • c-Jun
  • ATF-2
  • E2F
  • E2F-1

Genomic Locations for EPS15 Gene

Genomic Locations for EPS15 Gene
chr1:51,354,263-51,519,354
(GRCh38/hg38)
Size:
165,092 bases
Orientation:
Minus strand
chr1:51,819,935-51,985,000
(GRCh37/hg19)
Size:
165,066 bases
Orientation:
Minus strand

Genomic View for EPS15 Gene

Genes around EPS15 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EPS15 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EPS15 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EPS15 Gene

Proteins for EPS15 Gene

  • Protein details for EPS15 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P42566-EPS15_HUMAN
    Recommended name:
    Epidermal growth factor receptor substrate 15
    Protein Accession:
    P42566
    Secondary Accessions:
    • B2R8J7
    • D3DPJ2
    • Q5SRH4

    Protein attributes for EPS15 Gene

    Size:
    896 amino acids
    Molecular mass:
    98656 Da
    Quaternary structure:
    • Interacts with SGIP1 (PubMed:26822536). Interacts with HGS; the interaction bridges the interaction of STAM or STAM2 with EPS15. Isoform 2 interacts with HGS and AP2A2. Part of a complex at least composed of EPS15, HGS, and either STAM or STAM2. Binds AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds STON2 and EPN1. Interacts (via its SH3-binding sites) with CRK. Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts with FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2. Interacts (via UIM repeats) with CORO7 (when ubiquitinated at Lys-472). Interacts (via UIM domains) with UBQLN1 (via ubiquitin-like domain) and can interact with both the ubiquitinated and the non-ubiquitinated forms of UBQLN1. Interacts with UBQLN2 (By similarity) (PubMed:10757979, PubMed:11062555, PubMed:12551915, PubMed:16159959, PubMed:16314522, PubMed:16325581, PubMed:16903783, PubMed:18199683, PubMed:18200045, PubMed:18362181, PubMed:20448150, PubMed:21762413, PubMed:22484487, PubMed:22648170, PubMed:24768539, PubMed:8662907, PubMed:9721102, PubMed:9723620). Interacts with vaccinia virus protein A36 (PubMed:27670116).
    • (Microbial infection) Interacts with vaccinia virus protein A36 (PubMed:27670116).

    Three dimensional structures from OCA and Proteopedia for EPS15 Gene

    Alternative splice isoforms for EPS15 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EPS15 Gene

Post-translational modifications for EPS15 Gene

  • Phosphorylation on Tyr-849 is involved in the internalization of EGFR. Not required for membrane translocation after EGF treatment or for targeting to coated pits, but essential for a subsequent step in EGFR endocytosis (By similarity). Phosphorylated on serine upon DNA damage, probably by ATM or ATR.
  • Ubiquitinated.
  • Ubiquitination at isoforms=2890, Lys860, Lys818, Lys801, isoforms=2754, Lys638, isoforms=2495, and Lys413
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for EPS15 Gene

Domains & Families for EPS15 Gene

Gene Families for EPS15 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for EPS15 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P42566

UniProtKB/Swiss-Prot:

EPS15_HUMAN :
  • The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.
Domain:
  • The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.
  • The UIM (ubiquitin-interacting motif) repeats specifically bind Lys-33-linked ubiquitin.
genes like me logo Genes that share domains with EPS15: view

Function for EPS15 Gene

Molecular function for EPS15 Gene

UniProtKB/Swiss-Prot Function:
Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.
GENATLAS Biochemistry:
EGFR pathway substrate,mouse eps15 homolog,likely involved in cell growth regulation

Phenotypes From GWAS Catalog for EPS15 Gene

Gene Ontology (GO) - Molecular Function for EPS15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 9303539
GO:0017124 SH3 domain binding IEA --
GO:0031593 polyubiquitin modification-dependent protein binding IDA 24768539
GO:0042802 identical protein binding IEA,IPI 9182572
genes like me logo Genes that share ontologies with EPS15: view
genes like me logo Genes that share phenotypes with EPS15: view

Animal Models for EPS15 Gene

MGI Knock Outs for EPS15:
  • Eps15 Eps15<tm1a(KOMP)Wtsi>
  • Eps15 Eps15<tm1Noff>

Animal Model Products

Clone Products

  • Addgene plasmids for EPS15

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EPS15 Gene

Localization for EPS15 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPS15 Gene

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Membrane, clathrin-coated pit. Note=Recruited to the plasma membrane upon EGFR activation and localizes to coated pits. Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments and in cytoplasmic juxtanuclear structures called aggresomes. {ECO:0000269 PubMed:16159959}.
Isoform 2: Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes with HGS on bilayered clathrin coats on endosomes.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EPS15 gene
Compartment Confidence
plasma membrane 5
cytosol 5
endosome 4
nucleus 3
cytoskeleton 2
lysosome 2
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Vesicles (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for EPS15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
GO:0005829 cytosol TAS,IEA --
GO:0005886 plasma membrane IDA 15465819
genes like me logo Genes that share ontologies with EPS15: view

Pathways & Interactions for EPS15 Gene

genes like me logo Genes that share pathways with EPS15: view

SIGNOR curated interactions for EPS15 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for EPS15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001921 positive regulation of receptor recycling IEA --
GO:0006895 Golgi to endosome transport IMP 24768539
GO:0006897 endocytosis IEA --
GO:0007173 epidermal growth factor receptor signaling pathway TAS 8183552
GO:0008283 cell proliferation TAS 8183552
genes like me logo Genes that share ontologies with EPS15: view

Drugs & Compounds for EPS15 Gene

(2) Drugs for EPS15 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for EPS15 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with EPS15: view

Transcripts for EPS15 Gene

Unigene Clusters for EPS15 Gene

Epidermal growth factor receptor pathway substrate 15:
Representative Sequences:

Clone Products

  • Addgene plasmids for EPS15

Alternative Splicing Database (ASD) splice patterns (SP) for EPS15 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18a · 18b ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
SP1: - - - - -
SP2: - - - - - - -
SP3: - -
SP4: - - -
SP5:

ExUns: 24 ^ 25 ^ 26 ^ 27 ^ 28 ^ 29
SP1:
SP2:
SP3:
SP4:
SP5:

Relevant External Links for EPS15 Gene

GeneLoc Exon Structure for
EPS15
ECgene alternative splicing isoforms for
EPS15

Expression for EPS15 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for EPS15 Gene

Protein differential expression in normal tissues from HIPED for EPS15 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (26.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for EPS15 Gene



Protein tissue co-expression partners for EPS15 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of EPS15 Gene:

EPS15

SOURCE GeneReport for Unigene cluster for EPS15 Gene:

Hs.83722

mRNA Expression by UniProt/SwissProt for EPS15 Gene:

P42566-EPS15_HUMAN
Tissue specificity: Ubiquitously expressed.

Evidence on tissue expression from TISSUES for EPS15 Gene

  • Blood(4.4)
  • Liver(4.4)
  • Nervous system(4.4)
  • Kidney(2.4)
  • Heart(2.1)
  • Muscle(2.1)
genes like me logo Genes that share expression patterns with EPS15: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for EPS15 Gene

Orthologs for EPS15 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for EPS15 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EPS15 34
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia EPS15 34 33
  • 93.12 (n)
OneToOne
dog
(Canis familiaris)
Mammalia EPS15 34
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Eps15 16 34 33
  • 89.45 (n)
rat
(Rattus norvegicus)
Mammalia Eps15 33
  • 88.85 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia EPS15 34
  • 69 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia EPS15 34
  • 59 (a)
OneToOne
chicken
(Gallus gallus)
Aves EPS15 34 33
  • 77.64 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EPS15 34
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia eps15 33
  • 65.79 (n)
zebrafish
(Danio rerio)
Actinopterygii eps15 34 33
  • 60.63 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Eps-15 34
  • 23 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea ehs-1 34
  • 27 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes EDE1 36 34
  • 14 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 38 (a)
OneToMany
Species where no ortholog for EPS15 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EPS15 Gene

ENSEMBL:
Gene Tree for EPS15 (if available)
TreeFam:
Gene Tree for EPS15 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EPS15: view image

Paralogs for EPS15 Gene

Paralogs for EPS15 Gene

(2) SIMAP similar genes for EPS15 Gene using alignment to 4 proteins:

  • EPS15_HUMAN
  • B1AUU8_HUMAN
  • H7BYP0_HUMAN
  • S4R3U1_HUMAN
genes like me logo Genes that share paralogs with EPS15: view

Variants for EPS15 Gene

Sequence variations from dbSNP and Humsavar for EPS15 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000030446 -- 51,366,182(-) C/A intron_variant
rs1000048607 -- 51,390,386(-) A/G intron_variant
rs1000074831 -- 51,512,423(-) AAGAGAA/AA genic_upstream_transcript_variant, intron_variant
rs1000084386 -- 51,437,223(-) A/G genic_upstream_transcript_variant, intron_variant
rs1000092260 -- 51,366,405(-) A/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for EPS15 Gene

Variant ID Type Subtype PubMed ID
nsv478230 CNV novel sequence insertion 20440878
nsv1077820 CNV deletion 25765185
esv3586036 CNV loss 21293372
esv3586035 CNV loss 21293372
esv3577855 CNV loss 25503493
esv3577854 CNV loss 25503493
esv3422673 CNV insertion 20981092
esv3367601 CNV duplication 20981092
esv3363534 CNV insertion 20981092
esv3308869 CNV mobile element insertion 20981092
esv3307818 CNV mobile element insertion 20981092
esv2659806 CNV deletion 23128226
esv25434 CNV loss 19812545

Variation tolerance for EPS15 Gene

Residual Variation Intolerance Score: 43.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.45; 88.65% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EPS15 Gene

Human Gene Mutation Database (HGMD)
EPS15
SNPedia medical, phenotypic, and genealogical associations of SNPs for
EPS15

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EPS15 Gene

Disorders for EPS15 Gene

MalaCards: The human disease database

(2) MalaCards diseases for EPS15 Gene - From: HGMD, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
vaccinia
spastic paraplegia 20, autosomal recessive
  • trs
- elite association - COSMIC cancer census association via MalaCards
Search EPS15 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

EPS15_HUMAN
  • Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1. The result is a rogue activator protein.

Additional Disease Information for EPS15

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with EPS15: view

No data available for Genatlas for EPS15 Gene

Publications for EPS15 Gene

  1. The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32. (PMID: 8183552) Wong WT … Di Fiore PP (Oncogene 1994) 2 3 4 22 58
  2. An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. (PMID: 18362181) Roxrud I … Stenmark H (The Journal of cell biology 2008) 3 4 22 58
  3. STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes. (PMID: 12551915) Bache KG … Stenmark H (The Journal of biological chemistry 2003) 3 4 22 58
  4. Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites. (PMID: 10757979) Enmon JL … Overduin M (Biochemistry 2000) 3 4 22 58
  5. Molecular mechanism of NPF recognition by EH domains. (PMID: 11062555) de Beer T … Overduin M (Nature structural biology 2000) 3 4 22 58

Products for EPS15 Gene

Sources for EPS15 Gene

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