Human Gene EPS15 (uc001csq.1) Description and Page Index
  Description: Homo sapiens epidermal growth factor receptor pathway substrate 15 (EPS15), transcript variant 1, mRNA.
RefSeq Summary (NM_001981): 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].
Transcript (Including UTRs)
   Position: hg19 chr1:51,819,935-51,984,995 Size: 165,061 Total Exon Count: 25 Strand: -
Coding Region
   Position: hg19 chr1:51,822,372-51,984,903 Size: 162,532 Coding Exon Count: 25 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:51,819,935-51,984,995)mRNA (may differ from genome)Protein (896 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: EPS15_HUMAN
DESCRIPTION: RecName: Full=Epidermal growth factor receptor substrate 15; Short=Protein Eps15; AltName: Full=Protein AF-1p;
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). 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.
SUBUNIT: Interacts with SGIP1 (By similarity). 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 STAM1 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.
INTERACTION: Q0JRZ9:FCHO2; NbExp=3; IntAct=EBI-396684, EBI-2609756; Q3UQN2:Fcho2 (xeno); NbExp=3; IntAct=EBI-396684, EBI-6094986; P16333:NCK1; NbExp=2; IntAct=EBI-396684, EBI-389883;
SUBCELLULAR LOCATION: 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.
SUBCELLULAR LOCATION: Isoform 2: Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes with HGS on bilayered clathrin coats on endosomes.
TISSUE SPECIFICITY: Ubiquitously expressed.
DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.
PTM: 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.
DISEASE: Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein.
SIMILARITY: Contains 2 EF-hand domains.
SIMILARITY: Contains 3 EH domains.
SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR used a siRNA mixture of EPS15 and EPS15L1, and a Dab2 mutant with impaired binding to EH domain-containing proteins EPS15 and ITSN1 suggesting a partially overlapping role of the EH domain- containing proteins (PubMed:22648170).
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AF1pID11.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): EPS15
CDC HuGE Published Literature: EPS15
Positive Disease Associations: Rhinitis, Allergic, Seasonal
Related Studies:
  1. Rhinitis, Allergic, Seasonal
    Adaikalavan Ramasamy et al. The Journal of allergy and clinical immunology 2011, A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order., The Journal of allergy and clinical immunology. [PubMed 22036096]
    This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses.

-  MalaCards Disease Associations
  MalaCards Gene Search: EPS15
Diseases sorted by gene-association score: vaccinia (16), troyer syndrome (12)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 31.71 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 829.25 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -16.0592-0.174 Picture PostScript Text
3' UTR -568.652437-0.233 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011992 - EF-hand-like_dom
IPR018247 - EF_Hand_1_Ca_BS
IPR018249 - EF_HAND_2
IPR002048 - EF_hand_Ca-bd
IPR000261 - EPS15_homology
IPR003903 - Ubiquitin-int_motif

Pfam Domains:
PF02809 - Ubiquitin interaction motif
PF12763 - Cytoskeletal-regulatory complex EF hand

SCOP Domains:
47473 - EF-hand

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1C07
- NMR MuPIT

1EH2
- NMR MuPIT

1F8H
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1FF1 - NMR MuPIT 2IV9 - X-ray MuPIT 2JXC - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P42566
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0017124 SH3 domain binding
GO:0031593 polyubiquitin binding
GO:0042802 identical protein binding
GO:0045296 cadherin binding
GO:0046872 metal ion binding

Biological Process:
GO:0001921 positive regulation of receptor recycling
GO:0006895 Golgi to endosome transport
GO:0006897 endocytosis
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0008283 cell proliferation
GO:0015031 protein transport
GO:0016032 viral process
GO:0016050 vesicle organization
GO:0019065 receptor-mediated endocytosis of virus by host cell
GO:0032456 endocytic recycling
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway
GO:0042127 regulation of cell proliferation
GO:0046718 viral entry into host cell
GO:0048268 clathrin coat assembly
GO:0061024 membrane organization

Cellular Component:
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005769 early endosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005905 clathrin-coated pit
GO:0009925 basal plasma membrane
GO:0016020 membrane
GO:0016235 aggresome
GO:0016324 apical plasma membrane
GO:0030122 AP-2 adaptor complex
GO:0030132 clathrin coat of coated pit
GO:0030136 clathrin-coated vesicle
GO:0031901 early endosome membrane
GO:0043231 intracellular membrane-bounded organelle
GO:0060170 ciliary membrane


-  Descriptions from all associated GenBank mRNAs
  Z29064 - H.sapiens AF-1p mRNA.
U07707 - Human epidermal growth factor receptor substrate (eps15) mRNA, complete cds.
BC054006 - Homo sapiens epidermal growth factor receptor pathway substrate 15, mRNA (cDNA clone MGC:61536 IMAGE:6164633), complete cds.
DQ367924 - Homo sapiens epidermal growth factor receptor pathway substrate 15 mRNA, complete cds.
AK313396 - Homo sapiens cDNA, FLJ93931, Homo sapiens epidermal growth factor receptor pathway substrate 15(EPS15), mRNA.
KJ904462 - Synthetic construct Homo sapiens clone ccsbBroadEn_13856 EPS15-like gene, encodes complete protein.
AB384758 - Synthetic construct DNA, clone: pF1KB3218, Homo sapiens EPS15 gene for epidermal growth factor receptor substrate 15, complete cds, without stop codon, in Flexi system.
LF383890 - JP 2014500723-A/191393: Polycomb-Associated Non-Coding RNAs.
BX647676 - Homo sapiens mRNA; cDNA DKFZp686D16141 (from clone DKFZp686D16141).
AF052132 - Homo sapiens clone 23743 mRNA sequence.
AK090936 - Homo sapiens cDNA FLJ33617 fis, clone BRAMY2019055, highly similar to Epidermal growth factor receptor substrate 15.
AX746691 - Sequence 216 from Patent EP1308459.
JD550762 - Sequence 531786 from Patent EP1572962.
JD504063 - Sequence 485087 from Patent EP1572962.
JD509830 - Sequence 490854 from Patent EP1572962.
JD537693 - Sequence 518717 from Patent EP1572962.
JD528301 - Sequence 509325 from Patent EP1572962.
JD496566 - Sequence 477590 from Patent EP1572962.
JD180914 - Sequence 161938 from Patent EP1572962.
JD469595 - Sequence 450619 from Patent EP1572962.
LF356141 - JP 2014500723-A/163644: Polycomb-Associated Non-Coding RNAs.
AK294297 - Homo sapiens cDNA FLJ55050 complete cds, highly similar to Epidermal growth factor receptor substrate 15.
JD366013 - Sequence 347037 from Patent EP1572962.
JD046722 - Sequence 27746 from Patent EP1572962.
JD507423 - Sequence 488447 from Patent EP1572962.
JD563303 - Sequence 544327 from Patent EP1572962.
JD041471 - Sequence 22495 from Patent EP1572962.
JD358113 - Sequence 339137 from Patent EP1572962.
AK308128 - Homo sapiens cDNA, FLJ98076.
LF356140 - JP 2014500723-A/163643: Polycomb-Associated Non-Coding RNAs.
LF356139 - JP 2014500723-A/163642: Polycomb-Associated Non-Coding RNAs.
LF356137 - JP 2014500723-A/163640: Polycomb-Associated Non-Coding RNAs.
LF356136 - JP 2014500723-A/163639: Polycomb-Associated Non-Coding RNAs.
LF356135 - JP 2014500723-A/163638: Polycomb-Associated Non-Coding RNAs.
LF356134 - JP 2014500723-A/163637: Polycomb-Associated Non-Coding RNAs.
MA619467 - JP 2018138019-A/191393: Polycomb-Associated Non-Coding RNAs.
MA591718 - JP 2018138019-A/163644: Polycomb-Associated Non-Coding RNAs.
MA591717 - JP 2018138019-A/163643: Polycomb-Associated Non-Coding RNAs.
MA591716 - JP 2018138019-A/163642: Polycomb-Associated Non-Coding RNAs.
MA591714 - JP 2018138019-A/163640: Polycomb-Associated Non-Coding RNAs.
MA591713 - JP 2018138019-A/163639: Polycomb-Associated Non-Coding RNAs.
MA591712 - JP 2018138019-A/163638: Polycomb-Associated Non-Coding RNAs.
MA591711 - JP 2018138019-A/163637: Polycomb-Associated Non-Coding RNAs.
LF356130 - JP 2014500723-A/163633: Polycomb-Associated Non-Coding RNAs.
LF356129 - JP 2014500723-A/163632: Polycomb-Associated Non-Coding RNAs.
LF356128 - JP 2014500723-A/163631: Polycomb-Associated Non-Coding RNAs.
AK129853 - Homo sapiens cDNA FLJ26343 fis, clone HRT03401, highly similar to Epidermal growth factor receptor substrate 15.
LF356126 - JP 2014500723-A/163629: Polycomb-Associated Non-Coding RNAs.
LF356125 - JP 2014500723-A/163628: Polycomb-Associated Non-Coding RNAs.
AY187922 - Homo sapiens MLL/AF1p fusion mRNA, partial sequence.
JD391656 - Sequence 372680 from Patent EP1572962.
JD397645 - Sequence 378669 from Patent EP1572962.
MA591707 - JP 2018138019-A/163633: Polycomb-Associated Non-Coding RNAs.
MA591706 - JP 2018138019-A/163632: Polycomb-Associated Non-Coding RNAs.
MA591705 - JP 2018138019-A/163631: Polycomb-Associated Non-Coding RNAs.
MA591703 - JP 2018138019-A/163629: Polycomb-Associated Non-Coding RNAs.
MA591702 - JP 2018138019-A/163628: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04144 - Endocytosis

BioCarta from NCI Cancer Genome Anatomy Project
h_ndkDynaminPathway - Endocytotic role of NDK, Phosphins and Dynamin

Reactome (by CSHL, EBI, and GO)

Protein P42566 (Reactome details) participates in the following event(s):

R-HSA-8862280 FCHo proteins bind nascent clathrin-coated pit
R-HSA-183072 EGFR non-clathrin mediated endocytosis
R-HSA-8867044 EGFR binds EPS15, EPN1, EPS15L1
R-HSA-8875490 EPS15 and HGS bind ubiquitinated MET
R-HSA-8876262 EPS15 and HGS bind CBL-monoubiquitinated MET engaged with Listeria InlB
R-HSA-8866283 ARBB recruits GPCRs into clathrin-coated pits
R-HSA-8867756 CLASP proteins and cargo are recruited to the nascent clathrin-coated pit
R-HSA-8856813 AAK1 phosphorylates AP-2 mu subunit at T156
R-HSA-8856808 Recruitment of AP-2 complex and clathrin
R-HSA-8871194 RAB5 and GAPVD1 bind AP-2
R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating
R-HSA-8868659 Clathrin recruits auxilins to the clathrin-coated vesicle
R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission
R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle
R-HSA-8868648 SYNJ hydrolyze PI(4,5)P2 to PI(4)P
R-HSA-8866275 UBQLNs bind UIM-containing adaptor proteins
R-HSA-8866279 Epsin family proteins bind ubiquitinated cargo
R-HSA-182986 CBL-mediated ubiquitination of CIN85
R-HSA-182990 Sprouty sequesters CBL away from active EGFR
R-HSA-8867041 EGFR phosphorylates EPS15
R-HSA-8867047 PTPN3 dephosphorylates EPS15
R-HSA-8868071 Clathrin recruits PIK3C2A
R-HSA-8868230 SNX9 recruits components of the actin polymerizing machinery
R-HSA-8867754 F- and N- BAR domain proteins bind the clathrin-coated pit
R-HSA-8868236 BAR domain proteins recruit dynamin
R-HSA-8868072 Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2
R-HSA-8868651 Endophilins recruit synaptojanins to the clathrin-coated pit
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-182971 EGFR downregulation
R-HSA-6807004 Negative regulation of MET activity
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-199991 Membrane Trafficking
R-HSA-177929 Signaling by EGFR
R-HSA-6806834 Signaling by MET
R-HSA-8876384 Listeria monocytogenes entry into host cells
R-HSA-5653656 Vesicle-mediated transport
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-5663205 Infectious disease
R-HSA-162582 Signal Transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: AF1P, B2R8J7, D3DPJ2, EPS15_HUMAN, NM_001981, NP_001972, P42566, Q5SRH4
UCSC ID: uc001csq.1
RefSeq Accession: NM_001981
Protein: P42566 (aka EPS15_HUMAN)
CCDS: CCDS557.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001981.2
exon count: 25CDS single in 3' UTR: no RNA size: 5220
ORF size: 2691CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5569.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.