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

Summary

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

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
identify USP9X as a novel regulator of EGFR endocytosis
Title: USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15.
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.
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.
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 EBI GWAS CatalogPubMed

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-74809 (e-PCR)
- UniSTS:29452

SHGC-74808 (e-PCR)
- UniSTS:70679

A006V07 (e-PCR)
- UniSTS:29472

SHGC-74806 (e-PCR)
- UniSTS:9533

SHGC-74820 (e-PCR)
- UniSTS:73543

SHGC-155448 (e-PCR)
- UniSTS:182087

SHGC-111272 (e-PCR)
- UniSTS:168267

SHGC-74807 (e-PCR)
- UniSTS:74578

AL009788 (e-PCR)
- UniSTS:80751

SHGC-37192 (e-PCR)
- UniSTS:3703

SHGC-74762 (e-PCR)
- UniSTS:77213

AL033736 (e-PCR)
- UniSTS:93605

RH80074 (e-PCR)
- UniSTS:92072

RH70977 (e-PCR)
- UniSTS:9442

D1S3566 (e-PCR)
- UniSTS:30434

G07235 (e-PCR)
- UniSTS:22522

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables cadherin binding	HDA more info	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 more info	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)

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
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, B1AUU8

Related

ENSP00000516334.1, ENST00000706288.1
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, A0A994J5W4

Related

ENSP00000516336.1, ENST00000706292.1
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

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

51354263..51519266 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

B1AUU8
XM_017000617.3 → XP_016856106.1 epidermal growth factor receptor substrate 15 isoform X2

UniProtKB/TrEMBL

B1AUU8

Related

ENSP00000360795.2, ENST00000371730.6
XM_017000616.3 → XP_016856105.1 epidermal growth factor receptor substrate 15 isoform X1

UniProtKB/TrEMBL

B1AUU8
XM_047449243.1 → XP_047305199.1 epidermal growth factor receptor substrate 15 isoform X4

UniProtKB/TrEMBL

A0A994J5W4

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

51234162..51399178 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

Q7Z5V0
XM_054335060.1 → XP_054191035.1 epidermal growth factor receptor substrate 15 isoform X2

UniProtKB/TrEMBL

Q7Z5V0
XM_054335059.1 → XP_054191034.1 epidermal growth factor receptor substrate 15 isoform X1

UniProtKB/TrEMBL

Q7Z5V0
XM_054335062.1 → XP_054191037.1 epidermal growth factor receptor substrate 15 isoform X4

UniProtKB/TrEMBL

A0A994J5W4