CD3E CD3 epsilon subunit of T-cell receptor complex [Homo sapiens (human)] - Gene

Summary

Official Symbol: CD3Eprovided by HGNC
Official Full Name: CD3 epsilon subunit of T-cell receptor complexprovided by HGNC
Primary source: HGNC:HGNC:1674
See related: Ensembl:ENSG00000198851 MIM:186830; AllianceGenome:HGNC:1674
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: T3E; TCRE; IMD18; CD3epsilon
Summary: The protein encoded by this gene is the CD3-epsilon polypeptide, which together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. The epsilon polypeptide plays an essential role in T-cell development. Defects in this gene cause immunodeficiency. This gene has also been linked to a susceptibility to type I diabetes in women. [provided by RefSeq, Jul 2008]
Expression: Biased expression in lymph node (RPKM 92.6), appendix (RPKM 45.9) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (118304730..118316173)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (118321077..118332497)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (118175445..118186888)

Chromosome 11 - NC_000011.10 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: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient.
Title: Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient.
Biallelic Form of a Known CD3E Mutation in a Patient with Severe Combined Immunodeficiency.
Title: Biallelic Form of a Known CD3E Mutation in a Patient with Severe Combined Immunodeficiency.
Multiple Signaling Roles of CD3epsilon and Its Application in CAR-T Cell Therapy.
Title: Multiple Signaling Roles of CD3ε and Its Application in CAR-T Cell Therapy.
Actin polymerization promotes the recruitment of Nck to the TCR, enhancing downstream signaling, such as phosphorylation of CD3epsilon and lymphocyte activation.
Title: Actin polymerization regulates recruitment of Nck to CD3ε upon T-cell receptor triggering.
The ionic CD3-epsilon -Lck interaction controls the phosphorylation level of the T-cell receptor.
Title: Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling.
A novel pathogenic frameshift variant of CD3E gene has been found in two unrelated T-B+ NK+ severe combined immunodeficiency infants from Turkey.
Title: A novel pathogenic frameshift variant of CD3E gene in two T-B+ NK+ SCID patients from Turkey.
the stalk domains of NKp30 and NKp46, another NCR employing CD3zeta for signaling, were not exchangeable without drastic deficiencies in folding, plasma membrane targeting, and/or ligand-induced receptor signaling.
Title: The Stalk Domain of NKp30 Contributes to Ligand Binding and Signaling of a Preassembled NKp30-CD3ζ Complex.
The inducible recruitment of WASp to the TCR-CD3 complex is partially dependent of tyrosine phosphorylation of Cd3e.
Title: Evidence for inducible recruitment of Wiskott-Aldrich syndrome protein to T cell receptor-CD3 complex in Jurkat T cells.
increase. Our results indicate that the change in CD3zeta-chain expression from the baseline is an independent predictor of residual and recurrent head and neck squamous cell carcinoma.
Title: Change in CD3ζ-chain expression is an independent predictor of disease status in head and neck cancer patients.
Data suggest that HIV-1 gp41 transmembrane domain (TMD) directly interacts with TMDs of the T-cell receptor and it's CD3-antigen co-receptors (delta, gamma, and epsilon); these interactions appear to be involved in immune evasion mechanism of HIV-1.
Title: The Transmembrane Domain of HIV-1 gp41 Inhibits T-Cell Activation by Targeting Multiple T-Cell Receptor Complex Components through Its GxxxG Motif.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Immunodeficiency 18 MedGen: C3810127 OMIM: 615615 GeneReviews: Not available	not available

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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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 inhibits CD3-induced Lck activation and cellular tyrosine phosphorylation, particularly of phosphoinositide-specific phospholipase C-gamma-1	PubMed
	env	Binding of HIV-1 gp120 to the CD4 receptor molecule results in co-stimulation of CD3-induced T cell activation	PubMed
	env	HIV-1 envelope glycoproteins gp120 and gp160 directly and specifically impair the CD3/TcR-mediated activation of phospholipase C (PLC) via the CD4 molecule in uninfected T cells	PubMed
	env	HIV-1 gp120 induces CD4 association with lymphocyte surface molecules CD3, CD11a, CD27, CD45RA, CD45RB, CD45RO, CD49d, CD38, CD26, CD59, CD95 and class I MHC molecules	PubMed
	env	Treatment of CD4+ T cells with HIV-1 gp120 significantly increases CD4 association with CD3, CD45RA, CD45RB, CD59, CD38, CD26 and HLA class I, and decreases that with CD45RC	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 interacts with CD3E; predicted interaction to be relevant to viral egress at plasma membrane/extracellular matrix	PubMed
Envelope transmembrane glycoprotein gp41	env	Gp41 TMD co-localizes with the CD3-TCR complex and inhibits T-cell activation induced by antibodies to CD3	PubMed
	env	HIV-1 gp41 peptide (amino acids 581-597) inhibits lymphoproliferation stimulated via the T-cell-activation molecules CD3, CD2, and CD28, as well as via direct stimulation mediated by phorbol ester combined with ionomycin	PubMed
Nef	nef	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Nef may antagonize restriction activity of CD3E against production of infectious wild-type HIV-1	PubMed
	nef	HIV-1 nef alleles from the great majority of primate lentiviruses, including HIV-2, downregulate TCR-CD3 from infected T cells and thereby block their responsiveness to activation	PubMed
	nef	HIV-1 Nef interacts with CD3 in living cells	PubMed
	nef	HIV-1 Nef impairs the generation of a CD3epsilon(+)CD5(+) CD1a(+) T cell differentiation precursor stage that initiates a D-J rearrangement of the TCRbeta locus	PubMed
Pr55(Gag)	gag	Monocyte-derived macrophages selectively capture and engulf HIV-1-infected CD4+ T cells as HIV-1 Gag interacts with CD3 and Caspase 3 markers, leading to efficient macrophage infection	PubMed
	gag	CD3/28-treated resting CD4+ T cells produce more HIV-1 Gag protein than untreated cells	PubMed
	gag	Interferon-gamma can counteract the inhibitory effect of peptides based on the Capsid protein of HIV-1 Gag on antibody response to SRC	PubMed
	gag	Peptides corresponding to amino acids 218-238 of the Capsid protein of HIV-1 Gag inhibited anti-CD3-induced lymphoproliferation but did not directly affect anti-CD2 activation	PubMed
	gag	Synthetic peptides corresponding to amino acids 218-238 of the Capsid protein of HIV-1 Gag have been shown to inhibit in a dose dependent manner the induction of a specific antibody response to the sheep red cell (SRC) antigen through the T3-Ti complex	PubMed
Tat	tat	HIV-1 Tat interacts with CD3 and CD28 to co-stimulate IL-2 and IL-8 expression	PubMed
Vpr	vpr	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpr may antagonize restriction activity of CD3E against production of infectious wild-type HIV-1	PubMed
Vpu	vpu	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpu may antagonize restriction activity of CD3E against production of infectious wild-type HIV-1	PubMed
	vpu	HIV-1 Vpu interacts with CD3 in living cells	PubMed
capsid	gag	Interferon-gamma can counteract the inhibitory effect of HIV-1 Capsid based peptides on antibody response to SRC	PubMed
	gag	Peptides corresponding to amino acids 218-238 of HIV-1 Capsid inhibited anti-CD3-induced lymphoproliferation but did not directly affect anti-CD2 activation	PubMed
	gag	Synthetic peptides corresponding to amino acids 218-238 of HIV-1 Capsid have been shown to inhibit in a dose dependent manner the induction of a specific antibody response to the sheep red cell (SRC) antigen through the T3-Ti complex	PubMed
matrix	gag	HIV-1 MA co-localizes with CD3 marker protein in monocyte-derived macrophages cocultured with HIV-1-infected primary CD4+ T-cells	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

RH18074 (e-PCR)
- UniSTS:69634

D11S4380 (e-PCR)
- UniSTS:11963

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH3 domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables T cell receptor binding	NAS Non-traceable Author Statement more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	NAS Non-traceable Author Statement more info	PubMed
enables signaling receptor complex adaptor activity	NAS Non-traceable Author Statement more info	PubMed
enables transmembrane signaling receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane signaling receptor activity	IC Inferred by Curator more info	PubMed
enables transmembrane signaling receptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in T cell activation	NAS Non-traceable Author Statement more info	PubMed
involved_in T cell anergy	IEA Inferred from Electronic Annotation more info
involved_in T cell costimulation	IEA Inferred from Electronic Annotation more info
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in adaptive immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in alpha-beta T cell activation	NAS Non-traceable Author Statement more info	PubMed
involved_in apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor signaling pathway	IC Inferred by Curator more info	PubMed
involved_in cell surface receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in cerebellum development	IEA Inferred from Electronic Annotation more info
involved_in dendrite development	IEA Inferred from Electronic Annotation more info
involved_in gamma-delta T cell activation	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative thymic T cell selection	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell anergy	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell-cell adhesion mediated by integrin	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of cell-matrix adhesion	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-2 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-4 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of type II interferon production	IEA Inferred from Electronic Annotation more info
involved_in positive thymic T cell selection	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein-containing complex assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in signal complex assembly	TAS Traceable Author Statement more info	PubMed
involved_in smoothened signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
part_of T cell receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of alpha-beta T cell receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of alpha-beta T cell receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of alpha-beta T cell receptor complex	IPI Inferred from Physical Interaction more info	PubMed
part_of alpha-beta T cell receptor complex	ISS Inferred from Sequence or Structural Similarity more info
located_in cell body	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of gamma-delta T cell receptor complex	NAS Non-traceable Author Statement more info	PubMed
located_in immunological synapse	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: T-cell surface glycoprotein CD3 epsilon chain

Names: CD3-epsilon; CD3e antigen, epsilon polypeptide (TiT3 complex); CD3e molecule, epsilon (CD3-TCR complex); T-cell antigen receptor complex, epsilon subunit of T3; T-cell surface antigen T3/Leu-4 epsilon chain

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.

Genomic

NG_007383.1 RefSeqGene

Range

5001..16596

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_38

mRNA and Protein(s)

NM_000733.4 → NP_000724.1 T-cell surface glycoprotein CD3 epsilon chain precursor

See identical proteins and their annotated locations for NP_000724.1

Status: REVIEWED

Source sequence(s)

AK292612, BC049847, BP366535

Consensus CDS

CCDS31685.1

UniProtKB/Swiss-Prot

A8K997, P07766

UniProtKB/TrEMBL

E9PSH8

Related

ENSP00000354566.4, ENST00000361763.9

Conserved Domains (2) summary

smart00077
Location:185 → 205

ITAM; Immunoreceptor tyrosine-based activation motif

cd07692
Location:36 → 117

IgC1_CD3_epsilon; Immunoglobulin (Ig)-like domain of Cluster of Differentiation (CD) 3 epsilon chain; member of the C1-set of IgSF domains