CD3D CD3 delta subunit of T-cell receptor complex [Homo sapiens (human)] - Gene

Summary

Official Symbol: CD3Dprovided by HGNC
Official Full Name: CD3 delta subunit of T-cell receptor complexprovided by HGNC
Primary source: HGNC:HGNC:1673
See related: Ensembl:ENSG00000167286 MIM:186790; AllianceGenome:HGNC:1673
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: T3D; IMD19; CD3DELTA; CD3-DELTA
Summary: The protein encoded by this gene is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. The encoded membrane protein represents the delta subunit of the CD3 complex, and along with four other CD3 subunits, binds either TCR alpha/beta or TCR gamma/delta to form the TCR/CD3 complex on the surface of T-cells. Defects in this gene are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (SCIDBNK). Two transcript variants encoding different isoforms have been found for this gene. Other variants may also exist, but the full-length natures of their transcripts has yet to be defined. [provided by RefSeq, Feb 2009]
Expression: Biased expression in lymph node (RPKM 30.2), appendix (RPKM 14.7) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (118338954..118342705, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (118355312..118360628, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (118209669..118213420, complement)

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
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?

Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma.
Title: Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma.
Comprehensive analysis reveals a prognostic and therapeutic biomarker CD3D in the breast carcinoma microenvironment.
Title: Comprehensive analysis reveals a prognostic and therapeutic biomarker CD3D in the breast carcinoma microenvironment.
PCR and transcriptome analysis suggest that the genes CD3D and PKRCQ together can be used as a model for differentiating between B-cell and T-cell acute lymphoblastic leukemia.
Title: CD3D and PRKCQ work together to discriminate between B-cell and T-cell acute lymphoblastic leukemia.
we demonstrate that the incorporation of a 2A self-processing peptide derived from foot-and-mouth disease virus conveying co-translational cleavage into a two-chain anti-CD3 x anti-CEA diabody gene enables near-equimolar expression of diabody chains 1 and 2, and thus increases the final amount of assembled diabody.
Title: Balanced secretion of anti-CEA × anti-CD3 diabody chains using the 2A self-cleaving peptide maximizes diabody assembly and tumor-specific cytotoxicity.
A FOXP3(+)CD3(+)CD56(+)-expressed T-cell population with immunosuppressive function and reduced patient survival has been identified in cancer tissues of human hepatocellular carcinoma.
Title: Identification of a FOXP3(+)CD3(+)CD56(+) population with immunosuppressive function in cancer tissues of human hepatocellular carcinoma.
The docking site for CD3 subunits on the T Cell receptor beta chain has been identified by solution NMR.
Title: Identification of the Docking Site for CD3 on the T Cell Receptor β Chain by Solution NMR.
analysis of the molecular organization of the TCR-CD3 complex
Title: Molecular architecture of the αβ T cell receptor-CD3 complex.
Two cases of SCID with CD3delta gene mutation in Mexican Mennonite infants are described.
Title: The respiratory presentation of severe combined immunodeficiency in two Mennonite children at a tertiary centre highlighting the importance of recognizing this pediatric emergency.
The surface TCR expression of primary alphabeta and gammadelta T cells from healthy donors carrying a single null or leaky mutation in CD3G (gamma+/-) or CD3D (delta+/-, delta+/leaky) with that of normal controls, were compared.
Title: Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression.
Altered expression of the TCR signaling related genes CD3 and FcepsilonRIgamma in patients with aplastic anemia.
Title: Altered expression of the TCR signaling related genes CD3 and FcεRIγ in patients with aplastic anemia.

Submit: New GeneRIF Correction See all GeneRIFs (31)

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

Associated conditions

Description	Tests
Immunodeficiency 19 MedGen: C3810147 OMIM: 615617 GeneReviews: Not available	Compare labs

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 CD3D; 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	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
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
Vpu	vpu	HIV-1 Vpu interacts with CD3 in living cells	PubMed
capsid	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
	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
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

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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

CD3D (e-PCR), detects polymorphism
- UniSTS:61984

CD3D (e-PCR), detects polymorphism
- UniSTS:62342

GDB:179879 (e-PCR)
- UniSTS:155056

RH93888 (e-PCR)
- UniSTS:85703

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction 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

Process	Evidence Code	Pubs
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 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 positive thymic T cell selection	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive thymic T cell selection	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
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 clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
is_active_in external side of 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 plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: T-cell surface glycoprotein CD3 delta chain

Names: CD3 antigen, delta subunit; CD3 delta; CD3d antigen, delta polypeptide (TiT3 complex); CD3d molecule, delta (CD3-TCR complex); OKT3, delta chain; T-cell receptor T3 delta 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_009891.1 RefSeqGene

Range

5001..8671

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_37

mRNA and Protein(s)

NM_000732.6 → NP_000723.1 T-cell surface glycoprotein CD3 delta chain isoform A precursor

See identical proteins and their annotated locations for NP_000723.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (A).

Source sequence(s)

BC070321

Consensus CDS

CCDS8394.1

UniProtKB/Swiss-Prot

A8MVP6, P04234

UniProtKB/TrEMBL

B0YIY4

Related

ENSP00000300692.4, ENST00000300692.9

Conserved Domains (3) summary

pfam02189
Location:146 → 165

ITAM; Immunoreceptor tyrosine-based activation motif

pfam16680
Location:30 → 104

Ig_4; T-cell surface glycoprotein CD3 delta chain

cd07691
Location:33 → 37

IgC1_CD3_gamma_delta; Ig strand B [structural motif]
NM_001040651.2 → NP_001035741.1 T-cell surface glycoprotein CD3 delta chain isoform B precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region, compared to variant 1. The encoded protein (B) is shorter and lacks the transmembrane domain, compared to isoform A.

Source sequence(s)

AP001582, BC070321, CD014058

Consensus CDS

CCDS41724.1

UniProtKB/Swiss-Prot

P04234

Related

ENSP00000376622.2, ENST00000392884.3

Conserved Domains (2) summary

pfam02189
Location:102 → 121

ITAM; Immunoreceptor tyrosine-based activation motif

cl11960
Location:25 → 91

Ig; Immunoglobulin domain

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_000011.10 Reference GRCh38.p14 Primary Assembly

Range

118338954..118342705 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

118355312..118360628 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054370480.1 → XP_054226455.1 T-cell surface glycoprotein CD3 delta chain isoform X1

UniProtKB/Swiss-Prot

A8MVP6, P04234

UniProtKB/TrEMBL

B0YIY4