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Protein

T-cell surface glycoprotein CD3 delta chain

Gene

CD3D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition of this role of signal transduction in T-cell activation, CD3D plays an essential role in thymocyte differentiation. Indeed, participates in correct intracellular TCR-CD3 complex assembly and surface expression. In absence of a functional TCR-CD3 complex, thymocytes are unable to differentiate properly. Interacts with CD4 and CD8 and thus serves to establish a functional link between the TCR and coreceptors CD4 and CD8, which is needed for activation and positive selection of CD4 or CD8 T-cells(PubMed:12215456).3 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: CAFA
  • transcription coactivator activity Source: MGI
  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cell surface receptor signaling pathway Source: UniProtKB
  • membrane organization Source: Reactome
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive thymic T cell selection Source: UniProtKB
  • protein homooligomerization Source: CAFA
  • regulation of immune response Source: Reactome
  • T cell costimulation Source: Reactome
  • T cell differentiation Source: MGI
  • T cell receptor signaling pathway Source: Reactome

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-202424. Downstream TCR signaling.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-389948. PD-1 signaling.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD3 delta chain
Alternative name(s):
T-cell receptor T3 delta chain
CD_antigen: CD3d
Gene namesi
Name:CD3D
Synonyms:T3D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000167286.9.
HGNCiHGNC:1673. CD3D.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 105ExtracellularSequence analysisAdd BLAST84
Transmembranei106 – 126HelicalSequence analysisAdd BLAST21
Topological domaini127 – 171CytoplasmicSequence analysisAdd BLAST45

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 19 (IMD19)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive form of severe combined immunodeficiency characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T-cell negative, B-cell positive, NK-cell positive phenotype.
See also OMIM:615617

Keywords - Diseasei

SCID

Organism-specific databases

DisGeNETi915.
MalaCardsiCD3D.
MIMi615617. phenotype.
OpenTargetsiENSG00000167286.
Orphaneti169160. T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta.
PharmGKBiPA26215.

Chemistry databases

ChEMBLiCHEMBL2364168.
DrugBankiDB09052. Blinatumomab.
DB00075. Muromonab.

Polymorphism and mutation databases

BioMutaiCD3D.
DMDMi115985.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Add BLAST21
ChainiPRO_000001648722 – 171T-cell surface glycoprotein CD3 delta chainAdd BLAST150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi37 ↔ 731 Publication
Glycosylationi38N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei149PhosphotyrosineCombined sources1
Modified residuei160PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP04234.
PaxDbiP04234.
PeptideAtlasiP04234.
PRIDEiP04234.

PTM databases

iPTMnetiP04234.
PhosphoSitePlusiP04234.
SwissPalmiP04234.

Expressioni

Tissue specificityi

CD3D is mostly present on T-lymphocytes with its TCR-CD3 partners. Present also in fetal NK-cells.1 Publication

Gene expression databases

BgeeiENSG00000167286.
CleanExiHS_CD3D.
ExpressionAtlasiP04234. baseline and differential.
GenevisibleiP04234. HS.

Organism-specific databases

HPAiCAB013055.

Interactioni

Subunit structurei

The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with coreceptors CD4 and CD8 (PubMed:1396954, PubMed:12215456).5 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: CAFA

Protein-protein interaction databases

BioGridi107353. 9 interactors.
DIPiDIP-42855N.
ELMiP04234.
IntActiP04234. 6 interactors.
MINTiMINT-3374023.
STRINGi9606.ENSP00000300692.

Structurei

Secondary structure

1171
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 29Combined sources4
Beta strandi32 – 36Combined sources5
Beta strandi41 – 46Combined sources6
Beta strandi50 – 52Combined sources3
Helixi53 – 55Combined sources3
Beta strandi57 – 62Combined sources6
Helixi63 – 65Combined sources3
Beta strandi68 – 73Combined sources6
Beta strandi84 – 91Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XIWX-ray1.90B/F23-100[»]
DisProtiDP00505.
ProteinModelPortaliP04234.
SMRiP04234.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04234.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini138 – 166ITAMPROSITE-ProRule annotationAdd BLAST29

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWAX. Eukaryota.
ENOG410Y2TD. LUCA.
GeneTreeiENSGT00510000046930.
HOGENOMiHOG000015287.
HOVERGENiHBG005278.
InParanoidiP04234.
KOiK06450.
OMAiMCQSCVE.
OrthoDBiEOG091G0U7X.
PhylomeDBiP04234.
TreeFamiTF335892.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiView protein in InterPro
IPR015484. CD3_esu/gsu/dsu.
IPR015485. CD3D.
IPR036179. Ig-like_dom_sf.
IPR013783. Ig-like_fold.
IPR032052. Ig_4.
IPR003110. Phos_immunorcpt_sig_ITAM.
PANTHERiPTHR10570. PTHR10570. 1 hit.
PTHR10570:SF5. PTHR10570:SF5. 1 hit.
PfamiView protein in Pfam
PF16680. Ig_4. 1 hit.
PF02189. ITAM. 1 hit.
SMARTiView protein in SMART
SM00077. ITAM. 1 hit.
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiView protein in PROSITE
PS51055. ITAM_1. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P04234-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT
60 70 80 90 100
LLSDITRLDL GKRILDPRGI YRCNGTDIYK DKESTVQVHY RMCQSCVELD
110 120 130 140 150
PATVAGIIVT DVIATLLLAL GVFCFAGHET GRLSGAADTQ ALLRNDQVYQ
160 170
PLRDRDDAQY SHLGGNWARN K
Length:171
Mass (Da):18,930
Last modified:March 20, 1987 - v1
Checksum:i6C1F248150186D21
GO
Isoform 2 (identifier: P04234-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     92-136: MCQSCVELDPATVAGIIVTDVIATLLLALGVFCFAGHETGRLSGA → T

Note: No experimental confirmation available.
Show »
Length:127
Mass (Da):14,484
Checksum:i1E879A1CC76B9856
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049646147Q → R. Corresponds to variant dbSNP:rs45510201Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04580092 – 136MCQSC…RLSGA → T in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03934 Genomic DNA. Translation: CAA27573.1.
M12727, M12726 Genomic DNA. Translation: AAA51792.1.
CD014058 mRNA. No translation available.
AP001582 Genomic DNA. No translation available.
BC039035 mRNA. Translation: AAH39035.1.
BC070321 mRNA. Translation: AAH70321.1.
X01451 Genomic DNA. Translation: CAA25683.1.
CCDSiCCDS41724.1. [P04234-2]
CCDS8394.1. [P04234-1]
PIRiA94706. RWHUD1.
RefSeqiNP_000723.1. NM_000732.4. [P04234-1]
NP_001035741.1. NM_001040651.1. [P04234-2]
XP_016874032.1. XM_017018543.1. [P04234-1]
UniGeneiHs.504048.

Genome annotation databases

EnsembliENST00000300692; ENSP00000300692; ENSG00000167286. [P04234-1]
ENST00000392884; ENSP00000376622; ENSG00000167286. [P04234-2]
GeneIDi915.
KEGGihsa:915.
UCSCiuc001pss.2. human. [P04234-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCD3D_HUMAN
AccessioniPrimary (citable) accession number: P04234
Secondary accession number(s): A8MVP6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: March 20, 1987
Last modified: November 22, 2017
This is version 181 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references