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Protein

T-cell surface glycoprotein CD3 delta chain

Gene

CD3D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 by RNA polymerase II Source: MGI
  • positive thymic T cell selection Source: UniProtKB
  • protein homooligomerization Source: CAFA
  • regulation of immune response 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
SIGNORiP04234

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
MIMi186790 gene
neXtProtiNX_P04234

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
ProteomicsDBi51692

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
MINTiP04234
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

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: June 20, 2018
This is version 186 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

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