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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

The CD3 complex mediates signal transduction.

GO - Molecular functioni

  1. protein heterodimerization activity Source: UniProtKB
  2. transcription coactivator activity Source: MGI
  3. transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  1. cell surface receptor signaling pathway Source: UniProtKB
  2. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  3. positive thymic T cell selection Source: UniProtKB
  4. regulation of immune response Source: Reactome
  5. T cell costimulation Source: Reactome
  6. T cell differentiation Source: MGI
  7. T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiREACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
REACT_12555. Downstream TCR signaling.
REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
REACT_12596. Translocation of ZAP-70 to Immunological synapse.
REACT_12623. Generation of second messenger molecules.
REACT_19324. PD-1 signaling.

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
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:1673. CD3D.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 10584ExtracellularSequence AnalysisAdd
BLAST
Transmembranei106 – 12621HelicalSequence AnalysisAdd
BLAST
Topological domaini127 – 17145CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. alpha-beta T cell receptor complex Source: Ensembl
  2. cytoplasm Source: UniProtKB
  3. integral component of membrane Source: UniProtKB-KW
  4. plasma membrane Source: Reactome
  5. T cell receptor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.

See also OMIM:608971
Immunodeficiency 19 (IMD19)2 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

MIMi608971. phenotype.
615617. phenotype.
Orphaneti169160. T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta.
PharmGKBiPA26215.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Add
BLAST
Chaini22 – 171150T-cell surface glycoprotein CD3 delta chainPRO_0000016487Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi37 ↔ 731 Publication
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Glycosylationi74 – 741N-linked (GlcNAc...)Sequence Analysis
Modified residuei149 – 1491Phosphotyrosine2 Publications
Modified residuei160 – 1601Phosphotyrosine1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP04234.
PaxDbiP04234.
PRIDEiP04234.

PTM databases

PhosphoSiteiP04234.

Expressioni

Gene expression databases

BgeeiP04234.
CleanExiHS_CD3D.
ExpressionAtlasiP04234. baseline and differential.
GenevestigatoriP04234.

Organism-specific databases

HPAiCAB013055.

Interactioni

Subunit structurei

The TCR/CD3 complex of T-lymphocytes consists of either a TCR alpha/beta or TCR gamma/delta heterodimer coexpressed at the cell surface with the invariant subunits of CD3 labeled gamma, delta, epsilon, zeta, and eta.1 Publication

Protein-protein interaction databases

BioGridi107353. 9 interactions.
DIPiDIP-42855N.
IntActiP04234. 4 interactions.
MINTiMINT-3374023.
STRINGi9606.ENSP00000300692.

Structurei

Secondary structure

1
171
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 294Combined sources
Beta strandi32 – 365Combined sources
Beta strandi41 – 466Combined sources
Beta strandi50 – 523Combined sources
Helixi53 – 553Combined sources
Beta strandi57 – 626Combined sources
Helixi63 – 653Combined sources
Beta strandi68 – 736Combined sources
Beta strandi84 – 918Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1XIWX-ray1.90B/F23-100[»]
DisProtiDP00505.
ProteinModelPortaliP04234.
SMRiP04234. Positions 23-95.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04234.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini138 – 16629ITAMPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 ITAM domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG41968.
GeneTreeiENSGT00510000046930.
HOGENOMiHOG000015287.
HOVERGENiHBG005278.
InParanoidiP04234.
KOiK06450.
OMAiMCQSCVE.
OrthoDBiEOG7S4X7Q.
PhylomeDBiP04234.
TreeFamiTF335892.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR015484. CD3_esu/gsu/dsu.
IPR015485. CD3D.
IPR013783. Ig-like_fold.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]
PANTHERiPTHR10570. PTHR10570. 1 hit.
PTHR10570:SF6. PTHR10570:SF6. 1 hit.
PfamiPF02189. ITAM. 1 hit.
[Graphical view]
SMARTiSM00077. ITAM. 1 hit.
[Graphical view]
PROSITEiPS51055. ITAM_1. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti147 – 1471Q → R.
Corresponds to variant rs45510201 [ dbSNP | Ensembl ].
VAR_049646

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei92 – 13645MCQSC…RLSGA → T in isoform 2. 1 PublicationVSP_045800Add
BLAST

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]
UniGeneiHs.504048.

Genome annotation databases

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

Polymorphism databases

DMDMi115985.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

CD3Dbase

CD3D mutation db

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]
UniGeneiHs.504048.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1XIWX-ray1.90B/F23-100[»]
DisProtiDP00505.
ProteinModelPortaliP04234.
SMRiP04234. Positions 23-95.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107353. 9 interactions.
DIPiDIP-42855N.
IntActiP04234. 4 interactions.
MINTiMINT-3374023.
STRINGi9606.ENSP00000300692.

Chemistry

ChEMBLiCHEMBL2364168.
DrugBankiDB00075. Muromonab.

PTM databases

PhosphoSiteiP04234.

Polymorphism databases

DMDMi115985.

Proteomic databases

MaxQBiP04234.
PaxDbiP04234.
PRIDEiP04234.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi915.
GeneCardsiGC11M118212.
HGNCiHGNC:1673. CD3D.
HPAiCAB013055.
MIMi186790. gene.
608971. phenotype.
615617. phenotype.
neXtProtiNX_P04234.
Orphaneti169160. T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta.
PharmGKBiPA26215.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG41968.
GeneTreeiENSGT00510000046930.
HOGENOMiHOG000015287.
HOVERGENiHBG005278.
InParanoidiP04234.
KOiK06450.
OMAiMCQSCVE.
OrthoDBiEOG7S4X7Q.
PhylomeDBiP04234.
TreeFamiTF335892.

Enzyme and pathway databases

ReactomeiREACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
REACT_12555. Downstream TCR signaling.
REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
REACT_12596. Translocation of ZAP-70 to Immunological synapse.
REACT_12623. Generation of second messenger molecules.
REACT_19324. PD-1 signaling.

Miscellaneous databases

ChiTaRSiCD3D. human.
EvolutionaryTraceiP04234.
GeneWikiiCD3D.
GenomeRNAii915.
NextBioi3784.
PROiP04234.
SOURCEiSearch...

Gene expression databases

BgeeiP04234.
CleanExiHS_CD3D.
ExpressionAtlasiP04234. baseline and differential.
GenevestigatoriP04234.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR015484. CD3_esu/gsu/dsu.
IPR015485. CD3D.
IPR013783. Ig-like_fold.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]
PANTHERiPTHR10570. PTHR10570. 1 hit.
PTHR10570:SF6. PTHR10570:SF6. 1 hit.
PfamiPF02189. ITAM. 1 hit.
[Graphical view]
SMARTiSM00077. ITAM. 1 hit.
[Graphical view]
PROSITEiPS51055. ITAM_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Exon/intron organization of the genes coding for the delta chains of the human and murine T-cell receptor/T3 complex."
    van den Elsen P., Georgopoulos K., Shepley B.-A., Orkin S., Terhorst C.
    Proc. Natl. Acad. Sci. U.S.A. 83:2944-2948(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Isolation of cDNA clones encoding the 20K T3 glycoprotein of human T-cell receptor complex."
    van den Elsen P., Shepley B.-A., Borst J., Coligan J.E., Markham A.F., Orkin S., Terhorst C.
    Nature 312:413-418(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "T3 delta pre-mRNA is transcribed from a non-TATA promoter and is alternatively spliced in human T cells."
    Tunnacliffe A., Sims J.E., Rabbitts T.H.
    EMBO J. 5:1245-1252(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "PCR isolation and cloning of novel splice variant mRNAs from known drug target genes."
    Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R., Au-Young J., Stuve L.L.
    Genomics 83:566-571(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Blood.
  7. Cited for: PROTEIN SEQUENCE OF 128-171.
  8. "Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency."
    Dadi H.K., Simon A.J., Roifman C.M.
    N. Engl. J. Med. 349:1821-1828(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN T(-)B(+)NK(+) SCID.
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-149, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
    Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
    Anal. Chem. 76:2763-2772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-149, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  11. "Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3."
    de Saint Basile G., Geissmann F., Flori E., Uring-Lambert B., Soudais C., Cavazzana-Calvo M., Durandy A., Jabado N., Fischer A., Le Deist F.
    J. Clin. Invest. 114:1512-1517(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN IMD19.
  12. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-160, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  13. Cited for: INVOLVEMENT IN IMD19.
  14. "Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment."
    Arnett K.L., Harrison S.C., Wiley D.C.
    Proc. Natl. Acad. Sci. U.S.A. 101:16268-16273(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 23-100 IN COMPLEX WITH CD3E AND ANTIBODY FRAGMENT, SUBUNIT, DISULFIDE BOND.

Entry informationi

Entry nameiCD3D_HUMAN
AccessioniPrimary (citable) accession number: P04234
Secondary accession number(s): A8MVP6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: March 20, 1987
Last modified: March 4, 2015
This is version 158 of the entry and version 1 of the sequence. [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
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.