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P04234

- CD3D_HUMAN

UniProt

P04234 - CD3D_HUMAN

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Protein
T-cell surface glycoprotein CD3 delta chain
Gene
CD3D, T3D
Organism
Homo sapiens (Human)
Status
Reviewed - 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. T cell costimulation Source: Reactome
  2. T cell differentiation Source: MGI
  3. T cell receptor signaling pathway Source: Reactome
  4. cell surface receptor signaling pathway Source: UniProtKB
  5. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  6. positive thymic T cell selection Source: UniProtKB
  7. regulation of immune response 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: Chromosome 11

Organism-specific databases

HGNCiHGNC:1673. CD3D.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 10584Extracellular Reviewed prediction
Add
BLAST
Transmembranei106 – 12621Helical; Reviewed prediction
Add
BLAST
Topological domaini127 – 17145Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. T cell receptor complex Source: UniProtKB
  2. alpha-beta T cell receptor complex Source: Ensembl
  3. cytoplasm Source: UniProtKB
  4. integral component of membrane Source: UniProtKB-KW
  5. plasma membrane Source: Reactome
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) [MIM:608971]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Immunodeficiency 19 (IMD19) [MIM:615617]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications

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 – 2121
Add
BLAST
Chaini22 – 171150T-cell surface glycoprotein CD3 delta chain
PRO_0000016487Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi37 ↔ 731 Publication
Glycosylationi38 – 381N-linked (GlcNAc...) Reviewed prediction
Glycosylationi74 – 741N-linked (GlcNAc...) Reviewed prediction
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

ArrayExpressiP04234.
BgeeiP04234.
CleanExiHS_CD3D.
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.
IntActiP04234. 3 interactions.
MINTiMINT-3374023.
STRINGi9606.ENSP00000300692.

Structurei

Secondary structure

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

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP04234.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini138 – 16629ITAM
Add
BLAST

Sequence similaritiesi

Contains 1 ITAM domain.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG41968.
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. Align

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

MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT    50
LLSDITRLDL GKRILDPRGI YRCNGTDIYK DKESTVQVHY RMCQSCVELD 100
PATVAGIIVT DVIATLLLAL GVFCFAGHET GRLSGAADTQ ALLRNDQVYQ 150
PLRDRDDAQY SHLGGNWARN K 171
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.
VSP_045800Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS41724.1. [P04234-2 ]
CCDS8394.1. [P04234-1 ]
PIRi A94706. RWHUD1.
RefSeqi NP_000723.1. NM_000732.4. [P04234-1 ]
NP_001035741.1. NM_001040651.1. [P04234-2 ]
UniGenei Hs.504048.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1XIW X-ray 1.90 B/F 23-100 [» ]
DisProti DP00505.
ProteinModelPortali P04234.
SMRi P04234. Positions 23-95.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107353. 9 interactions.
IntActi P04234. 3 interactions.
MINTi MINT-3374023.
STRINGi 9606.ENSP00000300692.

Chemistry

ChEMBLi CHEMBL2364168.

PTM databases

PhosphoSitei P04234.

Polymorphism databases

DMDMi 115985.

Proteomic databases

MaxQBi P04234.
PaxDbi P04234.
PRIDEi P04234.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000300692 ; ENSP00000300692 ; ENSG00000167286 . [P04234-1 ]
ENST00000392884 ; ENSP00000376622 ; ENSG00000167286 . [P04234-2 ]
GeneIDi 915.
KEGGi hsa:915.
UCSCi uc001pss.1. human. [P04234-1 ]

Organism-specific databases

CTDi 915.
GeneCardsi GC11M118212.
HGNCi HGNC:1673. CD3D.
HPAi CAB013055.
MIMi 186790. gene.
608971. phenotype.
615617. phenotype.
neXtProti NX_P04234.
Orphaneti 169160. T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta.
PharmGKBi PA26215.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG41968.
HOGENOMi HOG000015287.
HOVERGENi HBG005278.
InParanoidi P04234.
KOi K06450.
OMAi MCQSCVE.
OrthoDBi EOG7S4X7Q.
PhylomeDBi P04234.
TreeFami TF335892.

Enzyme and pathway databases

Reactomei REACT_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

ChiTaRSi CD3D. human.
EvolutionaryTracei P04234.
GeneWikii CD3D.
GenomeRNAii 915.
NextBioi 3784.
PROi P04234.
SOURCEi Search...

Gene expression databases

ArrayExpressi P04234.
Bgeei P04234.
CleanExi HS_CD3D.
Genevestigatori P04234.

Family and domain databases

Gene3Di 2.60.40.10. 1 hit.
InterProi IPR015484. CD3_esu/gsu/dsu.
IPR015485. CD3D.
IPR013783. Ig-like_fold.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view ]
PANTHERi PTHR10570. PTHR10570. 1 hit.
PTHR10570:SF6. PTHR10570:SF6. 1 hit.
Pfami PF02189. ITAM. 1 hit.
[Graphical view ]
SMARTi SM00077. ITAM. 1 hit.
[Graphical view ]
PROSITEi PS51055. ITAM_1. 1 hit.
[Graphical view ]
ProtoNeti Search...

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(1986) [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(1984) [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(1986) [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(2004) [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(2004) [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(2003) [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(2004) [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(2004) [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(2009) [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(2004) [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: September 3, 2014
This is version 153 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

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