P04234 (CD3D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
T-cell surface glycoprotein CD3 delta chain

Alternative name(s):
T-cell receptor T3 delta chain
CD_antigen=CD3d

Gene names

Name:	CD3D
Synonyms:	T3D

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	171 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The CD3 complex mediates signal transduction.
Subunit structure	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. Ref.12
Subcellular location	Membrane; Single-pass type I membrane protein.
Involvement in disease	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. Ref.8
Sequence similarities	Contains 1 ITAM domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	SCID
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 2017177. Source: MGI positive thymic T cell selection Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	T cell receptor complex Non-traceable author statement PubMed 9485181. Source: UniProtKB alpha-beta T cell receptor complex Inferred from electronic annotation. Source: Compara cytoplasm Non-traceable author statement PubMed 1831653. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	transcription coactivator activity Inferred from direct assay PubMed 2017177. Source: MGI transmembrane signaling receptor activity Inferred by curator PubMed 9485181. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P04234-1)

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.

Isoform 2 (identifier: P04234-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 171

150

T-cell surface glycoprotein CD3 delta chain

PRO_0000016487

Regions

Topological domain

22 – 105

84

Extracellular Potential

Transmembrane

106 – 126

21

Helical; Potential

Topological domain

127 – 171

45

Cytoplasmic Potential

Domain

138 – 166

29

ITAM

Amino acid modifications

Modified residue

149

1

Phosphotyrosine Ref.9 Ref.10

Modified residue

160

1

Phosphotyrosine Ref.11

Glycosylation

38

1

N-linked (GlcNAc...) Potential

Glycosylation

74

1

N-linked (GlcNAc...) Potential

Disulfide bond

37 ↔ 73

Ref.12

Natural variations

Alternative sequence

92 – 136

45

MCQSC…RLSGA → T in isoform 2.

VSP_045800

Natural variant

147

1

Q → R.
Corresponds to variant rs45510201 [ dbSNP | Ensembl ].

VAR_049646

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

171

Helix Strand Turn

Details...

Beta strand

26 – 29

4

Beta strand

32 – 36

5

Beta strand

41 – 46

6

Beta strand

50 – 52

3

Helix

53 – 55

3

Beta strand

57 – 62

6

Helix

63 – 65

3

Beta strand

68 – 73

6

Beta strand

84 – 91

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 20, 1987. Version 1. Checksum: 6C1F248150186D21	FASTA	171	18,930
	10 20 30 40 50 60 MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL 70 80 90 100 110 120 GKRILDPRGI YRCNGTDIYK DKESTVQVHY RMCQSCVELD PATVAGIIVT DVIATLLLAL 130 140 150 160 170 GVFCFAGHET GRLSGAADTQ ALLRNDQVYQ PLRDRDDAQY SHLGGNWARN K
	Isoform 2 [UniParc]. Checksum: 1E879A1CC76B9856	FASTA	127	14,484
	10 20 30 40 50 60 MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL 70 80 90 100 110 120 GKRILDPRGI YRCNGTDIYK DKESTVQVHY RTADTQALLR NDQVYQPLRD RDDAQYSHLG GNWARNK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] 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]	"Dephosphorylation of the human T lymphocyte CD3 antigen." Alexander D., Goris J., Marais R., Rothbard J., Merlevede W., Crumpton M.J. Eur. J. Biochem. 181:55-65(1989) [PubMed] [Europe PMC] [Abstract] 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]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-149, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"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.
+	Additional computationally mapped references.

Web resources

CD3Dbase

CD3D mutation db

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00022934.
IPI00759573.

PIR

RWHUD1. A94706.

RefSeq

NP_000723.1. NM_000732.4.
NP_001035741.1. NM_001040651.1.

UniGene

Hs.504048.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XIW	X-ray	1.90	B/F	23-100	[»]

DisProt

DP00505.

ProteinModelPortal

P04234.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04234. 1 interaction.

MINT

MINT-3374023.

STRING

9606.ENSP00000300692.

PTM databases

PhosphoSite

P04234.

Polymorphism databases

DMDM

115985.

Proteomic databases

PaxDb

P04234.

PRIDE

P04234.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000300692; ENSP00000300692; ENSG00000167286.
ENST00000392884; ENSP00000376622; ENSG00000167286.

GeneID

915.

KEGG

hsa:915.

UCSC

uc001pss.1. human.

Organism-specific databases

CTD

915.

GeneCards

GC11M118212.

HGNC

HGNC:1673. CD3D.

HPA

CAB013055.

MIM

186790. gene.
608971. phenotype.

neXtProt

NX_P04234.

Orphanet

169160. Severe combined immunodeficiency T- B+ due to CD3delta/CD3epsilon/CD3zeta.

PharmGKB

PA26215.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41968.

HOGENOM

HOG000015287.

HOVERGEN

HBG005278.

InParanoid

P04234.

KO

K06450.

OMA

IIVTDVI.

OrthoDB

EOG4VHK7K.

PhylomeDB

P04234.

Enzyme and pathway databases

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P04234.

Bgee

P04234.

CleanEx

HS_CD3D.

Genevestigator

P04234.

GermOnline

ENSG00000167286. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR015485. CD3_delta.
IPR015484. CD3_gsu/dsu.
IPR013783. Ig-like_fold.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]

PANTHER

PTHR10570. PTHR10570. 1 hit.
PTHR10570:SF1. PTHR10570:SF1. 1 hit.

Pfam

PF02189. ITAM. 1 hit.
[Graphical view]

SMART

SM00077. ITAM. 1 hit.
[Graphical view]

PROSITE

PS51055. ITAM_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CD3D. human.

EvolutionaryTrace

P04234.

GenomeRNAi

915.

NextBio

3784.

SOURCE

Search...

Entry information

Entry name

CD3D_HUMAN

Accession

Primary (citable) accession number: P04234
Secondary accession number(s): A8MVP6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	March 20, 1987
Last modified:	May 1, 2013
This is version 139 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.