T-cell surface glycoprotein CD3 delta chain

Details

Name
T-cell surface glycoprotein CD3 delta chain
Kind
protein
Synonyms
  • T-cell receptor T3 delta chain
  • T3D
Gene Name
CD3D
UniProtKB Entry
P04234Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0006727|T-cell surface glycoprotein CD3 delta chain
MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDL
GKRILDPRGIYRCNGTDIYKDKESTVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLAL
GVFCFAGHETGRLSGAADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNK
Number of residues
171
Molecular Weight
18929.38
Theoretical pI
5.21
GO Classification
Functions
transmembrane signaling receptor activity
Processes
cell surface receptor signaling pathway / positive thymic T cell selection / T cell receptor signaling pathway
Components
alpha-beta T cell receptor complex / cytoplasm / plasma membrane / T cell receptor complex
General Function
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)
Specific Function
identical protein binding
Pfam Domain Function
Signal Regions
1-21
Transmembrane Regions
106-126
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0017107|T-cell surface glycoprotein CD3 delta chain (CD3D)
ATGGAACATAGCACGTTTCTCTCTGGCCTGGTACTGGCTACCCTTCTCTCGCAAGTGAGC
CCCTTCAAGATACCTATAGAGGAACTTGAGGACAGAGTGTTTGTGAATTGCAATACCAGC
ATCACATGGGTAGAGGGAACGGTGGGAACACTGCTCTCAGACATTACAAGACTGGACCTG
GGAAAACGCATCCTGGACCCACGAGGAATATATAGGTGTAATGGGACAGATATATACAAG
GACAAAGAATCTACCGTGCAAGTTCATTATCGAATGTGCCAGAGCTGTGTGGAGCTGGAT
CCAGCCACCGTGGCTGGCATCATTGTCACTGATGTCATTGCCACTCTGCTCCTTGCTTTG
GGAGTCTTCTGCTTTGCTGGACATGAGACTGGAAGGCTGTCTGGGGCTGCCGACACACAA
GCTCTGTTGAGGAATGACCAGGTCTATCAGCCCCTCCGAGATCGAGATGATGCTCAGTAC
AGCCACCTTGGAGGAAACTGGGCTCGGAACAAGTGA
Chromosome Location
11
Locus
11q23.3
External Identifiers
ResourceLink
UniProtKB IDP04234
UniProtKB Entry NameCD3D_HUMAN
GenBank Gene IDX01451
GeneCard IDCD3D
GenAtlas IDCD3D
HGNC IDHGNC:1673
PDB ID(s)1XIW, 6JXR, 7FJD, 7FJE, 7FJF, 7PHR, 8ES7, 8ES8, 8ES9, 8JC0, 8JCB, 8WXE, 8WY0, 8WYI, 8YC0
KEGG IDhsa:915
NCBI Gene ID915
General References
  1. van den Elsen P, Georgopoulos K, Shepley BA, Orkin S, Terhorst C: Exon/intron organization of the genes coding for the delta chains of the human and murine T-cell receptor/T3 complex. Proc Natl Acad Sci U S A. 1986 May;83(9):2944-8. [Article]
  2. van den Elsen P, Shepley BA, Borst J, Coligan JE, Markham AF, Orkin S, Terhorst C: Isolation of cDNA clones encoding the 20K T3 glycoprotein of human T-cell receptor complex. Nature. 1984 Nov 29-Dec 5;312(5993):413-8. [Article]
  3. Tunnacliffe A, Sims JE, Rabbitts TH: T3 delta pre-mRNA is transcribed from a non-TATA promoter and is alternatively spliced in human T cells. EMBO J. 1986 Jun;5(6):1245-52. [Article]
  4. Jin P, Fu GK, Wilson AD, Yang J, Chien D, Hawkins PR, Au-Young J, Stuve LL: PCR isolation and cloning of novel splice variant mRNAs from known drug target genes. Genomics. 2004 Apr;83(4):566-71. [Article]
  5. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Alexander D, Goris J, Marais R, Rothbard J, Merlevede W, Crumpton MJ: Dephosphorylation of the human T lymphocyte CD3 antigen. Eur J Biochem. 1989 Apr 15;181(1):55-65. [Article]
  8. Dadi HK, Simon AJ, Roifman CM: Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency. N Engl J Med. 2003 Nov 6;349(19):1821-8. [Article]
  9. Salomon AR, Ficarro SB, Brill LM, Brinker A, Phung QT, Ericson C, Sauer K, Brock A, Horn DM, Schultz PG, Peters EC: Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):443-8. Epub 2003 Jan 9. [Article]
  10. Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC: Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. Anal Chem. 2004 May 15;76(10):2763-72. [Article]
  11. 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: Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3. J Clin Invest. 2004 Nov;114(10):1512-7. [Article]
  12. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  13. Yu GP, Nadeau KC, Berk DR, de Saint Basile G, Lambert N, Knapnougel P, Roberts J, Kavanau K, Dunn E, Stiehm ER, Lewis DB, Umetsu DT, Puck JM, Cowan MJ: Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID. Pediatr Transplant. 2011 Nov;15(7):733-41. doi: 10.1111/j.1399-3046.2011.01563.x. Epub 2011 Aug 23. [Article]
  14. Arnett KL, Harrison SC, Wiley DC: Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment. Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16268-73. Epub 2004 Nov 8. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Muromonabapproved, investigationalyestargetDetails
Blinatumomabapproved, investigationalyestargetantibodyactivatorDetails