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Protein

T-cell surface glycoprotein CD3 zeta chain

Gene

CD247

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, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity).By similarity4 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: CAFA
  • protein tyrosine kinase binding Source: CAFA
  • transmembrane signaling receptor activity Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Host-virus interaction, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-164944 Nef and signal transduction
R-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-2029481 FCGR activation
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-389948 PD-1 signaling
SignaLinkiP20963
SIGNORiP20963

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD3 zeta chain
Alternative name(s):
T-cell receptor T3 zeta chain
CD_antigen: CD247
Gene namesi
Name:CD247
Synonyms:CD3Z, T3Z, TCRZ
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000198821.10
HGNCiHGNC:1677 CD247
MIMi186780 gene
neXtProtiNX_P20963

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 – 30ExtracellularSequence analysis9
Transmembranei31 – 51HelicalSequence analysisAdd BLAST21
Topological domaini52 – 164CytoplasmicSequence analysisAdd BLAST113

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 25 (IMD25)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.
See also OMIM:610163

Organism-specific databases

DisGeNETi919
MalaCardsiCD247
MIMi610163 phenotype
OpenTargetsiENSG00000198821
Orphaneti85408 Juvenile rheumatoid factor-negative polyarthritis
85410 Oligoarticular juvenile arthritis
169160 T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
PharmGKBiPA26219

Chemistry databases

DrugBankiDB00075 Muromonab

Polymorphism and mutation databases

BioMutaiCD247
DMDMi23830999

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Add BLAST21
ChainiPRO_000001649322 – 164T-cell surface glycoprotein CD3 zeta chainAdd BLAST143

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei58PhosphoserineCombined sources1
Modified residuei64PhosphotyrosineCombined sources1
Modified residuei72PhosphotyrosineCombined sources1
Modified residuei83PhosphotyrosineCombined sources1
Modified residuei111PhosphotyrosineCombined sources1
Modified residuei123PhosphotyrosineCombined sources1
Modified residuei142PhosphotyrosineCombined sources1
Modified residuei153PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP20963
PeptideAtlasiP20963
PRIDEiP20963
ProteomicsDBi53833
53834 [P20963-3]

PTM databases

iPTMnetiP20963
PhosphoSitePlusiP20963

Expressioni

Tissue specificityi

CD3Z is expressed in normal lymphoid tissue and in peripheral blood mononuclear cells (PBMCs) (PubMed:11722641).1 Publication

Gene expression databases

BgeeiENSG00000198821
CleanExiHS_CD247
GenevisibleiP20963 HS

Organism-specific databases

HPAiCAB004651
HPA008750

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 (PubMed:17055436). Interacts with SLA (PubMed:10449770). Interacts with TRAT1 (PubMed:11390434). Interacts with DOCK2 (PubMed:12176041). Interacts with SLA2. Interacts with SHB (PubMed:9484780). Interacts with ZAP70 (PubMed:26783323, PubMed:7659156). Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain) (PubMed:7544002). Interacts with PTPRC (PubMed:15684325). Interacts with CRK; this interaction regulates CD3Z phosphorylation (PubMed:28465009).10 Publications
(Microbial infection) Interacts with HIV-1 Nef; this interaction up-regulates the expression of the Fas ligand (FASLG) at the cell surface.1 Publication
(Microbial infection) Interacts with HIV-2 Nef protein; this interaction induces down-regulation of cell surface TCR/CD3 complexes.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: CAFA
  • protein tyrosine kinase binding Source: CAFA

Protein-protein interaction databases

BioGridi107357, 29 interactors
CORUMiP20963
DIPiDIP-35404N
ELMiP20963
IntActiP20963, 160 interactors
MINTiP20963
STRINGi9606.ENSP00000354782

Structurei

Secondary structure

1164
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 54Combined sources24
Helixi64 – 73Combined sources10
Turni74 – 76Combined sources3
Helixi77 – 79Combined sources3

3D structure databases

DisProtiDP00200
ProteinModelPortaliP20963
SMRiP20963
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20963

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 89ITAM 1PROSITE-ProRule annotationAdd BLAST29
Domaini100 – 128ITAM 2PROSITE-ProRule annotationAdd BLAST29
Domaini131 – 159ITAM 3PROSITE-ProRule annotationAdd BLAST29

Domaini

The ITAM domains mediate interaction with SHB.

Sequence similaritiesi

Belongs to the CD3Z/FCER1G family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J0ID Eukaryota
ENOG411241T LUCA
GeneTreeiENSGT00390000018208
HOGENOMiHOG000234398
HOVERGENiHBG005280
InParanoidiP20963
KOiK06453
OMAiLHMQTLP
OrthoDBiEOG091G0QJC
PhylomeDBiP20963
TreeFamiTF330937

Family and domain databases

InterProiView protein in InterPro
IPR021663 CD3_zeta/IgE_Fc_rcpt_gamma
IPR003110 Phos_immunorcpt_sig_ITAM
IPR024128 T-cell_CD3_zeta
PANTHERiPTHR10035 PTHR10035, 1 hit
PfamiView protein in Pfam
PF02189 ITAM, 3 hits
PF11628 TCR_zetazeta, 1 hit
SMARTiView protein in SMART
SM00077 ITAM, 3 hits
PROSITEiView protein in PROSITE
PS51055 ITAM_1, 3 hits

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P20963-1) [UniParc]FASTAAdd to basket
Also known as: CD-3-zeta

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
MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF
60 70 80 90 100
LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP
110 120 130 140 150
QRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK
160
DTYDALHMQA LPPR
Length:164
Mass (Da):18,696
Last modified:October 10, 2002 - v2
Checksum:i9408260374856EE9
GO
Isoform 2 (identifier: P20963-2)
Also known as: CD-3-eta
Sequence is not available
Length:
Mass (Da):
Isoform 3 (identifier: P20963-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     101-101: Missing.

Show »
Length:163
Mass (Da):18,568
Checksum:i34898620B67167C7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60 – 61DA → EP in AAA60394 (PubMed:2974162).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_036459101Missing in isoform 3. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04132 mRNA Translation: AAA60394.1
AK313946 mRNA Translation: BAG36664.1
DQ072717 Genomic DNA Translation: AAY57330.1
AL031733 Genomic DNA No translation available.
AL359962 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW90792.1
BC025703 mRNA Translation: AAH25703.1
CCDSiCCDS1260.1 [P20963-3]
CCDS1261.1 [P20963-1]
PIRiA31768
RefSeqiNP_000725.1, NM_000734.3 [P20963-3]
NP_932170.1, NM_198053.2 [P20963-1]
UniGeneiHs.156445

Genome annotation databases

EnsembliENST00000362089; ENSP00000354782; ENSG00000198821 [P20963-1]
ENST00000392122; ENSP00000375969; ENSG00000198821 [P20963-3]
GeneIDi919
KEGGihsa:919
UCSCiuc001gei.5 human [P20963-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCD3Z_HUMAN
AccessioniPrimary (citable) accession number: P20963
Secondary accession number(s): B1AK49, Q5VX13, Q8TAX4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: October 10, 2002
Last modified: July 18, 2018
This is version 198 of the entry and version 2 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, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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