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Protein

T-cell surface glycoprotein CD3 zeta chain

Gene

Cd247

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme. 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 similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-MMU-202424. Downstream TCR signaling.
R-MMU-202427. Phosphorylation of CD3 and TCR zeta chains.
R-MMU-202430. Translocation of ZAP-70 to Immunological synapse.
R-MMU-202433. Generation of second messenger molecules.
R-MMU-2029481. FCGR activation.
R-MMU-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-MMU-2029485. Role of phospholipids in phagocytosis.
R-MMU-389948. PD-1 signaling.

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, Tcrz
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:88334. Cd247.

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

Disruption phenotypei

CD3Z deletion causes severely defective thymocyte differentiation (PubMed:8223495). Absence of CD3Z also leads to altered dendritic structure and motility in developing retina (PubMed:20188655).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Add BLAST21
ChainiPRO_000001649422 – 164T-cell surface glycoprotein CD3 zeta chainAdd BLAST143

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei22Blocked amino end (Gln)1
Modified residuei58PhosphoserineBy similarity1
Modified residuei72PhosphotyrosinePROSITE-ProRule annotationBy similarity1
Modified residuei83PhosphotyrosinePROSITE-ProRule annotationBy similarity1
Modified residuei111PhosphotyrosinePROSITE-ProRule annotationBy similarity1
Modified residuei123PhosphotyrosinePROSITE-ProRule annotationBy similarity1
Modified residuei142PhosphotyrosinePROSITE-ProRule annotationBy similarity1
Modified residuei153PhosphotyrosinePROSITE-ProRule annotationBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP24161.
PaxDbiP24161.
PRIDEiP24161.

PTM databases

iPTMnetiP24161.
PhosphoSitePlusiP24161.

Expressioni

Tissue specificityi

CD3Z is expressed in normal lymphoid tissue and in peripheral blood mononuclear cells (PBMCs). Expressed also in retinal ganglion cells (PubMed:20188655).Curated1 Publication

Gene expression databases

BgeeiENSMUSG00000005763.
CleanExiMM_CD247.
ExpressionAtlasiP24161. baseline and differential.
GenevisibleiP24161. MM.

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. Interacts with SLA (PubMed:10662792). Interacts with SLA2 (PubMed:11891219). Interacts with TRAT1. Interacts with DOCK2. Interacts with SHB. Interacts with ZAP70. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain). Interacts with PTPRC (By similarity). Interacts with CRK; this interaction regulates CD3Z phosphorylation (By similarity).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198598. 5 interactors.
CORUMiP24161.
ELMiP24161.
IntActiP24161. 7 interactors.
MINTiMINT-7895650.
STRINGi10090.ENSMUSP00000027849.

Structurei

3D structure databases

ProteinModelPortaliP24161.
SMRiP24161.
ModBaseiSearch...
MobiDBiSearch...

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.By similarity

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.
InParanoidiP29020.
KOiK06453.
OMAiLHMQTLP.
OrthoDBiEOG091G0QJC.

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 (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 CD-3-zeta (identifier: P24161-1) [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
MKWKVSVLAC ILHVRFPGAE AQSFGLLDPK LCYLLDGILF IYGVIITALY
60 70 80 90 100
LRAKFSRSAE TAANLQDPNQ LYNELNLGRR EEYDVLEKKR ARDPEMGGKQ
110 120 130 140 150
QRRRNPQEGV YNALQKDKMA EAYSEIGTKG ERRRGKGHDG LYQGLSTATK
160
DTYDALHMQT LAPR
Length:164
Mass (Da):18,637
Last modified:March 1, 1992 - v1
Checksum:i1B8022035A312831
GO
Isoform CD-3-eta (identifier: P24161-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     144-164: GLSTATKDTYDALHMQTLAPR → DSHFQAVQFG...PWPPSSSSQL

Show »
Length:206
Mass (Da):23,339
Checksum:i829256A2CF44E444
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti153Y → C in BAB30997 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_058346144 – 164GLSTA…TLAPR → DSHFQAVQFGNRREREGSEL TRTLGLRARPKGESTQQSSQ SCASVFSIPTLWSPWPPSSS SQL in isoform CD-3-eta. Add BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19729 Genomic DNA. Translation: AAA40171.1.
J04967 mRNA. Translation: AAA50301.1.
M33158 mRNA. Translation: AAA37398.1.
AK017904 mRNA. Translation: BAB30997.1.
BC052824 mRNA. Translation: AAH52824.1.
M76711 Genomic DNA. Translation: AAA40403.1.
CCDSiCCDS15443.1. [P24161-2]
CCDS48427.1. [P24161-1]
PIRiA35900.
A40104.
RefSeqiNP_001106862.1. NM_001113391.2. [P24161-1]
NP_112439.1. NM_031162.4. [P24161-2]
XP_011237047.1. XM_011238745.2. [P24161-1]
XP_017168774.1. XM_017313285.1. [P24161-1]
UniGeneiMm.217308.
Mm.245261.
Mm.475205.

Genome annotation databases

EnsembliENSMUST00000005907; ENSMUSP00000005907; ENSMUSG00000005763. [P24161-1]
ENSMUST00000027849; ENSMUSP00000027849; ENSMUSG00000005763. [P24161-2]
ENSMUST00000086002; ENSMUSP00000083165; ENSMUSG00000005763. [P24161-2]
ENSMUST00000187313; ENSMUSP00000140926; ENSMUSG00000005763. [P24161-2]
GeneIDi12503.
KEGGimmu:12503.
UCSCiuc007djn.2. mouse. [P24161-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCD3Z_MOUSE
AccessioniPrimary (citable) accession number: P24161
Secondary accession number(s): P29020, Q9D3G3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: November 22, 2017
This is version 159 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families