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Protein

T-cell surface glycoprotein CD3 zeta chain

Gene

CD247

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.

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 processHost-virus interaction

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.

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
Disulfide bondi32InterchainSequence analysis
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 similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiP20963.
PeptideAtlasiP20963.
PRIDEiP20963.

PTM databases

iPTMnetiP20963.
PhosphoSitePlusiP20963.

Expressioni

Gene expression databases

BgeeiENSG00000198821.
CleanExiHS_CD247.
GenevisibleiP20963. HS.

Organism-specific databases

HPAiCAB004651.
HPA008750.

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 (PubMed:17055436). CD3-zeta forms either homodimers or heterodimers with CD3-eta (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).9 Publications
(Microbial infection) Interacts with HIV-1; this interaction up-regulates the expression of the Fas ligand (FASLG) at the cell surface (PubMed:10224289). Interacts with HIV-2 Nef protein; this interaction induces down-regulation of cell surface TCR/CD3 complexes (PubMed:9811718, PubMed:16051847).3 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.
MINTiMINT-1517020.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TCENMR-B137-150[»]
1YGRX-ray2.90C/D80-85[»]
2HACNMR-A/B28-60[»]
2OQ1X-ray1.90B69-87[»]
3IK5X-ray2.05B/D63-80[»]
3IOZX-ray3.70B51-93[»]
4XZ1X-ray2.80B69-87[»]
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.
AL359962, AL031733 Genomic DNA. Translation: CAH69974.1.
AL359962, AL031733 Genomic DNA. Translation: CAH69975.1.
AL031733, AL359962 Genomic DNA. Translation: CAI21380.1.
AL031733, AL359962 Genomic DNA. Translation: CAI21381.1.
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: September 27, 2017
This is version 191 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