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Protein

T-cell surface glycoprotein CD3 gamma chain

Gene

CD3G

Organism
Homo sapiens (Human)
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 (PubMed:2470098). In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface (PubMed:8187769). Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G.3 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: CAFA
  • receptor signaling complex scaffold activity Source: UniProtKB
  • T cell receptor binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cell surface receptor signaling pathway Source: UniProtKB
  • establishment or maintenance of cell polarity Source: UniProtKB
  • Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  • membrane organization Source: Reactome
  • protein complex assembly Source: UniProtKB
  • protein homooligomerization Source: CAFA
  • protein transport Source: UniProtKB
  • regulation of immune response Source: Reactome
  • regulation of lymphocyte apoptotic process Source: UniProtKB
  • T cell activation Source: UniProtKB
  • T cell costimulation Source: Reactome
  • T cell receptor signaling pathway Source: Reactome

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-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.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
SIGNORiP09693.

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD3 gamma chain
Alternative name(s):
T-cell receptor T3 gamma chain
CD_antigen: CD3g
Gene namesi
Name:CD3G
Synonyms:T3G
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000160654.9.
HGNCiHGNC:1675. CD3G.

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 domaini23 – 116ExtracellularSequence analysisAdd BLAST94
Transmembranei117 – 137HelicalSequence analysisAdd BLAST21
Topological domaini138 – 182CytoplasmicSequence analysisAdd BLAST45

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 17 (IMD17)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive primary immunodeficiency characterized by highly variable clinical severity. Some patients have onset of severe recurrent infections in early infancy that may be lethal, whereas others may be only mildly affected or essentially asymptomatic into young adulthood. More severely affected patients may have evidence of autoimmune disease or enteropathy. The immunologic pattern is similar among patients, showing partial T-cell lymphopenia, decreased amounts of the CD3 complex, and impaired proliferative responses to T-cell receptor dependent stimuli. The phenotype in some patients is reminiscent of severe combined immunodeficiency.
See also OMIM:615607

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi153L → A: Abolishes lysosomal targeting. 2 Publications1
Mutagenesisi153L → I: Diminished but persistent lysosomal targeting. 1 Publication1
Mutagenesisi154L → A: Abolishes lysosomal targeting. 1 Publication1
Mutagenesisi154L → A: Diminished but persistent lysosomal targeting. 1 Publication1
Mutagenesisi154L → I: No effect. 1 Publication1
Mutagenesisi160Y → A: Abolishes lysosomal targeting. 1 Publication1
Mutagenesisi163L → A: Abolishes lysosomal targeting. 1 Publication1

Organism-specific databases

DisGeNETi917.
MalaCardsiCD3G.
MIMi615607. phenotype.
OpenTargetsiENSG00000160654.
Orphaneti169082. Combined immunodeficiency due to CD3gamma deficiency.
PharmGKBiPA26217.

Chemistry databases

ChEMBLiCHEMBL2364168.
DrugBankiDB00075. Muromonab.

Polymorphism and mutation databases

BioMutaiCD3G.
DMDMi115993.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Add BLAST22
ChainiPRO_000001461523 – 182T-cell surface glycoprotein CD3 gamma chainAdd BLAST160

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi46 ↔ 871 Publication
Glycosylationi52N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi92N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei145Phosphoserine2 Publications1
Modified residuei148Phosphoserine; by PKC3 Publications1

Post-translational modificationi

Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8 (PubMed:2470098). Phosphorylated also by PKC; leading to the TCR complex down-regulation (PubMed:8187769).2 Publications
Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP09693.
PaxDbiP09693.
PeptideAtlasiP09693.
PRIDEiP09693.

PTM databases

iPTMnetiP09693.
PhosphoSitePlusiP09693.

Expressioni

Gene expression databases

BgeeiENSG00000160654.
CleanExiHS_CD3G.
ExpressionAtlasiP09693. baseline and differential.
GenevisibleiP09693. HS.

Organism-specific databases

HPAiCAB017520.
HPA038494.

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.1 Publication

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: CAFA
  • receptor signaling complex scaffold activity Source: UniProtKB
  • T cell receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107355. 3 interactors.
ELMiP09693.
IntActiP09693. 1 interactor.
MINTiMINT-4656150.
STRINGi9606.ENSP00000431445.

Structurei

Secondary structure

1182
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni26 – 28Combined sources3
Beta strandi31 – 33Combined sources3
Beta strandi38 – 46Combined sources9
Beta strandi50 – 57Combined sources8
Beta strandi60 – 68Combined sources9
Beta strandi72 – 76Combined sources5
Helixi77 – 79Combined sources3
Beta strandi82 – 92Combined sources11
Beta strandi97 – 102Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SY6X-ray2.10A23-103[»]
DisProtiDP00508.
ProteinModelPortaliP09693.
SMRiP09693.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09693.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini37 – 94Ig-likeAdd BLAST58
Domaini149 – 177ITAMPROSITE-ProRule annotationAdd BLAST29

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi153 – 154Di-leucine motif1 Publication2

Domaini

A di-leucine motif and a tyrosine-based motif are individually sufficient to induce both endocytosis and delivery to lysosomes.

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWAX. Eukaryota.
ENOG410Y2TD. LUCA.
GeneTreeiENSGT00510000046930.
HOGENOMiHOG000015287.
HOVERGENiHBG005278.
InParanoidiP09693.
KOiK06452.
OMAiDRENDQY.
OrthoDBiEOG091G0MXQ.
PhylomeDBiP09693.
TreeFamiTF335892.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiView protein in InterPro
IPR015484. CD3_esu/gsu/dsu.
IPR036179. Ig-like_dom_sf.
IPR013783. Ig-like_fold.
IPR032052. Ig_4.
IPR003598. Ig_sub2.
IPR003110. Phos_immunorcpt_sig_ITAM.
PANTHERiPTHR10570. PTHR10570. 1 hit.
PfamiView protein in Pfam
PF16680. Ig_4. 1 hit.
PF02189. ITAM. 1 hit.
SMARTiView protein in SMART
SM00408. IGc2. 1 hit.
SM00077. ITAM. 1 hit.
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiView protein in PROSITE
PS51055. ITAM_1. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P09693-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQGKGLAVL ILAIILLQGT LAQSIKGNHL VKVYDYQEDG SVLLTCDAEA
60 70 80 90 100
KNITWFKDGK MIGFLTEDKK KWNLGSNAKD PRGMYQCKGS QNKSKPLQVY
110 120 130 140 150
YRMCQNCIEL NAATISGFLF AEIVSIFVLA VGVYFIAGQD GVRQSRASDK
160 170 180
QTLLPNDQLY QPLKDREDDQ YSHLQGNQLR RN
Length:182
Mass (Da):20,469
Last modified:July 1, 1989 - v1
Checksum:iEE65C0186FB9872B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049854131V → F. Corresponds to variant dbSNP:rs3753058Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04145 mRNA. Translation: CAA27764.1.
X06026
, X06027, X06028, X06029, X06030, X06031 Genomic DNA. Translation: CAA29428.1.
BC113830 mRNA. Translation: AAI13831.1.
CCDSiCCDS8395.1.
PIRiA25468.
RefSeqiNP_000064.1. NM_000073.2.
XP_006719004.1. XM_006718941.2.
UniGeneiHs.2259.

Genome annotation databases

EnsembliENST00000532917; ENSP00000431445; ENSG00000160654.
GeneIDi917.
KEGGihsa:917.
UCSCiuc001psu.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCD3G_HUMAN
AccessioniPrimary (citable) accession number: P09693
Secondary accession number(s): Q2HIZ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 22, 2017
This is version 167 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references