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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

The CD3 complex mediates signal transduction.

GO - Molecular functioni

  1. protein heterodimerization activity Source: UniProtKB
  2. receptor signaling complex scaffold activity Source: UniProtKB
  3. T cell receptor binding Source: UniProtKB
  4. transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  1. cell surface receptor signaling pathway Source: UniProtKB
  2. establishment or maintenance of cell polarity Source: UniProtKB
  3. Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  4. innate immune response Source: Reactome
  5. protein complex assembly Source: UniProtKB
  6. protein transport Source: UniProtKB
  7. regulation of immune response Source: Reactome
  8. regulation of lymphocyte apoptotic process Source: UniProtKB
  9. T cell activation Source: UniProtKB
  10. T cell costimulation Source: Reactome
  11. T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiREACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
REACT_12555. Downstream TCR signaling.
REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
REACT_12596. Translocation of ZAP-70 to Immunological synapse.
REACT_12623. Generation of second messenger molecules.
REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
REACT_160158. Role of phospholipids in phagocytosis.
REACT_160274. FCGR activation.
REACT_19324. PD-1 signaling.

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
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:1675. CD3G.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 11694ExtracellularSequence AnalysisAdd
BLAST
Transmembranei117 – 13721HelicalSequence AnalysisAdd
BLAST
Topological domaini138 – 18245CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. alpha-beta T cell receptor complex Source: Ensembl
  2. integral component of plasma membrane Source: UniProtKB
  3. plasma membrane Source: Reactome
  4. T cell receptor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi153 – 1531L → A: Abolishes lysosomal targeting. 1 Publication
Mutagenesisi153 – 1531L → I: Diminished but persistent lysosomal targeting. 1 Publication
Mutagenesisi154 – 1541L → A: Diminished but persistent lysosomal targeting. 1 Publication
Mutagenesisi154 – 1541L → I: No effect. 1 Publication
Mutagenesisi160 – 1601Y → A: Abolishes lysosomal targeting. 1 Publication
Mutagenesisi163 – 1631L → A: Abolishes lysosomal targeting. 1 Publication

Organism-specific databases

MIMi615607. phenotype.
Orphaneti169082. Combined immunodeficiency due to CD3gamma deficiency.
PharmGKBiPA26217.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Add
BLAST
Chaini23 – 182160T-cell surface glycoprotein CD3 gamma chainPRO_0000014615Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi46 ↔ 871 Publication
Glycosylationi52 – 521N-linked (GlcNAc...)Sequence Analysis
Glycosylationi92 – 921N-linked (GlcNAc...)Sequence Analysis
Modified residuei145 – 1451Phosphoserine2 Publications
Modified residuei148 – 1481Phosphoserine2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP09693.
PaxDbiP09693.
PeptideAtlasiP09693.
PRIDEiP09693.

PTM databases

PhosphoSiteiP09693.

Expressioni

Gene expression databases

BgeeiP09693.
CleanExiHS_CD3G.
ExpressionAtlasiP09693. baseline and differential.
GenevestigatoriP09693.

Organism-specific databases

HPAiCAB017520.
HPA038494.

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.1 Publication

Protein-protein interaction databases

BioGridi107355. 4 interactions.
IntActiP09693. 1 interaction.
MINTiMINT-4656150.
STRINGi9606.ENSP00000292144.

Structurei

Secondary structure

1
182
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi31 – 333
Beta strandi43 – 464
Beta strandi50 – 578
Beta strandi65 – 684
Helixi77 – 793
Beta strandi85 – 884
Beta strandi97 – 1026

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SY6X-ray2.10A23-103[»]
DisProtiDP00508.
ProteinModelPortaliP09693.
SMRiP09693. Positions 23-103.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09693.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini37 – 9458Ig-likeAdd
BLAST
Domaini149 – 17729ITAMPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi153 – 1542Di-leucine motif

Domaini

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

Sequence similaritiesi

Contains 1 ITAM domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG43749.
GeneTreeiENSGT00510000046930.
HOGENOMiHOG000015287.
HOVERGENiHBG005278.
InParanoidiP09693.
KOiK06452.
OMAiDRENDQY.
OrthoDBiEOG7S4X7Q.
PhylomeDBiP09693.
TreeFamiTF335892.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR015484. CD3_esu/gsu/dsu.
IPR013783. Ig-like_fold.
IPR003598. Ig_sub2.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]
PANTHERiPTHR10570. PTHR10570. 1 hit.
PfamiPF02189. ITAM. 1 hit.
[Graphical view]
SMARTiSM00408. IGc2. 1 hit.
SM00077. ITAM. 1 hit.
[Graphical view]
PROSITEiPS51055. ITAM_1. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1311V → F.
Corresponds to variant rs3753058 [ dbSNP | Ensembl ].
VAR_049854

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_006718941.1.
UniGeneiHs.2259.

Genome annotation databases

EnsembliENST00000532917; ENSP00000431445; ENSG00000160654.
GeneIDi917.
KEGGihsa:917.
UCSCiuc001psu.2. human.

Polymorphism databases

DMDMi115993.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

CD3Gbase

CD3G mutation db

Wikipedia

CD3 receptor entry

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_006718941.1.
UniGeneiHs.2259.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SY6X-ray2.10A23-103[»]
DisProtiDP00508.
ProteinModelPortaliP09693.
SMRiP09693. Positions 23-103.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107355. 4 interactions.
IntActiP09693. 1 interaction.
MINTiMINT-4656150.
STRINGi9606.ENSP00000292144.

Chemistry

ChEMBLiCHEMBL2364168.
DrugBankiDB00075. Muromonab.

PTM databases

PhosphoSiteiP09693.

Polymorphism databases

DMDMi115993.

Proteomic databases

MaxQBiP09693.
PaxDbiP09693.
PeptideAtlasiP09693.
PRIDEiP09693.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000532917; ENSP00000431445; ENSG00000160654.
GeneIDi917.
KEGGihsa:917.
UCSCiuc001psu.2. human.

Organism-specific databases

CTDi917.
GeneCardsiGC11P118248.
HGNCiHGNC:1675. CD3G.
HPAiCAB017520.
HPA038494.
MIMi186740. gene.
615607. phenotype.
neXtProtiNX_P09693.
Orphaneti169082. Combined immunodeficiency due to CD3gamma deficiency.
PharmGKBiPA26217.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG43749.
GeneTreeiENSGT00510000046930.
HOGENOMiHOG000015287.
HOVERGENiHBG005278.
InParanoidiP09693.
KOiK06452.
OMAiDRENDQY.
OrthoDBiEOG7S4X7Q.
PhylomeDBiP09693.
TreeFamiTF335892.

Enzyme and pathway databases

ReactomeiREACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
REACT_12555. Downstream TCR signaling.
REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
REACT_12596. Translocation of ZAP-70 to Immunological synapse.
REACT_12623. Generation of second messenger molecules.
REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
REACT_160158. Role of phospholipids in phagocytosis.
REACT_160274. FCGR activation.
REACT_19324. PD-1 signaling.

Miscellaneous databases

ChiTaRSiCD3G. human.
EvolutionaryTraceiP09693.
GeneWikiiCD3G.
GenomeRNAii917.
NextBioi3794.
PROiP09693.
SOURCEiSearch...

Gene expression databases

BgeeiP09693.
CleanExiHS_CD3G.
ExpressionAtlasiP09693. baseline and differential.
GenevestigatoriP09693.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR015484. CD3_esu/gsu/dsu.
IPR013783. Ig-like_fold.
IPR003598. Ig_sub2.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]
PANTHERiPTHR10570. PTHR10570. 1 hit.
PfamiPF02189. ITAM. 1 hit.
[Graphical view]
SMARTiSM00408. IGc2. 1 hit.
SM00077. ITAM. 1 hit.
[Graphical view]
PROSITEiPS51055. ITAM_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Primary structure of the T3 gamma subunit of the T3/T cell antigen receptor complex deduced from cDNA sequences: evolution of the T3 gamma and delta subunits."
    Krissansen G.W., Owen M.J., Verbi W., Crumpton M.J.
    EMBO J. 5:1799-1808(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Physical linkage of three CD3 genes on human chromosome 11."
    Tunnacliffe A., Buluwela L., Rabbitts T.H.
    EMBO J. 6:2953-2957(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. Cited for: PROTEIN SEQUENCE OF 139-182, PHOSPHORYLATION AT SER-145 AND SER-148.
  5. "The human T3 gamma chain is phosphorylated at serine 126 in response to T lymphocyte activation."
    Davies A.A., Cantrell D.A., Hexham J.M., Parker P.J., Rothbard J., Crumpton M.J.
    J. Biol. Chem. 262:10918-10921(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-145 AND SER-148.
  6. "A novel di-leucine motif and a tyrosine-based motif independently mediate lysosomal targeting and endocytosis of CD3 chains."
    Letourneur F., Klausner R.D.
    Cell 69:1143-1157(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF LEU-153; LEU-154; TYR-160 AND LEU-163.
  7. "Brief report: primary immunodeficiency caused by mutations in the gene encoding the CD3-gamma subunit of the T-lymphocyte receptor."
    Arnaiz-Villena A., Timon M., Corell A., Perez-Aciego P., Martin-Villa J.M., Regueiro J.R.
    N. Engl. J. Med. 327:529-533(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN IMD17.
  8. Cited for: INVOLVEMENT IN IMD17.
  9. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  10. "Crystal structure of the human T cell receptor CD3 epsilon gamma heterodimer complexed to the therapeutic mAb OKT3."
    Kjer-Nielsen L., Dunstone M.A., Kostenko L., Ely L.K., Beddoe T., Mifsud N.A., Purcell A.W., Brooks A.G., McCluskey J., Rossjohn J.
    Proc. Natl. Acad. Sci. U.S.A. 101:7675-7680(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 23-103 IN COMPLEX WITH CD3E AND ANTIBODY, SUBUNIT, DISULFIDE BOND.

Entry informationi

Entry nameiCD3G_HUMAN
AccessioniPrimary (citable) accession number: P09693
Secondary accession number(s): Q2HIZ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: January 7, 2015
This is version 147 of the entry and version 1 of the sequence. [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
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.