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CD4; T-cell surface glycoprotein CD4; T-cell surface antigen T4/Leu-3
Function:
- accessory protein for MHC class-II antigen/T-cell receptor interaction
- CD4+ T-cells are activated by simultaneous engagement of the T-cell receptor & CD4 by antigen-MHC II complexes on the surface of an antigen-presenting cell
- may regulate T-cell activation
- the signal is transduced by an associated tyrosine kinase lck-protein
- in vitro cross-linking of CD4 prior to engagement with the T-cell receptor, induces apoptosis
- induces the aggregation of lipid rafts
- palmitoylation & association with LCK contribute to the enrichment of CD4 in lipid rafts
- binds to P4HB/PDI
Structure:
- contains 3 Ig-like C2-type domains (immunoglobulin-like)
- contains 1 Ig-like V-type domain (immunoglobulin-like)
Compartment:
- cell membrane
- localizes to lipid rafts
Expression:
- expressed with CD3
- thymocytes ~80-90%
- mature T-cells ~60-65%
- T-helper & CD4/CD8+ thymocytes
- macrophages
- langerhans cells
- dendritic cells
- granulocytes
Pathology:
- CD4 is recognized by HIV gp120
- part of P4HB/PDI-CD4-CXCR4-gp120 complex
- interacts with HIV-1 Envelope polyprotein gp160 & protein Vpu
- removed from plasma membrane by HIV-1 Nef protein that increases clathrin-dependent endocytosis to target it to lysosomal degradation
- cell surface expression is also down-modulated by HIV-1 Envelope polyprotein gp160 that interacts with, & sequesters CD4 in the endoplasmic reticulum
Laboratory:
- a marker for T-helper cells
Interactions
molecular events
Related
CD4 cells in specimen
CD4 stimulated ATP immune response in blood
CD4/CD8 ratio
helper T cell (T4 lymphocyte, CD4+)
HIV envelope glycoprotein gp120
monocyte
General
adhesion receptor
cluster-of-differentiation antigen; cluster designation antigen; CD antigen
glycoprotein
immunoglobulin superfamily protein
Properties
SIZE: entity length = 458 aa
MW = 51 kD
COMPARTMENT: lysosome
plasma membrane
endoplasmic reticulum
MOTIF: signal sequence {1-25}
immunoglobulin superfamily domain {26-125}
MOTIF: cysteine residue {C41}
MODIFICATION: cysteine residue {C109}
cysteine residue {C109}
MODIFICATION: cysteine residue {C41}
immunoglobulin superfamily domain {126-203}
MOTIF: cysteine residue {C155}
MODIFICATION: cysteine residue {C184}
cysteine residue {C184}
MODIFICATION: cysteine residue {C155}
immunoglobulin superfamily domain {204-317}
MOTIF: N-glycosylation site {N296}
immunoglobulin superfamily domain {318-374}
MOTIF: N-glycosylation site {N325}
cysteine residue {C328}
MODIFICATION: cysteine residue {C370}
cysteine residue {C370}
MODIFICATION: cysteine residue {C328}
transmembrane domain {397-418}
cysteine residue {C419}
MODIFICATION: palmitate
COMPARTMENT: membrane
cysteine residue {C422}
MODIFICATION: palmitate
COMPARTMENT: membrane
HIV-1 Vpu-susceptibility {427-455}
Database Correlations
OMIM 186940
UniProt P01730
PFAM correlations
Entrez Gene 920
Kegg hsa:920
References
- Cotran et al Robbins Pathologic Basis of Disease,
W.B. Saunders Co, Philadelphia, PA 1989 pg 165
- Bolen JB, Rowley RB, Spana C, Tsygankov AY.
The Src family of tyrosine protein kinases in hemopoietic
signal transduction.
FASEB J. 1992 Dec;6(15):3403-9. Review.
PMID: 1281458
- http://www.pathologyoutlines.com/cdmarkers.html
15 October 2002
- Entrez Gene :accession 920
- Wikipedia; Note: CD4 entry
http://en.wikipedia.org/wiki/CD4
- UniProt :accession P01730
Component-of
molecular complex