CD127 IL-7R(α chain), CDw127, IL-7α, p90
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
B Cell
Bone Marrow
Thymocyte
Lymphoid Cell
Liver
T Cell
80 / 80

Expression
CD127 is expressed on pro-B cells, foetal liver, bone marrow lymphoid precursors, the majority of mature T cells, and thymocytes.  Expression is downregulated following T cell activation. 



Structure
MOLECULAR FAMILY NAME: Belongs to the hematopoietin superfamily.

CD127 is a single-pass type-1 a chain 459 aa glycoprotein.  It contains a 20 aa signal sequence, a 220 aa extracellular region which contains a N-terminal fibronectin type-3 domain with 4 conserved cysteine and a Trp-Ser-X-Trp-Ser WSXWS motif, a 25 aa transmembrane region and an 195 aa intracellular cytoplasmic domain which contains a membrane proximal acidic region followed by a serine-containing domain with a box 1 motif and a tyrosine containing domain.  The cytoplasmic domain is essential for signal transduction and has structural and functional motifs that recruit signal-transducing molecules  CD127 associates with CD132 to form a heterodimeric receptor complex at the cell surface.  CD127 is a cytokine receptor belonging to the hematopoietin receptor superfamily and Ig gene superfamily. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

A soluble form of human CD127 is produced by alternative splicing out exon 6 of the CD127 gene.

POST-TRANSLATIONAL MODIFICATION

CD127 has a signal sequence of 20 aa at the N terminal and 6 potential N-glycosylation sites in the extracellular domain and tyrosine residues phosphorylated by tyrosine kinase.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD127

L-7R has 2 classes with a low- kDa = 5-10 nM and a high affinity of kDa = 100 pM.  The association of CD127 and CD132 augments both IL-7R binding and internalization.  CD127 binds IL-7 with high affinity when associated with CD132. 
 
Molecule Comment
IL-7
CD132 (IL-2Rg) High affinity IL-7 receptor consists of CD127 and CD132
fyn
lyn
Jak1
PI3K
lck
 

Function
CD127 associates with CD132 (common γ chain) to form the high affinity IL-7 receptor and mediates all biological effects of IL-7.  The intracellular A region associates with the Src family tyrosine kinases p56lck and p59fyn. The intracellular S domain is thought to bind Janus tyrosine kinase 1 (JAK1) which promotes cell survival.  When CD127 is phosphorylated the tyrosine containing domain is a binding site for the signal transducer and activator of transcription 5 (STAT5), which plays a role in thymocyte differentiation.  IL-7R engagement stimulates Tyr phosphorylation and phosphatidylinositol turnover in B cell precursors and thymocytes.  Phosphorylation of Tyr449 in the T domain is required for IL-7 dependent activation of PI3K, which is essential for survival and proliferation of thymocytes.  CD127 may regulate immunoglobulin gene rearrangement.  The function of CD127 requires CD121b (IL-2) to function.  IL-7R stimulates the proliferation of pro- and pre-B cells, thymocytes and mature T cells and induces the activation of monocytes.  CD127 has been shown to play a role in the V(D)J recombination during lymphocyte development.  It is found to control the accessibility of the TCR-γ locus by STAT5 and histone acetylation. Knockout mice have severe defects in B- and T-cell development and knockout studies in mice suggested that blocking apoptosis is an essential function of CD127 during differentiation and activation of T lymphocytes. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD127 IN INTACT ANIMAL

Defects in CD127 may be associated with the pathogenesis of severe combined immunodeficiency (SCID).  Early lymphocyte expansion is severely impaired in CD127 deficient mice.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD127: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD127

Tyrosine kinases, Jak1 and Jak3 are candidates.

ADDITIONAL INSIGHTS

The low affinity of IL-7R has not been cloned yet.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3575P16871
MouseD34791P16872M29697
Antibodies

Revised June 25, 2008


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