ADAP(adhesion & degranulation promoting adaptor protein), SLP-76 associated protein (SLAP, SLAP-130)
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
T Cell, Mature
|115 / 135|
|ADAP is located on cytoplasmic cytoskeleton, plasma membrane, adhesion plaques ( or podosomes) and in nascent phagosomes. Some nuclear staining has been reported. ADAP is expressed on thymocytes, mature T cells, macrophages, mast cells/basophils and platelets. There is no expression in murine B cells. There is a different expression of two ADAP isoforms (120Kd and 130Kd) during thymocyte development.|
|MOLECULAR FAMILY NAME: ADAP -> adaptor protein.|
ADAP was originally identified in T-cells as a substrate of the src kinase p59fyn and as a binding partner of p59fyn and the hematopoietic adaptor SLP-76 (SH2-domain- containing leukocyte protein of 76 kDa.
ADAP is a relatively hydrophilic protein with a proline rich region that binds to SH3, multiple tyrosine residues, a possible protein kinase C and casein kinase phosphorylation sites, 2 putative lysine/glutamic acid rich nuclear localization sequences (NLS) and 2 SH3 domains that mediate protein. Two isoforms of the adaptor have been cloned in mice that differ due to differential splicing with a 46 amino acid insert. Two tyrosine-based motifs serve as binding sites for SLP-76 domain and one for the Fyn-T SH2 domain. The adaptor has one conventional SH3 domain and 1 C-terminal SH3-like domain.
The molecular mass is 120 (or 130)/130kD and was previously termed = SLAP-130/Fyb-130.
Two isoforms of the adaptor have been cloned from T-cells in mice that differ due to differential splicing with a 46 amino acid insert at residue 627. The isoforms, previously termed FYB-120 ( the same as SLAP-130) and FYB-130, are likely to be generated by differential splicing. Message stability has not been studied.
Two tyrosine residues are the predominant sites of p59fyn mediated phosphorylation. Possible alterations due to acylation or myristoylation have yet to be defined. There are possible multiple putative protein kinase C and casein kinase phosphorylation sites.
|LIGANDS AND MOLECULES ASSOCIATED WITH ADAP|
Co-precipitation of other actin-regulatory proteins such as WASP (Wiskott Aldrich Syndrome Protein) and Arp 2,3 has been reported.
|Most information on ADAP function has been derived from studies on T-cells. T-cells from ADAP deficient mice have impaired peripheral T-cell responses to anti-CD3 and show defects in integrin adhesion to fibronectin and ICAM-1. Thymic differentiation is normal by gross analysis of thymocyte subsets. Peripheral T-cells also show a defect in the clustering of integrins, but not in the capping of the TcR complex. Transfection studies show that ADAP can cooperate with the src kinase Fyn-T and adaptor SLP-76 to potential TcR/CD3 driven IL-2 transcription and enhance motility in response to chemokine stromal cell-derived factor. In other hematopoietic cells, ADAP has also been implicated in integrin adhesion and in integrin (β1) clustering (but not FcεRI) on basophils. Transfection studies show that ADAP can also regulate FcεRI induced degranulation (i.e. β-hexosaminidase release). ADAP co-localises with F-actin in adhesion plaques in mast cells/basophils and in the nascent phagosomes of macrophages. |
ADAP has no known enzmatic activity and appears to function primarily as an adaptor or scaffold protein.
DISEASE RELEVANCE AND FUNCTION OF ADAP IN INTACT ANIMAL
ADAP deficient mice are immuno-compromised with impaired peripheral T-cell responses. There is no information on disease relevance in humans.
Database accession numbers
Revised June 25, 2008