ADAP 

ADAP(adhesion & degranulation promoting adaptor protein), SLP-76 associated protein (SLAP, SLAP-130)

Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Unknown
Thymocyte
Basophil
Macrophage
Mast Cell
T Cell, Mature
Platelet
115 / 135

Expression
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.

Structure
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.

MOLECULAR MASS

The molecular mass is 120 (or 130)/130kD and was previously termed = SLAP-130/Fyb-130.

POST-TRANSCRIPTIONAL MODIFICATION

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.

POST-TRANSLATIONAL MODIFICATION

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
LIGANDS AND MOLECULES ASSOCIATED WITH ADAP

Molecule Comment
Slp-76 direct binding
Fyn direct binding
SKAP-55 direct binding
VASP direct binding
   







Co-precipitation of other actin-regulatory proteins such as WASP (Wiskott Aldrich Syndrome Protein) and Arp 2,3 has been reported.

Function
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. 

BIOCHEMICAL ACTIVITY

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.

Comments

MOLECULAR INTERACTION-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF ADAP

ADAP can bind to Fyn-T and SLP-76 and cooperates with them to enchance TcR/CD3 induction of IL-2 transcription in over expression studies in T cell lines.  ADAP can bind to vasodilator-stimulated phosphoproteins (VASP) via its EVH1 domain.

SUBSTRATES

No known enzymatic activity.

ENZYMES WHICH MODIFY ADAP: No information.

ADDITIONAL INSIGHTS

A related protein PRAM-1 is a novel adaptor protein regulated by retinoic acic (RA) and promyelocytic leukemia (PML)-RA receptor α in acute promyelocytic leukemia cells.  PRAM-1 is expressed at highest levels in myeloid cells.  ADAP shows an unusual connection to the src kinase p59fyn, being a substrate for the kinase (but not related p56lck) and having a binding site for the Fyn-SH2 domain (Y625DGI).



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
Antibodies

Revised June 25, 2008


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