The
Wiskott-Aldrich Syndrome Protein (
WASp) is a 502-
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
protein that is expressed in cells of the hematopoietic system. In the inactive state, WASp exists in an auto-inhibited conformation with sequences near its C-terminus binding to a region near its N-terminus. Its activation is dependent upon
Cdc42Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
and PIP2 acting to disrupt this interaction causing the WASp protein to 'open'.
The
Wiskott-Aldrich Syndrome Protein (
WASp) is a 502-
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
protein that is expressed in cells of the hematopoietic system. In the inactive state, WASp exists in an auto-inhibited conformation with sequences near its C-terminus binding to a region near its N-terminus. Its activation is dependent upon
Cdc42Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
and PIP2 acting to disrupt this interaction causing the WASp protein to 'open'. This exposes a domain near the WASp C-Terminus that binds to and activates the
Arp2/3 complexArp2/3 complex is a seven-subunit protein that plays a major role in the regulation of the actin cytoskeleton. It is a necessary component of the actin cytoskeleton and is therefore ubiquitous in actin cytoskeleton-containing eukaryotic cells...
. Activated Arp2/3 nucleates new F-
actinActin is a globular, roughly 42-kDa protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
. WASp is the founding member of a gene family which also includes the broadly expressed N-WASP (neuronal Wiskott-Aldrich Syndrome protein), and Scar.
Structure and Function
Genetic diseases associated with WASp
WASp is a product of the WAS gene and mutations in the WAS gene can lead to
Wiskott-Aldrich syndromeWiskott-Aldrich syndrome is a rare X-linked recessive disease characterized by eczema, thrombocytopenia , immune deficiency, and bloody diarrhea...
(an X-linked disease that mainly affects males with symptoms that include
thrombocytopeniaThrombocytopenia is the presence of relatively few platelets in blood.Generally speaking, in humans, a normal platelet count ranges from 150,000 and 450,000 per mm3. These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply...
,
eczemaEczema is a disease in a form of dermatitis, or inflammation of the epidermis. The term eczema is broadly applied to a range of persistent skin conditions. These include dryness and recurring skin rashes that are characterized by one or more of these symptoms: redness, skin edema , itching and...
, recurrent
infectionAn infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the...
s, and small-sized
plateletPlatelets, or thrombocytes , are small, irregularly-shaped anuclear cells , 2-3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is between 8 and 12 days...
s). Other, less inactivating mutations affecting the WAS gene cause X-linked thrombocytopeia, or XLT.
Interactions
Wiskott-Aldrich syndrome protein has been shown to
interactProtein-protein interactions involve not only the direct-contact association of protein molecules but also longer range interactions through the electrolyte, aqueous solution medium surrounding neighbor hydrated proteins over distances from less than one nanometer to distances of several tens of...
with
PLCG1Phospholipase C, gamma 1, also known as PLCG1, is a protein which in humans is encoded by the PLCG1 gene.-Function:The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate...
,
SrcSrc is a family of proto-oncogenic tyrosine kinases originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine...
,
NCK1Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.-Interactions:NCK1 has been shown to interact with DNM1, EIF2B2, KHDRBS1, Lymphocyte cytosolic protein 2, EPH receptor B1, SOCS7, MINK1, MAP4K1, MAP4K4, Abl gene, WIPF1, RRAS, Wiskott-Aldrich syndrome protein,...
,
ITSN2Intersectin-2 is a protein that in humans is encoded by the ITSN2 gene.-Interactions:ITSN2 has been shown to interact with Wiskott-Aldrich syndrome protein.-Further reading:...
,
FGRGardner-Rasheed feline sarcoma viral oncogene homolog, also known as FGR, is a protein which in humans is encoded by the FGR gene.- Function :This gene is a member of the Src family of protein tyrosine kinases...
,
Grb2Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....
,
PSTPIP1Proline-serine-threonine phosphatase-interacting protein 1 is an enzyme that in humans is encoded by the PSTPIP1 gene.-Interactions:PSTPIP1 has been shown to interact with PTPN12, PTPN18, BZW1, Abl gene, Wiskott-Aldrich syndrome protein and CD2....
,
CDC42Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
,
TRIP10Cdc42-interacting protein 4 is a protein that in humans is encoded by the TRIP10 gene.-Interactions:TRIP10 has been shown to interact with STAT3, Wiskott-Aldrich syndrome protein, Huntingtin, CDC42, AKAP9 and RHOQ.-Further reading:...
,
WIPF1WAS/WASL-interacting protein family member 1 is a protein that in humans is encoded by the WIPF1 gene.-Interactions:WIPF1 has been shown to interact with Wiskott-Aldrich syndrome protein, Cortactin and NCK1.-Further reading:...
,
FYNProto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...
,
Epidermal growth factor receptorThe epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
,
PIK3R1Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.-Interactions:PIK3R1 has been shown to interact with EPH receptor A2, KHDRBS1, Lymphocyte cytosolic protein 2, Janus kinase 2, GAB2, CD117, BCAR1, CD28, SHB, VIL2, PIK3CD, GAB1, HRAS,...
,
ITKIL2-inducible T-cell kinase, also known as ITK, is a protein which in humans is encoded by the ITK gene.- Function :This gene encodes an intracellular tyrosine kinase expressed in T-cells...
and
CRKLCrk-like protein is a protein that in humans is encoded by the CRKL gene.CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1.-Interactions:...
.
Further reading
External links