Wiskott-Aldrich syndrome protein
Encyclopedia
The Wiskott–Aldrich Syndrome Protein (WASp) is a 502-amino acid
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 Cdc42
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 complex
. Activated Arp2/3 nucleates new F-actin
. WASp is the founding member of a gene family which also includes the broadly expressed N-WASP (neuronal Wiskott–Aldrich Syndrome protein), and Scar.
, eczema
, recurrent infection
s, and small-sized platelet
s). Other, less inactivating mutations affecting the WAS gene cause X-linked thrombocytopeia, or XLT.
, Src
, NCK1
, ITSN2
, FGR
, Grb2
, PSTPIP1
, CDC42
, TRIP10
, WIPF1
, FYN
, Epidermal growth factor receptor
, PIK3R1
, ITK
and CRKL
.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
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 Cdc42
CDC42
Cell 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 complex
Arp2/3 complex
Arp2/3 complex is a seven-subunit protein that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most in actin cytoskeleton-containing eukaryotic cells....
. Activated Arp2/3 nucleates new F-actin
Actin
Actin is a globular, roughly 42-kDa moonlighting 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 syndrome (an X-linked disease that mainly affects males with symptoms that include thrombocytopeniaThrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
, recurrent infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s, and small-sized platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 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 interact with PLCG1PLCG1
Phospholipase C, gamma 1, also known as PLCG1, is a protein that 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...
, Src
Src (gene)
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...
, NCK1
NCK1
Cytoplasmic 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,...
, ITSN2
ITSN2
Intersectin-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:...
, FGR
FGR (gene)
Gardner-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...
, Grb2
Grb2
Growth 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....
, PSTPIP1
PSTPIP1
Proline-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....
, CDC42
CDC42
Cell 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 :...
, TRIP10
TRIP10
Cdc42-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:...
, WIPF1
WIPF1
WAS/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:...
, FYN
FYN
Proto-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 receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
, PIK3R1
PIK3R1
Phosphatidylinositol 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, EZR, PIK3CD, GAB1, HRAS,...
, ITK
ITK (gene)
IL2-inducible T-cell kinase, also known as ITK, is a protein that in humans is encoded by the ITK gene.- Function :This gene encodes an intracellular tyrosine kinase expressed in T-cells...
and CRKL
CRKL
Crk-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:...
.