TIAM1
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T-cell lymphoma invasion and metastasis-inducing protein 1 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''TIAM1''
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.


Structure

TIAM1 is tightly associate with
BAIAP2 Brain-specific angiogenesis inhibitor 1-associated protein 2 is a protein that in humans is encoded by the ''BAIAP2'' gene. Function The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor ( BAI1)-bindin ...
as a subunit. It contains one DH (DBL-homology) domain, one
PDZ domain The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane t ...
, two
PH domain In chemistry, pH (), historically denoting "potential of hydrogen" (or "power of hydrogen"), is a scale used to specify the acidity or basicity of an aqueous solution. Acidic solutions (solutions with higher concentrations of ions) are ...
s and one Ras-binding
RBD domain RBD is a Mexican Latin pop group that gained popularity from Televisa's telenovela ''Rebelde''. The group achieved international success from 2004 until their separation in 2009 and sold over 15 million records worldwide, making them one of ...
.


Function

TIAM1 modulates the activity of Rho GTP-binding proteins and connects extracellular signals to cytoskeletal activities. In addition, TIAM1 activates Rac1, CDC42, and to a lesser extent
RhoA Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the ''RHOA'' gene. While the effects of RhoA activity are not all well known, it i ...
.


Clinical significance

TIAM1 is found in virtually all
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
cell line An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cel ...
s examined including B- and T-
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enl ...
s,
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump i ...
s, melanomas and
carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoderma ...
s.


Interactions

T-cell lymphoma invasion and metastasis-inducing protein 1 has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...
with
ANK1 Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a protein that in humans is encoded by the ''ANK1'' gene. Tissue distribution The protein encoded by this gene, Ankyrin 1, is the prototype of the ankyrin family, was first discovered i ...
,
Myc ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes ref ...
, RAC1 and
PPP1R9B Neurabin-2 is a protein that in humans is encoded by the ''PPP1R9B'' gene. Spinophilin is a regulatory subunit of protein phosphatase-1 catalytic subunit (PP1; see MIM 176875) and is highly enriched in dendritic spines, specialized protrusions fr ...
. Tiam1 interacts also with para-
cingulin Cingulin (CGN; from the Latin ''cingere'' “to form a belt around”) is a cytosolic protein encoded by the ''CGN'' gene in humans localized at tight junctions (TJs) of vertebrate epithelial and endothelial cells. Discovery Cingulin was origi ...
, that plays a role in recruiting Tiam1 to junctions and thus activate Rac1 at epithelial junctions.


References


Further reading

* * * * * * * * * * * * * * * * * {{PDB Gallery, geneid=7074 Peripheral membrane proteins