ELMO1
Encyclopedia
Engulfment and cell motility protein 1 is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the ELMO1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. ELMO1 is located on chromosome number seven in humans and is located on chromosome number thirteen in mice.

Structure

The human engulfment and cell motility protein 1, ELMO1, is 720 residues in length. The protein contains the following three domains:
  • N-terminal Armadillo
    Armadillo repeats
    Armadillo repeats are named after the β-catenin-like Armadillo protein of the fruit fly Drosophila. These repeats are about 40 amino acids long and proteins that contain them have many tandemly repeated copies. Each Armadillo repeat is composed of a pair of alpha helices that form a hairpin...

     domain (residues 82-262)
  • central ELMO
    ELMO (protein)
    ELMO is a family of related proteins involved in intracellular signalling networks. These proteins have no intrinsic catalytic activity and instead function as adaptors which can regulate the activity of other proteins through their ability to mediate protein-protein interactions.This family...

     (Engulfment and Cell Motility) domain (301-492)
  • C-terminal pleckstrin homology domain
    Pleckstrin homology domain
    Pleckstrin homology domain is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton....

     (residues 527-674)


ELMO1 also has a pro-rich motif at the extreme C terminus. Secondary structure analysis has predicted that there are alpha-helical regions at both the N and C-terminus.

The structure of the pleckstrin homology domain of ELMO1 has been determine by X-ray crystallography.

Function

The protein encoded by this gene interacts with the dedicator of cyto-kinesis 1 protein to promote phagocytosis and effect cell shape changes. Similarity to a C. elegans protein suggests that this protein may function in apoptosis and in cell migration. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms.

Interactions

ELMO1 has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Dock180 and HCK
HCK
Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the HCK gene.-Interactions:HCK has been shown to interact with BCR gene, ELMO1, Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1.-Further reading:...

. ELMO1 directly interacts with the SH3 domain of HCK. The association between ELMO1 and HCK is dependent on polyproline interactions.

When ELMO1 is complexed with DOCK180, Rac GTPase
Rac (GTPase)
Rac is a subfamily of the Rho family of GTPases, small signaling G proteins .The subgroup include:*Rac1*Rac2*Rac3*RhoG...

-dependent biological processes are activated. The pH domain of ELMO1 functions in trans to stabilize DOCK180 and make it resistant to degradation. When ELMO1 binds to DOCK180 it relieves the steric inhibition of DOCK180 which then activates the Rac GTPase. The pro-rich motif of the C terminus on ELMO1 is essential for the binding of ELMO1 to the SH3 domain at the N terminus of DOCK180. The complex of ELMO1 and DOCK180 act as a regulator of Rac during development of a cell and cell migration. Mutation of both interaction sites for DOCK180 on ELMO1 will lead to the disruption of the ELMO1-DOCK180 complex. ELMO1 complexed with both DOCK180 and CrkII leads to maximal efficiency of phagocytosis in the cell. This complex of molecules happens upstream of Rac during phagocytosis.
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