EVH1 domain
Encyclopedia
The EVH1 domain is an evolutionary conserved protein domain
.
The EVH1 domain is found in multi-domain protein
s implicated in a diverse range of signalling, nuclear transport
and cytoskeletal
events. This domain of around 115 amino acid
s is present in species ranging from yeast
to mammal
s. Many EVH1-containing proteins associate with actin-based structure
s and play a role in cytoskeletal
organisation. EVH1 domains
recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues.
WASP family proteins contain a EVH1 (WH1) in their N-terminus which bind proline-rich sequence
s in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N-terminal region, which seems to bind a different sequence motif
present in the C-terminal part of RanGTP
protein.
Tertiary structure of the WH1 domain of the Mena protein revealed structure
similarities with the pleckstrin
(PH) domain. The overall fold
consists of a compact parallel beta-sandwich, closed along one edge by a long alpha helix
. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecules target ligands
.
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
.
The EVH1 domain is found in multi-domain 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...
s implicated in a diverse range of signalling, nuclear transport
Nuclear transport
The entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes . Although small molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association with karyopherins called importins to enter the nucleus...
and cytoskeletal
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
events. This domain of around 115 amino acid
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...
s is present in species ranging from yeast
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
to mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s. Many EVH1-containing proteins associate with actin-based structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
s and play a role in cytoskeletal
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
organisation. EVH1 domains
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues.
WASP family proteins contain a EVH1 (WH1) in their N-terminus which bind proline-rich sequence
Sequence (biology)
A sequence in biology is the one-dimensional ordering of monomers, covalently linked within in a biopolymer; it is also referred to as the primary structure of the biological macromolecule.-See also:* Protein sequence* DNA sequence...
s in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N-terminal region, which seems to bind a different sequence motif
Sequence motif
In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance...
present in the C-terminal part of RanGTP
Ran (biology)
Ran is a small 25Kda protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily....
protein.
Tertiary structure of the WH1 domain of the Mena protein revealed structure
Cis-regulatory element
A cis-regulatory element or cis-element is a region of DNA or RNA that regulates the expression of genes located on that same molecule of DNA . This term is constructed from the Latin word cis, which means "on the same side as". These cis-regulatory elements are often binding sites for one or...
similarities with the pleckstrin
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....
(PH) domain. The overall fold
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
consists of a compact parallel beta-sandwich, closed along one edge by a long alpha helix
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecules target ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
.
Examples
Human genes encoding proteins containing the EVH1 domain include:- ENAH, EVL
- HOMER1HOMER1Homer protein homolog 1 or Homer1 is a neuronal protein that in humans is encoded by the HOMER1 gene. Other names are Vesl and PSD-Zip45.-Domain structure:...
, HOMER2HOMER2Homer protein homolog 2 is a protein that in humans is encoded by the HOMER2 gene.-Further reading:...
, HOMER3HOMER3Homer protein homolog 3 is a protein that in humans is encoded by the HOMER3 gene.-Interactions:HOMER3 has been shown to interact with TRPC1 and RYR1.... - SPRED1, SPRED2SPRED2Sprouty-related, EVH1 domain-containing protein 2 is a protein that in humans is encoded by the SPRED2 gene.- Function :SPRED2 is a member of the Sprouty /SPRED family of proteins that regulate growth factor-induced activation of the MAP kinase cascade Sprouty-related, EVH1 domain-containing...
, SPRED3SPRED3Sprouty-related, EVH1 domain-containing protein 3 also known as Spred-3 is a protein that in humans is encoded by the SPRED3 gene.Spred-3 is a member of the Sprouty family of proteins that regulate growth factor-induced activation of the MAP kinase cascade.... - VASPVasodilator-stimulated phosphoproteinVasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the VASP gene.- Function :Vasodilator-stimulated phosphoprotein is a member of the Ena-VASP protein family. Ena-VASP family members contain an N-terminal EVH1 domain that binds proteins containing E/DFPPPPXD/E motifs...
, WASWiskott-Aldrich syndrome proteinThe Wiskott–Aldrich Syndrome Protein 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...
, WASLWASL (gene)Neural Wiskott-Aldrich syndrome protein is a protein that in humans is encoded by the WASL gene.The Wiskott-Aldrich syndrome family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton...