Three-finger proteins or three-finger protein domains (3FP or TFPD) are a

protein superfamily A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology (biology), homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if n ...

consisting of small, roughly 60-80

amino acid residue Protein structure is the molecular geometry, three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single ami ...

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...

s with a common

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...

: three

beta strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

loops extended from a

hydrophobic core The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar ...

stabilized by

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

s. The family is named for the outstretched "fingers" of the three loops. Members of the family have no

enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

activity, but are capable of forming protein-protein interactions with high specificity and

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

. The founding members of the family, also the best characterized by structure, are the

three-finger toxin Three-finger toxins (abbreviated 3FTx) are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic prote ...

s found in

snake venom Snake venom is a highly toxic saliva containing zootoxins that facilitates in the immobilization and digestion of prey. This also provides defense against threats. Snake venom is injected by unique fangs during a bite, whereas some species are a ...

, which have a variety of

pharmacological Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

effects, most typically by disruption of

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...

signaling. The family is also represented in non-toxic proteins, which have a wide

taxonomic Taxonomy is the practice and science of categorization or classification. A taxonomy (or taxonomical classification) is a scheme of classification, especially a hierarchical classification, in which things are organized into groups or types. ...

distribution; 3FP domains occur in the

extracellular domain An ectodomain is the domain of a membrane protein that extends into the extracellular space (the space outside a cell). Ectodomains are usually the parts of proteins that initiate contact with surfaces, which leads to signal transduction.A notable ...

s of some

cell-surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral me ...

s as well as in GPI-anchored and

secreted 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...

globular protein In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (formi ...

s, usually involved in signaling.

Three-finger toxins

The founding members of the 3FP family are the

s (3FTx) often found in

. 3FTx proteins are widely distributed in venomous snake families, but are particularly enriched in the

family Family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its ...

Elapidae Elapidae (, commonly known as elapids ; grc, ἔλλοψ ''éllops'' "sea-fish") is a family of snakes characterized by their permanently erect fangs at the front of the mouth. Most elapids are venomous, with the exception of the genus Emydoceph ...

, in which the relative proportion of 3FTx to other venom toxins can reach 95%. Many 3FTx proteins are

neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...

s, though the mechanism of toxicity varies significantly even among proteins of relatively high

sequence identity In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Ali ...

; common protein targets include those involved in

signaling, such as the

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ne ...

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

s, and

acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme Enzymes () are proteins that a ...

. Another large subfamily of 3FTx proteins is the

cardiotoxin Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by chemotherapy (a usual example is th ...

s (also known as cytotoxins or cytolysins); this group is directly

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

most likely due to interactions with

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s and possibly other components of the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

Ly6/uPAR family

The Ly6/uPAR family broadly describes a

gene family A gene family is a set of several similar genes, formed by duplication of a single original gene, and generally with similar biochemical functions. One such family are the genes for human hemoglobin subunits; the ten genes are in two clusters on ...

containing three-finger

s that are not toxic and not venom components; these are often known as

LU domain The LU domain (LY6, Ly-6 antigen/urokinase plasminogen activator receptor, uPAR) is an evolutionarily conserved protein domain of the three-finger protein superfamily. This domain is found in the extracellular domains of cell-surface receptors an ...

s and can be found in the

s of

s and in either GPI-anchored or

s. The family is named for two representative groups of members, the small globular protein lymphocyte antigen 6 (LY6) family and the urokinase plasminogen activator receptor (uPAR). Other receptors with LU domains include members of the transforming growth factor beta receptor (TGF-beta) superfamily, such as the

activin type 2 receptor The activin type 2 receptors belong to a larger TGF-beta receptor family and modulate signals for transforming growth factor beta ligands. These receptors are involved in a host of physiological processes including, growth, cell differentiation, ...

; and bone morphogenetic protein receptor, type IA. Other LU domain proteins are small globular proteins such as CD59 antigen,

LYNX1 Ly6/neurotoxin 1 is a protein in humans that is encoded by the ''LYNX1'' gene. Alternatively spliced variants encoding different isoforms have been identified. Function This gene encodes a member of the Ly-6/ neurotoxin gene family, a group o ...

SLURP1 Secreted Ly-6/uPAR-related protein 1 is a protein that in humans is encoded by the ''SLURP1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''ge ...

, and

SLURP2 {{Short pages monitor