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Structural domain ("domain") is an element of overall structure within a protein that is self-stabilizing and often folds independently of the rest of the protein chain. Most domains can be classified into a smaller number of "folds". Many domains are not unique to the proteins produced by one gene or one gene family but instead appear in a variety of proteins. The domains found most commonly are often called promiscuous. Structural domains vary in length from between about 25 amino acids up to 500 amino acids in length. The shortest domains such as zinc fingers are stabilised by metal ions or disulphide bridges. Domains often are named and singled out because they play an important role in the biological function of the protein they belong to; for example, the "calcium-binding" domain of calmodulin. Because they are self-stabilizing, domains can be "swapped" by genetic engineering between one protein and another to make chimera proteins. A domain may be composed of none, one, or many structural motifs.

Important tools in determining domains are structural alignment and sequence alignment.

Designability is the number of amino acid sequences that encode a fold. Folds with higher designability may be more resistant to disease and mutation. Many hereditary disease-associated proteins have folds estimated to be of low designability.^[1]

Contents 1 Examples 2 See also 3 References 4 External links 4.1 Domain databases

• Arginine Finger

• Armadillo repeats. Named after the β-catenin-like Armadillo protein of the fruit fly Drosophila.

• Basic Leucine zipper domain (bZIP domain) is found in many DNA-binding eukaryotic proteins. One part of the domain contains a region that mediates sequence-specific DNA-binding properties and the Leucine zipper that is required for the dimerization of two DNA-binding regions. The DNA-binding region comprises a number of basic aminoacids such as arginine and lysine

• Cadherin repeats. Cadherins function as Ca²⁺-dependent cell-cell adhesion proteins. Cadherin domains are extracellular regions which mediate cell-to-cell homophilic binding between cadherins on the surface of adjacent cells.

• Death effector domain (DED) allows protein-protein binding by homotypic interactions (DED-DED). Caspase proteases trigger apoptosis via proteolytic cascades. Pro-Caspase-8 and pro-caspase-9 bind to specific adaptor molecules via DED domains and this leads to autoactivation of caspases.

• Immunoglobulin-like domains are found in proteins of the immunoglobulin superfamily (IgSF). They contain about 70-110 amino acids and are classified into different categories (IgV, IgC1, IgC2 and IgI) according to their size and function.^[2] They possess a characteristic fold in which two beta sheets form a “sandwich” that is stabilized by interactions between conserved cysteines and other charged amino acids. They are important for protein-to-protein interactions in processes of cell adhesion, cell activation, and molecular recognition. These domains are commonly found in molecules with roles in the immune system.

• Phosphotyrosine-binding domain (PTB). PTB domains usually bind to phosphorylated tyrosine residues. They are often found in signal transduction proteins. PTB-domain binding specificity is determined by residues to the amino-terminal side of the phosphotyrosine. Examples: the PTB domains of both SHC and IRS-1 bind to a NPXpY sequence. PTB-containing proteins such as SHC and IRS-1 are important for insulin responses of human cells.

• Pleckstrin homology domain (PH). PH domains bind phosphoinositides with high affinity. Specificity for PtdIns(3)P, PtdIns(4)P, PtdIns(3,4)P2, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 have all been observed. Given the fact that phosphoinositides are sequestered to various cell membranes (due to their long lipophilic tail) the PH domains usually causes recruitment of the protein in question to a membrane where the protein can excert a certain function in cell signalling, cytosceletal reorganization or membrane trafficking. PH domains can also bind to other proteins, for example the PH domain of OSBP to ARF. Recruitment to the Golgi in this case is dependent on both, PtdIns and ARF. A large number of PH domains have poor affinity for phosphoinositides and are hypothesized to function as protein binding domains.

• Src homology 2 domain (SH2). SH2 domains are often found in signal transduction proteins. SH2 domains confer binding to phosphorylated tyrosine (pTyr). Named after the phosphotyrosine binding domain of the src viral oncogene, which is itself a tyrosine kinase. See also: SH3 domain.

• Zinc finger DNA binding domain (ZnF_GATA). ZnF_GATA domain-containing proteins are typically transcription factors that usually bind to the DNA sequence [AT]GATA[AG] of promoters.

• Protein domains
• Motif domain
• Protein family
• structural biology

1. ^ Wong P, Frishman D (2006). "Fold designability, distribution, and disease". PLoS Comput Biol 2 (5): e40. PMID 16680196.  link
2. ^ Barclay A (2003). "Membrane proteins with immunoglobulin-like domains--a master superfamily of interaction molecules". Semin Immunol 15 (4): 215-23. PMID 14690046. 

• The Protein Families (Pfam) database clan browser provides easy access to information about protein structural domains. A clan contains two or more Pfam families that have arisen from a single evolutionary origin.

• NCBI Conserved Domain Database
• Pfam Domain Database
• SMART Domain Database
• Pawson Lab - Protein interaction domains
• Nash Lab - Protein interaction domains in Signal Transduction
• Definition and assignment of structural domains in proteins.

Protein tertiary structure
General:	Structural domain | Protein folding
All-α folds:	Helix bundle | Globin fold | Homeodomain fold | Alpha solenoid
All-β folds:	Immunoglobulin fold | Beta barrel | Beta-propeller domain
α/β folds:	TIM barrel | Leucine-rich repeat | Flavodoxin fold | Thioredoxin fold | Trefoil knot fold
α+β folds:	Ferredoxin fold | Ribonuclease A | SH2-like fold
Irregular folds:	Conotoxin
←Secondary structure	Structure determination methods	Quaternary structure→