In molecular biology, phosphotyrosine-binding domains are

protein domains 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 se ...

which bind to

phosphotyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is f ...

. The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein

tensin Tensin was first identified as a 220 kDa multi-domain protein localized to the specialized regions of plasma membrane called integrin-mediated focal adhesions (which are formed around a transmembrane core of an αβ integrin heterodimer). Genome se ...

tends to be found at the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

. Tensin is a multi-domain protein that binds to

actin filaments Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other p ...

and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix).

Human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

tensin has

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

-binding sites, an SH2 () domain and a region similar to the tumour suppressor PTEN. The PTB domain interacts with the

cytoplasmic The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell and ...

tails of beta

integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...

by binding to an NPXY motif. The phosphotyrosine-binding domain of

insulin receptor substrate-1 Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the ''IRS1'' gene. It is a 180 kDa protein with amino acid sequence of 1242 residues. It contains a single pleckstrin homology (PH) domain at the N-t ...

is not related to the phosphotyrosine-binding domain of tensin. Insulin receptor substrate-1

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s contain both a

pleckstrin homology domain Pleckstrin homology domain (PH domain) or (PHIP) 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. This domain can bind phosph ...

and a phosphotyrosine binding (PTB) domain. The PTB domains facilitate interaction with the activated

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

phosphorylated In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

insulin receptor The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose h ...

. The PTB domain is situated towards the

N terminus N, or n, is the fourteenth letter of the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages, and others worldwide. Its name in English is ''en'' (pronounced ), plural ''ens''. History ...

. Two

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

s in this domain are responsible for

hydrogen bonding In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...

phosphotyrosine residues on an Ac-LYASSNPApY- NH2 peptide in the juxtamembrane region of the insulin receptor. Further interactions via "bridged"

water molecule Water () is a polar inorganic compound that is at room temperature a tasteless and odorless liquid, which is nearly colorless apart from an inherent hint of blue. It is by far the most studied chemical compound and is described as the "univ ...

s are coordinated by residues an Asn and a Ser residue. The PTB domain has a compact, 7-stranded

beta-sandwich Beta-sandwich or β-sandwich domains consisting of 80 to 350 amino acids occur commonly in proteins. They are characterized by two opposing antiparallel beta sheets (β-sheets). The number of strands found in such domains may differ from one prote ...

structure, capped by a C-terminal

helix A helix (; ) is a shape like a cylindrical coil spring or the thread of a machine screw. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is for ...

. The substrate

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

fits into an L-shaped surface cleft formed from the C-terminal helix and strands 5 and 6.

Human proteins containing these domains

APBA1;

APBA2 Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the ''APBA2'' gene. Structure This protein has phosphotyrosine-binding domain (PTB domain or PID) in the middle and two PDZ domains at C-term ...

; APBA3; APPL1; EPS8; EPS8L1; EPS8L2; EPS8L3; TENC1; TNS;

TNS1 Tensin-1 is a protein that in humans is encoded by the ''TNS1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to p ...

; TNS3;

TNS4 Tensin-4 is a protein that in humans is encoded by the ''TNS4'' gene. References Further reading

* * * * * * * * * * * * {{gene-17-stub ...

;

DOK1 Docking protein 1 is a protein that in humans is encoded by the ''DOK1'' gene. Function Docking protein 1 is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the c ...

;

DOK2 Lee Joon-kyung (; born March 28, 1990) better known by his stage name Dok2 (, pronounced as Dokki), is a South Korean rapper, record producer and co-founder of now-defunct Illionaire Records. Biography Early life Dok2's mother is Korean, and ...

; DOK3; DOK4; DOK5; DOK6; DOK7; FRS2; FRS3;

IRS1 Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the ''IRS1'' gene. It is a 180 kDa protein with amino acid sequence of 1242 residues. It contains a single pleckstrin homology (PH) domain at the N-t ...

;

IRS2 Insulin receptor substrate 2 is a protein that in humans is encoded by the ''IRS2'' gene. Function This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth fact ...

;

IRS4 Insulin receptor substrate 4 is a protein that in humans is encoded by the ''IRS4'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA tha ...

;

NOS1AP Nitric oxide synthase 1 adaptor protein (NOS1AP) also known as carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (CAPON) is a protein that in humans is encoded by the ''NOS1AP'' gene. This gene encodes a cytosolic protein th ...

;

TLN1 Talin-1 is a protein that in humans is encoded by the ''TLN1'' gene. Talin-1 is ubiquitously expressed, and is localized to costamere structures in cardiac muscle, cardiac and skeletal muscle cells, and to focal adhesions in smooth muscle and non ...

;

TLN2 Talin-2 is a protein in humans that is encoded by the ''TLN2'' gene. It belongs to the talin protein family. This gene encodes a protein related to TLN1, talin-1, a cytoskeletal protein that plays a significant role in the assembly of actin filam ...

References

External links

* Protein domains Protein families Membrane proteins {{membrane-protein-stub

Human proteins containing these domains

See also

References

External links