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 s ...
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 non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
.
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 s ...
tends to be found at the
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
. 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 pr ...
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'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
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 over ...
-binding sites, an
SH2 () domain and a region similar to the
tumour suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
PTEN.
The PTB domain interacts with the
cytoplasmic
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. Th ...
tails of beta
integrin
Integrins are transmembrane receptors that facilitate 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, ...
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 ''IRS-1'' gene. It is a 131 kDa protein with amino acid sequence of 1242 residues. It contains a single pleckstrin homology (PH) domain at the N-te ...
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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
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 phospha ...
and a phosphotyrosine binding (PTB) domain. The PTB
domains facilitate
interaction
Interaction is action that occurs between two or more objects, with broad use in philosophy and the sciences. It may refer to:
Science
* Interaction hypothesis, a theory of second language acquisition
* Interaction (statistics)
* Interactions o ...
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 non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
-
phosphorylated
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
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 ho ...
. The PTB domain is situated towards the
N terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
. Two
arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
s in this domain are responsible for
hydrogen bonding
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...
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 "uni ...
s are coordinated by
residue
Residue may refer to:
Chemistry and biology
* An amino acid, within a peptide chain
* Crop residue, materials left after agricultural processes
* Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...
s an Asn and a Ser residue.
The PTB domain has a compact, 7-stranded
beta-sandwich
Beta-sandwich, 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 protein ...
structure, capped by a C-terminal
helix
A helix () is a shape like a corkscrew or spiral staircase. 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 formed as two intertwined helices, ...
. The substrate
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
fits into an L-shaped surface cleft formed from the C-terminal helix and strands 5 and 6.
Human proteins containing these domains
APBA1
Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the ''APBA1'' gene.
Function
The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adaptor protein that in ...
;
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-termi ...
;
APBA3
Amyloid beta A4 precursor protein-binding family A member 3 is a protein that in humans is encoded by the ''APBA3'' gene.
Function
The protein encoded by this gene is a member of the X11 protein family. It is an adapter protein that interacts ...
;
APPL1
Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1), or DCC-interacting protein 13-alpha (DIP13alpha), is a protein that in humans is encoded by the ''APPL1'' gene. APPL1 contains several key interactory domain ...
;
EPS8
Epidermal growth factor receptor kinase substrate 8 is an enzyme that in humans is encoded by the ''EPS8'' gene.
Function
This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as par ...
;
EPS8L1
Epidermal growth factor receptor kinase substrate 8-like protein 1 is an enzyme that in humans is encoded by the ''EPS8L1'' gene.
This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a subst ...
;
EPS8L2
Epidermal growth factor receptor kinase substrate 8-like protein 2 is an enzyme that in humans is encoded by the ''EPS8L2'' gene.
This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a subst ...
;
EPS8L3
Epidermal growth factor receptor kinase substrate 8-like protein 3 is an enzyme that in humans is encoded by the ''EPS8L3'' gene.
This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a subst ...
;
TENC1
Tensin-like C1 domain-containing phosphatase is an enzyme that in humans is encoded by the ''TENC1'' gene.
The protein encoded by this gene belongs to the tensin family. Tensin is a focal adhesion molecule that binds to actin filaments and partici ...
;
TNS;
TNS1
Tensin-1 is a protein that in humans is encoded by the ''TNS1'' gene.
The protein encoded by this gene localizes to focal adhesions
In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies throu ...
;
TNS3;
TNS4
Tensin-4 is a protein that in humans is encoded by the ''TNS4'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''ge ...
;
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 h ...
;
DOK3
Docking protein 3 is a protein that in humans is encoded by the ''DOK3'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth ...
;
DOK4
Docking protein 4 is a protein that in humans is encoded by the ''DOK4'' gene.
References
Further reading
*
*
*
*
*
*
*
*
{{gene-16-stub ...
;
DOK5
Docking protein 5 is a protein that in humans is encoded by the ''DOK5'' gene.
Function
The protein encoded by this gene is a member of the DOK family of membrane proteins, which are adapter proteins involved in signal transduction. The encode ...
;
DOK6;
DOK7;
FRS2
Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the ''FRS2'' gene.
FRS2 is an 80 kDa membrane-anchored signal transducing adaptor protein (STAP) that links specific activated Receptor Tyrosine Kinases (RTKs) ...
;
FRS3
Fibroblast growth factor receptor substrate 3 is a protein that in humans is encoded by the ''FRS3'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." mean ...
;
IRS1
Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the ''IRS-1'' gene. It is a 131 kDa protein with amino acid sequence of 1242 residues. It contains a single pleckstrin homology (PH) domain at the N-te ...
;
IRS2;
IRS4
Insulin receptor substrate 4 is a protein that in humans is encoded by the ''IRS4'' gene.
IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyros ...
;
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 tha ...
;
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 and skeletal muscle cells, and to focal adhesions in smooth muscle and non-muscle cells. Tal ...
;
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 talin 1, a cytoskeletal protein that plays a significant role in the assembly of actin filaments. Tali ...
See also
*
SH2 domain
The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphory ...
s also bind phosphorylated tyrosines
References
External links
*
Protein domains
Protein families
Membrane proteins
{{membrane-protein-stub