Annexin is a common name for a group of cellular
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. They are mostly found in eukaryotic organisms (animal, plant and fungi).
In humans, the annexins are found inside the
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
. However some annexins (Annexin A1, Annexin A2, and Annexin A5) can be
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 ...
from the
cytoplasm
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. The ...
to outside cellular environments, such as blood.
Annexin is also known as ''lipocortin''. Lipocortins suppress
phospholipase A2
The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyse the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glyce ...
. Increased expression of the gene coding for annexin-1 is one of the mechanisms by which
glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s (such as
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
) inhibit
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
.
Introduction
The
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 ...
family of annexins has continued to grow since their association with intracellular membranes was first reported in 1977.
The recognition that these proteins were members of a broad family first came from protein sequence comparisons and their cross-reactivity with antibodies.
One of these workers (Geisow) coined the name Annexin shortly after.
As of 2002 160 annexin proteins have been identified in 65 different species.
The criteria that a protein has to meet to be classified as an annexin are: it has to be capable of binding negatively charged
phospholipids
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 ...
in a
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
dependent manner and must contain a 70 amino acid repeat sequence called an annexin repeat. Several proteins consist of annexin with other domains like gelsolin.
The basic structure of an annexin is composed of two major domains. The first is located at the COOH terminal and is called the “core” region. The second is located at the NH2 terminal and is called the “head” region.
The core region consists of an alpha helical disk. The convex side of this disk has type 2 calcium-binding sites. They are important for allowing interaction with the phospholipids at the
plasma 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 (t ...
.
The N terminal region is located on the concave side of the core region and is important for providing a binding site for cytoplasmic proteins. In some annexins it can become phosphorylated and can cause affinity changes for calcium in the core region or alter cytoplasmic protein interaction.
Annexins are important in various cellular and physiological processes such as providing a membrane scaffold, which is relevant to changes in the cell's shape. Also, annexins have been shown to be involved in trafficking and organization of
vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
s,
exocytosis
Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
,
endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
and also calcium
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
formation.
Annexins have also been found outside the cell in the extracellular space and have been linked to
fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other c ...
,
coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
,
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
.
The first study to identify annexins was published by Creutz ''et al.'' (1978).
These authors used bovine
adrenal glands
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
and identified a calcium dependent protein that was responsible for aggregation of granules amongst each other and the plasma membrane. This protein was given the name
synexin, which comes from the Greek word “synexis” meaning “meeting”.
Structure
Several subfamilies of annexins have been identified based on structural and functional differences. However, all annexins share a common organizational theme that involves two distinct regions, an annexin core and an amino (N)-terminus.
The annexin core is highly conserved across the annexin family and the N-terminus varies greatly.
The variability of 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 ami ...
is a physical construct for variation between subfamilies of annexins.
The 310 amino acid annexin core has four annexin repeats, each composed of 5 alpha-helices.
The exception is annexin A-VI that has two annexin core domains connected by a flexible linker.
A-VI was produced via duplication and fusion of the genes for A-V and A-X and therefore will not be discussed in length. The four annexin repeats produce a curved protein and allow functional differences based on the structure of the curve.
The concave side of the annexin core interacts with the N-terminus and cytosolic
second messengers
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
, while the convex side of the annexin contains calcium binding sites.
Each annexin core contains one type II, also known as an annexin type, calcium binding site; these binding sites are the typical location of ionic membrane interactions.
However, other methods of membrane connections are possible. For example, A-V exposes a
tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
residue, upon calcium binding, which can interact with the
hydrocarbon
In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons are examples of group 14 hydrides. Hydrocarbons are generally colourless and hydrophobic, and their odors are usually weak or ex ...
chains of the
lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
.
The diverse structure of the N-terminus confers specificity to annexin intracellular signaling. In all annexins the N-terminus is thought to sit inside the concave side of the annexin core and folds separately from the rest of the protein.
The structure of this region can be divided into two broad categories, short and long N-termini. A short N-terminus, as seen in A-III, can consist of 16 or less amino acids and travels along the concave protein core interacting via
hydrogen bonds
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 ...
.
Short N-termini are thought to stabilize the annexin complex in order to increase calcium binding and can be the sites for post-translational modifications.
Long N-termini can contain up to 40 residues and have a more complex role in annexin signaling.
For example, in A-I the N-terminus folds into an
amphipathic
An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compoun ...
alpha-helix and inserts into the protein core, displacing helix D of annexin repeat III.
However, when calcium binds, the N-terminus is pushed from the annexin core by conformational changes within the protein.
Therefore, the N-terminus can interact with other proteins, notably the
S-100 protein
The S100 proteins are a family of low molecular-weight proteins found in vertebrates characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand-type") conformation. At least 21 different S100 proteins are known. They are enc ...
family, and includes
phosphorylation
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, wh ...
sites which allow for further signaling.
A-II can also use its long N-terminal to form a heterotrimer between a S100 protein and two peripheral annexins.
The structural diversity of annexins is the grounds for the functional range of these complex, intracellular messengers.
Cellular localization
Membrane
Annexins are characterized by their calcium dependent ability to bind to negatively charged phospholipids (i.e. membrane walls).
They are located in some but not all of the membranous surfaces within a cell, which would be evidence of a heterogeneous distribution of Ca
2+ within the cell.
Nuclei
Annexin species (II,V,XI) have been found within the membranes.
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
activity has been shown to increase the concentrations of Annexins II,V within the nucleus.
Annexin XI is predominantly located within the nucleus, and absent from the nucleoli.
During prophase, annexin XI will translocate to the nuclear envelope.
Bone
Annexins are abundant in bone matrix vesicles, and are speculated to play a role in Ca
2+ entry into vesicles during
hydroxyapatite
Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. ...
formation.
The subject area has not been thoroughly studied, however it has been speculated that annexins may be involved in closing the neck of the matrix vesicle as it is endocytosed.
Role in vesicle transport
Exocytosis
Annexins have been observed to play a role along the
exocytotic
Exocytosis () is a form of active transport and solvent drag, bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell (''wikt:ex-#Prefix, exo-'' + ''cytosis''). As an active transport mechanism, ...
pathway, specifically in the later stages, near or at the plasma membrane.
Evidence of annexins or annexin-like proteins are involved in exocytosis has been found in lower organisms, such as the ''
Paramecium
''
''Paramecium'' ( , ; also spelled ''Paramoecium'') is a genus of eukaryotic, unicellular ciliates, commonly studied as a representative of the ciliate group. ''Paramecia'' are widespread in freshwater, brackish, and marine environments and a ...
''.
Through antibody recognition, there is evidence of the annexin like proteins being involved in the positioning and attachment of secretory
organelles
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
in the organism ''Paramecium''.
Annexin VII was the first annexin to be discovered while searching for proteins that promote the contact and fusion of
chromaffin granules.
In Vitro studies however have shown that annexin VII does not promote the fusion of membranes, only the close attachment to one another.
Endocytosis
Annexins have been found to be involved in the transport and also sorting of endocytotic events. Annexin one is a substrate of the EGF (
epidermal growth factor
Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds.
EGF was originally descr ...
)
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
which becomes phosphorylated on its N terminus when the receptor is internalized.
Unique
endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
targeting sequences have been found in the N terminus of annexins I and II, which would be useful in sorting of endocytotic vesicles.
Annexins are present in several different endocytotic processes. Annexin VI is thought to be involved in
clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. Whe ...
coated budding events, while annexin II participates in both
cholesteryl ester
300px, Cholesterol oleate, a member of the cholesteryl ester family
Cholesteryl ester, a dietary lipid, is an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol. Chole ...
internalization and the biogenesis of multi-vesicular endosomes.
Membrane scaffolding
Annexins can function as scaffolding proteins to anchor other proteins to the cell membrane. Annexins assemble as trimers,
where this trimer formation is facilitated by calcium influx and efficient membrane binding. This trimer assembly is often stabilized by other membrane-bound annexin cores in the vicinity. Eventually, enough annexin trimers will assemble and bind the cell membrane. This will induce the formation of membrane-bound annexin networks. These networks can induce the indentation and vesicle budding during an exocytosis event.
While different types of annexins can function as membrane scaffolds, annexin A-V is the most abundant membrane-bound annexin scaffold. Annexin A-V can form 2-dimensional networks when bound to the
phosphatidylserine
Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via ap ...
unit of the membrane.
Annexin A-V is effective in stabilizing changes in cell shape during endocytosis and exocytosis, as well as other cell membrane processes. Alternatively, annexins A-I and A-II bind phosphatidylserine and
phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soyb ...
units in the cell membrane, and are often found forming monolayered clusters that lack a definite shape.
In addition, annexins A-I and A-II have been shown to bind
PIP2
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...
(phosphatidylinositol-4,5-bisphosphate) in the cell membrane and facilitate actin assembly near the membrane.
More recently, annexin scaffolding functions have been linked to medical applications. These medical implications have been uncovered with in vivo studies where the path of a fertilized egg is tracked to the uterus. After fertilization, the egg must enter a canal for which the opening is up to five times smaller than the diameter of the egg. Once the fertilized egg has passed through the opening, annexins are believed to promote membrane folding in an accordion-like fashion to return the stretched membrane back to its original form. Though this was discovered in the
nematode
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...
annexin NEX-1, it is believed that a similar mechanism takes place in humans and other mammals.
Membrane organization and trafficking
Several annexins have been shown to have active roles in the organization of the membrane. Annexin A-II has been extensively studied in this aspect of annexin function and is noted to be heavily involved in the organization of
lipids
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
in the bilayer near sites of actin
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
assembly. Annexin A-II can bind
PIP2
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...
in the cell membrane in vivo with a relatively high binding affinity.
In addition, Annexin A-II can bind other membrane lipids such as
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
, where this binding is made possible by the influx of calcium ions.
The binding of Annexin A-II to lipids in the bilayer orchestrates the organization of lipid rafts in the bilayer at sites of
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 ...
assembly. In fact, annexin A-II is itself an actin-binding protein and therefore it can form a region of interaction with actin by means of its filamentous actin properties. In turn, this allows for further cell-cell interactions between monolayers of cells like
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
and
endothelial cells
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
.
In addition to annexin A-II, annexin A-XI has also been shown to organize cell membrane properties. Annexin A-XI is believed to be highly involved in the last stage of
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
:
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
. It is in this stage that daughter cells separate from one another because annexin A-XI inserts a new membrane that is believed to be required for abscission. Without annexin A-XI, it is believed that the daughter cells with not fully separate and may undergo
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
.
Clinical significance
Apoptosis and inflammation
Annexin A-I seems to be one of the most heavily involved annexins in
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
responses. Upon
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
or damage to tissues, annexin A-I is believed to reduce
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
of tissues by interacting with annexin A-I receptors on
leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
. In turn, the activation of these receptors functions to send the leukocytes to the site of infection and target the source of inflammation directly.
As a result, this inhibits leukocyte (specifically
neutrophils
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
) extravasation and down regulates the magnitude of the inflammatory response. Without annexin A-I in mediating this response, neutrophil extravasation is highly active and worsens the inflammatory response in damaged or infected tissues.
Annexin A-I has also been implicated in apoptotic mechanisms in the cell. When expressed on the surface of neutrophils, annexin A-I promotes pro-apoptotic mechanisms. Alternatively, when expressed on the cell surface, annexin A-I promotes the removal of cells that have undergone apoptosis.
Moreover, annexin A-I has further medical implications in the treatment of
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. Annexin A-I can be used as a cell surface protein to mark some forms of
tumors
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
that can be targeted by various
immunotherapies
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
with
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against annexin A-I.
Coagulation
Annexin A-V is the major player when it comes to mechanisms of
coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
. Like other annexin types, annexin A-V can also be expressed on the cell surface and can function to form 2-dimensional crystals to protect the lipids of the cell membrane from involvement in coagulation mechanisms.
Medically speaking, phospholipids can often be recruited in autoimmune responses, most commonly observed in cases of fetal loss during pregnancy. In such cases, antibodies against annexin A-V destroy its 2-dimensional crystal structure and uncover the phospholipids in the membrane, making them available for contribution to various coagulation mechanisms.
Fibrinolysis
While several annexins may be involved in mechanisms of
fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other c ...
, annexin A-II is the most prominent in mediating these responses. The expression of annexin A-II on the cell surface is believed to serve as a receptor for
plasminogen
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...
, which functions to produce
plasmin
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encoded ...
. Plasmin initiates fibrinolysis by degrading
fibrin
Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...
. The destruction of fibrin is a natural preventative measure because it prevents the formation of blood clots by fibrin networks.
Annexin A-II has medical implications because it can be utilized in treatments for various
cardiovascular diseases
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...
that thrive on blood clotting through fibrin networks.
Types/subfamilies
*
Annexin, type I
*
Annexin, type II
*
Annexin, type III
*
Annexin, type IV
*
Annexin, type V
*
Annexin, type VI
*
Alpha giardin
*
Annexin, type X
*
Annexin, type VIII
*
Annexin, type XXXI
*
Annexin, type fungal XIV
*
Annexin, type plant
*
Annexin, type XIII
*
Annexin, type VII
*
Annexin like protein
*
Annexin XI
Human proteins containing this domain
ANXA1;
ANXA10;
ANXA11
Annexin A11 is a protein that in humans is encoded by the ''ANXA11'' gene.
Function
This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conse ...
;
ANXA13;
ANXA2
Annexin A2 also known as annexin II is a protein that in humans is encoded by the ''ANXA2'' gene.
Annexin 2 is involved in diverse cellular processes such as cell motility (especially that of the epithelial cells), linkage of membrane-associated ...
;
ANXA3;
ANXA4
Annexin A4 is a protein that in humans is encoded by the ''ANXA4'' gene.
Function
Annexin IV (ANX4) belongs to the annexin
Annexin is a common name for a group of cellular proteins. They are mostly found in eukaryotic organisms (animal, pla ...
;
ANXA5;
ANXA6
Annexin A6 is a protein that in humans is encoded by the ''ANXA6'' gene.
Function
Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Although their functions are still not clearly defined, several m ...
;
ANXA7
Annexin A7 is a protein that in humans is encoded by the ''ANXA7'' gene.
Annexin VII is a member of the annexin family of calcium-dependent phospholipid binding proteins. The Annexin VII gene contains 14 exons and spans approximately 34 kb of DNA ...
;
ANXA8;
ANXA8L1;
ANXA8L2
Annexin A8-like protein 2 is a protein that in humans is encoded by the ''ANXA8L2'' gene.
This gene encodes a member of the annexin family of evolutionarily conserved Ca2+ and phospholipid binding proteins. The encoded protein may function as an ...
;
ANXA9
Annexin A9 is a protein that in humans is encoded by the ''ANXA9'' gene.
Function
The annexins are a family of calcium-dependent phospholipid-binding proteins. Members of the annexin family contain 4 internal repeat domains, each of which incl ...
;
References
Further reading
*
*
External links
European Annexin Homepage acquired on 20 August 2005
* - Calculated spatial positions of annexins in membranes (the initially bound state)
Annexins repeated domainin
PROSITE
PROSITE is a protein database. It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformati ...
{{Calcium-binding proteins
Protein domains
Protein families
Peripheral membrane proteins