Lipocalin
Encyclopedia
The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroid
s, bilin
s, retinoid
s, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture. This is an eight stranded antiparallel beta-barrel with a repeated + 1 topology enclosing an internal ligand binding site.
These proteins are found in gram negative bacteria, vertebrate
cells, and invertebrate
cells, and in plants. Lipocalins have been associated with many biological processes, among them immune response, pheromone
transport, biological prostaglandin
synthesis, retinoid
binding, and cancer
cell interactions.
and detoxification processes caused by immune system activation in mammals. They are known respiratory allergen
s of mice, cats, dogs, horses, and other animals. Examples of lipocalin proteins involved in immune system responses include alpha-1-microglobulin, alpha-1-acid glycoprotein, and c8gamma. Structural information for many immune system influencing lipocalin proteins is available, while their exact role in biological systems is still somewhat unclear. Human allergenic reactions to lipocalins have not been extensively investigated.
mucus
of rodents. Major urinary proteins
, a lipocalin subfamily, are found in mouse and rat urine and may act as protein pheromones themselves.
, (vitamin A), is an important micronutrient
that affects eyesight, cell differentiation, immune system function, bone growth, and tumor
suppression. Retinol absorption and metabolism depends on lipocalins that act as binding proteins. Retinyl esters (present in meats) and beta-carotene
(present in plants) are the two main sources of retinoids in the diet. After intake, they are converted to retinol, successively metabolized, and finally bound to retinol binding proteins (lipocalins) in the blood plasma
.
proteins, their intracellular
effects are not obvious, and demand further study. However, lipophilic
ligands, present as substituent
s to the lipocalins, have the ability to enter the cell, where they can act as tumor
protease
inhibitors. This research suggests another possible route of protein-tumor investigations.
letters of the genus; a space; the first letter of the species name; a space and an Arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.
The allergens in this family include allergens with the following designations: Bla g 4, Bos d 2, Bos d 5, Can f 1, Can f 2, Fel d 4, Equ c 1 and Equ c 2.
which has been rolled into a cylindrical shape. Inside this barrel is located a ligand binding site, which plays an important role in the lipocalin classification as a transport protein. If lipocalins are genetically engineered in the attempt to modify their binding properties, they are called anticalin
s.
(protein HC); major urinary proteins
; alpha-1-acid glycoprotein (orosomucoid
); aphrodisin; apolipoprotein D
; beta-lactoglobulin
; complement component C8
gamma chain; crustacyanin; epididymal-retinoic acid binding protein (E-RABP); insectacyanin; odorant binding protein
(OBP); human pregnancy-associated endometrial alpha-2 globulin (PAEP
); probasin (PB), a prostatic protein; prostaglandin D synthase; purpurin; Von Ebner's gland protein (VEGP
); and lizard epididymal secretory protein IV (LESP IV).
Human proteins that contain lipocalin domain include:
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s, bilin
Bilin (biochemistry)
Bilins, bilanes or bile pigments are biological pigments formed in many organisms as a metabolic product of certain porphyrins. Bilin was named as a bile pigment of mammals, but can also be found in lower vertebrates, invertebrates, as well as red algae, green plants and cyanobacteria...
s, retinoid
Retinoid
The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....
s, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture. This is an eight stranded antiparallel beta-barrel with a repeated + 1 topology enclosing an internal ligand binding site.
These proteins are found in gram negative bacteria, vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
cells, and invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
cells, and in plants. Lipocalins have been associated with many biological processes, among them immune response, pheromone
Pheromone
A pheromone is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting outside the body of the secreting individual to impact the behavior of the receiving individual...
transport, biological prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
synthesis, retinoid
Retinoid
The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....
binding, and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cell interactions.
Immune response
Lipocalin proteins are involved in inflammationInflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and detoxification processes caused by immune system activation in mammals. They are known respiratory allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
s of mice, cats, dogs, horses, and other animals. Examples of lipocalin proteins involved in immune system responses include alpha-1-microglobulin, alpha-1-acid glycoprotein, and c8gamma. Structural information for many immune system influencing lipocalin proteins is available, while their exact role in biological systems is still somewhat unclear. Human allergenic reactions to lipocalins have not been extensively investigated.
Pheromone transport
The lipocalin family has been connected with the transport of mammalian pheromones due to easily observable protein-pheromone interactions. Lipocalins are comparatively small in size, and are thus less complicated to study as opposed to large, bulky proteins. They can also bind to various ligands for different biological purposes. Lipocalins have been detected as carrier proteins of important pheromones in the nasalNose
Anatomically, a nose is a protuberance in vertebrates that houses the nostrils, or nares, which admit and expel air for respiration in conjunction with the mouth. Behind the nose are the olfactory mucosa and the sinuses. Behind the nasal cavity, air next passes through the pharynx, shared with the...
mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
of rodents. Major urinary proteins
Major urinary proteins
Major urinary proteins , also known as α2u-globulins, are a subfamily of proteins found in abundance in the urine and other secretions of many animals. Mups provide a small range of identifying information about the donor animal, when detected by the vomeronasal organ of the receiving animal. They...
, a lipocalin subfamily, are found in mouse and rat urine and may act as protein pheromones themselves.
Prostaglandin synthesis
This family of proteins plays a part in the biological system of terminal prostaglandin synthesis.Retinoid binding
RetinolRetinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....
, (vitamin A), is an important micronutrient
Micronutrient
Micronutrients are nutrients required by humans and other living things throughout life in small quantities to orchestrate a whole range of physiological functions, but which the organism itself cannot produce. For people, they include dietary trace minerals in amounts generally less than 100...
that affects eyesight, cell differentiation, immune system function, bone growth, and tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
suppression. Retinol absorption and metabolism depends on lipocalins that act as binding proteins. Retinyl esters (present in meats) and beta-carotene
Beta-carotene
β-Carotene is a strongly-coloured red-orange pigment abundant in plants and fruits. It is an organic compound and chemically is classified as a hydrocarbon and specifically as a terpenoid , reflecting its derivation from isoprene units...
(present in plants) are the two main sources of retinoids in the diet. After intake, they are converted to retinol, successively metabolized, and finally bound to retinol binding proteins (lipocalins) in the blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
.
Cancer cell interactions
Because lipocalins are extracellularExtracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
proteins, their intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
effects are not obvious, and demand further study. However, lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
ligands, present as substituent
Substituent
In organic chemistry and biochemistry, a substituent is an atom or group of atoms substituted in place of a hydrogen atom on the parent chain of a hydrocarbon...
s to the lipocalins, have the ability to enter the cell, where they can act as tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
inhibitors. This research suggests another possible route of protein-tumor investigations.
Allergens
Some of the proteins in this family are allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans. This nomenclature system is defined by a designation that is composed of the first threeletters of the genus; a space; the first letter of the species name; a space and an Arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.
The allergens in this family include allergens with the following designations: Bla g 4, Bos d 2, Bos d 5, Can f 1, Can f 2, Fel d 4, Equ c 1 and Equ c 2.
Structure
Although lipocalins are a broad family of greatly varied proteins, their three-dimensional structure is a unifying characteristic. Lipocalins have an eight-stranded, antiparallel, symmetrical β-barrel fold, which is in essence a beta sheetBeta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
which has been rolled into a cylindrical shape. Inside this barrel is located a ligand binding site, which plays an important role in the lipocalin classification as a transport protein. If lipocalins are genetically engineered in the attempt to modify their binding properties, they are called anticalin
Anticalin
Anticalins are artificial proteins that are able to bind to antigens, either to proteins or to small molecules. They are not structurally related to antibodies, which makes them a type of antibody mimetic. Instead, they are derived from human lipocalins which are a family of naturally binding...
s.
Family members
The name "lipocalin" has been proposed for this protein family, but cytosolic fatty acid binding proteins are also included. The sequences of most members of the family, the core or kernel lipocalins, are characterised by three short conserved stretches of residues, while others, the outlier lipocalin group, share only one or two of these. Proteins known to belong to this family include alpha-1-microglobulinMicroglobulin
Microglobulin refers to a globulin of relatively small molecular weight. It can be contrasted to macroglobulin.,Examples include:* Beta-2 microglobulin* Alpha-1-microglobulin...
(protein HC); major urinary proteins
Major urinary proteins
Major urinary proteins , also known as α2u-globulins, are a subfamily of proteins found in abundance in the urine and other secretions of many animals. Mups provide a small range of identifying information about the donor animal, when detected by the vomeronasal organ of the receiving animal. They...
; alpha-1-acid glycoprotein (orosomucoid
Orosomucoid
Orosomucoid or alpha-1-acid glycoprotein is an acute phase plasma alpha-globulin glycoprotein and is modulated by two polymorphic genes. It is synthesized primarily in hepatocytes and has a normal plasma concentration between 0.6-1.2 mg/mL...
); aphrodisin; apolipoprotein D
Apolipoprotein D
Apolipoprotein D is a protein that in humans is encoded by the APOD gene.- Function :Apolipoprotein D is a component of high density lipoprotein that has no marked similarity to other apolipoprotein sequences...
; beta-lactoglobulin
Beta-lactoglobulin
right|thumbnail|300px|Structure of a β-lactoglobulin subunit Ribbons denote the [[secondary structure]], with arrows for beta strands and spirals for alpha-helices. Rendered with [[Kinemage]]...
; complement component C8
C8 complex
Complement component 8 is a protein involved in the complement system. A hereditary deficiency of C8 can result in increased susceptibility to Neisseria infections, such as meningitis and gonorrhea.-References:...
gamma chain; crustacyanin; epididymal-retinoic acid binding protein (E-RABP); insectacyanin; odorant binding protein
Odorant binding protein
Odorant binding proteins are abundant small soluble proteins secreted in the nasal mucus of many animal species and in the sensillar lymph of chemosensory sensilla of insects....
(OBP); human pregnancy-associated endometrial alpha-2 globulin (PAEP
PAEP
Glycodelin is a protein that in humans is encoded by the PAEP gene.-Further reading:...
); probasin (PB), a prostatic protein; prostaglandin D synthase; purpurin; Von Ebner's gland protein (VEGP
LCN1
Lipocalin-1 is a protein that in humans is encoded by the LCN1 gene.-Further reading:...
); and lizard epididymal secretory protein IV (LESP IV).
Human proteins that contain lipocalin domain include:
- AMBP, APODApolipoprotein DApolipoprotein D is a protein that in humans is encoded by the APOD gene.- Function :Apolipoprotein D is a component of high density lipoprotein that has no marked similarity to other apolipoprotein sequences...
- C8G, CRABP1CRABP1Cellular retinoic acid-binding protein 1 is a protein that in humans is encoded by the CRABP1 gene.-Further reading:...
, CRABP2CRABP2Cellular retinoic acid-binding protein 2 is a protein that in humans is encoded by the CRABP2 gene.-Interactions:CRABP2 has been shown to interact with Cyclin D3.-Further reading:... - FABP1FABP1Fatty acid-binding protein 1 also known as liver-type fatty acid-binding protein is a protein that in humans is encoded by the FABP1 gene.- Function :FABP1 encodes the fatty acid-binding protein found in liver...
, FABP2FABP2Fatty acid-binding protein 2 also known as Intestinal-type fatty acid-binding protein is a protein that in humans is encoded by the FABP2 gene.- Function :...
, FABP3, FABP4, FABP5FABP5Fatty acid-binding protein, epidermal is a protein that in humans is encoded by the FABP5 gene.-Further reading:...
, FABP6FABP6Fatty acid binding protein 6, ileal , also known as FABP6, is a protein which in humans is encoded by the FABP6 gene.- Function :...
, FABP7FABP7Fatty acid binding protein 7, brain , is a human gene.FABP7 is expressed, during development, in radial glia by the activation of Notch receptors... - LCN1LCN1Lipocalin-1 is a protein that in humans is encoded by the LCN1 gene.-Further reading:...
, LCN2LCN2Lipocalin-2 , also known as oncogene 24p3 or neutrophil gelatinase-associated lipocalin , is a protein that in humans is encoded by the LCN2 gene.- Function :...
, LCN8, LCN9, LCN10, LCN12 - OBP2AOBP2AOdorant-binding protein 2a is a protein that in humans is encoded by the OBP2A gene.-Further reading:...
, OBP2B - ORM1ORM1Alpha-1-acid glycoprotein 1 is a protein that in humans is encoded by the ORM1 gene.-Interactions:ORM1 has been shown to interact with Plasminogen activator inhibitor-1.-Further reading:...
, ORM2 - PAEPPAEPGlycodelin is a protein that in humans is encoded by the PAEP gene.-Further reading:...
, PERF15, PMP2PMP2Myelin P2 protein is a protein that in humans is encoded by the PMP2 gene.-Further reading:...
, PTGDSProstaglandin D2 synthaseProstaglandin-H2 D-isomerase is an enzyme that in humans is encoded by the PTGDS gene.-Further reading:... - RBP1RBP1Retinol binding protein 1, cellular, also known as RBP1, is a protein that in humans is encoded by the RBP1 gene.- Function :RBP1 is the carrier protein involved in the transport of retinol from the liver storage site to peripheral tissue...
, RBP2RBP2Retinol-binding protein 2 is a protein that in humans is encoded by the RBP2 gene.-Further reading:...
, RBP4, RBP5, RBP7 - UNQ2541
External links
- Lipocalins in SCOP database - Calculated spatial positions of some Lipocalins in membranes