Kringle Domains are autonomous
protein domain
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 ...
s that fold into large
loops stabilized by 3 disulfide linkages. These are important in
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 ...
–protein interactions with blood
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 ...
factors. Their name refers to the
Kringle
Kringle (, ) is a Northern European pastry, a variety of pretzel. Pretzels were introduced by Roman Catholic monks in the 13th century in Denmark, and from there they spread throughout Scandinavia and evolved into several kinds of sweet, salty ...
, a Scandinavian pastry which they somewhat resemble.
Kringle domains have been found in
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 ...
,
hepatocyte
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, ...
growth factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
s,
prothrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
, and
apolipoprotein(a)
Lipoprotein(a) is a low-density lipoprotein variant containing a protein called apolipoprotein(a). Genetic and epidemiological studies have identified lipoprotein(a) as a risk factor for atherosclerosis and related diseases, such as coronary heart ...
.
Kringles are found throughout the
blood clotting
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 ...
and fibrinolytic proteins. Kringle domains are believed to play a role in binding mediators (e.g., membranes, other proteins or phospholipids), and in the regulation of proteolytic activity.
Kringle domains
are characterised by a triple loop, 3-disulfide bridge structure, whose conformation is defined by a number of hydrogen bonds and small pieces of anti-parallel beta-sheet. They are found in a varying number of copies in some plasma proteins including prothrombin and urokinase-type plasminogen
activator, which are serine proteases belonging to MEROPS peptidase family S1A.
Human proteins containing this domain
ATF
The Bureau of Alcohol, Tobacco, Firearms and Explosives (BATFE), commonly referred to as the ATF, is a domestic law enforcement agency within the United States Department of Justice. Its responsibilities include the investigation and preven ...
;
F12;
F2;
HABP2;
HGF;
HGFAC
Hepatocyte growth factor activator is a protein that in humans is encoded by the HGFAC gene.
The protein encoded by this gene belongs to peptidase family S1. It is first synthesized as an inactive single-chain precursor before being activated to ...
;
KREMEN1
Kremen protein 1 is a protein that in humans is encoded by the ''KREMEN1'' gene. ''Kremen1'' is conserved in chordates including amphioxus and most vertebrate species. The protein is a type I transmembrane receptor of ligands Dickkopf1, Dickkopf2, ...
;
KREMEN2;
LPA;
LPAL2;
MST1
Macrophage-stimulating protein (MSP), also known as hepatocyte growth factor-like protein (HLP, HGFL, or HGFLP), is a protein that in humans is encoded by the ''MST1'' (''macrophage-stimulating 1'') gene
In biology, the word gene (from , ...
;
PIK3IP1
Phosphoinositide-3-kinase-interacting protein 1 is an enzyme that in humans is encoded by the ''PIK3IP1'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." m ...
;
PLAT
In the United States, a plat ( or ) (plan) is a cadastral map, drawn to scale, showing the divisions of a piece of land. United States General Land Office surveyors drafted township plats of Public Lands Surveys to show the distance and bear ...
;
PLAU
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally i ...
;
PLG;
PRSS12
Trypsin-1, also known as cationic trypsinogen, is a protein that in humans is encoded by the ''PRSS1'' gene. Trypsin-1 is the main isoform of trypsinogen secreted by pancreas, the others are trypsin-2 (anionic trypsinogen), and trypsin-3 (meso- ...
;
ROR1
Tyrosine-protein kinase transmembrane receptor ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is an enzyme that in humans is encoded by the ''ROR1'' gene. ROR1 is a member of the receptor tyrosine kinase-like orpha ...
;
ROR2
Tyrosine-protein kinase transmembrane receptor ROR2, also known as neurotrophic tyrosine kinase, receptor-related 2, is a protein that in humans is encoded by the ''ROR2'' gene located on position 9 of the long arm of chromosome 9. This protein ...
;
References
External links
Kringle 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 ...
KR domain entry in the SMART database
{{Protein domains
Protein domains
Peripheral membrane proteins