Taxonomic distribution of proteins containing KR domains

The KR domain within your query sequence starts at position 23 and ends at position 103, and its E-value is 3.64e-17.

The kringle domains of human plasminogen.

Castellino FJ, McCance SG
Ciba Found Symp. 1997; 212: 46-60

The mature form of the zymogen, human plasminogen (HPlg), contains 791 amino acids present in a single polypeptide chain. The fibrinolytic enzyme, human plasmin (HPlm), is formed from HPlg as a result of activator-catalysed cleavage of the Arg561-Val562 peptide bond in HPlg. The resulting HPlm contains a heavy chain of 561 amino acid residues, originating from the N-terminus of HPlg, doubly disulfide-linked to a light chain of 230 amino acid residues. This latter region, containing the C-terminus of HPlg, is homologous to serine proteases such as trypsin and elastase. The heavy chain of HPlm consists of five repeating triple-disulfide-linked peptide regions, c. 80 amino acid residues in length, termed kringles (K), that are responsible for interactions of HPlg and HPlm with substrates, inhibitors and regulators of HPlg activation. Important among the ligands of the kringles are positive activation effectors, typified by lysine and its analogues, and negative activation effectors, such as Cl-. The kringle domains of HPlg that participate in these binding interactions are K1, K4 and K5, and perhaps K2. These modules appear to function as independent domains. The amino acid residues important in these kringle/ligand binding interactions have been proposed by structural determinations, and their relative importance quantified by site-directed mutagenesis experimentation.

Evolution of plasminogen-related growth factors (HGF/SF and HGF1/MSP).

Gherardi E, GonzalezManzano R, Cottage A, Hawker K, Aparicio S
Ciba Found Symp. 1997; 212: 24-35

HGF/SF and HGF1/MSP define a novel growth factor family whose members share the domain structure and the proteolytic process of activation of the blood proteinase precursor plasminogen. The amino acid and RNA sequences of HGF/SF and HGF1/MSP, the intron-exon organization of their genes and the predicted 3D structure of individual domains indicate that HGF/SF and HGF1/MSP evolved along with plasminogen and other members of the kringle-serine proteinase (KSP) superfamily from an ancestral gene that contained a single copy of the kringle domain, a serine proteinase domain and an activation peptide connecting the two domains. A series of intragenic duplications of the kringle domain, gene duplications, exon shuffling and deletions is responsible for the genes currently present in mammals, avians and amphibians. Plasminogen, HGF/SF and HGF1/MSP represent paradigmatic examples of the modern, multi-domain proteins typically associated with vertebrate organisms and illustrate a novel evolutionary pathway that led to the emergence of molecules with growth regulatory activity from proteolytic enzymes.

Structure and order of the protein and carbohydrate domains of prothrombin fragment 1.

Harlos K, Boys CW, Holland SK, Esnouf MP, Blake CC
FEBS Lett. 1987; 224: 97-103

The three-dimensional structure of prothrombin fragment 1 has been determined by X-ray crystallography at 3.8 A resolution. The fragment is composed of a number of structural units, some of which are ordered while others are disordered. The ordered part of the structure includes a compact kringle unit, a helical domain and a carbohydrate chain. The kringle structure is organized around a close pair of buried disulfide bridges. One of its carbohydrate chains, that attached to Asn 101, is fully ordered, but the carbohydrate chain attached to Asn 77 appears to be disordered. The calcium binding unit is composed of a disordered part containing all ten gamma-carboxyglutamic acid residues and an ordered part forming the helical domain. The highly conserved residues Phe 41, Trp 42 and Tyr 45, which form a hydrophobic cluster on the first helix, interact around a crystallographic two-fold axis with the equivalent residues in another molecule to form a dimer in the crystal.

Three-dimensional structure of the kringle sequence: structure of prothrombin fragment 1.

Park CH, Tulinsky A
Biochemistry. 1986; 25: 3977-82

The three-dimensional structure of bovine prothrombin fragment 1 has been solved at 2.8-A resolution. The electron density clearly reveals four disulfide bridges along with more than 80% of the side chains completely in density, which correspond faithfully to the kringle sequence, its preceding 30 residues, and the dodecapeptide carboxy terminal; the polysaccharide and the first 35 residues of the amino terminal of fragment 1 are disordered or about 40% of the structure. The folding of the kringle sequence is based upon close disulfide van der Waals contacts between Cys-87-Cys-127 and Cys-115-Cys-139 (4.1 A between midpoints of the bridges), two antiparallel strands of highly conserved (113-118, 124-129) beta-structure, and the stacking of some conserved aromatic residues, all near the center of the folded structure. Moreover, the overall folding appears to be duplicated as a pair of stacked duplex loops with an antiparallel open loop. The overall shape of the kringle structure approximates an eccentric oblate ellipsoid of dimensions 11 X 28 X 30 A. The residues immediately preceding the kringle are dominated by alpha-helical structure (Phe-41-Cys-48; Leu-56-Glu-63). Residues Phe-41-Trp-42 and Tyr-45, which are conserved in factor IX, factor X, protein C, and protein Z, form another aromatic stacked cluster while the Cys-48-Cys-61 disulfide loop corresponds to the well-known alpha/beta structural unit. The dodecapeptide carboxy-terminal interkringle chain extends along the periphery of the kringle in its plane and forms a beta-structure with the kringle-closing Ser-140-Val-143 tetrapeptide.

Amino-acid sequence of activation cleavage site in plasminogen: homology with "pro" part of prothrombin.

Sottrup-Jensen L, Zajdel M, Claeys H, Petersen TE, Magnusson S
Proc Natl Acad Sci U S A. 1975; 72: 2577-81

A 38-residue fragment is isolated from carboxymethylated plasminogen. Residues 29-38 have the same sequence as the amino-terminal end of the light chain of plasmin. The sequence 1-28 is therefore the sequence of the carboxyl-terminal end of the heavy chain and contains the specific sequence at which urokinase (EC 3.4.99.26) and other plasminogen-activating serine proteases split. Two of the five carboxymethyl-cysteine residues in the isolated fragment are situated close to the cleavage site and the fragment is not itself a substrate for plasminogen-activators. Residues 1-11 show extensive sequence homology with residues 137-147 and 242-252 in prothrombin, which are located in corresponding regions of the two internally homologous 83-residue structures in the non-thrombin part of the molecule, indicating that such structures may be a common feature of the non-protease part of the larger serine protease zymogens.