Reactome | prekallikrein + kininogen -> prekallikrein:kininogen

prekallikrein + kininogen -> prekallikrein:kininogen

Stable Identifier

R-HSA-9857939

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region

Synonyms

KLKB1(20-638) + KNG1(19-644) -> KLKB1(20-638):KNG1(19-644)

ReviewStatus

5/5

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prekallikrein + kininogen -> prekallikrein:kininogen

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Plasma prekallikrein (PK, encoded by the KLBK1 gene and depicted here as KLKB1(20-638)), the zymogen of the protease kallikrein, primarily circulates as a complex with high molecular weight kininogen (HK, encoded by KNG1 and depicted here as KNG1(19-644)) (Mandle RJ et al., 1976; Scott CF et al., 1979). The N-terminal heavy chain of prekallikrein, which contains four apple domains (A1–A4), mediates binding to domain 6 (D6) of HK (KNG1(19-644)) (Thompson RE et al., 1979; Chung DW et al., 1986; Tait JF & Fujikawa K, 1987; Li C et al., 2023; Mohammed BM et al., 2024). HK links PK to negatively charged surfaces such as polyphosphates or to cell surface receptors, facilitating conversion of PK to plasma kallikrein (PKa) by factor XIIa or prolylcarboxypeptidase (Lin Y et al., 1997; Motta G et al., 1998; Mahdi F et al., 2003; Merkulova A et al., 2023). HK protects plasma kallikrein from inhibition by C1 inhibitor (C1INH, encoded by SERPING1). C1INH accounts for 42% of inhibition of plasma kallikrein, whereas α2-macroglobulin accounts for 48% inhibition of plasma kallikrein, making these two major inhibitors of plasma kallikrein (Schapira M et al 1981). The ambient concentrations of C1INH and prolylcarboxypeptidase regulate the amount of plasma kallikrein generated on endothelial cell membranes (Merkulova A et al., 2023). C1INH is also the major plasma protease inhibitor or FXIIa (de Agostini et al. 1984).

Literature References

PubMed ID	Title	Journal	Year
37068593	Structures of factor XI and prekallikrein bound to domain 6 of high-molecular weight kininogen reveal alternate domain 6 conformations and exosites Li, C, Barroeta, AB, Wong, SS, Kim, HJ, Pathak, M, Dreveny, I, Meijers, JCM, Emsley, J	J Thromb Haemost	2023
1069308	Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma Mandle, RJ, Colman, RW, Kaplan, AP	Proc Natl Acad Sci U S A	1976
37813198	High molecular weight kininogen interactions with the homologs prekallikrein and factor XI: importance to surface-induced coagulation Mohammed, BM, Sun, MF, Cheng, Q, Litvak, M, McCrae, KR, Emsley, J, McCarty, OJT, Gailani, D	J Thromb Haemost	2024
9427705	High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells: a novel mechanism for contact activation Motta, G, Rojkjaer, R, Hasan, AA, Cines, DB, Schmaier, AH	Blood	1998
3650269	Primary structure requirements for the binding of human high molecular weight kininogen to plasma prekallikrein and factor XI Tait, JF, Fujikawa, K	J Biol Chem	1987
291905	Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain Thompson, RE, Mandle, R, Kaplan, AP	Proc Natl Acad Sci U S A	1979