Plasma kallikrein

Last updated
Plasma kallikrein
Identifiers
EC no. 3.4.21.34
CAS no. 410538-33-9
Alt. namesserum kallikrein, kininogenin, kallikrein I, kallikrein II, kininogenase, kallikrein, callicrein, glumorin, padreatin, padutin, kallidinogenase, bradykininogenase, panceatic kallikrein, onokrein P, dilminal D, depot-Padutin, urokallikrein, urinary kallikrein
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Search
PMC articles
PubMed articles
NCBI proteins
KLKB1
Protein KLKB1 PDB 2anw.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases KLKB1 , KLK3, PPK, PKKD, PKK, kallikrein B1
External IDs OMIM: 229000 MGI: 102849 HomoloGene: 68097 GeneCards: KLKB1
Orthologs
SpeciesHumanMouse
Entrez

3818

16621

Ensembl

ENSG00000164344

ENSMUSG00000109764

UniProt

P03952

P26262

RefSeq (mRNA)

NM_000892
NM_001318394
NM_001318396

NM_008455

RefSeq (protein)

NP_000883
NP_001305323
NP_001305325

NP_032481

Location (UCSC) Chr 4: 186.21 – 186.26 Mb Chr 8: 45.72 – 45.75 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Plasma kallikrein (EC 3.4.21.34) is an enzyme [5] [6] [7] [8] [9] that catalyses the following chemical reaction:

Contents

Selective cleavage of some Arg- and Lys- bonds, including Lys-Arg and Arg-Ser in (human) kininogen to release bradykinin

Plasma kallikrein and its precursor are encoded by the KLKB1 gene. [10] [11]

This enzyme is formed from prekallikrein (Fletcher factor) by factor XIIa.

Function

Plasma prekallikrein is a glycoprotein that participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. It is synthesized in the liver and secreted into the blood as a single polypeptide chain. Plasma prekallikrein is converted to plasma kallikrein by factor XIIa by the cleavage of an internal Arg-Ile bond. Plasma kallikrein therefore is composed of a heavy chain and a light chain held together by a disulfide bond. The heavy chain originates from the amino-terminal end of the zymogen and contains 4 tandem repeats of 90 or 91 amino acids. Each repeat harbors a novel structure called the apple domain. The heavy chain is required for the surface-dependent pro-coagulant activity of plasma kallikrein. The light chain contains the active site or catalytic domain of the enzyme and is homologous to the trypsin family of serine proteases. Plasma prekallikrein deficiency causes a prolonged activated partial thromboplastin time in patients. [12]

Interactions

Kallikrein and prekallikrein have been shown to interact with High-molecular-weight kininogen. [13] [14] [15] [16]


Related Research Articles

<span class="mw-page-title-main">Factor XII</span> Mammalian protein involved in blood clotting

Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme of the serine protease class. In humans, factor XII is encoded by the F12 gene.

alpha-2-Macroglobulin Large plasma protein found in the blood

α2-Macroglobulin (α2M) or alpha-2-macroglobulin is a large plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the A2M gene.

High-molecular-weight kininogen is a circulating plasma protein which participates in the initiation of blood coagulation, and in the generation of the vasodilator bradykinin via the kallikrein-kinin system. HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or it binds to intact endothelial cells or platelets for functions other than coagulation.

The kinin–kallikrein system or simply kinin system is a poorly understood hormonal system with limited available research. It consists of blood proteins that play a role in inflammation, blood pressure control, coagulation and pain. Its important mediators bradykinin and kallidin are vasodilators and act on many cell types. Clinical symptoms include marked weakness, tachycardia, fever, leukocytosis and acceleration of ESR.

<span class="mw-page-title-main">Factor XI</span> Mammalian protein found in Homo sapiens

Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene.

The prothrombinase enzyme complex consists of factor Xa (a serine protease) and factor Va (a protein cofactor). The complex assembles on negatively charged phospholipid membranes in the presence of calcium ions. The prothrombinase complex catalyzes the conversion of prothrombin (factor II), an inactive zymogen, to thrombin (factor IIa), an active serine protease. The activation of thrombin is a critical reaction in the coagulation cascade, which functions to regulate hemostasis in the body. To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg271 and the other after Arg320. Although it has been shown that factor Xa can activate prothrombin when unassociated with the prothrombinase complex, the rate of thrombin formation is severely decreased under such circumstances. The prothrombinase complex can catalyze the activation of prothrombin at a rate 3 x 105-fold faster than can factor Xa alone. Thus, the prothrombinase complex is required for the efficient production of activated thrombin and also for adequate hemostasis.

Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known paralogue, while tissue kallikrein-related peptidases (KLKs) encode a family of fifteen closely related serine proteases. These genes are localised to chromosome 19q13, forming the largest contiguous cluster of proteases within the human genome. Kallikreins are responsible for the coordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation.

Prekallikrein (PK), also known as Fletcher factor, is an 85,000 Mr serine protease that complexes with high-molecular-weight kininogen. PK is the precursor of plasma kallikrein, which is a serine protease that activates kinins. PK is cleaved to produce kallikrein by activated Factor XII.

Kininogens are precursor proteins for kinins, biologically active polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, inflammatory regulation, and the regulation of the cardiovascular and renal systems.

<span class="mw-page-title-main">Complement component 5</span> Protein found in humans

Complement component 5 is a protein that in humans is encoded by the C5 gene.

<span class="mw-page-title-main">Complement component 1r</span> Protein-coding gene in humans

Complement C1r subcomponent is a protein involved in the complement system of the innate immune system. In humans, C1r is encoded by the C1R gene.

Renal tissue kallikrein is an enzyme.

<span class="mw-page-title-main">Coagulation factor XIII, A1 polypeptide</span> Protein found in humans

Coagulation factor XIII A chain is a protein that in humans is encoded by the F13A1 gene.

<span class="mw-page-title-main">KLK1</span> Protein-coding gene in the species Homo sapiens

Kallikrein-1 is a protein that in humans is encoded by the KLK1 gene. KLK1 is a member of the peptidase S1 family.

<span class="mw-page-title-main">Calpain-2 catalytic subunit</span> Protein-coding gene in the species Homo sapiens

Calpain-2 catalytic subunit is a protein that in humans is encoded by the CAPN2 gene.

<span class="mw-page-title-main">F13B</span> Mammalian protein found in Homo sapiens

Coagulation factor XIII B chain is a protein that in humans is encoded by the F13B gene.

<span class="mw-page-title-main">Kininogen 1</span> Protein-coding gene in the species Homo sapiens

Kininogen-1 (KNG1), also known as alpha-2-thiol proteinase inhibitor, Williams-Fitzgerald-Flaujeac factor or the HMWK-kallikrein factor is a protein that in humans is encoded by the KNG1 gene. Kininogen-1 is the precursor protein to high-molecular-weight kininogen (HMWK), low-molecular-weight kininogen (LMWK), and bradykinin.

<span class="mw-page-title-main">Calpain-1 catalytic subunit</span> Protein-coding gene in the species Homo sapiens

Calpain-1 catalytic subunit(CANP 1) is a protein that in humans is encoded by the CAPN1 gene.

<span class="mw-page-title-main">GP1BB</span> Protein-coding gene in the species Homo sapiens

Glycoprotein Ib (platelet), beta polypeptide (GP1BB) also known as CD42c, is a protein that in humans is encoded by the GP1BB gene.

<span class="mw-page-title-main">GP5 (gene)</span> Protein-coding gene in the species Homo sapiens

Glycoprotein V (platelet) (GP5) also known as CD42d (Cluster of Differentiation 42d), is a human gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164344 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000109764 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Heimark RL, Davie EW (1981). "[14] Bovine and human plasma prekallikrein". Bovine and human plasma prekallikrein. Methods in Enzymology. Vol. 80 Pt C. pp. 157–72. doi:10.1016/s0076-6879(81)80016-x. ISBN   978-0-12-181980-4. PMID   6918767.
  6. ↑ McRae BJ, Kurachi K, Heimark RL, Fujikawa K, Davie EW, Powers JC (December 1981). "Mapping the active sites of bovine thrombin, factor IXa, factor Xa, factor XIa, factor XIIa, plasma kallikrein, and trypsin with amino acid and peptide thioesters: development of new sensitive substrates". Biochemistry. 20 (25): 7196–206. doi:10.1021/bi00528a022. PMID   6976185.
  7. ↑ Silverberg M, Kaplan AP (1988). "[8] Prekallikrein". Prekallikrein. Methods in Enzymology. Vol. 163. pp. 85–95. doi:10.1016/0076-6879(88)63010-2. ISBN   978-0-12-182064-0. PMID   3237096.
  8. ↑ Seidah NG, Ladenheim R, Mbikay M, Hamelin J, Lutfalla G, Rougeon F, Lazure C, Chrétien M (October 1989). "The cDNA structure of rat plasma kallikrein". DNA. 8 (8): 563–74. doi:10.1089/dna.1989.8.563. PMID   2598771.
  9. ↑ Tsuda Y, Teno N, Okada Y, Wanaka K, Bohgaki M, Hijikata-Okunomiya A, Okamoto U, Naito T, Okamoto S (November 1989). "Synthesis of tripeptide chloromethyl ketones and examination of their inhibitory effects on plasmin and plasma kallikrein". Chemical & Pharmaceutical Bulletin. 37 (11): 3108–11. doi: 10.1248/cpb.37.3108 . PMID   2534361.
  10. ↑ Yu H, Bowden DW, Spray BJ, Rich SS, Freedman BI (April 1998). "Identification of human plasma kallikrein gene polymorphisms and evaluation of their role in end-stage renal disease". Hypertension. 31 (4): 906–11. doi:10.1161/01.hyp.31.4.906. PMID   9535413.
  11. ↑ Chung DW, Fujikawa K, McMullen BA, Davie EW (August 1986). "Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats". Biochemistry. 25 (9): 2410–7. doi:10.1021/bi00357a017. PMID   3521732.
  12. ↑ "Entrez Gene: KLKB1 kallikrein B, plasma (Fletcher factor) 1".
  13. ↑ Thompson RE, Mandle R, Kaplan AP (October 1979). "Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain". Proc. Natl. Acad. Sci. U.S.A. 76 (10): 4862–6. Bibcode:1979PNAS...76.4862T. doi: 10.1073/pnas.76.10.4862 . PMC   413037 . PMID   291905.
  14. ↑ Page JD, You JL, Harris RB, Colman RW (October 1994). "Localization of the binding site on plasma kallikrein for high-molecular-weight kininogen to both apple 1 and apple 4 domains of the heavy chain". Arch. Biochem. Biophys. 314 (1): 159–64. doi:10.1006/abbi.1994.1424. PMID   7944388.
  15. ↑ Herwald H, Jahnen-Dechent W, Alla SA, Hock J, Bouma BN, Müller-Esterl W (July 1993). "Mapping of the high molecular weight kininogen binding site of prekallikrein. Evidence for a discontinuous epitope formed by distinct segments of the prekallikrein heavy chain". J. Biol. Chem. 268 (19): 14527–35. doi: 10.1016/S0021-9258(19)85270-5 . PMID   7686159.
  16. ↑ Renné T, Dedio J, Meijers JC, Chung D, Müller-Esterl W (September 1999). "Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2". J. Biol. Chem. 274 (36): 25777–84. doi: 10.1074/jbc.274.36.25777 . PMID   10464316.

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