Plasma kallikrein (KLKB1)
The protein contains 638 amino acids for an estimated molecular weight of 71370 Da.
The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Blood coagulation
Blood coagulation, intrinsic pathway
Extracellular matrix disassembly
Extracellular matrix organization
Factor XII activation
Fibrinolysis
Negative regulation of blood coagulation, intrinsic pathway
Plasminogen activation
Positive regulation of fibrinolysis
Proteolysis
Zymogen activation
The reference OMIM entry for this protein is 229000
Kallikrein b, plasma, 1; klkb1
Prekallikrein; pkk
Fletcher factor
Klk3, formerly
CLONING
Chung et al. (1986) cloned a KLKB1 cDNA from a human liver cDNA library. Analysis of the cDNA indicated that plasma prekallikrein is synthesized as a precursor with a signal peptide of 19 amino acids. The mature form the protein that circulates in blood is a single-chain polypeptide of 619 amino acids. Plasma prekallikrein is converted to plasma kallikrein by factor XIIa (610619) by the cleavage of an internal arg-ile bond. Plasma kallikrein is composed of a heavy chain (371 amino acids) and a light chain (248 amino acids), which are held together by a disulfide bond. The heavy chain originates from the N-terminal end of the zymogen and contains 4 tandem repeats (apple domains) that contain 90 or 91 amino acids. The light chain of plasma kallikrein contains the catalytic portion of the enzyme and is homologous to the trypsin family of serine proteases. Prekallikrein and factor XI (264900) share 58% amino acid sequence identity. Wuepper (1973) and Weiss et al. (1974) presented evidence indicating identity of Fletcher factor (Hathaway et al., 1965) and prekallikrein.GENE FUNCTION
Tait and Fujikawa (1986) demonstrated that the kallikrein apple domains (A1 to A4) mediate the high affinity binding of the enzyme to its major substrate, high molecular weight kininogen (see 612358). Herwald et al. (1996) showed that the kallikrein-kininogen complex binds to cell surface receptors leading to the targeted action of bradykinin, the product of kallikrein-mediated proteolysis.GENE STRUCTURE
Beaubien et al. (1991) demonstrated that, like the F11 gene, the KLKB1 gene contains 15 exons. Beaubien et al. (1991) also demonstrated that the gene organization of the catalytic subunit of KLKB1 is similar to that of trypsin and other related serine proteases. The findings suggested that plasma kallikrein and factor XI were derived from a common ancestor through gene duplication.MAPPING
By in situ hybridization, Beaubien et al. (1991) mapped the KLKB1 gene to chromosome 4q35, where the F11 gene is located, and the mouse homolog to chromosome 8.MOLECULAR GENETICS
In a study of 591 African Americans with end-stage renal disease (ESRD) and 139 African American control subjects, Yu et al. (2000) identified 12 allelic variants in the 5-prime proximal promoter and 7 exons of the KLKB1 gene. One common polymorphism present in 30% of the study population at position 521 of KLKB1 cDNA leads to the replacement of asparagine with serine at codon 124 in the heavy chain of the A2 domain of the protein. Several polymorphisms were found at a slightly increased frequency among families with end-stage renal disease; however, none of these associations was statistically significant. Yu et al. (2000) found an association of certain alleles of 2 CA/GT repeat polymorphic markers with ESRD in African Americans, but no causative mutation was identified. In a 79-year-old Caucasian male with prekallikrein (Fletcher factor) deficiency (612423), Wynne Jones et al. (2004) identified a homozygous arg94-to-ter substitution in the KLKB1 gene (R94X; 229000.0001).HISTORY
For a history of the Fletcher factor, see 612423 and Giangrande (2003). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for KLKB1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 229000 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed