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kallikrein-14; hK14; kallikrein-like protein 6; KLK-L6 (KLK14, KLKL6)
Function:
- serine-type endopeptidase with a dual trypsin-like & chymotrypsin-like substrate specificity
- may activate/inactivate proteinase-activated receptors F2R, F2RL1 & F2RL3 & other kallikreins including KLK1, KLK3, KLK5 & KLK11
- may function in seminal clot liquefaction through direct cleavage of the semenogelin SEMG1 & SEMG2 & activation of KLK3
- may function through desmoglein DSG1 cleavage in epidermal desquamation, a process by which the most superficial corneocytes are shed from the skin surface
- has an autoproteolytic activity which may have a regulatory effect
- higher catalytic efficiency for the trypsin-like enzyme substrates S-2288, S-2222 & S-2302 compared to S-2586 a chymotrypsin-like enzyme substrate
- has a lower catalytic activity compared to trypsin towards S-2288, S-2222 & S-2302
- cleaves preferentially after Arg residues
- proteolytic cleavage of the activation peptide produces the active enzyme
- activated by citrate
Kinetic parameters:
- KM=0.3 mM for S-2288
- KM=0.2 mM for S-2222
- KM=0.2 mM for S-2302
- KM=0.7 mM for S-2586
- KM=0.045 mM for Gln-Ala-Arg synthetic peptide
- KM=0.043 mM for Val-Pro-Arg synthetic peptide
- KM=0.09 mM for Pro-Phe-Arg synthetic peptide
- KM=0.278 mM for Phe-Ser-Arg synthetic peptide
- KM=0.0577 mM for Leu-Gly-Arg synthetic peptide
- KM=0.139 mM for Gln-Gly-Arg synthetic peptide
- KM=0.173 mM for Gly-Pro-Arg synthetic peptide
- KM=0.0268 mM for Gln-Arg-Arg synthetic peptide
- KM=0.130 mM for Gly-Gly-Arg synthetic peptide
- KM=0.578 mM for Val-Leu-Lys synthetic peptide
- pH dependence: optimum pH is 8.0
Inhibition:
- inhibited by SERPINA1, SERPINC1, SERPINE1, SERPINF2, aprotinin, soybean, trypsin inhibitor & leupeptin
- inhibited by serine protease inhibitor SPINK5
- inhibited by Zn+2 & to a lower extent by Mn+2
Structure:
- belongs to the peptidase S1 family, kallikrein subfamily
- contains 1 peptidase S1 domain
Compartment: secreted, extracellular space
Expression:
- highly expressed in CNS, bone marrow & fetal liver
- also expressed in breast, thyroid, kidney, colon, pancreas, spleen, prostate, uterus, small intestine, placenta & skeletal muscle
- among 40 tissues tested, highest expression is detected in skin > breast & prostate (at protein level)
- expressed in stratum corneum by sweat ducts & sweat glands & detected in sweat (at protein level)
- up-regulated by steroid hormone
Pathology:
- may be involved in several aspects of tumor progression including growth, invasion & angiogenesis
Note:
- uncertain whether Met-1 or Met-17 is the initiator
General
glycoprotein
kallikrein
Properties
SIZE: entity length = 267 aa
MW = 29 kD
COMPARTMENT: plasma
MOTIF: signal sequence {1-34}
S1 domain {41-265}
MOTIF: cysteine residue {C47}
MODIFICATION: cysteine residue {C180}
cysteine residue {C68}
MODIFICATION: cysteine residue {C84}
histidine residue {H83}
cysteine residue {C84}
MODIFICATION: cysteine residue {C68}
aspartate residue {D127}
cysteine residue {C159}
MODIFICATION: cysteine residue {C226}
cysteine residue {C180}
MODIFICATION: cysteine residue {C47}
cysteine residue {C191}
MODIFICATION: cysteine residue {C205}
cysteine residue {C205}
MODIFICATION: cysteine residue {C191}
cysteine residue {C216}
MODIFICATION: cysteine residue {C241}
serine residue {S220}
cysteine residue {C226}
MODIFICATION: cysteine residue {C159}
cysteine residue {C241}
MODIFICATION: cysteine residue {C216}
Database Correlations
OMIM 606135
UniProt Q9P0G3
Pfam PF00089
Entrez Gene 43847
Kegg hsa:43847
References
- UniProt :accession Q9P0G3
- Entrez Gene :accession 43847