Kallikrein
Encyclopedia
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein (KLKB1
) has no known homologue, 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 co-ordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation.
, which must undergo proteolytic processing to become activated. This is facilitated by factor XII
, PRCP
or other stimuli.
Plasma kallikrein liberates kinin
s (bradykinin
and kallidin
) from the kininogens, peptides responsible for the regulation of blood pressure and activation of inflammation. It is also capable of generating plasmin
from plasminogen:
, KLK2
and KLK12
also participate in regulation of blood pressure via the activation of bradykinin. KLK2, KLK3, KLK4
, KLK5
and KLK14
are expressed in the prostate and are thought to be responsible for regulating semen liquefaction through hydrolysis of seminogelin. Desquamation
of the skin is likely controlled by KLK5, KLK7
and KLK14, which are expressed in the outermost layer of the epidermis and cleave cellular adhesion proteins. Additionally, KLK6
and KLK8
are associated with neuronal plasticity in the central nervous system.
, KLK2
, KLK3, KLK4
, KLK5
, KLK6
, KLK7
, KLK8
, KLK9
, KLK10
, KLK11
, KLK12
, KLK13
, KLK14
, KLK15
Prostate-specific antigen (PSA; hk3, human kallikrein gene 3) and human glandular kallikrein (hK2) are used as tumor marker
s for prostate cancer.
KLKB1
Plasma kallikrein is a protein that in humans is encoded by the KLKB1 gene.-Interactions:KLKB1 has been shown to interact with High-molecular-weight kininogen.-Further reading:...
) has no known homologue, 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 co-ordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation.
Occurrence
E. Werle reported in 1934 finding a substance in the pancreas of men and various animals in such great amounts that the pancreas could be taken for its site of origin. He named it kallikrein, by derivation from the Greek word for pancreas. Since then similar enzymes have been found in the biological fluids of humans and other mammals, as well as in some snake venoms.Plasma kallikrein
The KLKB1 gene encoding plasma kallikrein is located on chromosome 4q34-35. It is synthesised as an inactive precursor, prekallikreinPrekallikrein
Prekallikrein , also known as Fletcher factor, is a 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 . -...
, which must undergo proteolytic processing to become activated. This is facilitated by factor XII
Factor XII
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.- Function :...
, PRCP
PRCP
Lysosomal Pro-X carboxypeptidase is an enzyme that in humans is encoded by the PRCP gene.-Further reading:...
or other stimuli.
Plasma kallikrein liberates kinin
Kinin
A kinin is any of various structurally related polypeptides, such as bradykinin and kallikrein. They are members of the autacoid family.They act locally to induce vasodilation and contraction of smooth muscle.It is a component of the kinin-kallikrein system....
s (bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
and kallidin
Kallidin
Kallidin is a bioactive kinin formed in response to injury from kininogen precursors through the action of kallikreins.Kallidin is a decapeptide that can be converted to bradykinin by the aminopeptidase enzyme....
) from the kininogens, peptides responsible for the regulation of blood pressure and activation of inflammation. It is also capable of generating plasmin
Plasmin
Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...
from plasminogen:
Tissue kallikreins
Distinct from plasma kallikrein, tissue kallikreins (KLKs) are expressed throughout the human body and perform various physiological roles. As some kallikreins are able to catalyse the activation of other kallikreins, several cascades involving these proteases have been implicated in the regulation of homeostatic functions.Function
Similar to KLKB1, three tissue kallikreins KLK1KLK1
Kallikrein-1 is a protein that in humans is encoded by the KLK1 gene. KLK1 is a member of the peptidase S1 family.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK2
KLK2
Kallikrein-2 is a protein that in humans is encoded by the KLK2 gene, and is particularly associated with prostatic tissue.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
and KLK12
KLK12
Kallikrein-12 is a protein that in humans is encoded by the KLK12 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
also participate in regulation of blood pressure via the activation of bradykinin. KLK2, KLK3, KLK4
KLK4
Kallikrein-related peptidase 4 is a protein which in humans is encoded by the KLK4 gene.Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and...
, KLK5
KLK5
Kallikrein-related peptidase 5 , formerly known as stratum corneum tryptic enzyme , is a serine protease expressed in the epidermis. In humans it is encoded by the KLK5 gene. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its expression is...
and KLK14
KLK14
Kallikrein-14 is a protein that in humans is encoded by the KLK14 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
are expressed in the prostate and are thought to be responsible for regulating semen liquefaction through hydrolysis of seminogelin. Desquamation
Desquamation
Desquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...
of the skin is likely controlled by KLK5, KLK7
KLK7
Kallikrein-related peptidase 7 is a serine protease that in humans is encoded by the KLK7 gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme...
and KLK14, which are expressed in the outermost layer of the epidermis and cleave cellular adhesion proteins. Additionally, KLK6
KLK6
Kallikrein-6 is a protein that in humans is encoded by the KLK6 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
and KLK8
KLK8
Kallikrein-8 is a protein that in humans is encoded by the KLK8 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
are associated with neuronal plasticity in the central nervous system.
Genes
There are 15 known tissue kallikreins: KLK1KLK1
Kallikrein-1 is a protein that in humans is encoded by the KLK1 gene. KLK1 is a member of the peptidase S1 family.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK2
KLK2
Kallikrein-2 is a protein that in humans is encoded by the KLK2 gene, and is particularly associated with prostatic tissue.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK3, KLK4
KLK4
Kallikrein-related peptidase 4 is a protein which in humans is encoded by the KLK4 gene.Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and...
, KLK5
KLK5
Kallikrein-related peptidase 5 , formerly known as stratum corneum tryptic enzyme , is a serine protease expressed in the epidermis. In humans it is encoded by the KLK5 gene. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its expression is...
, KLK6
KLK6
Kallikrein-6 is a protein that in humans is encoded by the KLK6 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK7
KLK7
Kallikrein-related peptidase 7 is a serine protease that in humans is encoded by the KLK7 gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme...
, KLK8
KLK8
Kallikrein-8 is a protein that in humans is encoded by the KLK8 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK9
KLK9
Kallikrein-related peptidase 9 also known as KLK9 is an enzyme which in humans is encoded by the KLK9 gene.- Function :KLK9 belongs to the kallikrein subgroup of serine proteases, which have diverse physiologic functions in many tissues...
, KLK10
KLK10
Kallikrein-10 is a protein that in humans is encoded by the KLK10 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK11
KLK11
Kallikrein-11 is a protein that in humans is encoded by the KLK11 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK12
KLK12
Kallikrein-12 is a protein that in humans is encoded by the KLK12 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK13
KLK13
Kallikrein-13 is a protein that in humans is encoded by the KLK13 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK14
KLK14
Kallikrein-14 is a protein that in humans is encoded by the KLK14 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, KLK15
KLK15
Kallikrein-15 is a protein that in humans is encoded by the KLK15 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
Clinical significance
Kallikrein-related peptidases are targets of active investigation by drug researchers as possible biomarkers for cancer.Prostate-specific antigen (PSA; hk3, human kallikrein gene 3) and human glandular kallikrein (hK2) are used as tumor marker
Tumor marker
A tumor marker is a substance found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer...
s for prostate cancer.
See also
- PrekallikreinPrekallikreinPrekallikrein , also known as Fletcher factor, is a 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 . -...
- Kinin-kallikrein systemKinin-kallikrein systemThe kinin-kallikrein system or simply kinin system is a poorly understood system of blood proteins that plays a role in inflammation, blood pressure control, coagulation and pain...
- KininKininA kinin is any of various structurally related polypeptides, such as bradykinin and kallikrein. They are members of the autacoid family.They act locally to induce vasodilation and contraction of smooth muscle.It is a component of the kinin-kallikrein system....
- AprotininAprotininThe drug aprotinin , is the bovine version of the small protein basic pancreatic trypsin inhibitor, or BPTI, which inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery,...
- List of cutaneous conditions
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: S01.212