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Kallikrein-kinin (KKS) cascade pathway leads to the production of active kinin peptides whose signaling via two G-protein coupled (GPCR) receptors prompts a range of responses that include vasodilation, release of inflammatory mediators, stimulation of sensory neurons. Recent studies also point to a potential role in oxidative stress. All active peptides are derived from a single precursor - kininogen (Kng1). Alternative splicing of Kng1 gives rise to the high- and low-molecular weight kinino

Pathway Diagram:

Elsevier Inc. Bdkrb2 F12a --+> coagulation cascade pathway F12a --+> classical complement pathway highKng1 ---> BK Bdkrb1 des-Arg-kinins ---> inflammatory mediators release kinin signaling pathway des-Arg-kinins ---> vasodilation BK ---> inflammatory mediators release KD ---> inflammatory mediators release inflammatory mediators release des-Arg-kinins ---> sensory neuron stimulation vasodilation des-Arg-kinins sensory neuron stimulation KD ---> vasodilation BK ---> vasodilation BK ---> sensory neuron stimulation KD ---> sensory neuron stimulation KD BK lowKng1 ---> KD BK ---> des-Arg-kinins Kng1 lowKng1 highKng1 kininases Serping1 Serpina4 Serpina4 ---| Klk1 A2m ---| Klkb1 Serping1 ---| Klkb1 Prcp --+> Klkb1 F12a --+> Klkb1 classical complement pathway coagulation cascade pathway Serping1 ---| F12a Klkb1 --+> F12a Klk1 KD ---> des-Arg-kinins Bdkrb2 ---- BK Bdkrb2 ---- KD Bdkrb1 ---- des-Arg-kinins des-Arg-kinins ---> inactive kinins inactive kinins Cpn1 Cpm pKlkb1 highKng1 ---- pKlkb1 F12 --+> F12a F12 A2m Kng1 ---> highKng1 Prcp Klkb1 F12a BK ---> inactive kinins KD ---> inactive kinins Kng1 ---> lowKng1

Genes in Pathway:

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kallikrein-kinin cascade pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G A2m alpha-2-macroglobulin JBrowse link 4 154,309,426 154,359,138 RGD:7401223
G Ace angiotensin I converting enzyme JBrowse link 10 94,170,766 94,213,831 RGD:7401223
G Bdkrb1 bradykinin receptor B1 JBrowse link 6 129,437,423 129,441,553 RGD:7401223
G Bdkrb2 bradykinin receptor B2 JBrowse link 6 129,399,468 129,429,676 RGD:7401223
G Cpm carboxypeptidase M JBrowse link 7 60,654,350 60,714,620 RGD:7401223
G Cpn1 carboxypeptidase N subunit 1 JBrowse link 1 263,733,887 263,762,758 RGD:7401223
G F12 coagulation factor XII JBrowse link 17 9,736,577 9,744,420 RGD:7401223
G Klk1 kallikrein 1 JBrowse link 1 100,131,562 100,135,556 RGD:7401223
G Klkb1 kallikrein B1 JBrowse link 16 50,151,127 50,175,407 RGD:7401224
G Kng2 kininogen 2 JBrowse link 11 81,509,185 81,516,759 RGD:7401223
G Prcp prolylcarboxypeptidase JBrowse link 1 157,701,089 157,750,177 RGD:7401224
G Serpina4 serpin family A member 4 JBrowse link 6 127,743,883 127,753,047 RGD:7401223
G Serping1 serpin family G member 1 JBrowse link 3 72,161,230 72,171,109 RGD:7401223
G Xpnpep1 X-prolyl aminopeptidase 1 JBrowse link 1 273,708,217 273,758,247 RGD:7401223
G Xpnpep2 X-prolyl aminopeptidase 2 JBrowse link X 134,940,656 134,969,874 RGD:7401223
kinin signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Arrb1 arrestin, beta 1 JBrowse link 1 164,502,099 164,573,947 RGD:7411621
G Arrb2 arrestin, beta 2 JBrowse link 10 57,040,252 57,048,045 RGD:7411621
G Bdkrb1 bradykinin receptor B1 JBrowse link 6 129,437,423 129,441,553 RGD:7401223
G Bdkrb2 bradykinin receptor B2 JBrowse link 6 129,399,468 129,429,676 RGD:7401223
G Grk4 G protein-coupled receptor kinase 4 JBrowse link 14 81,261,708 81,339,516 RGD:7401225
G Kng2 kininogen 2 JBrowse link 11 81,509,185 81,516,759 RGD:7401223

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Functional Classkininasesthe kinin peptides metabolizing enzymes

Pathway Gene Annotations

Disease Annotations Associated with Genes in the kallikrein-kinin cascade pathway
Disease TermsGene Symbols
Abortion, SpontaneousF12
Acquired AngioedemaF12 , Kng2 , Serping1
Acute Coronary SyndromeF12
Acute Kidney InjuryA2m , Ace , Bdkrb2 , Klk1 , Kng2
Acute Lung InjurySerping1
Adenoma, Liver CellA2m
Allanson Pantzar McLeod SyndromeAce
Alpha-2-Macroglobulin DeficiencyA2m
Alveolitis, Extrinsic AllergicAce
Alzheimer DiseaseA2m , Ace
Anemia, HemolyticA2m
Angina, UnstableAce , Bdkrb1
AngioedemaF12 , Serping1 , Xpnpep2
Angioedemas, HereditaryF12 , Kng2 , Serping1
Angiotensin I-Converting Enzyme, Benign Serum IncreaseAce
Aortic Aneurysm, AbdominalAce
Aortic CoarctationAce
Arrhythmias, CardiacAce , Kng2
Arteriovenous FistulaAce
Arthritis, ExperimentalA2m , Ace , Klkb1 , Kng2
Arthritis, RheumatoidA2m , Bdkrb2
AsthmaAce , Bdkrb2
Atrial FibrillationAce
Autism Spectrum DisorderKlkb1
Autistic DisorderAce
Behcet SyndromeAce
Bipolar DisorderAce
Brain IschemiaAce
Breast NeoplasmsAce
Bronchiolitis ObliteransAce
BurnsA2m , Serping1
Carboxypeptidase N DeficiencyCpn1
Carcinoma in SituAce
Carcinoma, HepatocellularA2m , Ace , Serpina4
Carcinoma, Pancreatic DuctalAce
CardiomegalyA2m , Ace
Cardiomyopathy, AlcoholicAce
Cardiomyopathy, DilatedAce
Cardiomyopathy, HypertrophicAce
Cardiovascular DiseasesAce
Carotid Artery DiseasesAce
Carotid Artery ThrombosisKlkb1
Cerebral HemorrhageAce
Cerebral InfarctionAce , Serping1
Chemical and Drug Induced Liver InjuryKng2 , Serping1
Chemotherapy-Induced Febrile NeutropeniaAce
Chronic Intermittent HypoxiaAce
Colonic NeoplasmsA2m
Complement Component 4, Partial Deficiency OfSerping1
Congenital Hepatic FibrosisAce
Coronary Artery DiseaseAce
Coronary DiseaseAce , F12
Coronary RestenosisAce
Coronavirus InfectionsAce
CoughAce , Bdkrb2 , Kng2
Death, SuddenAce
Death, Sudden, CardiacKng2
Diabetes ComplicationsBdkrb1 , Bdkrb2
Diabetes Mellitus, ExperimentalAce , Bdkrb1 , Bdkrb2 , Klk1
Diabetes Mellitus, Type 1Ace
Diabetes Mellitus, Type 2Ace , F12
Diabetic AngiopathiesBdkrb1
Diabetic CardiomyopathiesA2m , Ace , Klk1
Diabetic NephropathiesAce , Bdkrb2 , Klk1 , Klkb1 , Kng2
Diabetic NeuropathiesBdkrb1
Diabetic RetinopathyAce , Bdkrb1 , Bdkrb2 , Serpina4
Drug EruptionsKng2
Drug HypersensitivityAce
EdemaBdkrb1 , Kng2
Encephalomyelitis, Autoimmune, ExperimentalA2m
Endomyocardial FibrosisAce
EndotoxemiaAce , F12 , Serping1
EosinophiliaBdkrb2 , Kng2
EpilepsyBdkrb1 , Bdkrb2
Epilepsy, Temporal LobeBdkrb1 , Bdkrb2
Extravasation of Diagnostic and Therapeutic MaterialsBdkrb2 , Kng2
Fabry DiseaseAce
Factor XII DeficiencyF12
Familial Cerebral Cavernous MalformationAce
Femur Head NecrosisA2m
Fetal DeathAce
Fetal Growth RetardationAce
FibrosisBdkrb1 , Klk1
Flaujeac Factor DeficiencyKng2
Gallbladder NeoplasmsAce
Gaucher DiseaseAce
Genetic Predisposition to DiseaseAce
GlomerulonephritisAce , Bdkrb1 , Klkb1
Glomerulonephritis, IGAAce
Glomerulonephritis, MembranousA2m
Glomerulosclerosis, Focal SegmentalBdkrb1
Glycogen Storage Disease Type VAce
Heart DiseasesA2m
Heart FailureAce
Hepatolenticular DegenerationA2m
Hereditary Angioedema Type IIIF12
Hereditary Angioedema Types I and IISerping1
Hernias, Diaphragmatic, CongenitalAce
HyperalgesiaBdkrb1 , Bdkrb2 , Kng2
HyperemiaBdkrb2 , Kng2
HypersensitivityAce , Kng2
HypertensionAce , Bdkrb1 , Bdkrb2 , F12 , Klk1 , Klkb1 , Kng2
Hypertension, PortalBdkrb2
Hypertension, Pregnancy-InducedAce
Hypertension, PulmonaryAce , Bdkrb2
Hypertension, RenovascularAce
Hypertensive NephrosclerosisAce
Hypertrophy, Left VentricularAce , Bdkrb1 , Bdkrb2
Hypertrophy, Right VentricularAce
HypotensionAce , Bdkrb2 , Kng2
Infant, Premature, DiseasesAce
Infarction, Middle Cerebral ArteryAce , F12
Infertility, MaleAce
InflammationA2m , Bdkrb1 , Bdkrb2 , Klk1
Inflammatory Bowel DiseasesKlkb1
Influenza, HumanSerping1
Insulin ResistanceAce , Bdkrb1
Intracranial AneurysmAce
Intracranial HemorrhagesSerping1
Ischemic Attack, TransientF12
Kallikrein, Decreased Urinary Activity ofKlk1
Kidney DiseasesAce
Kidney Failure, ChronicAce , Bdkrb1 , Klk1
Kidney Reperfusion InjuryAce , Bdkrb1
Leukemia, Myelogenous, Chronic, BCR-ABL PositiveAce
Leukemia, Myeloid, AcuteBdkrb1 , Bdkrb2
Liver CirrhosisA2m , Klkb1 , Serping1
Liver Cirrhosis, BiliaryAce
Liver Cirrhosis, ExperimentalA2m , Kng2 , Serpina4 , Xpnpep2
Liver Neoplasms, ExperimentalF12
Liver Reperfusion InjurySerping1
Lung DiseasesA2m , Ace , Bdkrb2
Lung Diseases, ObstructiveA2m
Lung NeoplasmsA2m , Ace
Lupus Erythematosus, SystemicAce , Klkb1
Lupus NephritisKlkb1 , Serping1
Macular DegenerationSerping1
Mammary Neoplasms, AnimalKng2
Memory DisordersAce
Meningitis, PneumococcalSerping1
Meningococcal InfectionsAce
Mesothelioma, MalignantSerpina4
Microvascular AnginaBdkrb1 , Bdkrb2
Microvascular Complications of Diabetes, Susceptibility To, 2Ace
Microvascular Complications of Diabetes, Susceptibility To, 3Ace
Microvascular Complications of Diabetes, Susceptibility To, 6Ace
Microvascular Complications of Diabetes, Susceptibility To, 7Ace
Mitral Valve ProlapseAce
Multiple MyelomaAce
Myocardial InfarctionAce , Bdkrb1 , Bdkrb2 , F12 , Klk1
Myocardial Reperfusion InjuryKng2 , Serping1
Neoplasm MetastasisAce
NephritisAce , Bdkrb1
Nephrosis, Puromycin AminonucleosideAce
Nephrotic SyndromeA2m , Ace
Non-alcoholic Fatty Liver DiseaseAce
Nonarteritic Anterior Ischemic Optic NeuropathyAce
Nonproliferative Diabetic RetinopathyA2m
ObesityAce , Bdkrb1
Ocular HypotensionAce
PainAce , Bdkrb1 , Bdkrb2 , Kng2
Pancreatic NeoplasmsAce
PancreatitisBdkrb2 , Klk1 , Serping1
Pancreatitis, Acute NecrotizingSerping1
Parkinson DiseaseA2m , Ace
Peritoneal FibrosisAce
PleurisyBdkrb1 , Bdkrb2
PneumoniaAce , Bdkrb2
Pneumonia, AspirationAce
Pneumonia, ViralAce
Polycystic Kidney, Autosomal DominantSerping1
Polycystic Kidney, Autosomal RecessiveAce
Precancerous ConditionsAce
Prekallikrein DeficiencyKlkb1
Primary MyelofibrosisBdkrb1 , Bdkrb2
Primary Ovarian InsufficiencyXpnpep2
Prostatic NeoplasmsAce
Psychoses, Substance-InducedAce
Pulmonary Disease, Chronic ObstructiveAce , Bdkrb2
Pulmonary EmbolismKlkb1
Pulmonary FibrosisAce , Bdkrb1
Purpura, Schoenlein-HenochAce , Kng2
Radiation nephropathyAce
Renal FibrosisAce , Bdkrb1
Renal InsufficiencyAce
Renal Tubular DysgenesisAce
Reperfusion InjuryAce , Klk1 , Serping1
Respiratory Distress Syndrome, AdultAce
Respiratory Tract DiseasesAce
RhinitisBdkrb1 , Bdkrb2
Rhinitis, AllergicAce
Sciatic NeuropathyBdkrb1 , Bdkrb2
Scleroderma, SystemicAce
Segmental GlomerulosclerosisAce
SepsisA2m , Klkb1
Severe Acute Respiratory SyndromeAce
Shock, SepticA2m , Serping1
Shock, TraumaticSerping1
Sleep Apnea, ObstructiveAce
Smith-Magenis SyndromeAce
Spondylitis, AnkylosingAce
Staphylococcal InfectionsAce
Stomach NeoplasmsAce
StrokeAce , F12 , Kng2
Thrombocythemia, EssentialBdkrb1 , Bdkrb2
ThrombosisBdkrb2 , Klkb1
Ureteral ObstructionAce
Urinary Bladder, OveractiveBdkrb1
Vascular System InjuriesAce , Bdkrb1 , Bdkrb2
Venous ThromboembolismAce , Kng2
Venous ThrombosisF12
Ventricular FibrillationAce
Ventricular RemodelingAce
Vesico-Ureteral RefluxKlk1
Vitreoretinopathy, ProliferativeKng2
Weight GainAce
Pathway Annotations Associated with Genes in the kallikrein-kinin cascade pathway
Pathway TermsGene Symbols
acenocoumarol pharmacodynamics pathwayF12 , Klkb1
alteplase pharmacodynamics pathwayF12 , Klkb1
Alzheimer disease pathwayA2m
aminocaproic acid pharmacodynamics pathwayF12 , Klkb1
angiotensin (1-7) signaling pathwayAce
angiotensin II signaling pathwayAce
anistreplase pharmacodynamics pathwayF12 , Klkb1
aprotinin pharmacodynamics pathwayF12 , Klkb1
argatroban pharmacodynamics pathwayF12 , Klkb1
benazepril pharmacodynamics pathwayAce
benazepril pharmacokinetics pathwayAce
bivalirudin pharmacodynamics pathwayF12 , Klkb1
calcium/calcium-mediated signaling pathwayBdkrb1 , Bdkrb2
candesartan pharmacodynamics pathwayAce
captopril pharmacodynamics pathwayAce
cilazapril pharmacodynamics pathwayAce
cilazapril pharmacokinetics pathwayAce
coagulation cascade pathwayA2m , Bdkrb1 , Bdkrb2 , F12 , Klkb1 , Kng2 , Serping1
complement system pathwayA2m , Bdkrb1 , Bdkrb2 , F12 , Klkb1 , Kng2 , Serping1
dicoumarol pharmacodynamics pathwayF12 , Klkb1
enalapril pharmacodynamics pathwayAce
enalapril pharmacokinetics pathwayAce
enoxaparin pharmacodynamics pathwayF12 , Klkb1
eprosartan pharmacodynamics pathwayAce
fondaparinux pharmacodynamics pathwayF12 , Klkb1
forasartsn pharmacodynamics pathwayAce
fosinopril pharmacodynamics pathwayAce
fosinopril pharmacokinetics pathwayAce
G protein mediated signaling pathway via Galphai familyBdkrb1 , Bdkrb2
G protein mediated signaling pathway via Galphaq familyBdkrb1 , Bdkrb2
heparin pharmacodynamics pathwayF12 , Klkb1
hypertrophic cardiomyopathy pathwayAce
immune response pathwayA2m
inflammatory response pathwayA2m
interleukin-6 signaling pathwayA2m
irbesartan pharmacodynamics pathwayAce
kallikrein-kinin cascade pathwayA2m , Ace , Bdkrb1 , Bdkrb2 , Cpm , Cpn1 , F12 , Klk1 , Klkb1 , Kng2 , Prcp , Serpina4 , Serping1 , Xpnpep1 , Xpnpep2
kinin signaling pathwayBdkrb1 , Bdkrb2 , Kng2
lisinopril pharmacodynamics pathwayAce
losartan pharmacodynamics pathwayAce
moexipril pharmacodynamics pathwayAce
moexipril pharmacokinetics pathwayAce
olmesartan pharmacodynamics pathwayAce
perindopril pharmacodynamics pathwayAce
phenindione pharmacodynamics pathwayF12 , Klkb1
quinapril pharmacodynamics pathwayAce
quinapril pharmacokinetics pathwayAce
ramipril pharmacodynamics pathwayAce
ramipril pharmacokinetics pathwayAce
renin-angiotensin cascade pathwayAce
reteplase pharmacodynamics pathwayF12 , Klkb1
spirapril pharmacodynamics pathwayAce
spirapril pharmacokinetics pathwayAce
syndecan signaling pathwayKng2
telmisartan pharmacodynamics pathwayAce
trandolapril pharmacodynamics pathwayAce
trandolapril pharmacokinetics pathwayAce
tranexamic acid pharmacodynamics pathwayF12 , Klkb1
transforming growth factor-beta Smad dependent signaling pathwayA2m
Trypanosoma cruzi infection pathwayAce , Bdkrb2
valsartan pharmacodynamics pathwayAce
warfarin pharmacodynamics pathwayF12 , Klkb1
Phenotype Annotations Associated with Genes in the kallikrein-kinin cascade pathway

References Associated with the kallikrein-kinin cascade pathway:

Ontology Path Diagram:

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