Gene Set Gene Set Qualifier Gene Name Alternative Names Recommended Name UniProt ID NCBI Gene ID EC Species Name Taxonomy ID Pathway Information Source Evidence Type PubMed ID Notes Notes/SubPathway BP Likely ACE P12821 1636 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 1668266 23619363 21628354 22932704 Cloned human testis ACE was active with angiotensin I (1668266). Mice with ACE expression absent in kidney (ACE restricted to myelomonocytic cells or liver) blunts hypertension induced by Ang II infusion or nitric oxide sythesis inhibition; reanal responses to high serum Ang II observed in WT mice were effectively prevented in mice lacking kidney ACE (23619363). In a Lebanese population of 270 subjects a possible association of two alleles with hypertension was found (21628354). In 427 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension study cohort, subjects with the D allele of the ACE I/D polymorphism showed significantly lower diastolic BP (22932704). Blood pressure/Vascular tone AAE Likely ACE Angiotensin-converting enzyme P12821 1636 Human 9606 GO E 17077303 ACE seems to be involved in AA release (human ACE expressed in CHO cells) BP Predicted ACE2 Q9BYF1 59272 Human 9606 Metabolism of angiotensinogen to angiotensins GO:BP REACT_147707.2 18258853 18258853 uses mice BP Gold Standard ACVRL1 P37023 94 Human 9606 GO:BP 14684682 ACVRL1 mutations were found in persons with hereditary haemorrhagic telangiectasia related arterial pulmonary hypertension and in two persons with primary pulmonary hypertension and no HHT BP Predicted ADIPOQ Q15848 9370 Human 9606 GO:BP 17327472 17327472 uses mice. Adiponectin injection decreases BP in dose-dependent manner. BP Likely ADM P35318 133 Human 9606 GO:BP 11410113 In 11410113 arteries were obtained from subgluteal biopsies of patients with coronary heart failure or disease. 200 pmol/l reduced the vasoconstrictor effects of ET-1 on the arteries obtained from biopsies in patients with CHF. BP Likely AGT P01019 183 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 23324949 23108647 22799745 A/A genotype at rs5049 was a risk factor for hypertension in Melanesian Solomon Islanders (23324949). In a study of 180 hypertensive and 188 normotensive subjects the single-nucleotide polymorphism variant g.15241A>G was associated with risk for developing essential hypertension (22799745). Adipocyte-AGT deficient mice maintained the diet-induced obesity phenotype, but did not display the obesity-induced increase in systolic BP or plasma Ang II concentrations (23108647). Blood pressure/Vascular tone BP Likely AGTR1 P30556 185 Human 9606 GO:BP 15117835 Ang II type 1 receptor antagonist irbesartan prevented vasoconstriction by Ang II in vitro in coronary microarteries from heart valve donors (15117835). AAE Gold Standard AGTR2 Type-2 angiotensin II receptor P50052 186 Human 9606 GO E 20157051 In human primary dermal fibroblasts, AT2R-coupled signaling involves activation of protein phosphatases, CYP-dependent epoxidation of arachidonic acid to EETs, and inhibition of NF-κB (20157051). BP Likely AGTR2 P50052 186 Human 9606 GO:BP 15117835 17159079 Ang II type 2 receptor antagonist PD123319 caused in increase in vasoconstriction by Ang II ex vivo in coronary microarteries from heart valve donors (15117835). Ang II-induced dilation was blunted by PD123319 in presence of valsartan ex vivo in small arteries from subcutaneous tissue from hypertensive diabetic patients after 1 year treatment with valsartan (17159079). BP Predicted AKT1 P31749 207 Human 9606 eNOS activation and regulation REACT_12389.1 E 10376603 Publications in Reactome (11988487,12799359): bovine and no direct assessment of effect on BP. In 10376603 sheer stress induces phosphorylation of AKT1, and AKT1 phosphorylation of eNOS increases its activity (mixed bovine and human evidence). 10376602 uses bovine AKT1. 10469573 uses bovine cells. Blood pressure/Vascular tone BP Likely ANPEP P15144 290 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 1978675 15687497 19330903 17242304 ANPEP from rabbit renal membranes hydrolyzes angiotensin III to yield angiotensin IV (1978675). Human ANPEP was identified and shown to cleave angiotensin III to generate angiotensin IV (15687497). A SNP in ANPEP was associated with 7mmHg increase in systolic BP in nonsmokers in a genome-wide linkage analysis in Mexican-Americans (19330903). Anpep gene lies within QTLs for blood pressure identified in Dahl salt-sensitive (SS/Jr)-Lewis and Dahl SS/Jr-salt-resistant (SR/Jr) crosses and a SNP is present in the SR but not SS rat (17242304). Blood pressure/Vascular tone AAE Gold Standard ANXA1 Annexin A1 P04083 301 Human 9606 GO E E 17932043 17873281 ANXA1 mechanistically links the EGF-triggered growth signal pathway with cPLA2, an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 (17932043). confluence-dependent interaction of cPLA(2)alpha and annexin A1 at the Golgi acts as a novel molecular switch controlling cPLA(2)alpha activity and endothelial cell prostaglandin generation (17873281). BP Predicted ATP6AP2 renin receptor O75787 10159 Human 9606 Metabolism of angiotensinogen to angiotensins GO:BP REACT_147707.2 12045255 15746149 Silent mutation (c.321C->T, p.D107D) was found in a family with X-linked mental retardation; it can cause exon skipping but the receptor still binds renin and facilitates Ang I generation on the cell surface; the mutation was not found in 900 healthy individuals (15746149). Fetal HMC were transformed and expressed the renin receptor on cell surface; these cells could bind renin; assays demonstrated that membrane-bound renin increased catalytic efficiency of angiotensinogen cleavage; receptor was localized to mesangium in glomeruli and vascular structures of kidney cortex and subendothelium in coronary arteries (12045255). AAE Predicted AVP Vasopressin-neurophysin 2-copeptin P01185 551 Human 9606 GO E 17254553 in RAT: Arginine vasopressin (AVP) induces immediate prostaglandin E(2) (PGE(2)) production in rat 3Y1 fibroblasts. The antagonist of vasopressin receptor V1a inhibited the AVP-induced PGE(2) synthesis. No evidence in humans found AAE Predicted AVPR1A Vasopressin V1a receptor P37288 552 Human 9606 GO E 17254553 in RAT: Arginine vasopressin (AVP) induces immediate prostaglandin E(2) (PGE(2)) production in rat 3Y1 fibroblasts. The antagonist of vasopressin receptor V1a inhibited the AVP-induced PGE(2) synthesis BP Likely BDKRB2 B2 bradykinin receptor P30411 624 Human 9606 GO E 17077303 PMID: 17077303 demonstrates BDKRB2 forms complexes with ACE at the PM BP Likely BMPR2 Q13873 659 Human 9606 GO:BP 18364108 In Chinese pedigree with familial pulmonary arterial hypertension an A-to-T transition at position 1157 segregated within the family and was not found in a panel of 200 chromosomes from normal subjects; no mutation was found in BMPR2 in 10 patients with idiopathic pulmonary arterial hypertension (18364108). BP Likely CALCA P06881 796 Human 9606 GO:BP 10642343 3266556 Systolic BP and mean arterial pressure was significantly higher in male and female CALCA knockout mice (10642343). CALCA evoked dose-dependent falls in perfusion pressure (with noradrenaline as vasocontrictor) in human isolated mesenteric vasculature and human mesenteric arterial rings (3266556). BP Predicted CALM1 P62158 801 Human 9606 eNOS activation and regulation REACT_12389.1 C C E 12842859 12482742 10551886 From Reactome: 10551886, 9188442: cattle 11825621, 8137944: rat 9712842: mice? In 12842859, eNOS and calmodulin have been coimmunoprecipitated from human endothelial cells. eNOS is activated by calmodulin. In 12482742: when agonists are used to stimulate endothelial NO production the addition of a CaM antagonist abolishes NO production and endothelium-dependent relaxation. In 10551886, calmodulin potentiates APT1 catalyzed eNOS depalmitoylation (non-human). Blood pressure/Vascular tone BP Predicted CARTPT Q16568 9607 Human 9606 GO:BP 11711504 Intracerebroventricular injection of CART 55-102 in male Japanese White rabbits elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity (11711504). BP Likely CAV1 Q03135 857 Human 9606 eNOS activation and regulation REACT_12389.1 E E 11498544 16807357 In 11498544, this gene was knocked out in mice and the analysis of the aortic rings and the VSMCs shows that cav-1/caveolae regulate three major vascular features that depend on NO and Ca2+ signaling: endothelium-dependent relaxation of arteries, myogenic tone, and stimulated contractility. In HUVECs in a complex with eNOS and NOSTRIN (16807357). Blood pressure/Vascular tone BP Predicted CD34 P28906 947 Human 9606 GO:BP 17505307 17505307 is in rats. CD34+ cell therapy significantly caused attenuation of heatstroke induced hypotension. AAE Likely CD74 P04233 972 Human 9606 GO E 12782713 PMID:12782713 - binding to MIF increases PGE2 production; NCBI's Gene database says: "It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. " BP Predicted CMA1 P23946 1215 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 E E E E 10899625 6807977 11502696 2266130 In 10899625 , human chymase generates angiotensin II (in vitro). In 6807977, human chymanse catalyzes angiotensin I to angiotensin II, In 11502696 chymase is implicated in the ACE-independent production of Ang II in human arteries and in 2266130 in the heart. Blood pressure/Vascular tone BP Predicted COL1A2 P08123 1278 Human 9606 GO:BP 17334644 Gene polymorphisms and resting BP was investigated in 2238 healthy Japanese individuals. Systolic BP was signifcantly higher in men with the SS genotype than in men of other genotypes (no difference in women). The prevalence of hypertension did not differ among genotypes for men. FC: I'm not sure why this paper is listed for COL1A2 because it does not look like there is evidence linking the gene to the regulation of BP. However, other genes are linked to BP (QPCT and CYP11B2). BP Likely CORIN Q9Y5Q5 10699 Human 9606 GO:BP 22437503 16216958 Restoring CORIN expression in heart rescues the hypertension phenotype in KO mice [but not in pregnant mice]; K317E and S472G mutations markedly reduced corin activity in processing pro-ANP in HEK293 cells (from citation, ANP is important in regulating BP- I did not follow this up) (22437503). Genotype-phenotype genetic association study using several population samples (Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Chicago Genetics of Hypertension Study) linked increased risk of prevalent hypertension to SNPs (16216958).. BP Predicted CPA3 P15088 1359 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 2708524 2443571 CPA3 was purified from human mast cells and could hydrolyze angiotensin I (2708524, 2443571). Blood pressure/Vascular tone BP Predicted CPS1 P31327 1373 Human 9606 GO:BP 14718356 CPS1 polymorphism significantly influences venous nitric oxide concentration and both NOS-dependent and -independent vasodilation, assessed by forearm blood flow (14718356). BP Predicted CTSG Cathepsin G P08311 1511 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 9570564 20889553 Membrane-bound cathepsin G on intact activated neutrophils converts angiotensin I and angiotensinogen to angiotensin II (9570564). Cathepsin G prepared from neutrophils convert angiotensin I to angiotensin II (6807977). Cathepsin G converts angiotensin I to angiotensin II (20889553). Blood pressure/Vascular tone BP Predicted CTSZ Cathepsin X Cathepsin Z Q9UBR2 1522 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 19800993 CTSZ converted angiotensin I into angiotensin II in vitro (19800993). Blood pressure/Vascular tone BP Likely CYP11B1 P15538 1584 Human 9606 GO:BP 2022736 Eleven patients with 11beta-hydroxylase deficiency had a single mutation in exon 8 of this gene; 8/11 patients were hypertensive but the authors cite a previous study that showed poor correlation between hypertension and blood levels of 11-deoxycorticosterone (2022736). 6 families were studied and there were individuals heterozygous for the mutation or without the mutation, but no phenotype is given for those family members. BP Likely CYP11B2 P19099 1585 Human 9606 GO:BP 14614232 17334644 In a study that measured resting BP in 2238 healthy Japanese individuals and genotyped several candiate genes, resting BP (systolic and diastolic) in men was significantly higher with the CT or TT genotype and the prevalence of hypertension differed significantly (17334644). Two Japanese patients with corticosterone methyl oxidase type II deficiency had the mutation (435Gly->Ser) in CYP11B2 which reduces the mutant enzyme's 18-hydroxylase activity to form 18-hydroxycorticosterone (14614232). BP Predicted DHFR Dihydrofolate reductase P00374 1719 Human 9606 eNOS activation and regulation REACT_12389.1 19666465 In mice: DHFR inhibition or knockdown diminishes the BH4:BH2 ratio and exacerbates eNOS uncoupling (19666465). Blood pressure/Vascular tone BP Predicted DNM2 P50570 1785 Human 9606 eNOS activation and regulation REACT_12389.1 16234328 16807357 In CHO-eNOS cells: NOSTRIN binds dynamin (16234328) and recruits dynamin to caveolin-positive structures (16807357). Blood pressure/Vascular tone AAE Gold Standard DRD2 Dopamine D2 receptor P14416 1813 Human 9606 GO E E C 8301582 9756380 22986366 PMID:8301582 shows stimulation of AA release by human receptor; PMID: 9756380 (in RAT); PMID: 22986366 review connection btwn dopamine and prostaglandins AAE Gold Standard DRD3 Dopamine D3 receptor P35462 1814 Human 9606 GO E 8301582 10201643 PMID:8301582 shows stimulation of AA release by human receptor; PMID: 10201643 shows effect of dopamine D3 receptor on AA release AAE Gold Standard DRD4 Dopamine D4 receptor P21917 1815 Human 9606 GO E C 7512953 22986366 PMID: 7512953 shows that activated human D4 receptors potentiate AA release; PMID: 22986366 review connection btwn dopamine and prostaglandins BP Likely ECE1 P42892 1889 Human 9606 GO:BP 7805846 Human ECE1 was cloned and isolated. The enzyme was shown to convert Big ET-1 to ET-1 (7805846). [FC: I assigned Likely because of the evidence linking ET-1 with vasoconstriction] AAE Likely EDN1 Endothelin-1 P05305 1906 Human 9606 GO E 9492062 in MOUSE: induced prostaglandin synthesis in osteoblast-like cell line MC3T3-E1 after 3h incubation, results suggest through induction of PGHS-2 BP Likely EDN1 P05305 1906 Human 9606 GO:BP 2649896 8982507 9422810 11410113 Big ET-1 and ET-1 induced vasoconstriction in arteries obtained from subgluteal biopsies of patients with coronary heart failure and disease(11410113). ET-1 was shown to be a potent constrictor of umbilical vein (9422810, 8982507) and artery (8982507). Human synthetic ET-1 induced vasocontriction in vitro in porcine coronary artery and depressor/pressor response in vivo in male Wistar rats (2649896). AAE Likely EDN2 Endothelin-2 P20800 1907 Human 9606 GO E 9492062 in MOUSE: induced prostaglandin synthesis in osteoblast-like cell line MC3T3-E1 after 3h incubation, results suggest through induction of PGHS-2 BP Likely EDN2 P20800 1907 Human 9606 GO:BP 2649896 8982507 9422810 This was shown to be a potent constrictor of umbilical vein (9422810, 8982507) and artery (8982507). Human synthetic ET-2 induced vasocontriction in vitro in porcine coronary artery and depressor/pressor response in vivo in male Wistar rats (2649896). BP Likely EDN3 P14138 1908 Human 9606 GO:BP 2649896 8982507 Human synthetic ET-3 induced vasocontriction in vitro in porcine coronary artery and depressor/pressor response in vivo in male Wistar rats (2649896). ET-3 was inactive on umbilical vein but contracts umbilical artery (8982507). BP Likely EDNRA P25101 1909 Human 9606 GO:BP 8982507 BQ123 ETA receptor antagonist completely inhibited the ET-1 induced contraction in umbilical artery without affecting response in umbilical vein (8982507). BP Likely EDNRB P24530 1910 Human 9606 GO:BP 8982507 BQ788 antagonizes efficiently the effect of ET-3, which is quite selective for the ETB receptor (8982507). BP Likely ENG P17813 2022 Human 9606 GO:BP 18974388 Transgenic mice overexpressing S-endoglin in endothelial cells showed hypertension, decreased hypertensive response to NO inhibition, decreased vasodilatory response to TGF-beta(1) administration, and decreased endothelial nitric oxide syntahse expression in lungs and kidneys; S-endoglin was found in endothelium and some endothelial cells of human coronary arteries, human veins and lungs; S-endoglin interacts with ALK5 (18974388). BP Predicted ENPEP Q07075 2028 Human 9606 Metabolism of angiotensinogen to angiotensins GO:BP REACT_147707.2 19608358 Recombinant ENPEP enzyme administered to spontaneously hypertensive rats during pregnancy decreased systolic BP (19608358). AAE Gold Standard FCER1A High affinity immunoglobulin epsilon receptor subunit alpha P12319 2205 Human 9606 GO E E 20523060 18036650 In human mast cells preincubation with Siglec-8 mAbs significantly (P < .05) inhibited FcεRI-dependent prostaglandin D2 release (18036650). in MICE: long-term culture (7 days) of BMMCs with 33 mMD-glucose increases the Fc epsilon RI-dependent release of LTC(4) without affecting surface expression levels of Fc epsilon RI. BP Predicted GCH1 P30793 2643 Human 9606 GO:BP 17717598 An investigation of common genetic variation in GCH1 found that C+243T was associated with diastolic and systolic BP, principally in females (17717598). BP Predicted GCHFR P30047 2644 Human 9606 eNOS activation and regulation REACT_12389.1 16778797 8502995 16696853 In epidermal melanocytes and keratinocytes, BH4 negatively regulates GTP cyclohydrolase via GCHFR (16778797). In rat liver: the regulatory protein GCHFR was discovered (8502995). Using the yeast 2-hybrid assay system, human GCH1 and GCHFR were shown to interact (16696853). Blood pressure/Vascular tone BP Predicted GCLC P48506 2729 Human 9606 GO:BP 12598062 Association study that found the T allele of a polymorphism (-129C/T) associated with impairment of endothelium-dependent dilation of coronary arteries and was highly frequent in patients with myocaridal infarction (12598062). BP Predicted GCLM P48507 2730 Human 9606 GO:BP 12975258 The minor -588T allele (-588C/T) had an independent association with impaired dilation or enhanced constriction of epicardial coronay arteries in response to acetylcholine (12975258). BP Likely HSP90AA1 P07900 3320 Human 9606 eNOS activation and regulation REACT_12389.1 E 9580552 In 9580552, inhibition of signalling through Hsp90 attenuates both agonist-stimulated production of nitric oxide and endothelium-dependent relaxation of isolated blood vessels (from rat) and HSP90AA1 was isolated from HUVEC. Blood pressure/Vascular tone BP Predicted HTR2B P41595 3357 Human 9606 GO:BP 15625277 R393X mutation transfected into LMTK- cells demonstrated a partial loss of NO coupling, assessed by the dose-response effect of agonists on NOS activity (15625277). AAE Gold Standard IL1B Interleukin-1 beta P01584 3553 Human 9606 GO E 17328065 PMID: 17328065: "PGE(2) formation and cyclooxygenase 2 (COX-2) protein expression were induced by IL-1beta.."; PMID: 8891309 for rat studies AAE Gold Standard KISS1R KiSS-1 receptor Q969F8 84634 Human 9606 GO E 11457843 KISS1R agonists stimulated arachidonic acid release from Chinese hamster ovary K1 cells expressing human KISS1R BP Predicted LRP5 O75197 4041 Human 9606 GO:BP 18721193 LRP5 SNPs F549F and V1119V were associated with higher systolic blood pressure in a cross-sectional association study of 73 Finnish children with premature adrenarche and 97 age- and gender-matched healthy controls. BP Predicted LYPLA1 O75608 10434 Human 9606 eNOS activation and regulation REACT_12389.1 E 10551886 In 10551886 LYPLA1 depalmitoylates eNOS (non-human evidence). Blood pressure/Vascular tone AAE Gold Standard MAPK9 Mitogen-activated protein kinase 9 P45984 5601 Human 9606 GO E 24902855 Transfection of human cardiomyocytes with MAPK9 (JNK2) attenuated thrombin-induced COX-2 protein and mRNA expression and PGE2 release. COX AAE Gold Standard MIF P14174 4282 Human 9606 GO E E 12782713 19299454 PMID:12782713 - MIF is involved in enhancing PGE2 production. 19299454 shows MIF upregulates COX-2 and PGE(2) secretion. BP Predicted MME P08473 4311 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 E 15283675 Recombinant human MME hydrolysed Ang I, Ang (1-9), Ang (1-7), (15283675). Blood pressure/Vascular tone AAE Predicted NCF1 Neutrophil cytosol factor 1 P14598 653361 Human 9606 GO E 11867678 component of the leukocyte NADPH oxidase. Could not find human evidence. In MICE: by 180 min post intraperitoneal challenge with LTB4, p47phox-/- mice had approx 5x higher LTB4 levels, suggesting a role for this gene in degradation of LTB4 AAE Predicted NMB Neuromedin-B P08949 4828 Human 9606 GO E 8532598 in RAT: NMB stimulated [3H]arachidonic acid release from C6 glioma cells. no evidence found in humans BP Gold Standard NOS1 P29475 4842 Human 9606 GO:BP 18048451 18391107 Brachial artery infusion of NOS1-specific inhibitor S-methyl-L-thiocitrulline caused dose-dependent reduction in basal flow and inhibited the forearm vasodilator response to mental stress (18391107). NOS-1 inhibitor 7-nitroindazole administered by intradermal microdialysis on vasodilation induced by whole-body heat stress attenuated cutatneous vascular conductance but had no effect when vasodilation was induced by local skin warming (18048451). BP Predicted NOS3 P29474 4846 Human 9606 eNOS activation and regulation GO:BP REACT_12389.1 8999856 HUVEC with eNOS knocked down failed to produce NO in response to ET-1 (8999856). BP Predicted NOSIP eNOS interacting protein Q9Y314 51070 Human 9606 eNOS activation and regulation REACT_12389.1 11149895 16135813 NO production was significantly reduced in eNOS-expressing CHO cells that transiently expressed NOSIP (11149895). In CHO cells expressing eNOS, cytoplasmic NOSIP translocates eNOS to the actin cytoskeleton and inhibits the activity, similar results in RNAi knockdown (16135813). Blood pressure/Vascular tone BP Predicted NOSTRIN eNOS traffic inducer Q8IVI9 115677 Human 9606 eNOS activation and regulation REACT_12389.1 12446846 16234328 16807357 NOSTRIN is expressed in microvascular endothelial cells and umbilical vein endothelial cells (12446846) and immunofluorescence demonstrated colocalization of NOSTRIN and eNOS in these cell types (12446846). In CHO cells expressing human eNOS and transfected with human NOSTRIN, antibodies to eNOS coprecipiate NOSTRIN and vice versa (12446846). A Y2H system with deletion of residues 434-506 (in large part represents the SH3 domain) or 471-506 nullified NOSTRIN binding to eNOS; and in vitro pull down with SH3 deleted did not pull down eNOS; thus NOSTRIN interacts with eNOS via the SH3 domain (12446846). In vitro human NOSTRIN pulls down eNOS (human), dynamin (rat or human, not specified), and N-WASP (rat) from lysates of CHO-eNOS cells (16234328). Rat dynamin-2, human NOSTRIN and eNOS colocalized in CHO cells stably expressing eNOS and transfected with dynamin-2 and NOSTRIN (16234328). In HUVECs NOSTRIN:eNOS:caveolin-1 assemble at the plasma membrane when cells are confluent (16807357). Blood pressure/Vascular tone BP Predicted NPPA P01160 4878 Human 9606 GO:BP 6230082 6547996 Human precursor protein CDD-ANF was cloned; in rat preproCDD-ANF mRNA is syntesized in atria but not in the ventricles and markedly decreases on water deprivation (6547996). "alpha-human atrial natriuretic polypeptide" had vasorelaxant activity when injected into rats (6230082). AAE Likely OXT Oxytocin-neurophysin 1 P01178 5020 Human 9606 GO E E 24916153 9575824 OXT induced COX-2 expression in human myometrial cells (24916153). Oxytocin stimulated PGE2 synthesis in CHO cells transfected with rat oxytocin receptor (9575824). BP Predicted P2RX4 Q99571 5025 Human 9606 GO:BP 11606481 15130891 Cardiac transgenic expression of human P2RX4 in mice exhibited significantly elevated basal cardiac contractility with greater rates of contraction and relaxation, left ventricular developed pressure and cardiac output compared with nontransgenic animals (11606481). P2X4R Tg mice crossed with CSQ mice (phenotype: hypertrophy, heart failure, and premature death) results in a survival benefit for the CSQ/P2X4R mouse (15130891). BP Predicted PCSK5 Q92824 5125 Human 9606 GO:BP 8901832 PCSK5 was colocalized with renin by immunohistochemistry in the zona glomerulosa of the adrenal gland, and when co-transfected with a human prorenin expression vector in cultured GH4C1 cells, active renin was secreted (8901832). AAE Predicted PDPN Podoplanin Q86YL7 10630 Human 9606 GO P 16869965 Knocking out gene in mice led to differentially expressed genes involved in prostaglandin metabolism at E18.5. AAE Gold Standard PLA2R1 Q13018 22925 Human 9606 Mike L. Keyword search E 7721806 UniProtKB keyword search: arachidonic acid. Soluble and membrane-bound human sPLA2 receptors both bind sPLA2 with high affinities (PMID 7721806) BP Predicted PLCB3 Q01970 5331 Human 9606 GO:BP 18468998 18468998 is in mice. alpha1D adrenergic receptor signals through a GPCR whcih activates phospholipase Cbeta (PLCB3). I this paper the alpha1D adrenergic receptor was knocked out, and those mice displayed a hypotensive phenotype and were resistant to salt-induced hypertension. At best, this evidence is indirect for the involvement of PLCB3 in regulation of BP. AAE Gold Standard POR P16435 5447 1.6.2.4 Human 9606 Literature E 19448135 11695850 14725854 9799565 Suggested by Chandra from evidence in literature cytochrome P450 BP Likely PPARG P37231 5468 Human 9606 GO:BP 10622252 Two family members (a mother and son) were heterozygous for the P467L mutation in PPARgamma and they had early onset severe insulin resistance and elevated blood pressure; family members without the mutation (homozygous) did not display the phenotype (10622252). A third, unrelated individual was heterozygous for a SNP resulting in V290M mutation. Her clinically unaffected mother and sister were wild type at the locus. BP Predicted PRKG2 cGMP-dependent protein kinase 2 Q13237 5593 Human 9606 eNOS activation and regulation REACT_12389.1 10531334 COS-1 cells transfected with cGKII phosphorylated human PTPS in vitro; a non-phosphorylated human PTPS mutant (S19A, expressed in COS-1 cells) had reduced activity; fibroblast extracts from mice lacking cGKII are reduced in PTPS-specific phosphorylation and phosphotransferase activity; thus, PTPS requires phosphorylation for enzyme activity (10531334). Blood pressure/Vascular tone BP Predicted PTS PTPS 6-pyruvoyl tetrahydrobiopterin synthase Q03393 5805 Human 9606 eNOS activation and regulation REACT_12389.1 3536512 8307017 PTS was purified from human liver (3536512) and has 7,8-dihydroneopterin triphosphate as a substrate (3536512, 8307017). Blood pressure/Vascular tone BP Likely REN P00797 5972 Human 9606 Metabolism of angiotensinogen to angiotensins GO:BP REACT_147707.2 12045255 Article opens, "The renin-angiotensin system (RAS) is critical for the control of blood pressure and salt balance in mammals." 12045255 identifies a renin receptor and that the binding of renin to the receptro induces (a) an increase of the catalytic efficiency of angiotensinogen conversion into Ang I by renin bound to the receptor compared with renin in the soluble phase. Renin receptor mRNA was found in several human tissues. AAE Gold Standard SIRT1 NAD-dependent protein deacetylase sirtuin-1 Q96EB6 23411 Human 9606 GO E 20042607 23257246 In MICE SIRT1 reduced the expression of COX-2 (20042607). PMID: 23257246 shows regulation of COX-2 through deacetylation of NfkB. AAE Gold Standard SPHK1 Sphingosine kinase 1 Q9NYA1 8877 Human 9606 GO E 23109673 SphK1 down-regulation by siRNA in human umbilical vein endothelial cells decreased cytokine-induced PGE(2) production primarily through inhibition of microsomal PGE synthase-1 (mPGES-1), not COX-2. BP Predicted SPR P35270 6697 Human 9606 eNOS activation and regulation REACT_12389.1 1883349 A full-length cDNA clone for SPR was isolated from a human liver cDNA library (1883349). Blood pressure/Vascular tone AAE Predicted SSTR4 Somatostatin receptor type 4 P31391 6754 Human 9606 GO E 8175684 in RAT: SSTR4 was functionally coupled to arachidonate release AAE Gold Standard SYK Tyrosine-protein kinase SYK P43405 6850 Human 9606 GO C E 25045209 18390758 PMID: 25045209 review - SYK regulates NFkB which regulates COX2 expression. Spleen tyrosine kinase (Syk) inhibitors piceatannol and R406 fully blocked AA release in response to immune complexes in monocyte-derived dendritic cells (18390758). AAE Gold Standard TLR2 Toll-like receptor 2 O60603 7097 Human 9606 GO E 19401382 In monocytes TLR2 ligand-induced increase of AA release was blocked by a neutralizing anti-hTLR2 antibody AAE Predicted TNFRSF11A RANK Tumor necrosis factor receptor superfamily member 11A Q9Y6Q6 8792 Human 9606 GO E 19940926 receptor for TNFSF11 AAE Gold Standard TNFRSF1A TNFR1 Tumor necrosis factor receptor superfamily member 1A P19438 7132 Human 9606 GO E 9330943 The TNF-R55 was found to be the major receptor species responsible for ligand binding activity, such as COX-2 induction and PGE2 synthesis, since a specific antireceptor TNF-R55 blocking antibody inhibited about 76% of TNF-alpha binding and TNF-alpha stimulated COX-2 induction and PGE2 production AAE Predicted TNFSF11 RANKL Tumor necrosis factor ligand superfamily member 11 O14788 8600 Human 9606 GO E 19940926 19940926: "These results show that RANKL/RANK can directly induce PGE2 production in isolated brain slices and that RANKL/RANK mediate the febrile response via induction of the COX2–PGE2–EP3 receptor system" (In MICE) AA and metabolites regulate RANKL BP Predicted WASL N-WASP O00401 8976 Human 9606 eNOS activation and regulation REACT_12389.1 16234328 NOSTRIN interacts with the actin nucleation promoting factor N-WASP by means of its SH3 domain, studied by co-expression of rat N-WASP and human NOSTRIN in CHO-eNOS cells (16234328). Blood pressure/Vascular tone BP Predicted ZDHHC21 DHHC-21 Q8IVQ6 340481 Human 9606 eNOS activation and regulation REACT_12389.1 16864653 8692835 8626455 Inhibition of DHHC-21 in endothelial cells reduces eNOS palmitoylation, eNOS targeting and stimulated NO production (16864653). In mouse cell line NIH 3T3, palmitoylation was shown to be necessary for targeting eNOS into caveolae (8692835). In African green monkey cell line COS-7, palmitoylation was shown to be required to target eNOS to caveolae (8626455). Blood pressure/Vascular tone