Property Summary

NCBI Gene PubMed Count 98
PubMed Score 186.22
PubTator Score 630.21

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (19)

Disease log2 FC p
malignant mesothelioma -2.100 4.0e-06
astrocytic glioma -2.900 9.8e-03
posterior fossa group B ependymoma -3.700 4.0e-08
oligodendroglioma -2.400 1.6e-02
glioblastoma multiforme -1.500 6.2e-08
group 4 medulloblastoma -3.500 2.8e-03
atypical teratoid / rhabdoid tumor -3.300 5.6e-04
lung cancer 5.400 2.3e-07
active Crohn's disease 5.656 3.2e-05
Parkinson's disease -1.200 3.0e-02
pancreatic cancer -1.600 1.2e-02
fibroadenoma 1.300 3.2e-05
interstitial cystitis 5.000 2.9e-04
lung carcinoma 6.300 9.7e-56
Alzheimer's disease -2.300 2.7e-02
Pick disease -1.900 1.5e-02
ulcerative colitis 3.200 1.1e-06
Down syndrome -1.700 5.2e-03
psoriasis 2.600 5.0e-52

Protein-protein Interaction (7)

Gene RIF (72)

PMID Text
26345846 these common variants in PCSK1 and POMC were not the major cause of obesity in the Thai subjects sampled. However, variants in PCSK1 did affect cholesterol level, LDL-C level, and waist circumference.
26229104 Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.
26207343 Data show that prohormone convertase 1/3 (PC1/3) endoplasmic reticulum-retained mutants induce endoplasmic reticulum stress.
25784503 we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
25355447 SNPs rs6232, rs6234, and rs6235 associated with obesity in Caucasians [review]
25272002 conclude that the N309K enzyme is able to cleave its own propeptide but is catalytically inert against in trans substrates, and that this variant accounts for the enteric and systemic endocrinopathies seen in the consanguineous kindred studied
25189249 FTO-rs9939609, TMEM18-rs6548238 and PCSK1-rs6234 polymorphisms are significantly associated with body mass index in a southern Chinese population.
25031086 rs6232 associated with body mass index
24964673 Thais carrying SNPs rs6234-5 are at increased risk of obesity, and the risk of severe obesity increases when carrying both rs6234-5 and rs3811951, but not with rs271939. Patients with genetic variations at rs3811951 are at risk of having low HDL-C levels.
24932808 PC1/3(S357G) exhibited a lower calcium dependence; a higher pH optimum.
24890885 We showed for the first time that a nonsense mutation in PCSK1 was likely to cause dominantly inherited human obesity, due to the inhibiting properties of the propeptide fragment encoded by the null allele
24618767 Epistases between single nucleotide polymorphisms within proprotein convertase subtilisin/kexin type 1(PCSK1) and dopamine beta-hydroxylase(DBH) genes are significantly associated with susceptibility or resistance to premature ovarian failure
24489861 Common genetic variants in PCSK1 are associated with coronary artery disease in Chinese patients with type 2 diabetes.
24443104 PCSK1 is overexpressed in fibrolamellar hepatocellular carcinoma.
24226266 The data of this study suggest that defects in the processing of hypothalamic neuropeptides in huntington disease may partially arise from decreased PC1/3 and PC2 expressions.
24140494 study indicates that the PCSK1 rs6235 SNP may contribute to the risk of overweight in men and predict obesity-related metabolic traits such as waist circumference and diastolic blood pressure in Taiwanese subjects
23800642 the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.
23451278 Common PCSK1 variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population.
23383060 novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population
23314902 PC1/3 overexpression induces morphological and phenotypic epithelial-mesenchymal transition changes of airway epithelial cells involved in the pathogenesis of nasal polyps
23121087 Data show the synthetic effect of SNPs on the indices of adiposity and risk of obesity in Chinese girls, but failed to replicate the effect of five separate variants of SEC16B rs10913469, SH2B1 rs4788102, PCSK1 rs6235, KCTD15 rs29941 and BAT2 rs2844479.
22737226 PCSK1 rs6232 is associated with childhood and adult class III obesity in the Mexican population
22592666 PCSK1 SNP rs6235 was associated with essential hypertension and blood pressure in the Han Chinese population
22552345 The potential variations in the exons and exon/intron junctions of caprine PC1 gene, were studied.
22210313 an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene.
22000902 triple-variant prohormone convertase 1 underwent significantly more proteolytic processing at the N- and C-termini than the double-variant isoforms
21935364 PCSK1 rs6232 G-allele and rs6235 C-allele have an effect on body composition which may be modified by sex
21720444 Our data suggest that SNPs in or near the PCSK1 locus contribute to obesity risk in the Greek population.
20734064 Observational study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20571754 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20534142 Observational study of gene-disease association. (HuGE Navigator)
20498726 The rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight in Chinese.
20498726 Observational study of gene-disease association. (HuGE Navigator)
20106974 Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection for proinsulin
19913121 Observational study of gene-disease association. (HuGE Navigator)
19876004 Observational study of gene-disease association. (HuGE Navigator)
19875984 common PCSK1 genetic variants are associated with obesity in the Chinese population
19875984 Observational study of gene-disease association. (HuGE Navigator)
19641380 Four genes, PCSK1, (P=0.008), EGFR,(P=0.003), PAX4,(P=0.008), and LYN,(P=0.002) consistently yielded statistical evidence for association with longevity.
19628676 The presence of PC and GOAT in the cells, as well as n-octanoic acid in the culture medium, was necessary to produce n-octanoyl ghrelin.
19528091 PCSK1 rs6232 and rs6235 SNPs are not major contributors to common obesity in the general population; however, the effect of rs6232 may be age-dependent.
19528091 Observational study of gene-disease association. (HuGE Navigator)
19339735 PC1 and PC2 were primarily expressed in neurons, whereas PACE4 appeared to be largely restricted to glia. Thus, elevated PACE4 may modulate the bioactivity of proteins secreted in the ONH and retina.
19164386 Observational study of gene-disease association. (HuGE Navigator)
19034419 Function for PAX6 in the regulation of proinsulin processing and glucose metabolism via modulation of PC1/3 production.
18604207 The nonsynonymous variants of PCSK1 rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children
18604207 Observational study of gene-disease association. (HuGE Navigator)
18549351 Suppression of Pdcd4 resulted in an increased release of CgA and Sg II and was accompanied by an up-regulation of intracellular PC1.
18096669 PC1/3 governs the endocrine and PC2 the neuronal processing of proCCK, whereas PC5/6 contributes only to a modest endocrine synthesis of CCK-22.
17990211 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17917309 defective PC1/3 expression may lead to preferential production of unprocessed, biologically inactive ACTH variants in sient corticotroph adenoma.
17595246 A novel missense mutation Ser307Leu in PC 1/3 linked to hyperphagia and obesity.
16928730 Observational study of gene-disease association. (HuGE Navigator)
16644867 PC1 has a role in obesity, hyperphagia and increased metabolic efficiency
16293189 PC1 and PC2 in are abnormally expressed and processed in human colorectal liver metastases
15807527 results have implications for the mechanism of granule sorting of PC3 as well as for the topology of PC2 and carboxypeptidase E, which have been reported to span the lipid membrane by homologous charged sequences
15127203 Observational study of gene-disease association. (HuGE Navigator)
15126519 Observational study of gene-disease association. (HuGE Navigator)
14617756 Data suggest that proprotein convertase 1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine.
14614908 PC1 is present in the human cortex to fulfill its role in proteolytic processing of neuropeptide precursors; no significant change in PC1 levels is observed in Alzheimer patients.
14574455 Polymorphism associated with insulin resistance affects insulin snssitivity by interacting with PPARgamma2.
12715715 Observational study of gene-disease association. (HuGE Navigator)
12147787 Observational study of gene-disease association. (HuGE Navigator)
12147786 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
12126783 Observational study of gene-disease association. (HuGE Navigator)
11739459 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
11720250 prominently expressed in PTHrP-expressing human cancer cell lines originating from tumors of the breast, lung, prostate, as well as lymphoma
8995623 PC1, one of the subtilisin/kexin family convertases, cleaves HIV-1 gp160 into gp120 and gp41 at amino acids 511-512
8940009 PC1, one of the subtilisin/kexin family convertases, cleaves HIV-1 gp160 into gp120 and gp41 at amino acids 511-512
8163529 PC1, one of the subtilisin/kexin family convertases, cleaves HIV-1 gp160 into gp120 and gp41 at amino acids 511-512
7639757 PC1, one of the subtilisin/kexin family convertases, cleaves HIV-1 gp160 into gp120 and gp41 at amino acids 511-512

AA Sequence

MERRAWSLQCTAFVLFCAWCALNSAKAKRQFVNEWAAEIPGGPEAASAIAEELGYDLLGQIGSLENHYLF      1 - 70
KHKNHPRRSRRSAFHITKRLSDDDRVIWAEQQYEKERSKRSALRDSALNLFNDPMWNQQWYLQDTRMTAA     71 - 140
LPKLDLHVIPVWQKGITGKGVVITVLDDGLEWNHTDIYANYDPEASYDFNDNDHDPFPRYDPTNENKHGT    141 - 210
RCAGEIAMQANNHKCGVGVAYNSKVGGIRMLDGIVTDAIEASSIGFNPGHVDIYSASWGPNDDGKTVEGP    211 - 280
GRLAQKAFEYGVKQGRQGKGSIFVWASGNGGRQGDNCDCDGYTDSIYTISISSASQQGLSPWYAEKCSST    281 - 350
LATSYSSGDYTDQRITSADLHNDCTETHTGTSASAPLAAGIFALALEANPNLTWRDMQHLVVWTSEYDPL    351 - 420
ANNPGWKKNGAGLMVNSRFGFGLLNAKALVDLADPRTWRSVPEKKECVVKDNDFEPRALKANGEVIIEIP    421 - 490
TRACEGQENAIKSLEHVQFEATIEYSRRGDLHVTLTSAAGTSTVLLAERERDTSPNGFKNWDFMSVHTWG    491 - 560
ENPIGTWTLRITDMSGRIQNEGRIVNWKLILHGTSSQPEHMKQPRVYTSYNTVQNDRRGVEKMVDPGEEQ    561 - 630
PTQENPKENTLVSKSPSSSSVGGRRDELEEGAPSQAMLRLLQSAFSKNSPPKQSPKKSPSAKLNIPYENF    631 - 700
YEALEKLNKPSQLKDSEDSLYNDYVDVFYNTKPYKHRDDRLLQALVDILNEEN                     701 - 753
//

Text Mined References (101)

PMID Year Title
26345846 2015 Association between rs155971 in the PCSK1 gene and the lipid profile of obese Thai children: a family-based study.
26229104 2015 Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.
26207343 2015 Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.
25784503 2015 Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.
25355447 2014 The association of common variants in PCSK1 with obesity: a HuGE review and meta-analysis.
25272002 2014 A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1/3 and impairs its enzymatic activity.
25231870 2014 Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
25189249 2014 Polymorphisms in FTO, TMEM18 and PCSK1 are associated with BMI in southern Chinese population.
25031086 2015 Common variants in PCSK1 influence blood pressure and body mass index.
24964673 2014 Effects of PCSK1 genetic variants on obesity among Thai children and their family members: in relation to health risk, and biochemical and anthropometric parameters.
24932808 2014 Biochemical and cell biological properties of the human prohormone convertase 1/3 Ser357Gly mutation: a PC1/3 hypermorph.
24890885 2015 A nonsense loss-of-function mutation in PCSK1 contributes to dominantly inherited human obesity.
24861553 2014 Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
24618767 2014 Epistasis between polymorphisms in PCSK1 and DBH is associated with premature ovarian failure.
24489861 2014 Genetic variants in PCSK1 gene are associated with the risk of coronary artery disease in type 2 diabetes in a Chinese Han population: a case control study.
24443104 2014 Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals an endocrine signature.
24226266 2013 Decreased hypothalamic prohormone convertase expression in huntington disease patients.
24140494 2014 Association of the rs6235 variant in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene with obesity and related traits in a Taiwanese population.
23966867 2013 Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
23903356 2013 Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.
23800642 Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.
23775089 2013 The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions.
23451278 2013 Contribution of common PCSK1 genetic variants to obesity in 8,359 subjects from multi-ethnic American population.
23383060 2013 Functional consequences of a novel variant of PCSK1.
23314902 2013 Overexpressed proprotein convertase 1/3 induces an epithelial-mesenchymal transition in airway epithelium.
23234360 2013 LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins.
23121087 2013 Sex-dependent associations of genetic variants identified by GWAS with indices of adiposity and obesity risk in a Chinese children population.
22737226 2012 PCSK1 rs6232 is associated with childhood and adult class III obesity in the Mexican population.
22679642 2012 The biology and therapeutic targeting of the proprotein convertases.
22592666 2012 The obesity-related polymorphism PCSK1 rs6235 is associated with essential hypertension in the Han Chinese population.
22581228 2012 A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
22552345 2012 Haplotype combination of the caprine PC1 gene sequence variants and association with growth traits in Chinese Haimen breed.
22344219 2012 Meta-analysis identifies common variants associated with body mass index in east Asians.
22210313 2012 Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity.
22000902 2011 Effects of rs6234/rs6235 and rs6232/rs6234/rs6235 PCSK1 single-nucleotide polymorphism clusters on proprotein convertase 1/3 biosynthesis and activity.
21935364 2011 The effect of PCSK1 variants on waist, waist-hip ratio and glucose metabolism is modified by sex and glucose tolerance status.
21873549 2011 Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
21805237 2011 The proprotein convertases, 20 years later.
21805236 2011 The prohormone theory and the proprotein convertases: it is all about serendipity.
21720444 2012 Common variants in FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 show evidence of association with adult obesity in the Greek population.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20571754 2010 Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population.
20534142 2010 Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion.
20498726 2010 Association of PCSK1 rs6234 with obesity and related traits in a Chinese Han population.
20106974 2010 Solution structure of proinsulin: connecting domain flexibility and prohormone processing.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19876004 2010 Obesity-related polymorphisms and their associations with the ability to regulate fat oxidation in obese Europeans: the NUGENOB study.
19875984 2010 Common PCSK1 haplotypes are associated with obesity in the Chinese population.
19641380 2009 Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans.
19628676 2009 Production of n-octanoyl-modified ghrelin in cultured cells requires prohormone processing protease and ghrelin O-acyltransferase, as well as n-octanoic acid.
19528091 2009 Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study.
19339735 2009 Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head.
19164386 2009 Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden.
19034419 2009 Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3).
18604207 2008 Common nonsynonymous variants in PCSK1 confer risk of obesity.
18549351 2008 Knockdown of Pdcd4 results in induction of proprotein convertase 1/3 and potent secretion of chromogranin A and secretogranin II in a neuroendocrine cell line.
18343183 2008 The activation and physiological functions of the proprotein convertases.
18096669 2008 The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6.
17990211 2008 PC-1 genotype and IRS response to exercise training.
17917309 2007 Defective expression of prohormone convertase 1/3 in silent corticotroph adenoma.
17595246 2007 Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3.
16928730 2006 Identifying genetic susceptibilities to diabetes-related complications among individuals at low risk of complications: An application of tree-structured survival analysis.
16644867 2006 Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16293189 2005 Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases.
15807527 2005 Proprotein convertase PC3 is not a transmembrane protein.
15372022 2004 The DNA sequence and comparative analysis of human chromosome 5.
15127203 2004 Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. The Finnish Diabetes Prevention Study.
15126519 2004 The association of the K121Q polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14617756 2003 Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency.
14614908 2003 The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease.
14574455 2003 Evidence for genetic epistasis in human insulin resistance: the combined effect of PC-1 (K121Q) and PPARgamma2 (P12A) polymorphisms.
12715715 2002 [TNF-alpha PC-1 gene polymorphisms and pre-diabetes quantitative features in the Polish population].
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12147787 2002 PC-1 amino acid variant (K121Q) has no impact on progression of diabetic nephropathy in type 1 diabetic patients.
12147786 2002 The role of PC-1 and ACE genes in diabetic nephropathy in type 1 diabetic patients: evidence for a polygenic control of kidney disease progression.
12126783 ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients: a 10-year prospective study.
11739459 2001 The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance.
11720250 2001 Comparative tissue distribution of the processing enzymes "prohormone thiol protease," and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocrine tissues.
11435430 2001 Inhibitory specificity and potency of proSAAS-derived peptides toward proprotein convertase 1.
10771309 2000 Diminished prohormone convertase 3 expression (PC1/PC3) inhibits progastrin post-translational processing.
10530621 1999 Immunohistochemical expressions of prohormone convertase (PC)1/3 and PC2 in carcinoids of various organs.
10409610 1999 Proteolytic processing in the secretory pathway.
10391209 1999 Characterization of single-nucleotide polymorphisms in coding regions of human genes.
10087454 1999 Prohormone convertases 1 and 2 process ProPACAP and generate matured, bioactive PACAP38 and PACAP27 in transfected rat pituitary GH4C1 cells.
9521468 1998 Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy, and laser scanning microscopy.
9213372 1997 Immunohistochemical localization of the pro-peptide processing enzymes PC1/PC3 and PC2 in the human anal canal.
9207799 1997 Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene.
8916141 1996 Prohormone convertases (PC1/3 and PC2) in rat and human pancreas and islet cell tumors: subcellular immunohistochemical analysis.
8666140 1996 Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM.
8397508 1993 Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2.
7836407 1995 Differences in pH optima and calcium requirements for maturation of the prohormone convertases PC2 and PC3 indicates different intracellular locations for these events.
7797529 1995 Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct cAMP response elements.
4368999 1974 Peptide hormones.
3053705 1988 An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing.
1765368 1991 Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region).
1605851 1992 The cDNA sequence of the human pro-hormone and pro-protein convertase PC1.
1597471 1992 Proprotein conversion is determined by a multiplicity of factors including convertase processing, substrate specificity, and intracellular environment. Cell type-specific processing of human prorenin by the convertase PC1.
1547893 1992 Expression in human lung tumor cells of the proprotein processing enzyme PC1/PC3. Cloning and primary sequence of a 5 kb cDNA.