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PCSK1 (proprotein convertase subtilisin/kexin type 1)

Written2017-09Béatrice Demoures, Géraldine Siegfried and Abdel-Majid Khatib
INSERM U1029, Université Bordeaux,Pessac, France

Abstract PCSK1 is a serine protease involved in the proteolytic processing of a variety of protein precursors mainly neuropeptides and prohormones. In 1991, PC1/3; also known as PCSK1, PC1, PC3, and SPC3 was identified at the same time by two laboratories separately. The human and mouse PCSK1 genes are localized on chromosomes 5 and 13, respectively. The cleavage of these protein precursors is required for the mediation of their functions including the regulation of glucose homeostasis and food intake. The PCSK1 substrates that regulate these functions include proinsulin, proglucagon, proghrelin and proopiomelanocortin and others. PCSK1 polymorphisms were associated with risk of obesity and with various endocrine disorders. PCSK1 is also involved in the regulation of macrophage activation and cytokine secretion. The inhibition of PCSK1 activity was proposed to reverse the macrophage phenotype from an M2-like to an M1-like phenotype. PCSK1 is highly expressed in breast cancers and in neuroendocrine tumors including carcinoid tumors. The expression of this protease at the RNA and protein levels is also increased in liver colorectal metastasis, suggesting PCSK1 activity in tumorigenesis, however the evidence of PCSK1 roles in these cancers and probably others remain to be defined.

Keywords PCSK1, PC1, endocrine disorders, cancer, chromosome 5.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesNEC1
Alias_symbol (synonym)PC1
PC3
SPC3
Other alias
HGNC (Hugo) PCSK1
LocusID (NCBI) 5122
Atlas_Id 41671
Location 5q15  [Link to chromosome band 5q15]
Location_base_pair Starts at 96390336 and ends at 96433281 bp from pter ( according to hg19-Feb_2009)  [Mapping PCSK1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

 
  Figure 1: Genomic organization of PCSK1.
Description The PCSK1 gene is located on chromosome 5q15-21 in humans, and chromosome 13c in the mouse (Seidah NG et al. 1991a, Seidah NG et al. 1991b). The promoter of this gene contains cAMP-response elements (CRE-1 and CRE-2). Transcription factors such as cAMP-responsive element-binding protein 1 ( CREB1) and Activating Transcription Factor 1 ( ATF1) that can transactivate the PCSK1 promoter (Jansen E et al, 1997, Espinosa VP et al, 2008).
Transcription The DNA sequence of PCSK1contains 14 exons and the transcript length of 5068 bps is translated to a 753 residues protein. 4 spliced variants of PCSK1 are identified (splice variants) that code for 3 protein isoforms of 753 aa, 706 aa and 157 aa in length, respectively (M_000439, NM_001177875).

Protein

 
  Figure 2: Diagram representing the protein structure of PCSK1. PCSK1 is a multi-domain serine proteinase consisting of a signal peptide followed by prosegment, catalytic, middle, and cytoplasmic domain. The P domain just after the catalytic domain is required for the stabilization of the catalytic domain. The C-terminal domain is involved in the routing of PC1/3 to the secretory granules. 
Description PCSK1 is the third member of the proprotein convertase Subtilisin/Kexin-like family that was cloned from mammalian organisms, after furin and PC2 (Seidah NG et al. 1991, Smeekens SP et al, 1991, reviewed in Scamuffa N et al, 2006). The domain structure of PCSK1 precursor consists of four domains that include a prodomain (or prosegment), a catalytic domain, a P domain, and a carboxy-terminal domain (Figure 2). The propeptide domain is essential for the appropriate protein folding and exit from the endoplasmic reticulum (ER) of PCSK1 (Creemers JW1 et al, 1995). The catalytic domain is highly conserved among various species. Similar to the other members of the subtilisin superfamily the amino acids Asp, His, and Ser form the catalytic triad. The P domain presents a key role in the regulation of the PCSK1 activity through calcium and pH modulation (Zhou A1 et al, 1998). The carboxy-terminal domain is mainly involved in PCSK1 sorting into secretory granules (Dikeakos JD et al. 2009).
After the production of PCSK1 preproform in the endoplasmic reticulum and removal of its signal peptide, the 94kDa precursor of PCSK1 activation occurs after both N-and C-terminal domains cleavages. The 94kDa precursor undergoes an initial autocatalytic processing of its prosegment (prodomain). After protein scaffold and N-glycosylation, proPCSK1 exits the ER and sorts to the trans-Golgi network. In the early compartment, proPCSK1 is sulfated on its sugar residues. Lately during progression to the mildly acidic environment, an autocatalytic cleavage occurs to remove the prodomain and generates a 87kDa active PCSK1 form (reviewed in Ramos-Molina B et al , 2016 and Stijnen P et al 2016). The cleavage of proPCSK1 that generates the 87 kDa PCSK1 is calcium-independent and occurs at a neutral pH. PCSK1 is sorted after to immature secretory granules where is activated by a cleavages at the C-terminal area and generates the 74 and 66kDa active forms. The active forms are than accumulated in dense-core secretory granules prior secretion.
Expression PCSK1 is expressed in the neuroendocrine system such as brain, adrenal glands and in endocrine cells of the small intestine (reviewed in Ramos-Molina B et al , 2016 and Stijnen P et al 2016). Weak expression of PCSK1 is detected in adipocytes, α-cells of the pancreatic islets and certain types of immune cells. In brain, PC1 is mainly expressed in the hypothalamus (Dong W et al , 1997), but it is also found in cerebral cortex (Figure 3), hippocampus, and cerebellum (Billova S1, ET AL , 2007, Schäfer MK1, et al 1993). PC1/3 is also expressed in the adrenal medulla, pituitary, thyroid gland (Scopsi L et al. 1995, Day R ET AL 1992), endocrine pancreas (β-cells), liver and small intestine; including L and K cells (Tanaka S ET AL 1996). At low levels, PC1/3 was also detected in adipocytes (Min SYet al, 2016), in pancreatic islets (Itoh Y1, et al 1996), and in certain types of immune cells (LaMendolaet al 1997, Vindrola O et al 1994).
 
  Figure 3. Example of PCSK1 expression in the cerebral cortex and liver. Shown are overviews of stained tissues (circle) with high magnification of representative region (square). Adapted from Protein Atlas database.
Localisation In neuroendocrine cells, PCSK1 is mainly localized to the secretion granules and traffics within the regulated secretory pathway (Hornby PJ et al 1993, Malide D et al 1995). In macrophages PC1/3 is retained at the TGN as a pool that traffics to LAMP- related vesicles. PC1 vesicules are mostly detected during macrophages activation (Gagnon H et al, 2013)
Function PCSK1 cleaves protein precursors at the consensus motif (K/R)-Xn-(K/R)↓, with n=0, 2, 4 or 6, and X=any amino acids except Cys, to release mature proteins. PCSK1 favors cleavage after K/R motif, but is also able to cleave after other dibasic residues. PCSK1 often collaborates with PCSK2 to cleave substrates, such as neuropeptides and peptide hormones and its activity can be inhibited by the endogenous inhibitor proSAAS. PC1/3 gene disruption results in various developmental abnormalities' (reviewed in Ramos-Molina B et al , 2016 and Stijnen P et al 2016) and PC1/3 null mice exhibit growth retardation (reviewed in Scamuffa N et al, 2006). The adult mutant mice are 60% of the normal size and show similarities with mice having mutant growth hormone releasing hormone ( GHRH) receptor ( GHRHR). Further analysis indicated that insulin-like growth factor-1 ( IGF1) and GHRH levels were significantly decreased in these mice; that may explain the observed growth retardation. PCSK1 null mice process normally pituitary POMC to ACTH and have normal levels of blood corticosterone. Like PCSK2 null mice, PCSK1 null mice also develop hyperproinsulinemia. These mice maintain normal glucose (Glc) tolerance in response to injection of glucose, suggesting that their hyperproinsulinemia does not impair their glucose homeostasis. Previously, Jackson et al. (reviewed in Scamuffa N et al, 2006) reported a human case of PC1/3 deficiency. The latter is due to PCSK1 gene mutation that prevents activation and secretion of proPC1/3 from the endoplasmic reticulum. The patient showed neonatal obesity. Subsequent studies revealed the presence of various endocrine defects, including the presence of very high circulating levels of proinsulin and multiple forms of partially processed POMC [ACTH precursors intermediate], low-serum estradiol, follicle-stimulating hormone, and LH. In 2003, another PCSK1 deficiency female subject was reported. In addition to the shared phenotypes with the previous subject, this female infant presented severe diarrhea, which started on the third postnatal day. Metabolic studies revealed a defect in the absorption of monosaccharides and fat, revealing the role of PC1/3 in the small intestinal absorptive function. Although the phenotypes of the PCSK1 null mice differ from those observed in these patients (PCSK1 null mice are not obese), the findings confirmed the importance of PCSK1 as a key neuroendocrine convertase (reviewed in Ramos-Molina B et al , 2016 and Stijnen P et al 2016).
Homology An important paralog of this gene is PCSK2. Analysis of PCSK1 structure revealed that PCSK1 catalytic domain present a low percentage of homology with those of the other PCs (only 39% between PCSK1 and FURIN). The PCSK1 prodomain is formed by 83 residues and is highly conserved between orthologs (∼80% of sequence identity), although is not well conserved among paralogs of the convertase family (∼30-40%). The catalytic domain of PC1/3 is formed by 343 residues and is the most conserved region among proproteine convertases family members, with 50-60% sequence similarity. The P domain is a well-conserved region in PCs of approximately 150 residues and the Arg526-Arg-Gly-Asp529 (RRGD motif) is crucial for proper proPC1/3 processing and sorting to the secretory granules (reviewed in Ramos-Molina B et al , 2016 and Stijnen P et al 2016). The C-terminus of PCSK1 with 159 aa is involved in the sorting processes to the dense core secretory granules, as well as in PCSK1 activity and stability ((reviewed in Ramos-Molina B et al , 2016 and Stijnen P et al 2016).

Mutations

Germinal Various mutations were reported for human PCSK1 gene and were associated with various syndromes including obesity, malabsorptive diarrhea, hypogonadotropic hypogonadism, altered thyroid and adrenal function, and impaired regulation of plasma glucose levels (reviewed in Ramos-Molina B et al , 2016 and Stijnen P et al 2016).

Implicated in

  
Entity Breast cancer
Note PC1 is highly elevated in human breast carcinomas (Cheng et al.1997). Stable expression of PC1 in human breast cancer cells MCF-7 altered their growth rate and response to estrogen and anti-estrogen treatments (Cheng et al. 2001). The use of transgenic mouse model revealed that PCSK1 expression promote normal and neoplastic mammary development and growth (Blanchard A et al 2009).
  
  
Entity Colon cancer and colon cancer metastasis
Note PC1 expression and protein cleavage profiles are altered in colon cancer and liver colorectal metastasis, compared to unaffected and normal liver. Active PCSK1 protein is overexpressed in these tumors and was found to correlate with the mRNA profiles (Tzimas G, et al 2005)
  
  
Entity Neuroendocrine tumors
Note High expression of PCSK1 is reported for neural and/or endocrine phenotype (Takumi I et al 1998, Jin L et al, 1999, Kajiwara H et al. 1999). However the role and prognostic value of PCSK1 in endocrine-related cancers is still unclear.
  
  
Entity Endocrine disorders
Note PCSK1 deficiency is a very rare genetic disorder, few patient cases have been reported. In human, the lack of PCSK1 was reported to be associated with several cases of hypogonadotropic and/or hypogonadism (O'Rahilly et al, 1995). Several patients showed low serum estradiol, FSH, and LH (Jackson R et al 1997, Martèn MG et al 2013, Bandsma RH, et al 2013, Wilschanski ET AL 2014, Solorzano-Vargas RS et al 2013).
  

Bibliography

From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent clinical, pathologic, and enteroendocrine characteristics
Bandsma RH, Sokollik C, Chami R, Cutz E, Brubaker PL, Hamilton JK, Perlman K, Zlotkin S, Sigalet DL, Sherman PM, Martin MG, Avitzur Y
J Clin Gastroenterol 2013 Nov-Dec;47(10):834-43
PMID 24135795
 
Immunohistochemical expression and colocalization of somatostatin, carboxypeptidase-E and prohormone convertases 1 and 2 in rat brain
Billova S, Galanopoulou AS, Seidah NG, Qiu X, Kumar U
Neuroscience 2007 Jun 29;147(2):403-18
PMID 17543468
 
Targeted production of proprotein convertase PC1 enhances mammary development and tumorigenesis in transgenic mice
Blanchard A, Iwasiow B, Yarmill A, Fresnosa A, Silha J, Myal Y, Murphy LC, Chrétien M, Seidah N, Shiu RP
Can J Physiol Pharmacol 2009 Oct;87(10):831-8
PMID 20052009
 
Pro-protein convertase gene expression in human breast cancer
Cheng M, Watson PH, Paterson JA, Seidah N, Chrétien M, Shiu RP
Int J Cancer 1997 Jun 11;71(6):966-71
PMID 9185698
 
Elevated expression of proprotein convertases alters breast cancer cell growth in response to estrogen and tamoxifen
Cheng M, Xu N, Iwasiow B, Seidah N, Chrétien M, Shiu RP
J Mol Endocrinol 2001 Apr;26(2):95-105
PMID 11241161
 
Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum
Creemers JW, Vey M, Schäfer W, Ayoubi TA, Roebroek AJ, Klenk HD, Garten W, Van de Ven WJ
J Biol Chem 1995 Feb 10;270(6):2695-702
PMID 7852339
 
Distribution and regulation of the prohormone convertases PC1 and PC2 in the rat pituitary
Day R, Schafer MK, Watson SJ, Chrétien M, Seidah NG
Mol Endocrinol 1992 Mar;6(3):485-97
PMID 1316544
 
Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease
Dikeakos JD, Di Lello P, Lacombe MJ, Ghirlando R, Legault P, Reudelhuber TL, Omichinski JG
Proc Natl Acad Sci U S A 2009 May 5;106(18):7408-13
PMID 19376969
 
Cellular localization of the prohormone convertases in the hypothalamic paraventricular and supraoptic nuclei: selective regulation of PC1 in corticotrophin-releasing hormone parvocellular neurons mediated by glucocorticoids
Dong W, Seidel B, Marcinkiewicz M, Chrétien M, Seidah NG, Day R
J Neurosci 1997 Jan 15;17(2):563-75
PMID 8987779
 
Molecular Consequences of Proprotein Convertase 1/3 (PC1/3) Inhibition in Macrophages for Application to Cancer Immunotherapy: A Proteomic Study
Duhamel M, Rodet F, Delhem N, Vanden Abeele F, Kobeissy F, Nataf S, Pays L, Desjardins R, Gagnon H, Wisztorski M, Fournier I, Day R, Salzet M
Mol Cell Proteomics 2015 Nov;14(11):2857-77
PMID 26330543
 
Differential regulation of prohormone convertase 1/3, prohormone convertase 2 and phosphorylated cyclic-AMP-response element binding protein by short-term and long-term morphine treatment: implications for understanding the "switch" to opiate addiction
Espinosa VP, Liu Y, Ferrini M, Anghel A, Nie Y, Tripathi PV, Porche R, Jansen E, Stuart RC, Nillni EA, Lutfy K, Friedman TC
Neuroscience 2008 Oct 15;156(3):788-99
PMID 18771713
 
Proprotein convertase 1/3 (PC1/3) in the rat alveolar macrophage cell line NR8383: localization, trafficking and effects on cytokine secretion
Gagnon H, Refaie S, Gagnon S, Desjardins R, Salzet M, Day R
PLoS One 2013 Apr 24;8(4):e61557
PMID 23637853
 
Immunocytochemical localization of the neuropeptide-synthesizing enzyme PC1 in AtT-20 cells
Hornby PJ, Rosenthal SD, Mathis JP, Vindrola O, Lindberg I
Neuroendocrinology 1993 Nov;58(5):555-63
PMID 8115023
 
Prohormone convertases (PC1/3 and PC2) in rat and human pancreas and islet cell tumors: subcellular immunohistochemical analysis
Itoh Y, Tanaka S, Takekoshi S, Itoh J, Osamura RY
Pathol Int 1996 Oct;46(10):726-37
PMID 8916141
 
Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene
Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, Montague CT, Hutton JC, O'Rahilly S
Nat Genet 1997 Jul;16(3):303-6
PMID 9207799
 
Cell type-specific protein-DNA interactions at the cAMP response elements of the prohormone convertase 1 promoter
Jansen E, Ayoubi TA, Meulemans SM, Van de Ven WJ
Evidence for additional transactivators distinct from CREB/ATF family members J Biol Chem
PMID 8999965
 
Distribution and regulation of proconvertases PC1 and PC2 in human pituitary adenomas
Jin L, Kulig E, Qian X, Scheithauer BW, Young WF Jr, Davis DH, Seidah NG, Chretien M, Lloyd RV
Pituitary 1999 May;1(3-4):187-95
PMID 11081197
 
Immunohistochemical expressions of prohormone convertase (PC)1/3 and PC2 in carcinoids of various organs
Kajiwara H, Itoh Y, Itoh J, Yasuda M, Osamura RY
Tokai J Exp Clin Med 1999 Apr;24(1):13-20
PMID 10530621
 
Expression of PC3, carboxypeptidase E and enkephalin in human monocyte-derived macrophages as a tool for genetic studies
LaMendola J, Martin SK, Steiner DF
FEBS Lett 1997 Mar 3;404(1):19-22
PMID 9074629
 
Electron microscopic immunocytochemical evidence for the involvement of the convertases PC1 and PC2 in the processing of proinsulin in pancreatic beta-cells
Malide D, Seidah NG, Chrétien M, Bendayan M
J Histochem Cytochem 1995 Jan;43(1):11-9
PMID 7822759
 
Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort
Martín MG, Lindberg I, Solorzano-Vargas RS, Wang J, Avitzur Y, Bandsma R, Sokollik C, Lawrence S, Pickett LA, Chen Z, Egritas O, Dalgic B, Albornoz V, de Ridder L, Hulst J, Gok F, Aydoan A, Al-Hussaini A, Gok DE, Yourshaw M, Wu SV, Cortina G, Stanford S, Georgia S
Gastroenterology 2013 Jul;145(1):138-48
PMID 23562752
 
Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice
Min SY, Kady J, Nam M, Rojas-Rodriguez R, Berkenwald A, Kim JH, Noh HL, Kim JK, Cooper MP, Fitzgibbons T, Brehm MA, Corvera S
Nat Med 2016 Mar;22(3):312-8
PMID 26808348
 
Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function
O'Rahilly S, Gray H, Humphreys PJ, Krook A, Polonsky KS, White A, Gibson S, Taylor K, Carr C
N Engl J Med 1995 Nov 23;333(21):1386-90
PMID 7477119
 
PCSK1 Variants and Human Obesity
Ramos-Molina B, Martin MG, Lindberg I
Prog Mol Biol Transl Sci 2016;140:47-74
PMID 27288825
 
Proprotein convertases: lessons from knockouts
Scamuffa N, Calvo F, Chrétien M, Seidah NG, Khatib AM
FASEB J 2006 Oct;20(12):1954-63
PMID 17012247
 
Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis
Schäfer MK, Day R, Cullinan WE, Chrétien M, Seidah NG, Watson SJ
J Neurosci 1993 Mar;13(3):1258-79
 
Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues: their use as markers of neuroendocrine differentiation
Scopsi L, Gullo M, Rilke F, Martin S, Steiner DF
J Clin Endocrinol Metab 1995 Jan;80(1):294-301
PMID 7829629
 
Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11
Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, Chrétien M
1-11 2, and furin (mouse 7[D1-E2] region)
PMID 1765368
 
Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans
Smeekens SP, Avruch AS, LaMendola J, Chan SJ, Steiner DF
Proc Natl Acad Sci U S A 1991 Jan 15;88(2):340-4
PMID 1988934
 
PCSK1 Mutations and Human Endocrinopathies: From Obesity to Gastrointestinal Disorders
Stijnen P, Ramos-Molina B, O'Rahilly S, Creemers JW
Endocr Rev 2016 Aug;37(4):347-71
PMID 27187081
 
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
Takumi I, Steiner DF, Sanno N, Teramoto A, Osamura RY
Mod Pathol 1998 Mar;11(3):232-8
PMID 9521468
 
Immunocytochemical localization of prohormone convertases PC1/PC3 and PC2 in rat pancreatic islets
Tanaka S, Kurabuchi S, Mochida H, Kato T, Takahashi S, Watanabe T, Nakayama K
Arch Histol Cytol 1996 Aug;59(3):261-71
PMID 8874758
 
Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases
Tzimas GN, Chevet E, Jenna S, Nguyên DT, Khatib AM, Marcus V, Zhang Y, Chrétien M, Seidah N, Metrakos P
BMC Cancer 2005 Nov 17;5:149
PMID 16293189
 
Proteomics
Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist PH, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F
Tissue-based map of the human proteome Science
PMID 25613900
 
Prohormone convertases PC2 and PC3 in rat neutrophils and macrophages
Vindrola O, Mayer AM, Citera G, Spitzer JA, Espinoza LR
Parallel changes with proenkephalin-derived peptides induced by LPS in vivo Neuropeptides
PMID 7808596
 
A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1/3 and impairs its enzymatic activity
Wilschanski M, Abbasi M, Blanco E, Lindberg I, Yourshaw M, Zangen D, Berger I, Shteyer E, Pappo O, Bar-Oz B, Martín MG, Elpeleg O
PLoS One 2014 Oct 1;9(10):e108878
PMID 25272002
 
Exome sequencing finds a novel PCSK1 mutation in a child with generalized malabsorptive diarrhea and diabetes insipidus
Yourshaw M, Solorzano-Vargas RS, Pickett LA, Lindberg I, Wang J, Cortina G, Pawlikowska-Haddal A, Baron H, Venick RS, Nelson SF, Martín MG
J Pediatr Gastroenterol Nutr 2013 Dec;57(6):759-67
PMID 24280991
 
Differential processing of neuropeptide proprotein in human breast adenocarcinoma
Zhang JH, Zhou D, You J, Tang BS, Li PY, Tang SS
J Endocrinol Invest 2013 Oct;36(9):745-52
PMID 23580127
 
The prohormone convertases PC1 and PC2 mediate distinct endoproteolytic cleavages in a strict temporal order during proopiomelanocortin biosynthetic processing
Zhou A, Bloomquist BT, Mains RE
J Biol Chem 1993 Jan 25;268(3):1763-9
PMID 8380577
 
Regulatory roles of the P domain of the subtilisin-like prohormone convertases
Zhou A, Martin S, Lipkind G, LaMendola J, Steiner DF
J Biol Chem 1998 May 1;273(18):11107-14
PMID 9556596
 

Citation

This paper should be referenced as such :
Demoures B, Siegfried G, Khatib AM
PCSK1 (proprotein convertase subtilisin/kexin type 1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/PCSK1ID41671ch5q15.html


External links

Nomenclature
HGNC (Hugo)PCSK1   8743
Cards
AtlasPCSK1ID41671ch5q15.txt
Entrez_Gene (NCBI)PCSK1  5122  proprotein convertase subtilisin/kexin type 1
AliasesBMIQ12; NEC1; PC1; PC3; 
SPC3
GeneCards (Weizmann)PCSK1
Ensembl hg19 (Hinxton)ENSG00000175426 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000175426 [Gene_View]  chr5:96390336-96433281 [Contig_View]  PCSK1 [Vega]
ICGC DataPortalENSG00000175426
TCGA cBioPortalPCSK1
AceView (NCBI)PCSK1
Genatlas (Paris)PCSK1
WikiGenes5122
SOURCE (Princeton)PCSK1
Genetics Home Reference (NIH)PCSK1
Genomic and cartography
GoldenPath hg38 (UCSC)PCSK1  -     chr5:96390336-96433281 -  5q15   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PCSK1  -     5q15   [Description]    (hg19-Feb_2009)
EnsemblPCSK1 - 5q15 [CytoView hg19]  PCSK1 - 5q15 [CytoView hg38]
Mapping of homologs : NCBIPCSK1 [Mapview hg19]  PCSK1 [Mapview hg38]
OMIM162150   600955   612362   
Gene and transcription
Genbank (Entrez)AB208874 AK303888 AK308575 BC031211 BC130295
RefSeq transcript (Entrez)NM_000439 NM_001177875 NM_001177876
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PCSK1
Cluster EST : UnigeneHs.78977 [ NCBI ]
CGAP (NCI)Hs.78977
Alternative Splicing GalleryENSG00000175426
Gene ExpressionPCSK1 [ NCBI-GEO ]   PCSK1 [ EBI - ARRAY_EXPRESS ]   PCSK1 [ SEEK ]   PCSK1 [ MEM ]
Gene Expression Viewer (FireBrowse)PCSK1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5122
GTEX Portal (Tissue expression)PCSK1
Human Protein AtlasENSG00000175426-PCSK1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP29120   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP29120  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP29120
Splice isoforms : SwissVarP29120
Catalytic activity : Enzyme3.4.21.93 [ Enzyme-Expasy ]   3.4.21.933.4.21.93 [ IntEnz-EBI ]   3.4.21.93 [ BRENDA ]   3.4.21.93 [ KEGG ]   
PhosPhoSitePlusP29120
Domaine pattern : Prosite (Expaxy)P_HOMO_B (PS51829)    SUBTILASE_ASP (PS00136)    SUBTILASE_HIS (PS00137)    SUBTILASE_SER (PS00138)   
Domains : Interpro (EBI)Galactose-bd-like    Kexin/furin    Peptidase_S8/S53_dom    Peptidase_S8_Asp-AS    Peptidase_S8_His-AS    Peptidase_S8_Ser-AS    Peptidase_S8_subtilisin-rel    Proho_convert    Propept_inh    PrprotnconvertsP    S8_pro-domain   
Domain families : Pfam (Sanger)P_proprotein (PF01483)    Peptidase_S8 (PF00082)    Proho_convert (PF12177)    S8_pro-domain (PF16470)   
Domain families : Pfam (NCBI)pfam01483    pfam00082    pfam12177    pfam16470   
Conserved Domain (NCBI)PCSK1
DMDM Disease mutations5122
Blocks (Seattle)PCSK1
SuperfamilyP29120
Human Protein Atlas [tissue]ENSG00000175426-PCSK1 [tissue]
Peptide AtlasP29120
HPRD01201
IPIIPI00301961   IPI00966801   IPI00967321   IPI00964708   
Protein Interaction databases
DIP (DOE-UCLA)P29120
IntAct (EBI)P29120
FunCoupENSG00000175426
BioGRIDPCSK1
STRING (EMBL)PCSK1
ZODIACPCSK1
Ontologies - Pathways
QuickGOP29120
Ontology : AmiGOserine-type endopeptidase activity  serine-type endopeptidase activity  extracellular space  proteolysis  cell-cell signaling  metabolic process  peptide hormone processing  transport vesicle  secretory granule lumen  peptide biosynthetic process  
Ontology : EGO-EBIserine-type endopeptidase activity  serine-type endopeptidase activity  extracellular space  proteolysis  cell-cell signaling  metabolic process  peptide hormone processing  transport vesicle  secretory granule lumen  peptide biosynthetic process  
REACTOMEP29120 [protein]
REACTOME PathwaysR-HSA-422085 [pathway]   
NDEx NetworkPCSK1
Atlas of Cancer Signalling NetworkPCSK1
Wikipedia pathwaysPCSK1
Orthology - Evolution
OrthoDB5122
GeneTree (enSembl)ENSG00000175426
Phylogenetic Trees/Animal Genes : TreeFamPCSK1
HOVERGENP29120
HOGENOMP29120
Homologs : HomoloGenePCSK1
Homology/Alignments : Family Browser (UCSC)PCSK1
Gene fusions - Rearrangements
Tumor Fusion PortalPCSK1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPCSK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PCSK1
dbVarPCSK1
ClinVarPCSK1
1000_GenomesPCSK1 
Exome Variant ServerPCSK1
ExAC (Exome Aggregation Consortium)ENSG00000175426
GNOMAD BrowserENSG00000175426
Genetic variants : HAPMAP5122
Genomic Variants (DGV)PCSK1 [DGVbeta]
DECIPHERPCSK1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPCSK1 
Mutations
ICGC Data PortalPCSK1 
TCGA Data PortalPCSK1 
Broad Tumor PortalPCSK1
OASIS PortalPCSK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPCSK1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPCSK1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PCSK1
DgiDB (Drug Gene Interaction Database)PCSK1
DoCM (Curated mutations)PCSK1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PCSK1 (select a term)
intoGenPCSK1
NCG5 (London)PCSK1
Cancer3DPCSK1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM162150    600955    612362   
Orphanet11021   
DisGeNETPCSK1
MedgenPCSK1
Genetic Testing Registry PCSK1
NextProtP29120 [Medical]
TSGene5122
GENETestsPCSK1
Target ValidationPCSK1
Huge Navigator PCSK1 [HugePedia]
snp3D : Map Gene to Disease5122
BioCentury BCIQPCSK1
ClinGenPCSK1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5122
Chemical/Pharm GKB GenePA33089
Clinical trialPCSK1
Miscellaneous
canSAR (ICR)PCSK1 (select the gene name)
Probes
Litterature
PubMed110 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePCSK1
EVEXPCSK1
GoPubMedPCSK1
iHOPPCSK1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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