ID   NEC1_HUMAN              Reviewed;         753 AA.
AC   P29120; B7Z8T7; E9PHA1; P78478; Q92532;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 2.
DT   24-JAN-2024, entry version 211.
DE   RecName: Full=Neuroendocrine convertase 1;
DE            Short=NEC 1;
DE            EC=3.4.21.93;
DE   AltName: Full=Prohormone convertase 1;
DE   AltName: Full=Proprotein convertase 1;
DE            Short=PC1;
DE   Flags: Precursor;
GN   Name=PCSK1; Synonyms=NEC1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=1547893; DOI=10.1016/0014-5793(92)80169-h;
RA   Creemers J.W.M., Roebroek A.J.M., van de Ven W.J.M.;
RT   "Expression in human lung tumor cells of the proprotein processing enzyme
RT   PC1/PC3. Cloning and primary sequence of a 5 kb cDNA.";
RL   FEBS Lett. 300:82-88(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=1605851; DOI=10.1089/dna.1992.11.283;
RA   Seidah N.G., Hamelin J., Gaspar A.M., Day R., Chretien M.;
RT   "The cDNA sequence of the human pro-hormone and pro-protein convertase
RT   PC1.";
RL   DNA Cell Biol. 11:283-289(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-80 AND GLU-665.
RX   PubMed=8666140; DOI=10.2337/diab.45.7.897;
RA   Ohagi S., Sakaguchi H., Sanke T., Tatsuta H., Hanabusa T., Nanjo K.;
RT   "Human prohormone convertase 3 gene: exon-intron organization and molecular
RT   scanning for mutations in Japanese subjects with NIDDM.";
RL   Diabetes 45:897-901(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Trachea;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-60.
RX   PubMed=7797529; DOI=10.1074/jbc.270.25.15391;
RA   Jansen E.;
RT   "Neuroendocrine-specific expression of the human prohormone convertase 1
RT   gene. Hormonal regulation of transcription through distinct cAMP response
RT   elements.";
RL   J. Biol. Chem. 270:15391-15397(1995).
RN   [7]
RP   GLYCOSYLATION AT THR-632, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=23234360; DOI=10.1021/pr300963h;
RA   Halim A., Ruetschi U., Larson G., Nilsson J.;
RT   "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT   of human cerebrospinal fluid glycoproteins.";
RL   J. Proteome Res. 12:573-584(2013).
RN   [8]
RP   VARIANT PC1 DEFICIENCY ARG-483.
RX   PubMed=9207799; DOI=10.1038/ng0797-303;
RA   Jackson R.S., Creemers J.W., Ohagi S., Raffin-Sanson M.-L., Sanders L.,
RA   Montague C.T., Hutton J.C., O'Rahilly S.;
RT   "Obesity and impaired prohormone processing associated with mutations in
RT   the human prohormone convertase 1 gene.";
RL   Nat. Genet. 16:303-306(1997).
RN   [9]
RP   VARIANTS ASP-221; GLU-665 AND THR-690.
RX   PubMed=10391209; DOI=10.1038/10290;
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RT   "Characterization of single-nucleotide polymorphisms in coding regions of
RT   human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [10]
RP   ERRATUM OF PUBMED:10391209.
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RL   Nat. Genet. 23:373-373(1999).
RN   [11]
RP   VARIANT PC1 DEFICIENCY ALA-213 DEL.
RX   PubMed=14617756; DOI=10.1172/jci18784;
RA   Jackson R.S., Creemers J.W., Farooqi I.S., Raffin-Sanson M.-L., Varro A.,
RA   Dockray G.J., Holst J.J., Brubaker P.L., Corvol P., Polonsky K.S.,
RA   Ostrega D., Becker K.L., Bertagna X., Hutton J.C., White A., Dattani M.T.,
RA   Hussain K., Middleton S.J., Nicole T.M., Milla P.J., Lindley K.J.,
RA   O'Rahilly S.;
RT   "Small-intestinal dysfunction accompanies the complex endocrinopathy of
RT   human proprotein convertase 1 deficiency.";
RL   J. Clin. Invest. 112:1550-1560(2003).
RN   [12]
RP   VARIANT PC1 DEFICIENCY LEU-307, CHARACTERIZATION OF VARIANT PC1 DEFICIENCY
RP   LEU-307, AND VARIANTS GLU-665 AND THR-690.
RX   PubMed=17595246; DOI=10.1210/jc.2007-0687;
RA   Farooqi I.S., Volders K., Stanhope R., Heuschkel R., White A., Lank E.,
RA   Keogh J., O'Rahilly S., Creemers J.W.M.;
RT   "Hyperphagia and early-onset obesity due to a novel homozygous missense
RT   mutation in prohormone convertase 1/3.";
RL   J. Clin. Endocrinol. Metab. 92:3369-3373(2007).
RN   [13]
RP   VARIANT ASP-221, CHARACTERIZATION OF VARIANT ASP-221, AND POLYMORPHISM.
RX   PubMed=18604207; DOI=10.1038/ng.177;
RA   Benzinou M., Creemers J.W.M., Choquet H., Lobbens S., Dina C., Durand E.,
RA   Guerardel A., Boutin P., Jouret B., Heude B., Balkau B., Tichet J.,
RA   Marre M., Potoczna N., Horber F., Le Stunff C., Czernichow S., Sandbaek A.,
RA   Lauritzen T., Borch-Johnsen K., Andersen G., Kiess W., Koerner A.,
RA   Kovacs P., Jacobson P., Carlsson L.M.S., Walley A.J., Joergensen T.,
RA   Hansen T., Pedersen O., Meyre D., Froguel P.;
RT   "Common nonsynonymous variants in PCSK1 confer risk of obesity.";
RL   Nat. Genet. 40:943-945(2008).
CC   -!- FUNCTION: Involved in the processing of hormone and other protein
CC       precursors at sites comprised of pairs of basic amino acid residues.
CC       Substrates include POMC, renin, enkephalin, dynorphin, somatostatin,
CC       insulin and AGRP. {ECO:0000250|UniProtKB:P63239}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of protein hormones, neuropeptides and renin from
CC         their precursors, generally by hydrolysis of -Lys-Arg-|- bonds.;
CC         EC=3.4.21.93;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle.
CC       Note=Localized in the secretion granules.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P29120-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P29120-2; Sequence=VSP_046100;
CC   -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}.
CC   -!- POLYMORPHISM: Genetic variations in PCSK1 define the body mass index
CC       quantitative trait locus 12 (BMIQ12) [MIM:612362]. Variance in body
CC       mass index is a susceptibility factor for obesity.
CC       {ECO:0000269|PubMed:18604207}.
CC   -!- DISEASE: Proprotein convertase 1 deficiency (PC1 deficiency)
CC       [MIM:600955]: Characterized by obesity, hypogonadism, hypoadrenalism,
CC       reactive hypoglycemia as well as marked small-intestinal absorptive
CC       dysfunction It is due to impaired processing of prohormones.
CC       {ECO:0000269|PubMed:14617756, ECO:0000269|PubMed:17595246,
CC       ECO:0000269|PubMed:9207799}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC       {ECO:0000305}.
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DR   EMBL; X64810; CAA46031.1; -; mRNA.
DR   EMBL; M90753; AAA59918.1; -; mRNA.
DR   EMBL; D73407; BAA11133.1; -; Genomic_DNA.
DR   EMBL; AK303888; BAH14073.1; -; mRNA.
DR   EMBL; AC008951; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC108107; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; U24128; AAA73788.1; -; Genomic_DNA.
DR   CCDS; CCDS4081.1; -. [P29120-1]
DR   CCDS; CCDS54881.1; -. [P29120-2]
DR   PIR; S21106; KXHUC1.
DR   RefSeq; NP_000430.3; NM_000439.4. [P29120-1]
DR   RefSeq; NP_001171346.1; NM_001177875.1. [P29120-2]
DR   AlphaFoldDB; P29120; -.
DR   SMR; P29120; -.
DR   BioGRID; 111151; 15.
DR   IntAct; P29120; 3.
DR   STRING; 9606.ENSP00000308024; -.
DR   BindingDB; P29120; -.
DR   ChEMBL; CHEMBL3182; -.
DR   DrugBank; DB00030; Insulin human.
DR   GuidetoPHARMACOLOGY; 2382; -.
DR   MEROPS; S08.072; -.
DR   GlyConnect; 673; 1 O-Linked glycan (1 site).
DR   GlyCosmos; P29120; 3 sites, 2 glycans.
DR   GlyGen; P29120; 6 sites, 3 O-linked glycans (4 sites).
DR   iPTMnet; P29120; -.
DR   PhosphoSitePlus; P29120; -.
DR   BioMuta; PCSK1; -.
DR   DMDM; 116242674; -.
DR   EPD; P29120; -.
DR   jPOST; P29120; -.
DR   MassIVE; P29120; -.
DR   PaxDb; 9606-ENSP00000308024; -.
DR   PeptideAtlas; P29120; -.
DR   ProteomicsDB; 20489; -.
DR   ProteomicsDB; 54519; -. [P29120-1]
DR   Antibodypedia; 13091; 190 antibodies from 31 providers.
DR   DNASU; 5122; -.
DR   Ensembl; ENST00000311106.8; ENSP00000308024.2; ENSG00000175426.11. [P29120-1]
DR   Ensembl; ENST00000508626.5; ENSP00000421600.1; ENSG00000175426.11. [P29120-2]
DR   GeneID; 5122; -.
DR   KEGG; hsa:5122; -.
DR   MANE-Select; ENST00000311106.8; ENSP00000308024.2; NM_000439.5; NP_000430.3.
DR   UCSC; uc003kls.3; human. [P29120-1]
DR   AGR; HGNC:8743; -.
DR   CTD; 5122; -.
DR   DisGeNET; 5122; -.
DR   GeneCards; PCSK1; -.
DR   HGNC; HGNC:8743; PCSK1.
DR   HPA; ENSG00000175426; Tissue enhanced (brain, pituitary gland).
DR   MalaCards; PCSK1; -.
DR   MIM; 162150; gene.
DR   MIM; 600955; phenotype.
DR   MIM; 612362; phenotype.
DR   neXtProt; NX_P29120; -.
DR   OpenTargets; ENSG00000175426; -.
DR   Orphanet; 71528; Obesity due to prohormone convertase I deficiency.
DR   PharmGKB; PA33089; -.
DR   VEuPathDB; HostDB:ENSG00000175426; -.
DR   eggNOG; KOG3525; Eukaryota.
DR   GeneTree; ENSGT00940000157385; -.
DR   HOGENOM; CLU_002976_4_1_1; -.
DR   InParanoid; P29120; -.
DR   OMA; VWQKGFT; -.
DR   OrthoDB; 5474719at2759; -.
DR   PhylomeDB; P29120; -.
DR   TreeFam; TF314277; -.
DR   BRENDA; 3.4.21.93; 2681.
DR   PathwayCommons; P29120; -.
DR   Reactome; R-HSA-209952; Peptide hormone biosynthesis.
DR   Reactome; R-HSA-264876; Insulin processing.
DR   Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR   Reactome; R-HSA-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
DR   Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR   SignaLink; P29120; -.
DR   SIGNOR; P29120; -.
DR   BioGRID-ORCS; 5122; 7 hits in 1147 CRISPR screens.
DR   ChiTaRS; PCSK1; human.
DR   GeneWiki; Proprotein_convertase_1; -.
DR   GenomeRNAi; 5122; -.
DR   Pharos; P29120; Tchem.
DR   PRO; PR:P29120; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P29120; Protein.
DR   Bgee; ENSG00000175426; Expressed in type B pancreatic cell and 133 other cell types or tissues.
DR   ExpressionAtlas; P29120; baseline and differential.
DR   GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR   GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
DR   GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISS:BHF-UCL.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0030070; P:insulin processing; IEA:Ensembl.
DR   GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR   GO; GO:0031016; P:pancreas development; IEA:Ensembl.
DR   GO; GO:0043043; P:peptide biosynthetic process; ISS:BHF-UCL.
DR   GO; GO:0016486; P:peptide hormone processing; IBA:GO_Central.
DR   GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR   GO; GO:0050714; P:positive regulation of protein secretion; IEA:Ensembl.
DR   GO; GO:0016540; P:protein autoprocessing; IEA:Ensembl.
DR   GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR   GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR   GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR   GO; GO:0010157; P:response to chlorate; IEA:Ensembl.
DR   GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR   GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR   GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR   GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR   GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR   Gene3D; 6.10.250.3320; -; 1.
DR   Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR   Gene3D; 3.30.70.850; Peptidase S8, pro-domain; 1.
DR   Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1.
DR   InterPro; IPR008979; Galactose-bd-like_sf.
DR   InterPro; IPR034182; Kexin/furin.
DR   InterPro; IPR002884; P_dom.
DR   InterPro; IPR000209; Peptidase_S8/S53_dom.
DR   InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR   InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR   InterPro; IPR022398; Peptidase_S8_His-AS.
DR   InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR   InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR   InterPro; IPR022005; Proho_convert.
DR   InterPro; IPR032815; S8_pro-domain.
DR   InterPro; IPR038466; S8_pro-domain_sf.
DR   PANTHER; PTHR42884:SF14; NEUROENDOCRINE CONVERTASE 1; 1.
DR   PANTHER; PTHR42884; PROPROTEIN CONVERTASE SUBTILISIN/KEXIN-RELATED; 1.
DR   Pfam; PF01483; P_proprotein; 1.
DR   Pfam; PF00082; Peptidase_S8; 1.
DR   Pfam; PF12177; Proho_convert; 1.
DR   Pfam; PF16470; S8_pro-domain; 1.
DR   PRINTS; PR00723; SUBTILISIN.
DR   SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR   SUPFAM; SSF54897; Protease propeptides/inhibitors; 1.
DR   SUPFAM; SSF52743; Subtilisin-like; 1.
DR   PROSITE; PS51829; P_HOMO_B; 1.
DR   PROSITE; PS51892; SUBTILASE; 1.
DR   PROSITE; PS00136; SUBTILASE_ASP; 1.
DR   PROSITE; PS00137; SUBTILASE_HIS; 1.
DR   PROSITE; PS00138; SUBTILASE_SER; 1.
DR   Genevisible; P29120; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Cleavage on pair of basic residues;
KW   Cytoplasmic vesicle; Disease variant; Disulfide bond; Glycoprotein;
KW   Hydrolase; Obesity; Protease; Reference proteome; Serine protease; Signal;
KW   Zymogen.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   PROPEP          28..110
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000027057"
FT   CHAIN           111..753
FT                   /note="Neuroendocrine convertase 1"
FT                   /id="PRO_0000027058"
FT   DOMAIN          129..450
FT                   /note="Peptidase S8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   DOMAIN          460..597
FT                   /note="P/Homo B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT   REGION          596..662
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        596..616
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        618..632
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        633..652
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        167
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   ACT_SITE        208
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   ACT_SITE        382
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   CARBOHYD        173
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        632
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:23234360"
FT   DISULFID        225..374
FT                   /evidence="ECO:0000250"
FT   DISULFID        317..347
FT                   /evidence="ECO:0000250"
FT   DISULFID        467..494
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..59
FT                   /note="MERRAWSLQCTAFVLFCAWCALNSAKAKRQFVNEWAAEIPGGPEAASAIAEE
FT                   LGYDLLG -> MGKGSISFLFFS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_046100"
FT   VARIANT         80
FT                   /note="R -> Q (in dbSNP:rs1799904)"
FT                   /evidence="ECO:0000269|PubMed:8666140"
FT                   /id="VAR_013906"
FT   VARIANT         213
FT                   /note="Missing (in PC1 deficiency; dbSNP:rs137852823)"
FT                   /evidence="ECO:0000269|PubMed:14617756"
FT                   /id="VAR_022777"
FT   VARIANT         221
FT                   /note="N -> D (risk factor for obesity; induces a 10.4%
FT                   reduction of activity (P = 0.03) when compared to the
FT                   wild-type enzyme; dbSNP:rs6232)"
FT                   /evidence="ECO:0000269|PubMed:10391209,
FT                   ECO:0000269|PubMed:18604207"
FT                   /id="VAR_013907"
FT   VARIANT         307
FT                   /note="S -> L (in PC1 deficiency; in vitro the mutation
FT                   markedly impairs the catalytic activity of the enzyme;
FT                   however intracellular trafficking of this mutant enzyme
FT                   appears normal; retains some autocatalytic activity even
FT                   though it is completely inactive on other substrates;
FT                   dbSNP:rs137852824)"
FT                   /evidence="ECO:0000269|PubMed:17595246"
FT                   /id="VAR_055002"
FT   VARIANT         483
FT                   /note="G -> R (in PC1 deficiency; prevents processing of
FT                   pro-PCSK1 and leads to its retention in the endoplasmic
FT                   reticulum; dbSNP:rs137852821)"
FT                   /evidence="ECO:0000269|PubMed:9207799"
FT                   /id="VAR_022778"
FT   VARIANT         665
FT                   /note="Q -> E (in dbSNP:rs6234)"
FT                   /evidence="ECO:0000269|PubMed:10391209,
FT                   ECO:0000269|PubMed:17595246, ECO:0000269|PubMed:8666140"
FT                   /id="VAR_013908"
FT   VARIANT         690
FT                   /note="S -> T (in dbSNP:rs6235)"
FT                   /evidence="ECO:0000269|PubMed:10391209,
FT                   ECO:0000269|PubMed:17595246"
FT                   /id="VAR_013909"
FT   CONFLICT        357
FT                   /note="S -> G (in Ref. 1; CAA46031)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        370..371
FT                   /note="LH -> VD (in Ref. 3; BAA11133)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        617
FT                   /note="R -> G (in Ref. 4; BAH14073)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   753 AA;  84152 MW;  D3CBD1B92093A208 CRC64;
     MERRAWSLQC TAFVLFCAWC ALNSAKAKRQ FVNEWAAEIP GGPEAASAIA EELGYDLLGQ
     IGSLENHYLF KHKNHPRRSR RSAFHITKRL SDDDRVIWAE QQYEKERSKR SALRDSALNL
     FNDPMWNQQW YLQDTRMTAA LPKLDLHVIP VWQKGITGKG VVITVLDDGL EWNHTDIYAN
     YDPEASYDFN DNDHDPFPRY DPTNENKHGT RCAGEIAMQA NNHKCGVGVA YNSKVGGIRM
     LDGIVTDAIE ASSIGFNPGH VDIYSASWGP NDDGKTVEGP GRLAQKAFEY GVKQGRQGKG
     SIFVWASGNG GRQGDNCDCD GYTDSIYTIS ISSASQQGLS PWYAEKCSST LATSYSSGDY
     TDQRITSADL HNDCTETHTG TSASAPLAAG IFALALEANP NLTWRDMQHL VVWTSEYDPL
     ANNPGWKKNG AGLMVNSRFG FGLLNAKALV DLADPRTWRS VPEKKECVVK DNDFEPRALK
     ANGEVIIEIP TRACEGQENA IKSLEHVQFE ATIEYSRRGD LHVTLTSAAG TSTVLLAERE
     RDTSPNGFKN WDFMSVHTWG ENPIGTWTLR ITDMSGRIQN EGRIVNWKLI LHGTSSQPEH
     MKQPRVYTSY NTVQNDRRGV EKMVDPGEEQ PTQENPKENT LVSKSPSSSS VGGRRDELEE
     GAPSQAMLRL LQSAFSKNSP PKQSPKKSPS AKLNIPYENF YEALEKLNKP SQLKDSEDSL
     YNDYVDVFYN TKPYKHRDDR LLQALVDILN EEN
//