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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 Genevisible; P29120; HS.
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.
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 wild-
FT 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
//
