GenomeNet

Database: UniProt/SWISS-PROT
Entry: NEC1_HUMAN
LinkDB: NEC1_HUMAN
Original site: NEC1_HUMAN 
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   25-OCT-2017, entry version 174.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   enzyme 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
RT   molecular 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA   Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA   Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA   Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA   Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA   Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA   Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA   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
RT   1 gene. Hormonal regulation of transcription through distinct cAMP
RT   response 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
RT   structures 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.,
RA   Sanders L., Montague C.T., Hutton J.C., O'Rahilly S.;
RT   "Obesity and impaired prohormone processing associated with mutations
RT   in 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
RT   of human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [10]
RP   ERRATUM.
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/JCI200318784;
RA   Jackson R.S., Creemers J.W., Farooqi I.S., Raffin-Sanson M.-L.,
RA   Varro A., Dockray G.J., Holst J.J., Brubaker P.L., Corvol P.,
RA   Polonsky K.S., Ostrega D., Becker K.L., Bertagna X., Hutton J.C.,
RA   White A., Dattani M.T., Hussain K., Middleton S.J., Nicole T.M.,
RA   Milla P.J., Lindley K.J., O'Rahilly S.;
RT   "Small-intestinal dysfunction accompanies the complex endocrinopathy
RT   of 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
RP   DEFICIENCY 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.,
RA   Lank E., Keogh J., O'Rahilly S., Creemers J.W.M.;
RT   "Hyperphagia and early-onset obesity due to a novel homozygous
RT   missense 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
RP   POLYMORPHISM.
RX   PubMed=18604207; DOI=10.1038/ng.177;
RA   Benzinou M., Creemers J.W.M., Choquet H., Lobbens S., Dina C.,
RA   Durand E., Guerardel A., Boutin P., Jouret B., Heude B., Balkau B.,
RA   Tichet J., Marre M., Potoczna N., Horber F., Le Stunff C.,
RA   Czernichow S., Sandbaek A., Lauritzen T., Borch-Johnsen K.,
RA   Andersen G., Kiess W., Koerner A., Kovacs P., Jacobson P.,
RA   Carlsson L.M.S., Walley A.J., Joergensen T., Hansen T., Pedersen O.,
RA   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
CC       residues. Substrates include POMC, renin, enkephalin, dynorphin,
CC       somatostatin, insulin and AGRP. {ECO:0000250|UniProtKB:P63239}.
CC   -!- CATALYTIC ACTIVITY: Release of protein hormones, neuropeptides and
CC       renin from their precursors, generally by hydrolysis of -Lys-
CC       Arg-|- bonds.
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         Note=No experimental confirmation available.;
CC   -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}.
CC   -!- POLYMORPHISM: Genetic variations in PCSK1 define the body mass
CC       index quantitative trait locus 12 (BMIQ12) [MIM:612362]. Variance
CC       in body 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,
CC       hypoadrenalism, reactive hypoglycemia as well as marked small-
CC       intestinal absorptive dysfunction It is due to impaired processing
CC       of prohormones. {ECO:0000269|PubMed:14617756,
CC       ECO:0000269|PubMed:17595246, ECO:0000269|PubMed:9207799}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC       {ECO:0000305}.
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   UniGene; Hs.78977; -.
DR   ProteinModelPortal; P29120; -.
DR   SMR; P29120; -.
DR   BioGrid; 111151; 7.
DR   IntAct; P29120; 1.
DR   MINT; MINT-6630348; -.
DR   STRING; 9606.ENSP00000308024; -.
DR   BindingDB; P29120; -.
DR   ChEMBL; CHEMBL3182; -.
DR   DrugBank; DB00030; Insulin Human.
DR   DrugBank; DB00071; Insulin Pork.
DR   GuidetoPHARMACOLOGY; 2382; -.
DR   MEROPS; S08.072; -.
DR   iPTMnet; P29120; -.
DR   PhosphoSitePlus; P29120; -.
DR   UniCarbKB; P29120; -.
DR   BioMuta; PCSK1; -.
DR   DMDM; 116242674; -.
DR   EPD; P29120; -.
DR   PaxDb; P29120; -.
DR   PeptideAtlas; P29120; -.
DR   PRIDE; P29120; -.
DR   Ensembl; ENST00000311106; ENSP00000308024; ENSG00000175426. [P29120-1]
DR   Ensembl; ENST00000508626; ENSP00000421600; ENSG00000175426. [P29120-2]
DR   GeneID; 5122; -.
DR   KEGG; hsa:5122; -.
DR   UCSC; uc003kls.3; human. [P29120-1]
DR   CTD; 5122; -.
DR   DisGeNET; 5122; -.
DR   EuPathDB; HostDB:ENSG00000175426.10; -.
DR   GeneCards; PCSK1; -.
DR   HGNC; HGNC:8743; PCSK1.
DR   HPA; HPA048564; -.
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   eggNOG; KOG3525; Eukaryota.
DR   eggNOG; COG1404; LUCA.
DR   eggNOG; COG4935; LUCA.
DR   GeneTree; ENSGT00750000117358; -.
DR   HOGENOM; HOG000192536; -.
DR   HOVERGEN; HBG008705; -.
DR   InParanoid; P29120; -.
DR   KO; K01359; -.
DR   OMA; FEPRALK; -.
DR   OrthoDB; EOG091G05HI; -.
DR   PhylomeDB; P29120; -.
DR   TreeFam; TF314277; -.
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   ChiTaRS; PCSK1; human.
DR   GeneWiki; Proprotein_convertase_1; -.
DR   GenomeRNAi; 5122; -.
DR   PMAP-CutDB; P29120; -.
DR   PRO; PR:P29120; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   Bgee; ENSG00000175426; -.
DR   CleanEx; HS_PCSK1; -.
DR   ExpressionAtlas; P29120; baseline and differential.
DR   Genevisible; P29120; HS.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
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:0008152; P:metabolic process; TAS:ProtInc.
DR   GO; GO:0043043; P:peptide biosynthetic process; ISS:BHF-UCL.
DR   GO; GO:0016486; P:peptide hormone processing; TAS:Reactome.
DR   GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR   CDD; cd04059; Peptidases_S8_Protein_converta; 1.
DR   Gene3D; 2.60.120.260; -; 1.
DR   Gene3D; 3.40.50.200; -; 1.
DR   InterPro; IPR008979; Galactose-bd-like.
DR   InterPro; IPR034182; Kexin/furin.
DR   InterPro; IPR009020; Peptidase/Inhibitor_I9.
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; IPR002884; PrprotnconvertsP.
DR   InterPro; IPR032815; S8_pro-domain.
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; SSF49785; 1.
DR   SUPFAM; SSF52743; SSF52743; 1.
DR   SUPFAM; SSF54897; SSF54897; 1.
DR   PROSITE; PS51829; P_HOMO_B; 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   Complete proteome; Cytoplasmic vesicle; Disease mutation;
KW   Disulfide bond; Glycoprotein; Hydrolase; Obesity; Polymorphism;
KW   Protease; Reference proteome; Serine protease; Signal; Zymogen.
FT   SIGNAL        1     27       {ECO:0000255}.
FT   PROPEP       28    110       {ECO:0000255}.
FT                                /FTId=PRO_0000027057.
FT   CHAIN       111    753       Neuroendocrine convertase 1.
FT                                /FTId=PRO_0000027058.
FT   DOMAIN      162    451       Peptidase S8.
FT   DOMAIN      460    597       P/Homo B. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01173}.
FT   ACT_SITE    167    167       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    208    208       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    382    382       Charge relay system. {ECO:0000250}.
FT   CARBOHYD    173    173       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    401    401       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    632    632       O-linked (GalNAc...) threonine.
FT                                {ECO:0000269|PubMed:23234360}.
FT   DISULFID    225    374       {ECO:0000250}.
FT   DISULFID    317    347       {ECO:0000250}.
FT   DISULFID    467    494       {ECO:0000250}.
FT   VAR_SEQ       1     59       MERRAWSLQCTAFVLFCAWCALNSAKAKRQFVNEWAAEIPG
FT                                GPEAASAIAEELGYDLLG -> MGKGSISFLFFS (in
FT                                isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_046100.
FT   VARIANT      80     80       R -> Q (in dbSNP:rs1799904).
FT                                {ECO:0000269|PubMed:8666140}.
FT                                /FTId=VAR_013906.
FT   VARIANT     213    213       Missing (in PC1 deficiency).
FT                                {ECO:0000269|PubMed:14617756}.
FT                                /FTId=VAR_022777.
FT   VARIANT     221    221       N -> D (associated with susceptibility to
FT                                obesity; induces a 10.4% reduction of
FT                                activity (P = 0.03) when compared to the
FT                                wild-type enzyme; dbSNP:rs6232).
FT                                {ECO:0000269|PubMed:10391209,
FT                                ECO:0000269|PubMed:18604207}.
FT                                /FTId=VAR_013907.
FT   VARIANT     307    307       S -> L (in PC1 deficiency; in vitro the
FT                                mutation markedly impairs the catalytic
FT                                activity of the enzyme; however
FT                                intracellular trafficking of this mutant
FT                                enzyme appears normal; retains some
FT                                autocatalytic activity even though it is
FT                                completely inactive on other substrates;
FT                                dbSNP:rs137852824).
FT                                {ECO:0000269|PubMed:17595246}.
FT                                /FTId=VAR_055002.
FT   VARIANT     483    483       G -> R (in PC1 deficiency; prevents
FT                                processing of pro-PCSK1 and leads to its
FT                                retention in the endoplasmic reticulum;
FT                                dbSNP:rs137852821).
FT                                {ECO:0000269|PubMed:9207799}.
FT                                /FTId=VAR_022778.
FT   VARIANT     665    665       Q -> E (in dbSNP:rs6234).
FT                                {ECO:0000269|PubMed:10391209,
FT                                ECO:0000269|PubMed:17595246,
FT                                ECO:0000269|PubMed:8666140}.
FT                                /FTId=VAR_013908.
FT   VARIANT     690    690       S -> T (in dbSNP:rs6235).
FT                                {ECO:0000269|PubMed:10391209,
FT                                ECO:0000269|PubMed:17595246}.
FT                                /FTId=VAR_013909.
FT   CONFLICT    357    357       S -> G (in Ref. 1; CAA46031).
FT                                {ECO:0000305}.
FT   CONFLICT    370    371       LH -> VD (in Ref. 3; BAA11133).
FT                                {ECO:0000305}.
FT   CONFLICT    617    617       R -> G (in Ref. 4; BAH14073).
FT                                {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
//
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