PCSK9_MOUSE
ID PCSK9_MOUSE Reviewed; 694 AA.
AC Q80W65; B1AZI4; Q3UEH7; Q8BXW9; Q8CFT6;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Proprotein convertase subtilisin/kexin type 9;
DE EC=3.4.21.-;
DE AltName: Full=Neural apoptosis-regulated convertase 1;
DE Short=NARC-1;
DE AltName: Full=Proprotein convertase 9;
DE Short=PC9;
DE AltName: Full=Subtilisin/kexin-like protease PC9;
DE Flags: Precursor;
GN Name=Pcsk9; Synonyms=Narc1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RA Chiang L.W.;
RT "Narc-1, novel subtilase-like homologs.";
RL Patent number WO0157081, 09-AUG-2001.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=12897189; DOI=10.1194/jlr.m300203-jlr200;
RA Maxwell K.N., Soccio R.E., Duncan E.M., Sehayek E., Breslow J.L.;
RT "Novel putative SREBP and LXR target genes identified by microarray
RT analysis in liver of cholesterol-fed mice.";
RL J. Lipid Res. 44:2109-2119(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION OF PROPEPTIDE CLEAVAGE SITE, AND CHARACTERIZATION.
RX PubMed=12552133; DOI=10.1073/pnas.0335507100;
RA Seidah N.G., Benjannet S., Wickham L., Marcinkiewicz J., Jasmin S.B.,
RA Stifani S., Basak A., Prat A., Chretien M.;
RT "The secretory proprotein convertase neural apoptosis-regulated convertase
RT 1 (NARC-1): liver regeneration and neuronal differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:928-933(2003).
RN [7]
RP AUTOCATALYTIC CLEAVAGE SITE.
RX PubMed=14622975; DOI=10.1016/j.abb.2003.09.011;
RA Naureckiene S., Ma L., Sreekumar K., Purandare U., Lo C.F., Huang Y.,
RA Chiang L.W., Grenier J.M., Ozenberger B.A., Jacobsen J.S., Kennedy J.D.,
RA DiStefano P.S., Wood A., Bingham B.;
RT "Functional characterization of Narc 1, a novel proteinase related to
RT proteinase K.";
RL Arch. Biochem. Biophys. 420:55-67(2003).
RN [8]
RP PHOSPHORYLATION AT SER-50, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18498363; DOI=10.1111/j.1742-4658.2008.06495.x;
RA Dewpura T., Raymond A., Hamelin J., Seidah N.G., Mbikay M., Chretien M.,
RA Mayne J.;
RT "PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and
RT circulates as a phosphoprotein in humans.";
RL FEBS J. 275:3480-3493(2008).
RN [9]
RP FUNCTION.
RX PubMed=22580899; DOI=10.1161/atvbaha.112.250043;
RA Sun H., Samarghandi A., Zhang N., Yao Z., Xiong M., Teng B.B.;
RT "Proprotein convertase subtilisin/kexin type 9 interacts with
RT apolipoprotein B and prevents its intracellular degradation, irrespective
RT of the low-density lipoprotein receptor.";
RL Arterioscler. Thromb. Vasc. Biol. 32:1585-1595(2012).
RN [10]
RP FUNCTION.
RX PubMed=22481440; DOI=10.1007/s00018-012-0977-6;
RA Kysenius K., Muggalla P., Maetlik K., Arumaee U., Huttunen H.J.;
RT "PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and
RT signaling.";
RL Cell. Mol. Life Sci. 69:1903-1916(2012).
CC -!- FUNCTION: Crucial player in the regulation of plasma cholesterol
CC homeostasis. Binds to low-density lipid receptor family members: low
CC density lipoprotein receptor (LDLR), very low density lipoprotein
CC receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and
CC apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation
CC in intracellular acidic compartments. Acts via a non-proteolytic
CC mechanism to enhance the degradation of the hepatic LDLR through a
CC clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of
CC LDLR from endosomes to the cell surface or direct it to lysosomes for
CC degradation. Can induce ubiquitination of LDLR leading to its
CC subsequent degradation. Inhibits intracellular degradation of APOB via
CC the autophagosome/lysosome pathway in a LDLR-independent manner.
CC Involved in the disposal of non-acetylated intermediates of BACE1 in
CC the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-
CC mediated Na(+) absorption by reducing ENaC surface expression primarily
CC by increasing its proteasomal degradation. Regulates neuronal apoptosis
CC via modulation of LRP8/APOER2 levels and related anti-apoptotic
CC signaling pathways. {ECO:0000269|PubMed:22481440,
CC ECO:0000269|PubMed:22580899}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000305};
CC -!- ACTIVITY REGULATION: Its proteolytic activity is autoinhibited by the
CC non-covalent binding of the propeptide to the catalytic domain.
CC Inhibited by EGTA.
CC -!- SUBUNIT: Monomer. Can self-associate to form dimers and higher
CC multimers which may have increased LDLR degrading activity. The
CC precursor protein but not the mature protein may form multimers.
CC Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full-length
CC immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The
CC pro-PCSK9 form (via C-terminal domain) interacts with LDLR. Interacts
CC (via the C-terminal domain) with ANXA2 (via repeat Annexin 1); the
CC interaction inhibits the degradation of LDLR.
CC {ECO:0000250|UniProtKB:Q8NBP7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Secreted. Endosome
CC {ECO:0000250}. Lysosome {ECO:0000250}. Cell surface {ECO:0000250}.
CC Endoplasmic reticulum {ECO:0000250}. Golgi apparatus {ECO:0000250}.
CC Note=Autocatalytic cleavage is required to transport it from the
CC endoplasmic reticulum to the Golgi apparatus and for the secretion of
CC the mature protein. Localizes to the endoplasmic reticulum in the
CC absence of LDLR and co-localizes to the cell surface and to the
CC endosomes/lysosomes in the presence of LDLR. The sorting to the cell
CC surface and endosomes is required in order to fully promote LDLR
CC degradation (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Hepatocytes, kidney mesenchymal cells, intestinal
CC ileum, colon epithelia and embryonic brain telencephalon neurons.
CC -!- DEVELOPMENTAL STAGE: In the embryo, expressed in the liver at 9 dpc, in
CC the skin and transiently in the telencephalon at 12 dpc, and in the
CC kidney, small intestine and cerebellum at 15 dpc.
CC -!- INDUCTION: Down-regulated following a high-cholesterol diet.
CC {ECO:0000269|PubMed:12897189}.
CC -!- DOMAIN: The C-terminal domain (CRD) is essential for the LDLR-binding
CC and degrading activities. {ECO:0000250}.
CC -!- DOMAIN: The catalytic domain is responsible for mediating its self-
CC association. {ECO:0000250}.
CC -!- PTM: Cleavage by furin and PCSK5 generates a truncated inactive protein
CC that is unable to induce LDLR degradation. {ECO:0000250}.
CC -!- PTM: Undergoes autocatalytic cleavage in the endoplasmic reticulum to
CC release the propeptide from the N-terminus and the cleavage of the
CC propeptide is strictly required for its maturation and activation. The
CC cleaved propeptide however remains associated with the catalytic domain
CC through non-covalent interactions, preventing potential substrates from
CC accessing its active site. As a result, it is secreted from cells as a
CC propeptide-containing, enzymatically inactive protein (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation protects the propeptide against proteolysis.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP31672.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE28934.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC60362.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AX207688; CAC60362.1; ALT_INIT; Unassigned_DNA.
DR EMBL; AY273821; AAP31672.1; ALT_INIT; mRNA.
DR EMBL; AK149520; BAE28934.1; ALT_INIT; mRNA.
DR EMBL; AL954352; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038085; AAH38085.1; -; mRNA.
DR CCDS; CCDS18418.1; -.
DR RefSeq; NP_705793.1; NM_153565.2.
DR AlphaFoldDB; Q80W65; -.
DR SMR; Q80W65; -.
DR ComplexPortal; CPX-129; LDLR-PCSK9 complex.
DR ComplexPortal; CPX-141; ANXA2-PCSK9 complex.
DR IntAct; Q80W65; 1.
DR MINT; Q80W65; -.
DR STRING; 10090.ENSMUSP00000055757; -.
DR MEROPS; S08.039; -.
DR GlyGen; Q80W65; 1 site.
DR iPTMnet; Q80W65; -.
DR PhosphoSitePlus; Q80W65; -.
DR CPTAC; non-CPTAC-3369; -.
DR MaxQB; Q80W65; -.
DR PaxDb; Q80W65; -.
DR PeptideAtlas; Q80W65; -.
DR PRIDE; Q80W65; -.
DR ProteomicsDB; 288003; -.
DR ABCD; Q80W65; 1 sequenced antibody.
DR Antibodypedia; 33231; 739 antibodies from 43 providers.
DR DNASU; 100102; -.
DR Ensembl; ENSMUST00000049507; ENSMUSP00000055757; ENSMUSG00000044254.
DR GeneID; 100102; -.
DR KEGG; mmu:100102; -.
DR UCSC; uc008tyi.2; mouse.
DR CTD; 255738; -.
DR MGI; MGI:2140260; Pcsk9.
DR VEuPathDB; HostDB:ENSMUSG00000044254; -.
DR eggNOG; KOG1153; Eukaryota.
DR GeneTree; ENSGT00490000043472; -.
DR HOGENOM; CLU_011263_11_0_1; -.
DR InParanoid; Q80W65; -.
DR OMA; CNKAAWR; -.
DR OrthoDB; 921536at2759; -.
DR PhylomeDB; Q80W65; -.
DR TreeFam; TF106271; -.
DR BRENDA; 3.4.21.61; 3474.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8866427; VLDLR internalisation and degradation.
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR Reactome; R-MMU-8964038; LDL clearance.
DR BioGRID-ORCS; 100102; 2 hits in 77 CRISPR screens.
DR PRO; PR:Q80W65; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q80W65; protein.
DR Bgee; ENSMUSG00000044254; Expressed in epithelium of small intestine and 127 other tissues.
DR Genevisible; Q80W65; MM.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:HGNC-UCL.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:1990667; C:PCSK9-AnxA2 complex; ISS:BHF-UCL.
DR GO; GO:1990666; C:PCSK9-LDLR complex; ISS:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0034185; F:apolipoprotein binding; IDA:UniProtKB.
DR GO; GO:0034190; F:apolipoprotein receptor binding; ISO:MGI.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; IDA:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:HGNC-UCL.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:HGNC-UCL.
DR GO; GO:0030547; F:signaling receptor inhibitor activity; ISO:MGI.
DR GO; GO:0019871; F:sodium channel inhibitor activity; ISO:MGI.
DR GO; GO:0034189; F:very-low-density lipoprotein particle binding; IDA:UniProtKB.
DR GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:HGNC-UCL.
DR GO; GO:0009267; P:cellular response to starvation; IDA:HGNC-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:HGNC-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:MGI.
DR GO; GO:0001822; P:kidney development; IEP:HGNC-UCL.
DR GO; GO:0042157; P:lipoprotein metabolic process; IDA:MGI.
DR GO; GO:0001889; P:liver development; IEP:HGNC-UCL.
DR GO; GO:0032802; P:low-density lipoprotein particle receptor catabolic process; ISS:UniProtKB.
DR GO; GO:0032799; P:low-density lipoprotein receptor particle metabolic process; IDA:MGI.
DR GO; GO:0007041; P:lysosomal transport; ISO:MGI.
DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; ISO:MGI.
DR GO; GO:1905596; P:negative regulation of low-density lipoprotein particle receptor binding; ISO:MGI.
DR GO; GO:1905598; P:negative regulation of low-density lipoprotein receptor activity; ISO:MGI.
DR GO; GO:0002091; P:negative regulation of receptor internalization; ISO:MGI.
DR GO; GO:0001920; P:negative regulation of receptor recycling; ISO:MGI.
DR GO; GO:1905601; P:negative regulation of receptor-mediated endocytosis involved in cholesterol transport; ISO:MGI.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0022008; P:neurogenesis; IEP:HGNC-UCL.
DR GO; GO:0030182; P:neuron differentiation; IDA:HGNC-UCL.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:MGI.
DR GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:HGNC-UCL.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:0016540; P:protein autoprocessing; ISS:HGNC-UCL.
DR GO; GO:0016485; P:protein processing; ISO:MGI.
DR GO; GO:0032803; P:regulation of low-density lipoprotein particle receptor catabolic process; IMP:MGI.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0010469; P:regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:0006641; P:triglyceride metabolic process; IDA:MGI.
DR CDD; cd04077; Peptidases_S8_PCSK9_ProteinaseK_like; 1.
DR Gene3D; 3.30.70.80; -; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR041254; PCSK9_C1.
DR InterPro; IPR041052; PCSK9_C2.
DR InterPro; IPR041051; PCSK9_C3.
DR InterPro; IPR034193; PCSK9_ProteinaseK-like.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR010259; S8pro/Inhibitor_I9.
DR InterPro; IPR037045; S8pro/Inhibitor_I9_sf.
DR Pfam; PF05922; Inhibitor_I9; 1.
DR Pfam; PF18459; PCSK9_C1; 1.
DR Pfam; PF18464; PCSK9_C2; 1.
DR Pfam; PF18463; PCSK9_C3; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Autocatalytic cleavage; Calcium; Cholesterol metabolism;
KW Cytoplasm; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Golgi apparatus; Hydrolase; Lipid metabolism; Lysosome; Phosphoprotein;
KW Protease; Reference proteome; Secreted; Serine protease; Signal;
KW Steroid metabolism; Sterol metabolism; Sulfation; Zymogen.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT PROPEP 35..155
FT /id="PRO_0000027122"
FT CHAIN 156..694
FT /note="Proprotein convertase subtilisin/kexin type 9"
FT /id="PRO_0000027123"
FT DOMAIN 158..470
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 453..694
FT /note="C-terminal domain"
FT /evidence="ECO:0000250"
FT MOTIF 499..501
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 189
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 229
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 389
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT SITE 155..156
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT SITE 221..222
FT /note="Cleavage; by furin and PCSK5"
FT /evidence="ECO:0000250"
FT MOD_RES 41
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18498363"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NBP7"
FT CARBOHYD 536
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 226..258
FT /evidence="ECO:0000255"
FT DISULFID 326..361
FT /evidence="ECO:0000255"
FT DISULFID 460..530
FT /evidence="ECO:0000255"
FT DISULFID 480..529
FT /evidence="ECO:0000255"
FT DISULFID 489..512
FT /evidence="ECO:0000255"
FT DISULFID 537..604
FT /evidence="ECO:0000255"
FT DISULFID 555..603
FT /evidence="ECO:0000255"
FT DISULFID 565..591
FT /evidence="ECO:0000255"
FT DISULFID 611..682
FT /evidence="ECO:0000255"
FT DISULFID 629..681
FT /evidence="ECO:0000255"
FT DISULFID 638..657
FT /evidence="ECO:0000255"
FT CONFLICT 17..19
FT /note="Missing (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="A -> T (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="D -> G (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="H -> Y (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="E -> A (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="R -> Q (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="R -> H (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
FT CONFLICT 626
FT /note="T -> A (in Ref. 1; CAC60362)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 694 AA; 74823 MW; 977BD4BD1FAF98C0 CRC64;
MGTHCSAWLR WPLLPLLPPL LLLLLLLCPT GAGAQDEDGD YEELMLALPS QEDGLADEAA
HVATATFRRC SKEAWRLPGT YIVVLMEETQ RLQIEQTAHR LQTRAARRGY VIKVLHIFYD
LFPGFLVKMS SDLLGLALKL PHVEYIEEDS FVFAQSIPWN LERIIPAWHQ TEEDRSPDGS
SQVEVYLLDT SIQGAHREIE GRVTITDFNS VPEEDGTRFH RQASKCDSHG THLAGVVSGR
DAGVAKGTSL HSLRVLNCQG KGTVSGTLIG LEFIRKSQLI QPSGPLVVLL PLAGGYSRIL
NAACRHLART GVVLVAAAGN FRDDACLYSP ASAPEVITVG ATNAQDQPVT LGTLGTNFGR
CVDLFAPGKD IIGASSDCST CFMSQSGTSQ AAAHVAGIVA RMLSREPTLT LAELRQRLIH
FSTKDVINMA WFPEDQQVLT PNLVATLPPS THETGGQLLC RTVWSAHSGP TRTATATARC
APEEELLSCS SFSRSGRRRG DWIEAIGGQQ VCKALNAFGG EGVYAVARCC LVPRANCSIH
NTPAARAGLE THVHCHQKDH VLTGCSFHWE VEDLSVRRQP ALRSRRQPGQ CVGHQAASVY
ASCCHAPGLE CKIKEHGISG PSEQVTVACE AGWTLTGCNV LPGASLTLGA YSVDNLCVAR
VHDTARADRT SGEATVAAAI CCRSRPSAKA SWVQ
