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UniProtKB - Q80W65 (PCSK9_MOUSE)

Entry version 151 (16 Oct 2019)
Sequence version 2 (07 Nov 2003)
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Protein

Proprotein convertase subtilisin/kexin type 9

Gene

Pcsk9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na+ channel (ENaC)-mediated Na+ absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.2 Publications

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Ca2+Curated

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei189Charge relay systemPROSITE-ProRule annotation1
Active sitei229Charge relay systemPROSITE-ProRule annotation1
Active sitei389Charge relay systemPROSITE-ProRule annotation1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processApoptosis, Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism
LigandCalcium

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-8866427 VLDLR internalisation and degradation
R-MMU-8957275 Post-translational protein phosphorylation
R-MMU-8964038 LDL clearance

Protein family/group databases

MEROPS protease database

More...MEROPSi		S08.039

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Proprotein convertase subtilisin/kexin type 9 (EC:3.4.21.-)
Alternative name(s):
Neural apoptosis-regulated convertase 1
Short name:
NARC-1
Proprotein convertase 9
Short name:
PC9
Subtilisin/kexin-like protease PC9
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Pcsk9
Synonyms:Narc1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...MGIi		MGI:2140260 Pcsk9

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Secreted

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 34Sequence analysisAdd BLAST34
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_000002712235 – 155Add BLAST121
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000027123156 – 694Proprotein convertase subtilisin/kexin type 9Add BLAST539

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei41SulfotyrosineBy similarity1
Modified residuei50Phosphoserine1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi226 ↔ 258Sequence analysis
Disulfide bondi326 ↔ 361Sequence analysis
Disulfide bondi460 ↔ 530Sequence analysis
Disulfide bondi480 ↔ 529Sequence analysis
Disulfide bondi489 ↔ 512Sequence analysis
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi536N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi537 ↔ 604Sequence analysis
Disulfide bondi555 ↔ 603Sequence analysis
Disulfide bondi565 ↔ 591Sequence analysis
Disulfide bondi611 ↔ 682Sequence analysis
Disulfide bondi629 ↔ 681Sequence analysis
Disulfide bondi638 ↔ 657Sequence analysis
Modified residuei691PhosphoserineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation.By similarity
Undergoes autocatalytic cleavage in the endoplasmic reticulum to release the propeptide from the N-terminus and the cleavage of the propeptide is strictly required for its maturation and activation. The cleaved propeptide however remains associated with the catalytic domain through non-covalent interactions, preventing potential substrates from accessing its active site. As a result, it is secreted from cells as a propeptide-containing, enzymatically inactive protein (By similarity).By similarity
Phosphorylation protects the propeptide against proteolysis.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei155 – 156Cleavage; by autolysisBy similarity2
Sitei221 – 222Cleavage; by furin and PCSK5By similarity2

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation, Zymogen

Proteomic databases

The CPTAC Assay portal

More...CPTACi		non-CPTAC-3369

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q80W65

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q80W65

PeptideAtlas

More...PeptideAtlasi		Q80W65

PRoteomics IDEntifications database

More...PRIDEi		Q80W65

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q80W65

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q80W65

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Hepatocytes, kidney mesenchymal cells, intestinal ileum, colon epithelia and embryonic brain telencephalon neurons.

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

In the embryo, expressed in the liver at 9 dpc, in the skin and transiently in the telencephalon at 12 dpc, and in the kidney, small intestine and cerebellum at 15 dpc.

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Down-regulated following a high-cholesterol diet.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSMUSG00000044254 Expressed in 173 organ(s), highest expression level in lobe of liver

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q80W65 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer. Can self-associate to form dimers and higher multimers which may have increased LDLR degrading activity. The precursor protein but not the mature protein may form multimers.

Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full-length immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The pro-PCSK9 form (via C-terminal domain) interacts with LDLR.

Interacts (via the C-terminal domain) with ANXA2 (via repeat Annexin 1); the interaction inhibits the degradation of LDLR.

By similarity

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-129 LDLR-PCSK9 complex
CPX-141 ANXA2-PCSK9 complex

Protein interaction database and analysis system

More...IntActi		Q80W65, 1 interactor

Molecular INTeraction database

More...MINTi		Q80W65

STRING: functional protein association networks

More...STRINGi		10090.ENSMUSP00000055757

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q80W65

Database of comparative protein structure models

More...ModBasei		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini158 – 470Peptidase S8PROSITE-ProRule annotationAdd BLAST313

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni453 – 694C-terminal domainBy similarityAdd BLAST242

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi499 – 501Cell attachment siteSequence analysis3

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities.By similarity
The catalytic domain is responsible for mediating its self-association.By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the peptidase S8 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1153 Eukaryota
COG1404 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00490000043472

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000049267

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q80W65

KEGG Orthology (KO)

More...KOi		K13050

Identification of Orthologs from Complete Genome Data

More...OMAi		FAQSVPW

Database of Orthologous Groups

More...OrthoDBi		921536at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q80W65

TreeFam database of animal gene trees

More...TreeFami		TF106271

Family and domain databases

Conserved Domains Database

More...CDDi		cd04077 Peptidases_S8_PCSK9_ProteinaseK_like, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.30.70.80, 1 hit
3.40.50.200, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR041254 PCSK9_C
IPR041052 PCSK9_C2
IPR041051 PCSK9_C3
IPR034193 PCSK9_ProteinaseK-like
IPR000209 Peptidase_S8/S53_dom
IPR036852 Peptidase_S8/S53_dom_sf
IPR015500 Peptidase_S8_subtilisin-rel
IPR037045 S8pro/Inhibitor_I9_sf

Pfam protein domain database

More...Pfami		View protein in Pfam
PF18459 PCSK9_C1, 1 hit
PF18464 PCSK9_C2, 1 hit
PF18463 PCSK9_C3, 1 hit
PF00082 Peptidase_S8, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00723 SUBTILISIN

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF52743 SSF52743, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51892 SUBTILASE, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

Q80W65-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGTHCSAWLR WPLLPLLPPL LLLLLLLCPT GAGAQDEDGD YEELMLALPS 
        60         70         80         90        100
QEDGLADEAA HVATATFRRC SKEAWRLPGT YIVVLMEETQ RLQIEQTAHR 
       110        120        130        140        150
LQTRAARRGY VIKVLHIFYD LFPGFLVKMS SDLLGLALKL PHVEYIEEDS 
       160        170        180        190        200
FVFAQSIPWN LERIIPAWHQ TEEDRSPDGS SQVEVYLLDT SIQGAHREIE 
       210        220        230        240        250
GRVTITDFNS VPEEDGTRFH RQASKCDSHG THLAGVVSGR DAGVAKGTSL 
       260        270        280        290        300
HSLRVLNCQG KGTVSGTLIG LEFIRKSQLI QPSGPLVVLL PLAGGYSRIL 
       310        320        330        340        350
NAACRHLART GVVLVAAAGN FRDDACLYSP ASAPEVITVG ATNAQDQPVT 
       360        370        380        390        400
LGTLGTNFGR CVDLFAPGKD IIGASSDCST CFMSQSGTSQ AAAHVAGIVA 
       410        420        430        440        450
RMLSREPTLT LAELRQRLIH FSTKDVINMA WFPEDQQVLT PNLVATLPPS 
       460        470        480        490        500
THETGGQLLC RTVWSAHSGP TRTATATARC APEEELLSCS SFSRSGRRRG 
       510        520        530        540        550
DWIEAIGGQQ VCKALNAFGG EGVYAVARCC LVPRANCSIH NTPAARAGLE 
       560        570        580        590        600
THVHCHQKDH VLTGCSFHWE VEDLSVRRQP ALRSRRQPGQ CVGHQAASVY 
       610        620        630        640        650
ASCCHAPGLE CKIKEHGISG PSEQVTVACE AGWTLTGCNV LPGASLTLGA 
       660        670        680        690 
YSVDNLCVAR VHDTARADRT SGEATVAAAI CCRSRPSAKA SWVQ
Length:694
Mass (Da):74,823
Last modified:November 7, 2003 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i977BD4BD1FAF98C0
GO

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAP31672 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence BAE28934 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence CAC60362 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti17 – 19Missing in CAC60362 (Ref. 1) Curated3
Sequence conflicti34A → T in CAC60362 (Ref. 1) Curated1
Sequence conflicti189D → G in CAC60362 (Ref. 1) Curated1
Sequence conflicti196H → Y in CAC60362 (Ref. 1) Curated1
Sequence conflicti200E → A in CAC60362 (Ref. 1) Curated1
Sequence conflicti305R → Q in CAC60362 (Ref. 1) Curated1
Sequence conflicti534R → H in CAC60362 (Ref. 1) Curated1
Sequence conflicti626T → A in CAC60362 (Ref. 1) Curated1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AX207688 Unassigned DNA Translation: CAC60362.1 Different initiation.
AY273821 mRNA Translation: AAP31672.1 Different initiation.
AK149520 mRNA Translation: BAE28934.1 Different initiation.
AL954352 Genomic DNA No translation available.
BC038085 mRNA Translation: AAH38085.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS18418.1

NCBI Reference Sequences

More...RefSeqi		NP_705793.1, NM_153565.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENSMUST00000049507; ENSMUSP00000055757; ENSMUSG00000044254

Database of genes from NCBI RefSeq genomes

More...GeneIDi		100102

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		mmu:100102

UCSC genome browser

More...UCSCi		uc008tyi.2 mouse

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AX207688 Unassigned DNA Translation: CAC60362.1 Different initiation.
AY273821 mRNA Translation: AAP31672.1 Different initiation.
AK149520 mRNA Translation: BAE28934.1 Different initiation.
AL954352 Genomic DNA No translation available.
BC038085 mRNA Translation: AAH38085.1
CCDSiCCDS18418.1
RefSeqiNP_705793.1, NM_153565.2

3D structure databases

SMRiQ80W65
ModBaseiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-129 LDLR-PCSK9 complex
CPX-141 ANXA2-PCSK9 complex
IntActiQ80W65, 1 interactor
MINTiQ80W65
STRINGi10090.ENSMUSP00000055757

Protein family/group databases

MEROPSiS08.039

PTM databases

iPTMnetiQ80W65
PhosphoSitePlusiQ80W65

Proteomic databases

CPTACinon-CPTAC-3369
MaxQBiQ80W65
PaxDbiQ80W65
PeptideAtlasiQ80W65
PRIDEiQ80W65

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		Q80W65

Genome annotation databases

EnsembliENSMUST00000049507; ENSMUSP00000055757; ENSMUSG00000044254
GeneIDi100102
KEGGimmu:100102
UCSCiuc008tyi.2 mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		255738
MGIiMGI:2140260 Pcsk9

Phylogenomic databases

eggNOGiKOG1153 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00490000043472
HOGENOMiHOG000049267
InParanoidiQ80W65
KOiK13050
OMAiFAQSVPW
OrthoDBi921536at2759
PhylomeDBiQ80W65
TreeFamiTF106271

Enzyme and pathway databases

ReactomeiR-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-8866427 VLDLR internalisation and degradation
R-MMU-8957275 Post-translational protein phosphorylation
R-MMU-8964038 LDL clearance

Miscellaneous databases

Protein Ontology

More...PROi		PR:Q80W65

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSMUSG00000044254 Expressed in 173 organ(s), highest expression level in lobe of liver
GenevisibleiQ80W65 MM

Family and domain databases

CDDicd04077 Peptidases_S8_PCSK9_ProteinaseK_like, 1 hit
Gene3Di3.30.70.80, 1 hit
3.40.50.200, 1 hit
InterProiView protein in InterPro
IPR041254 PCSK9_C
IPR041052 PCSK9_C2
IPR041051 PCSK9_C3
IPR034193 PCSK9_ProteinaseK-like
IPR000209 Peptidase_S8/S53_dom
IPR036852 Peptidase_S8/S53_dom_sf
IPR015500 Peptidase_S8_subtilisin-rel
IPR037045 S8pro/Inhibitor_I9_sf
PfamiView protein in Pfam
PF18459 PCSK9_C1, 1 hit
PF18464 PCSK9_C2, 1 hit
PF18463 PCSK9_C3, 1 hit
PF00082 Peptidase_S8, 1 hit
PRINTSiPR00723 SUBTILISIN
SUPFAMiSSF52743 SSF52743, 1 hit
PROSITEiView protein in PROSITE
PS51892 SUBTILASE, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiPCSK9_MOUSE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q80W65
Secondary accession number(s): B1AZI4
, Q3UEH7, Q8BXW9, Q8CFT6
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: November 7, 2003
Last modified: October 16, 2019
This is version 151 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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