A8T658

SS
Gene name
PCSK9
Protein name
Proprotein convertase subtilisin/kexin type 9
Names
Proprotein convertase 9, PC9, Subtilisin/kexin-like protease PC9
Species
Pongo pygmaeus (Bornean orangutan)
KEGG Pathway
EC number
Protein Class

Descriptions

At cell surface, proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the LDLR and is internalized as a complex with the LDLR. PCSK9 remains bound to the LDLR and prevents the LDLR from folding over itself to adopt a closed conformation. As a consequence, the LDLR fails to recycle back to the cell membrane. PCSK9 has a function to reduce the number of LDLRs and is a key regulator of plasma LDL cholesterol levels. Accorind to a study with human PCSK9, the autoinhibitory region negatively affect the ability of PCSK9 to bind to the LDLR and fine-tune the activity of PCSK9 towards the LDLR.

Autoinhibitory domains (AIDs)

29-58 (Part of predomain) SS

Target domain

154-419 (Peptidase domain)

Relief mechanism

Cleavage

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for A8T658

Entry ID Method Resolution Chain Position Source
AF-A8T658-F1 Predicted AlphaFoldDB

No variants for A8T658

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for A8T658

No associated diseases with A8T658

4 regional properties for A8T658

Type Name Position InterPro Accession
domain Peptidase S8 propeptide/proteinase inhibitor I9 75 - 147 IPR010259
domain Proteinase K-like catalytic domain 154 - 419 IPR034193
domain Proprotein convertase subtilisin/kexin type 9, C-terminal domain 2 533 - 598 IPR041052
domain Proprotein convertase subtilisin/kexin type 9, C-terminal domain 1 448 - 529 IPR041254

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Secreted
  • Endosome
  • Lysosome
  • Cell surface
  • Endoplasmic reticulum
  • Golgi apparatus
  • Autocatalytic cleavage is required to transport it from the endoplasmic reticulum to the Golgi apparatus and for the secretion of the mature protein
  • Localizes to the endoplasmic reticulum in the absence of LDLR and colocalizes to the cell surface and to the endosomes/lysosomes in the presence of LDLR
  • The sorting to the cell surface and endosomes is required in order to fully promote LDLR degradation (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
cell surface The external part of the cell wall and/or plasma membrane.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
early endosome A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
extracellular region The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
late endosome A prelysosomal endocytic organelle differentiated from early endosomes by lower lumenal pH and different protein composition. Late endosomes are more spherical than early endosomes and are mostly juxtanuclear, being concentrated near the microtubule organizing center.
lysosome A small lytic vacuole that has cell cycle-independent morphology found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions.

5 GO annotations of molecular function

Name Definition
apolipoprotein binding Binding to an apolipoprotein, the protein component of a lipoprotein complex.
low-density lipoprotein particle binding Binding to a low-density lipoprotein particle, a lipoprotein particle that is rich in cholesterol esters and low in triglycerides, is typically composed of APOB100 and APOE, and has a density of 1.02-1.06 g/ml and a diameter of between 20-25 nm.
protein self-association Binding to a domain within the same polypeptide.
serine-type endopeptidase activity Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a catalytic mechanism that involves a catalytic triad consisting of a serine nucleophile that is activated by a proton relay involving an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine).
very-low-density lipoprotein particle binding Binding to a very-low-density lipoprotein particle, a triglyceride-rich lipoprotein particle that is typically composed of APOB100, APOE and APOCs and has a density of about 1.006 g/ml and a diameter of between 20-80 nm.

4 GO annotations of biological process

Name Definition
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
cholesterol metabolic process The chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. It is a component of the plasma membrane lipid bilayer and of plasma lipoproteins and can be found in all animal tissues.
low-density lipoprotein particle receptor catabolic process The chemical reactions and pathways resulting in the breakdown of a low-density lipoprotein particle receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
regulation of neuron apoptotic process Any process that modulates the occurrence or rate of cell death by apoptotic process in neurons.

No homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
No homologous proteins
10 20 30 40 50 60
MGTVSSRRSW WPLPLLLLLL LGPAGARAQE DEDGDYEELV LALRSEEDGL AEAPEHGATA
70 80 90 100 110 120
TFHRCAKDPW RLPGTYVVVL KEETHRSQSE RTARRLQAQA ARRGYLTKIL HVFHDLLPGF
130 140 150 160 170 180
LVKMSGDLLE LALKLPHVDY IEEDSSVFAQ SIPWNLERIT PPRYRADEYQ PPDGGSLVEV
190 200 210 220 230 240
YLLDTSIQSD HREIEGRVMV TDFENVPEED GTRFHRQASK CDSHGTHLAG VVSGRDAGVA
250 260 270 280 290 300
KGASMRSLRV LNCQGKGTVS GTLIGLEFIR KSQLVQPVGP LVVLMPLAGG YSRVLNAACQ
310 320 330 340 350 360
RLARAGVVLV TAAGNFRDDA CLYSPASAPE VITVGATNAQ DQPVTLGTLG TNFGRCVDLF
370 380 390 400 410 420
APGEDIIGAS SDCSTCFVSQ SGTSQAAAHV AGIAAMMLSV EPELTLAELR QRLIHFSAKD
430 440 450 460 470 480
VINEVWFPED QRVLTPNLVA ALPPSTHGAG WQLFCRTVWS AHSGPTRMAT AIARCAPDEE
490 500 510 520 530 540
LLSCSSFSRS GKRRGERMEA QGGKLVCRAH NAFGGEGVCA IARCCLLPQA NCSVHTAPPA
550 560 570 580 590 600
GSGMGTRVLC HQQVHVLTGC SSHWEVEDLG THKPPVLRPR GQPNQCVGHR EASIHASCCR
610 620 630 640 650 660
APGLECKVKE HGIPAPQEQV TVACEEGWTL TGCSALPGTS HVLGAYAVDN TCVVRSRDIS
670 680
TTGSTSEEAM AAVAICCRRR HLAQASQELQ