| Tclin | Proprotein convertase subtilisin/kexin type 9 |
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 (PubMed:18039658). 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 (PubMed:18799458, PubMed:17461796, PubMed:18197702, PubMed:22074827). 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 (PubMed:18660751). 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.
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
Comments
Property Summary
| Ligand Count | 3 |
| NCBI Gene PubMed Count | 418 |
| PubMed Score | 1735.13 |
| PubTator Score | 891.42 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Coronary artery disease | 268 | 5.489 | 2.7 |
| HYPERCHOLESTEROLEMIA, AUTOSOMAL DOMINANT, 3 | 1 | 0.0 | 0.0 |
| Disease | Target Count |
|---|---|
| Hyperlipoproteinemia Type IIa | 11 |
| Disease | Target Count | P-value |
|---|---|---|
| psoriasis | 6694 | 1.6e-95 |
| lung adenocarcinoma | 2716 | 1.7e-03 |
| active Crohn's disease | 922 | 7.5e-03 |
| active ulcerative colitis | 764 | 1.5e-02 |
| pancreatic ductal adenocarcinoma liver metastasis | 1962 | 1.6e-02 |
| intraductal papillary-mucinous neoplasm (IPMN) | 3291 | 1.9e-02 |
| medulloblastoma, large-cell | 6241 | 5.0e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Cardiovascular system disease | 246 | 0.0 | 3.0 |
| Kidney cancer | 2613 | 0.0 | 2.7 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Abetalipoproteinemia | 7 | 0.0 | 5.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Lipid metabolism disorder | 114 | 6.164 | 3.1 |
| lung cancer | 4740 | 5.588 | 2.8 |
| diabetes mellitus | 1728 | 3.817 | 1.9 |
| Cerebrovascular disease | 238 | 3.666 | 1.8 |
| Arcus Senilis | 11 | 3.442 | 1.7 |
| Nasopharyngitis | 11 | 3.192 | 1.6 |
| Heart disease | 306 | 3.127 | 1.6 |
| Adenocarcinoma | 122 | 3.093 | 1.5 |
| Disease | Target Count |
|---|---|
| Hypercholesterolemia, Familial | 23 |
| Nephroblastoma | 51 |
| Disease | log2 FC | p |
|---|---|---|
| active Crohn's disease | 2.798 | 7.5e-03 |
| active ulcerative colitis | 2.294 | 1.5e-02 |
| intraductal papillary-mucinous neoplasm ... | 1.100 | 1.9e-02 |
| lung adenocarcinoma | -1.200 | 1.7e-03 |
| medulloblastoma, large-cell | 1.200 | 5.0e-02 |
| pancreatic ductal adenocarcinoma liver m... | -1.790 | 1.6e-02 |
| psoriasis | 2.500 | 1.6e-95 |
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKD 1 - 70 PWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHV 71 - 140 DYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPE 141 - 210 EDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPV 211 - 280 GPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGT 281 - 350 LGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA 351 - 420 KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFS 421 - 490 RSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLT 491 - 560 GCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGW 561 - 630 TLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ 631 - 692 //
