| Tchem | Transmembrane protease serine 2 |
Serine protease that proteolytically cleaves and activates the viral spike glycoproteins which facilitate virus-cell membrane fusions; spike proteins are synthesized and maintained in precursor intermediate folding states and proteolysis permits the refolding and energy release required to create stable virus-cell linkages and membrane coalescence. Facilitates human SARS coronavirus (SARS-CoV) infection via two independent mechanisms, proteolytic cleavage of ACE2, which might promote viral uptake, and cleavage of coronavirus spike glycoprotein which activates the glycoprotein for cathepsin L-independent host cell entry. Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity.
This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]
This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]
Comments
Property Summary
| Ligand Count | 4 |
| NCBI Gene PubMed Count | 160 |
| PubMed Score | 438.22 |
| PubTator Score | 388.20 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Prostatic Neoplasms | 495 | 0.0 | 0.0 |
| Disease | Target Count | P-value |
|---|---|---|
| lung carcinoma | 2843 | 8.0e-49 |
| psoriasis | 6694 | 4.1e-22 |
| ovarian cancer | 8520 | 2.2e-09 |
| osteosarcoma | 7950 | 8.5e-08 |
| non-small cell lung cancer | 2890 | 4.4e-07 |
| Breast cancer | 3578 | 4.5e-07 |
| lung adenocarcinoma | 2716 | 8.2e-07 |
| nasopharyngeal carcinoma | 1058 | 5.4e-06 |
| medulloblastoma, large-cell | 6241 | 1.7e-04 |
| lung cancer | 4740 | 4.5e-04 |
| adult high grade glioma | 3801 | 1.6e-03 |
| interstitial cystitis | 2312 | 2.5e-03 |
| intraductal papillary-mucinous neoplasm (IPMN) | 3291 | 2.8e-03 |
| gastric carcinoma | 807 | 4.0e-02 |
| Disease | log2 FC | p |
|---|---|---|
| adult high grade glioma | 1.100 | 1.6e-03 |
| Breast cancer | -1.400 | 4.5e-07 |
| gastric carcinoma | -1.900 | 4.0e-02 |
| interstitial cystitis | -2.400 | 2.5e-03 |
| intraductal papillary-mucinous neoplasm ... | 1.400 | 2.8e-03 |
| lung adenocarcinoma | -1.500 | 8.2e-07 |
| lung cancer | -2.800 | 4.5e-04 |
| lung carcinoma | -4.400 | 8.0e-49 |
| medulloblastoma, large-cell | 1.100 | 1.7e-04 |
| nasopharyngeal carcinoma | -1.300 | 5.4e-06 |
| non-small cell lung cancer | -1.439 | 4.4e-07 |
| osteosarcoma | 1.670 | 8.5e-08 |
| ovarian cancer | 1.700 | 2.2e-09 |
| psoriasis | -1.400 | 4.1e-22 |
| Species | Source | Disease |
|---|---|---|
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA | ||
| Inparanoid OMA | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA | ||
| OMA EggNOG | ||
| OMA EggNOG |
CHEMBL1809251
pKi 7.17
CHEMBL1809250
pKi 7.28
CHEMBL1229259
pKi 7.70
![Structure of compound 5 [PMID: 21741839]](/idg/structure/505c0caa-aa49-4fa8-bd15-8af044941d86.svg)
compound 5 [PMID: 21741839]
pKi 7.70
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPK 1 - 70 SPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCP 71 - 140 GGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDDSGSTSFM 141 - 210 KLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHV 211 - 280 CGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMK 281 - 350 LQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI 351 - 420 TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRA 421 - 490 DG 491 - 492 //
