Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T51597
(Former ID: TTDNR00634)
|
|||||
| Target Name |
Acidic mammalian chitinase (CHIA)
|
|||||
| Synonyms |
Lung-specific protein TSA1902; CHIA; AMCase
Click to Show/Hide
|
|||||
| Gene Name |
CHIA
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to IL-13 and inflammation in response to IL-13. Stimulates chemokine production by pulmonary epithelial cells. Protects lung epithelial cells against apoptosis and promotes phosphorylation of AKT1. Its function in the inflammatory response and in protecting cells against apoptosis is inhibited by allosamidin, suggesting that the function of this protein depends on carbohydrate binding. .
Click to Show/Hide
|
|||||
| BioChemical Class |
Glycosylase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.2.1.14
|
|||||
| Sequence |
MTKLILLTGLVLILNLQLGSAYQLTCYFTNWAQYRPGLGRFMPDNIDPCLCTHLIYAFAG
RQNNEITTIEWNDVTLYQAFNGLKNKNSQLKTLLAIGGWNFGTAPFTAMVSTPENRQTFI TSVIKFLRQYEFDGLDFDWEYPGSRGSPPQDKHLFTVLVQEMREAFEQEAKQINKPRLMV TAAVAAGISNIQSGYEIPQLSQYLDYIHVMTYDLHGSWEGYTGENSPLYKYPTDTGSNAY LNVDYVMNYWKDNGAPAEKLIVGFPTYGHNFILSNPSNTGIGAPTSGAGPAGPYAKESGI WAYYEICTFLKNGATQGWDAPQEVPYAYQGNVWVGYDNIKSFDIKAQWLKHNKFGGAMVW AIDLDDFTGTFCNQGKFPLISTLKKALGLQSASCTAPAQPIEPITAAPSGSGNGSGSSSS GGSSGGSGFCAVRANGLYPVANNRNAFWHCVNGVTYQQNCQAGLVFDTSCDCCNWA Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T89CUT | |||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Allosamizoline | Ligand Info | |||||
| Structure Description | The Acidic Mammalian Chitinase catalytic domain in complex with methylallosamidin | PDB:3FY1 | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | Yes | [2] |
| PDB Sequence |
YQLTCYFTNW
31 AQYRPGLGRF41 MPDDINPCLC51 THLIYAFAGM61 QNNEITTIEW71 NDVTLYQAFN 81 GLKNKNSQLK91 TLLAIGGWNF101 GTAPFTAMVS111 TPENRQTFIT121 SVIKFLRQYE 131 FDGLDFDWEY141 PGSRGSPPQD151 KHLFTVLVQE161 MREAFEQEAK171 QINKPRLMVT 181 AAVAAGISNI191 QSGYEIPQLS201 QYLDYIHVMT211 YDLHGSWEGY221 TGENSPLYKY 231 PTDTGSNAYL241 NVDYVMNYWK251 DNGAPAEKLI261 VGFPTYGHNF271 ILSNPSNTGI 281 GAPTSGAGPA291 GPYAKESGIW301 AYYEICTFLK311 NGATQGWDAP321 QEVPYAYQGN 331 VWVGYDNVKS341 FDIKAQWLKH351 NKFGGAMVWA361 IDLDDFTGTF371 CNQGKFPLIS 381 TLKKALGLQS391 ASCTAPA
|
|||||
|
|
||||||
| Ligand Name: 2-Methyl-3-{[4-(Pyridin-2-Yl)piperazin-1-Yl]methyl}-1h-Indole | Ligand Info | |||||
| Structure Description | AMCase in complex with Compound 2 | PDB:3RM8 | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [3] |
| PDB Sequence |
YQLTCYFTNW
31 AQYRPGLGRF41 MPDDINPCLC51 THLIYAFAGM61 QNNEITTIEW71 NDVTLYQAFN 81 GLKNKNSQLK91 TLLAIGGWNF101 GTAPFTAMVS111 TPENRQTFIT121 SVIKFLRQYE 131 FDGLDFDWEY141 PGSRGSPPQD151 KHLFTVLVQE161 MREAFEQEAK171 QINKPRLMVT 181 AAVAAGISNI191 QSGYEIPQLS201 QYLDYIHVMT211 YDLHGSWEGY221 TGENSPLYKY 231 PTDTGSNAYL241 NVDYVMNYWK251 DNGAPAEKLI261 VGFPTYGHNF271 ILSNPSNTGI 281 GAPTSGAGPA291 GPYAKESGIW301 AYYEICTFLK311 NGATQGWDAP321 QEVPYAYQGN 331 VWVGYDNVKS341 FDIKAQWLKH351 NKFGGAMVWA361 IDLDDFTGTF371 CNQGKFPLIS 381 TLKKALGLQS391 ASCTAPA
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Amino sugar and nucleotide sugar metabolism | hsa00520 | Affiliated Target |
|
| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Acidic mammalian chitinase tuning after enteric helminths eradication in inflammatory respiratory disease patients. Parasite Immunol. 2018 Nov;40(11):e12583. | |||||
| REF 2 | Triad of polar residues implicated in pH specificity of acidic mammalian chitinase. Protein Sci. 2009 Mar;18(3):569-78. | |||||
| REF 3 | Identification and characterization of acidic mammalian chitinase inhibitors. J Med Chem. 2010 Aug 26;53(16):6122-8. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.