Target Information
| Target General Information | Top | |||||
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| Target ID |
T01725
(Former ID: TTDNR00736)
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| Target Name |
Protein-cysteine N-palmitoyltransferase HHAT (HHAT)
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| Synonyms |
Skinny hedgehog protein 1; Melanoma antigen recognized by T-cells 2; MART-2; Hedgehog acyltransferase; HHAT
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| Gene Name |
HHAT
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling. May bind GTP. .
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.3.1.-
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| Sequence |
MLPRWELALYLLASLGFHFYSFYEVYKVSREHEEELDQEFELETDTLFGGLKKDATDFEW
SFWMEWGKQWLVWLLLGHMVVSQMATLLARKHRPWILMLYGMWACWCVLGTPGVAMVLLH TTISFCVAQFRSQLLTWLCSLLLLSTLRLQGVEEVKRRWYKTENEYYLLQFTLTVRCLYY TSFSLELCWQQLPAASTSYSFPWMLAYVFYYPVLHNGPILSFSEFIKQMQQQEHDSLKAS LCVLALGLGRLLCWWWLAELMAHLMYMHAIYSSIPLLETVSCWTLGGLALAQVLFFYVKY LVLFGVPALLMRLDGLTPPALPRCVSTMFSFTGMWRYFDVGLHNFLIRYVYIPVGGSQHG LLGTLFSTAMTFAFVSYWHGGYDYLWCWAALNWLGVTVENGVRRLVETPCIQDSLARYFS PQARRRFHAALASCSTSMLILSNLVFLGGNEVGKTYWNRIFIQGWPWVTLSVLGFLYCYS HVGIAWAQTYATD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Palmitoyl-CoA | Ligand Info | |||||
| Structure Description | Human Hedgehog acyltransferase (HHAT) in complex with palmitoyl-CoA and two Fab antibody fragments | PDB:7MHY | ||||
| Method | Electron microscopy | Resolution | 2.70 Å | Mutation | No | [2] |
| PDB Sequence |
MLPRWELALY
10 LLASLGFHFY20 SFYEVYKVSR30 EHEEELDQEF40 ELETDTLFGG50 LKKDATDFEW 60 SFWMEWGKQW70 LVWLLLGHMV80 VSQMATLLAR90 KHRPWILMLY100 GMWACWCVLG 110 TPGVAMVLLH120 TTISFCVAQF130 RSQLLTWLCS140 LLLLSTLRLQ150 GVEEVKRRWY 160 KTENEYYLLQ170 FTLTVRCLYY180 TSFSLELCWQ190 QLPAASTSYS200 FPWMLAYVFY 210 YPVLHNGPIL220 SFSEFIKQMQ230 QQEHDSLKAS240 LCVLALGLGR250 LLCWWWLAEL 260 MAHLMYMHAI270 YSSIPLLETV280 SCWTLGGLAL290 AQVLFFYVKY300 LVLFGVPALL 310 MRLDGLTPPA320 LPRCVSTMFS330 FTGMWRYFDV340 GLHNFLIRYV350 YIPVGGSQHG 360 LLGTLFSTAM370 TFAFVSYWHG380 GYDYLWCWAA390 LNWLGVTVEN400 GVRRLVETPC 410 IQDSLARYFS420 PQARRRFHAA430 LASCSTSMLI440 LSNLVFLGGN450 EVGKTYWNRI 460 FIQGWPWVTL470 SVLGFLYCYS480 HVGIAWAQTY490 A
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PHE17
3.785
HIS18
4.375
CYS282
4.116
TRP283
3.860
GLY286
3.636
GLY287
4.964
ALA289
4.394
LEU290
3.618
VAL293
3.528
PHE296
3.352
VAL325
3.130
SER326
4.396
MET328
3.895
PHE331
3.772
THR332
4.581
MET334
3.565
TRP335
3.279
ARG336
3.026
PHE338
4.162
ASP339
4.056
LEU342
3.515
HIS343
3.255
LEU346
3.926
ILE347
3.461
TYR351
3.492
ILE352
3.476
GLY356
2.790
SER357
3.303
GLN358
4.113
THR368
4.140
THR371
3.895
PHE372
3.443
VAL375
3.849
HIS379
3.382
ASP383
4.962
CYS387
3.474
TRP388
3.685
LEU391
4.442
LEU394
3.544
GLY395
4.133
VAL396
4.058
VAL398
3.519
GLU399
3.130
ASN400
4.661
VAL402
3.235
ARG403
2.873
VAL406
3.675
LEU415
4.465
PHE419
4.061
ARG424
3.923
PHE427
3.586
HIS428
2.715
LEU431
3.358
ALA432
4.064
CYS434
4.660
SER435
3.082
THR436
4.083
SER437
4.395
MET438
3.464
LEU439
3.994
ILE440
3.666
LEU441
4.317
ASN443
2.933
LEU444
4.670
VAL445
4.446
PHE446
3.657
LEU447
4.375
ASN450
3.667
GLY453
4.343
LYS454
3.746
TYR456
4.632
TRP457
3.962
ILE460
4.968
VAL468
4.619
SER471
3.903
VAL472
3.806
PHE475
4.217
LEU476
4.440
TYR479
3.310
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Cholesterol | Ligand Info | |||||
| Structure Description | Structure of Hedgehog acyltransferase (HHAT) in complex with megabody 177 bound to non-hydrolysable palmitoyl-CoA (Composite Map) | PDB:7Q1U | ||||
| Method | Electron microscopy | Resolution | 2.70 Å | Mutation | Yes | [3] |
| PDB Sequence |
MLPRWELALY
10 LLASLGFHFY20 SFYEVYKVSR30 EHEEELDQEF40 ELETDTLFGG50 LKKDATDFEW 60 SFWMEWGKQW70 LVWLLLGHMV80 VSQMATLLAR90 KHRPWILMLY100 GMWACWCVLG 110 TPGVAMVLLH120 TTISFCVAQF130 RSQLLTWLCS140 LLLLSTLRLQ150 GVEEVKRRWY 160 KTENEYYLLQ170 FTLTVRCLYY180 TNFSLELCTS198 YSFPWMLAYV208 FYYPVLHNGP 218 ILSFSEFIKQ228 MQQQEHDSLK238 ASLCVLALGL248 GRLLCWWWLA258 ELMAHLMYMH 268 AIYSSIPLLE278 TVSCWTLGGL288 ALAQVLFFYV298 KYLVLFGVPA308 LLMRLDGLTP 318 PALPRCVSTM328 FSFTGMWRYF338 DVGLHNFLIR348 YVYIPVGGSQ358 HGLLGTLFST 368 AMTFAFVSYW378 HGGYDYLWWA389 ALNWLGVTVE399 NGVRRLVETP409 CIQDSLARYF 419 SPQARRRFHA429 ALASCSTSML439 ILSNLVFLGG449 NEVGKTYWNR459 IFIQGWPWVT 469 LSVLGFLYCY479 SHVGIAWAQT489 YATD
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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 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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Hedgehog signaling pathway | hsa04340 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 8.07E-07 |
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| Closeness centrality | 1.73E-01 | Radiality | 1.28E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.03E+01 | Topological coefficient | 5.49E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. Oncogene. 2015 Jan 8;34(2):263-8. | |||||
| REF 2 | Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT. Science. 2021 Jun 11;372(6547):1215-1219. | |||||
| REF 3 | Structure, mechanism, and inhibition of Hedgehog acyltransferase. Mol Cell. 2021 Dec 16;81(24):5025-5038.e10. | |||||
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