TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


2.A.50.1.4
SKI1, HHAT or MART2 (The Sonic Hedgehog) of 493 aas and 11 - 13 TMSs. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). Jiang et al. 2021 presented cryo-EM structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures revealed how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis (Jiang et al. 2021). The Sonic Hedgehog (SHH) morphogen pathway is fundamental for embryonic development and stem cell maintenance and is implicated in various cancers. A key step in signaling is transfer of a palmitate group to the SHH N terminus, catalyzed by HHAT. Coupland et al. 2021 presented a high-resolution cryo-EM structure of HHAT bound to substrate analog palmityl-coenzyme A and a SHH-mimetic megabody, revealing a heme group bound to HHAT that is essential for HHAT function. A structure of HHAT bound to potent small-molecule inhibitor IMP-1575 revealed conformational changes in the active site that occlude substrate binding. The analysis provided a detailed view of the mechanism by which HHAT adapts the membrane environment to transfer an acyl chain across the endoplasmic reticulum membrane. This structure of a membrane-bound O-acyltransferase (MBOAT) superfamily member provides a blueprint for other protein-substrate MBOATs and a template for future drug discovery (Coupland et al. 2021).

Accession Number:Q5VTY9
Protein Name:Protein-cysteine N-palmitoyltransferase HHAT
Length:493
Molecular Weight:57313.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

Structure:
6P64   6UJO   6UJQ   6UK2   6UK4     

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MLPRWELALY LLASLGFHFY SFYEVYKVSR EHEEELDQEF ELETDTLFGG LKKDATDFEW 
61:	SFWMEWGKQW LVWLLLGHMV VSQMATLLAR KHRPWILMLY GMWACWCVLG TPGVAMVLLH 
121:	TTISFCVAQF RSQLLTWLCS LLLLSTLRLQ GVEEVKRRWY KTENEYYLLQ FTLTVRCLYY 
181:	TSFSLELCWQ QLPAASTSYS FPWMLAYVFY YPVLHNGPIL SFSEFIKQMQ QQEHDSLKAS 
241:	LCVLALGLGR LLCWWWLAEL MAHLMYMHAI YSSIPLLETV SCWTLGGLAL AQVLFFYVKY 
301:	LVLFGVPALL MRLDGLTPPA LPRCVSTMFS FTGMWRYFDV GLHNFLIRYV YIPVGGSQHG 
361:	LLGTLFSTAM TFAFVSYWHG GYDYLWCWAA LNWLGVTVEN GVRRLVETPC IQDSLARYFS 
421:	PQARRRFHAA LASCSTSMLI LSNLVFLGGN EVGKTYWNRI FIQGWPWVTL SVLGFLYCYS 
481:	HVGIAWAQTY ATD