Literature summary for 2.3.1.225 extracted from

Mitchell, D. A.; Vasudevan, A.; Linder, M. E.; Deschenes, R. J.
Protein palmitoylation by a family of DHHC protein S-acyltransferases (2006), J. Lipid Res., 47, 1118-1127.

Search for more literature for 2.3.1.225

Activating Compound

Activating Compound	Comment	Organism	Structure
Erf4	required by Erf2 for activity, Erf2 and Erf4 copurify as a complex and interact in a yeast two-hybrid assay	Saccharomyces cerevisiae

Cloned(Commentary)

Cloned (Comment)	Organism
expression of human DHHC9 in Saccharomyces cerevisiae fails to complement an erf2DELTA strain	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
C159S	the DHHC15 mutant shows reduced activity compared to the wild-type	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
2-Bromopalmitate	-	Drosophila melanogaster
2-Bromopalmitate	-	Homo sapiens
2-Bromopalmitate	-	Saccharomyces cerevisiae

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytoplasmic vesicle	HIP14 resides on the Golgi and can be observed on cytoplasmic vesicles	Homo sapiens	31410	-
endoplasmic reticulum membrane	ERF2 encodes a protein with four predicted membrane-spanning domains	Saccharomyces cerevisiae	5789	-
Golgi membrane	HIP14 resides on the Golgi and can be observed on cytoplasmic vesicles	Homo sapiens	139	-
plasma membrane	ERF2 encodes a protein with four predicted membrane-spanning domains	Saccharomyces cerevisiae	5886	-

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
42000	-	x * 42000, Erf2	Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
palmitoyl-CoA + [Ga protein]-L-cysteine	Homo sapiens	substrate of DHHC3 and DHHC7	[Ga protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [GAP-43 protein]-L-cysteine	Homo sapiens	substrate of DHHC7 and DHHC15	[GAP-43 protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Lck]-L-cysteine	Homo sapiens	nonreceptor tyrosine kinase	[Lck]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [protein]-L-cysteine	Drosophila melanogaster	-	[protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [protein]-L-cysteine	Homo sapiens	-	[protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [protein]-L-cysteine	Saccharomyces cerevisiae	-	[protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [PSD95]-L-cysteine	Homo sapiens	possible substrate of DHHC15 and, to a lesser extent, DHHC2, DHHC3, and DHHC7	[Ras]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Ras]-L-cysteine	Homo sapiens	by Ras PAT containing the DHHC9 protein subunit	[Ras]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Ras]-L-cysteine	Saccharomyces cerevisiae	yeast Ras protein is a substrate of Erf2	[Ras]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [SNAP-25]-L-cysteine	Homo sapiens	substrate of DHHC3 and DHHC7	[SNAP-25]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Vac8]-L-cysteine	Saccharomyces cerevisiae	Vac8 is a substrate of Pfa3, Vac8 is a myristoylated and palmitoylated protein that localizes to the vacuolar membrane and is required for vacuolar fusion	[Vac8]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Yck2]-L-cysteine	Saccharomyces cerevisiae	yeast casein kinase Yck2 is a substrate of Akr1	[Yck2]-S-palmitoyl-L-cysteine + CoA	-	r

Organism

Organism	UniProt	Comment	Textmining
Drosophila melanogaster	-	-	-
Homo sapiens	-	-	-
Homo sapiens	Q8IUH5	DHHC17 or HIP14	-
Homo sapiens	Q9Y397	DHHC9	-
Saccharomyces cerevisiae	-	genes ERF2, PFA3, SWF1, and AKR1	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	DHHC9	Homo sapiens	-
colon	DHHC9	Homo sapiens	-
heart	DHHC9	Homo sapiens	-
kidney	DHHC9	Homo sapiens	-
liver	DHHC9	Homo sapiens	-
lung	DHHC9	Homo sapiens	-
additional information	HIP14 is ubiquitously expressed	Homo sapiens	-
additional information	the Ras PAT activity of DHHC9/GCP16 appears to be restricted to a subset of tissues	Homo sapiens	-
placenta	DHHC9	Homo sapiens	-
skeletal muscle	DHHC9	Homo sapiens	-
small intestine	DHHC9	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	complexity of HIP14's substrate specificity, in vitro, HIP14 has PAT activity for the N-terminal fragment of htt(1-548), SNAP-25, PSD-95, GAD65, and synaptotagmin I but not for synaptotagmin VII and paralemmin	Homo sapiens	?	-	?
palmitoyl-CoA + [Ga protein]-L-cysteine	substrate of DHHC3 and DHHC7	Homo sapiens	[Ga protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [GAD65]-L-cysteine	-	Homo sapiens	[GAD65]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [GAP-43 protein]-L-cysteine	substrate of DHHC7 and DHHC15	Homo sapiens	[GAP-43 protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [htt(1-548)]-L-cysteine	N-terminal fragment of htt(1-548)	Homo sapiens	[htt(1-548)]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Lck]-L-cysteine	nonreceptor tyrosine kinase	Homo sapiens	[Lck]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [protein]-L-cysteine	-	Drosophila melanogaster	[protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [protein]-L-cysteine	-	Homo sapiens	[protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [protein]-L-cysteine	-	Saccharomyces cerevisiae	[protein]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [PSD-95]-L-cysteine	low activity	Homo sapiens	[PSD-95]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [PSD95]-L-cysteine	-	Homo sapiens	[Ras]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [PSD95]-L-cysteine	possible substrate of DHHC15 and, to a lesser extent, DHHC2, DHHC3, and DHHC7	Homo sapiens	[Ras]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Ras]-L-cysteine	by Ras PAT containing the DHHC9 protein subunit	Homo sapiens	[Ras]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Ras]-L-cysteine	yeast Ras protein is a substrate of Erf2	Saccharomyces cerevisiae	[Ras]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [SNAP-25]-L-cysteine	-	Homo sapiens	[SNAP-25]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [SNAP-25]-L-cysteine	substrate of DHHC3 and DHHC7	Homo sapiens	[SNAP-25]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Snc1]-L-cysteine	yeast SNARES Snc1, Syn8, and Tlg1 are substrates of Swf1, palmitoylating at cysteine residues near the cytoplasmic side of their single transmembrane span	Saccharomyces cerevisiae	[Snc1]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Syn8]-L-cysteine	yeast SNARES Snc1, Syn8, and Tlg1 are substrates of Swf1, palmitoylating at cysteine residues near the cytoplasmic side of their single transmembrane span	Saccharomyces cerevisiae	[Syn8]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [synaptotagmin I ]-L-cysteine	-	Homo sapiens	[synaptotagmin I ]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Tlg1]-L-cysteine	yeast SNARES Snc1, Syn8, and Tlg1 are substrates of Swf1, palmitoylating at cysteine residues near the cytoplasmic side of their single transmembrane span	Saccharomyces cerevisiae	[Tlg1]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Vac8]-L-cysteine	Vac8 is a substrate of Pfa3, Vac8 is a myristoylated and palmitoylated protein that localizes to the vacuolar membrane and is required for vacuolar fusion	Saccharomyces cerevisiae	[Vac8]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Vac8]-L-cysteine	Vac8 is a substrate of Pfa3 performing S-palmitoylation of up to three N-terminal cysteines, Vac8 is N-myristoylated at an N-terminal glycine residue. Vac8 is not palmitoylated by Akr1, Erf2/Erf4, Pfa4, or Pfa5 in vitro	Saccharomyces cerevisiae	[Vac8]-S-palmitoyl-L-cysteine + CoA	-	r
palmitoyl-CoA + [Yck2]-L-cysteine	yeast casein kinase Yck2 is a substrate of Akr1	Saccharomyces cerevisiae	[Yck2]-S-palmitoyl-L-cysteine + CoA	-	r

Subunits

Subunits	Comment	Organism
?	x * 42000, Erf2	Saccharomyces cerevisiae

Synonyms

Synonyms	Comment	Organism
Akr1	-	Saccharomyces cerevisiae
DHHC17	-	Homo sapiens
Erf2	-	Saccharomyces cerevisiae
HIP14	-	Homo sapiens
Pat	-	Drosophila melanogaster
Pat	-	Homo sapiens
Pat	-	Saccharomyces cerevisiae
Pfa3	-	Saccharomyces cerevisiae
protein acyltransferase	-	Drosophila melanogaster
protein acyltransferase	-	Homo sapiens
protein acyltransferase	-	Saccharomyces cerevisiae
Ras PAT	-	Homo sapiens
Swf1	-	Saccharomyces cerevisiae

General Information

General Information	Comment	Organism
evolution	homology and phylogeny of DHHC proteins, overview	Homo sapiens
evolution	the enzymes belong to the DHHC family, homology and phylogeny of DHHC proteins, overview	Saccharomyces cerevisiae
malfunction	expression of DHHC15 mutant C159S reduced PSD-95 synaptic clustering as well as the clustering of cell-surface AMPA receptor GluR2 subunits, which is dependent upon PSD-95 palmitoylation	Homo sapiens
malfunction	human HIP14 complements the temperature-sensitive growth phenotype rescuing the defect in receptor endocytosis that results from deleting AKR1. Expression of human DHHC9 in yeast fails to complement an erf2DELTA strain. Deletion of the SWF1 gene abolishes the palmitoylation of Snc1, Syn8, and Tlg1 in vivo. Vac8 palmitoylation is significantly reduced but not absent in cells lacking Pfa3. Deletion of the ERF2 gene results in a decrease in Ras2 palmitoylation and a reduced presence on the plasma membrane. The erf2 erf4 double mutant is no more severe than either of the single mutants, and overexpression of ERF2 suppresses some but not all alleles of erf4	Saccharomyces cerevisiae
additional information	DHHC9 is a subunit of a human Ras PAT, but has no S-palmitoylation activity on its own, expression of human DHHC9 in yeast fails to complement an erf2DELTA strain	Homo sapiens
additional information	Erf2, Pfa3, and Akr1 share a common sequence referred to as aDHHC(aspartate-histidinehistidine-cysteine) domain. The DHHC domain of Erf2 is located between transmembrane 2 (TM2) and TM3. The DHHC motif is essential for catalytic activity in vitro and the function of these proteins in vivo	Saccharomyces cerevisiae
physiological function	protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Membrane localization of Yck2 is dependent on Akr1. S-Palmitoylation of up to three N-terminal cysteines og Vac8 is proposed to influence its function through localization of the protein to specific vacuolar membrane microdomains. Enzyme Swf1 is a PAT for transmembraneproteins palmitoylated at juxtamembranous cysteine residues. If Tlg1 is not palmitoylated by Swf1, it becomes asubstrate for the ubiquitin ligase, Tul1, palmitoylation appears to act as a stability factor, protecting Tlg1 from the cellular quality control machinery	Saccharomyces cerevisiae
physiological function	protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Palmitoylation plays a vital role in the nervous system, where substrates are abundant	Drosophila melanogaster
physiological function	protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Palmitoylation plays a vital role in the nervous system, where substrates are abundant	Homo sapiens
physiological function	protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Palmitoylation plays a vital role in the nervous system, where substrates are abundant. DHHC15 is a regulator of PSD-95 palmitoylation in vivo	Homo sapiens
physiological function	protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Palmitoylation plays a vital role in the nervous system, where substrates are abundant. HIP14 complements the temperature-sensitive growth phenotype and rescues the defect in receptor endocytosis that results from deleting yeast AKR1. role for HIP14 as a regulator of neuronal protein trafficking mediated by its PAT activity. HIP14's oncogenic properties are mediated through Ras proteins	Homo sapiens