Q8VDZ4 · ZDHC5_MOUSE
- ProteinPalmitoyltransferase ZDHHC5
- GeneZdhhc5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids715 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflammation, fatty acid uptake, bacterial sensing or cardiac functions (PubMed:21820437, PubMed:22081607, PubMed:38530158).
Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) (PubMed:24562000).
Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins (By similarity).
Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2 (By similarity).
Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2 (By similarity).
Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes (By similarity).
Participates also in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane (PubMed:30605677).
Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis (PubMed:30605677).
Controls oligodendrocyte development by catalyzing STAT3 palmitoylation (PubMed:34724258).
Acts as a regulator of inflammatory response by mediating palmitoylation of NLRP3 and GSDMD (By similarity).
Palmitoylates NLRP3 to promote inflammasome assembly and activation (By similarity).
Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD (PubMed:38530158).
Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) (PubMed:24562000).
Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins (By similarity).
Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2 (By similarity).
Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2 (By similarity).
Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes (By similarity).
Participates also in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane (PubMed:30605677).
Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis (PubMed:30605677).
Controls oligodendrocyte development by catalyzing STAT3 palmitoylation (PubMed:34724258).
Acts as a regulator of inflammatory response by mediating palmitoylation of NLRP3 and GSDMD (By similarity).
Palmitoylates NLRP3 to promote inflammasome assembly and activation (By similarity).
Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD (PubMed:38530158).
Miscellaneous
In neural stem cells, rapidly degraded through the proteasome pathway following growth factors withdrawal, a strategy used to induce differentiation.
Catalytic activity
- hexadecanoyl-CoA + L-cysteinyl-[protein] = CoA + S-hexadecanoyl-L-cysteinyl-[protein]This reaction proceeds in the forward direction.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 134 | S-palmitoyl cysteine intermediate | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | dendrite | |
Cellular Component | GABA-ergic synapse | |
Cellular Component | glutamatergic synapse | |
Cellular Component | nucleoplasm | |
Cellular Component | phagocytic vesicle | |
Cellular Component | plasma membrane | |
Cellular Component | postsynapse | |
Cellular Component | postsynaptic specialization, intracellular component | |
Molecular Function | palmitoyltransferase activity | |
Molecular Function | protein-cysteine S-palmitoyltransferase activity | |
Biological Process | innate immune response | |
Biological Process | lipid transport | |
Biological Process | positive regulation of pattern recognition receptor signaling pathway | |
Biological Process | positive regulation of protein localization to phagocytic vesicle | |
Biological Process | positive regulation of protein localization to plasma membrane | |
Biological Process | positive regulation of pyroptotic inflammatory response | |
Biological Process | protein localization to plasma membrane | |
Biological Process | regulation of postsynaptic membrane neurotransmitter receptor levels |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePalmitoyltransferase ZDHHC5
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8VDZ4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-13 | Cytoplasmic | ||||
Sequence: MPAESGKRFKPSK | ||||||
Transmembrane | 14-34 | Helical | ||||
Sequence: YVPVSAAAIFLVGATTLFFAF | ||||||
Topological domain | 35-52 | Extracellular | ||||
Sequence: TCPGLSLNVSPAVPIYNA | ||||||
Transmembrane | 53-73 | Helical | ||||
Sequence: IMFLFVLANFSMATFMDPGIF | ||||||
Topological domain | 74-148 | Cytoplasmic | ||||
Sequence: PRAEEDEDKEDDFRAPLYKTVEIKGIQVRMKWCATCRFYRPPRCSHCSVCDNCVEEFDHHCPWVNNCIGRRNYRY | ||||||
Transmembrane | 149-169 | Helical | ||||
Sequence: FFLFLLSLTAHIMGVFGFGLL | ||||||
Topological domain | 170-191 | Extracellular | ||||
Sequence: YVLYHIEELSGVRTAVTMAVMC | ||||||
Transmembrane | 192-212 | Helical | ||||
Sequence: VAGLFFIPVAGLTGFHVVLVA | ||||||
Topological domain | 213-715 | Cytoplasmic | ||||
Sequence: RGRTTNEQVTGKFRGGVNPFTNGCCNNVSRVLCSSPAPRYLGRPKKEKTIVIRPPFLRPEVSDGQITVKIMDNGIQGELRRTKSKGSLEITESQSADAEPPPPPKPDLSRYTGLRTHLSLATNEDSSLLGKDSPPTPTMYKYRPGYSSSSTSAAMPHSSSAKLSRGDSLKEPTSIADSSRHPSYRSEPSLEPESFRSPTFGKSFHFDPLSSGSRSSSLKSAQGTGFELGQLQSIRSEGTTSTSYKSLANQTRNGSLSYDSLLTPSDSPDFESVQAGPEPDPPLGYTSPFLSARLAQQREAERHPRLLPTGPPHREPSPVRYDNLSRHIVASLQEREKLLRQSPPLAGREEEPGLGDSGIQSTPGSGHAPRTSSSSDDSKRSPLSKTPLGRPAVPRFGKPDGLRSRGLGSPEPGTTAPYLGRSISYSSQKAPSGVSETEEVALQPLLTPKDEVQLKTTYSKSNGQPKSIGSASPGPGQPPLSSPTRGGVKKVSGVGGTTYEISV |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Deletion mutant mice are born at half the expected rate, and survivors show a marked deficit in contextual fear conditioning, an indicator of defective hippocampal-dependent learning (PubMed:20178993).
Loss of ZDHHC5 in oligodendrocytes inhibits myelination and reduces the expression levels of myelin-related and anti-apoptosis genes (PubMed:34724258).
Loss of ZDHHC5 in oligodendrocytes inhibits myelination and reduces the expression levels of myelin-related and anti-apoptosis genes (PubMed:34724258).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 134 | Loss of palmitoyltransferase activity. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 29 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000212869 | 1-715 | Palmitoyltransferase ZDHHC5 | |||
Sequence: MPAESGKRFKPSKYVPVSAAAIFLVGATTLFFAFTCPGLSLNVSPAVPIYNAIMFLFVLANFSMATFMDPGIFPRAEEDEDKEDDFRAPLYKTVEIKGIQVRMKWCATCRFYRPPRCSHCSVCDNCVEEFDHHCPWVNNCIGRRNYRYFFLFLLSLTAHIMGVFGFGLLYVLYHIEELSGVRTAVTMAVMCVAGLFFIPVAGLTGFHVVLVARGRTTNEQVTGKFRGGVNPFTNGCCNNVSRVLCSSPAPRYLGRPKKEKTIVIRPPFLRPEVSDGQITVKIMDNGIQGELRRTKSKGSLEITESQSADAEPPPPPKPDLSRYTGLRTHLSLATNEDSSLLGKDSPPTPTMYKYRPGYSSSSTSAAMPHSSSAKLSRGDSLKEPTSIADSSRHPSYRSEPSLEPESFRSPTFGKSFHFDPLSSGSRSSSLKSAQGTGFELGQLQSIRSEGTTSTSYKSLANQTRNGSLSYDSLLTPSDSPDFESVQAGPEPDPPLGYTSPFLSARLAQQREAERHPRLLPTGPPHREPSPVRYDNLSRHIVASLQEREKLLRQSPPLAGREEEPGLGDSGIQSTPGSGHAPRTSSSSDDSKRSPLSKTPLGRPAVPRFGKPDGLRSRGLGSPEPGTTAPYLGRSISYSSQKAPSGVSETEEVALQPLLTPKDEVQLKTTYSKSNGQPKSIGSASPGPGQPPLSSPTRGGVKKVSGVGGTTYEISV | ||||||
Modified residue | 91 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 247 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 294 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 296 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 299 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 303 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 345 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 348 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 350 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 380 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 398 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 406 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 409 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 411 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 415 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 425 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 429 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 432 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 436 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 529 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 554 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 617 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 621 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 659 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 684 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 694 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 697 | Omega-N-methylarginine | ||||
Sequence: R |
Post-translational modification
Phosphorylation regulates association with endocytic proteins and its subcellular localization. Phosphorylation by LYN during fatty acid uptake leads to inactivation of the activity.
Autopalmitoylated (By similarity).
Palmitoylation of the C-terminal tail regulates stimulation-dependent plasma membrane motility (By similarity).
Palmitoylation of the C-terminal tail regulates stimulation-dependent plasma membrane motility (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly enriched in brain, detectable in liver and heart, and undetectable in most other tissues.
Induction
In neural stem cells, rapid up-regulation by EGF, combined with FGF2 and heparin.
Gene expression databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8VDZ4 | GOLGA7B Q9D428 | 2 | EBI-7057556, EBI-25635843 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 104-154 | DHHC | ||||
Sequence: KWCATCRFYRPPRCSHCSVCDNCVEEFDHHCPWVNNCIGRRNYRYFFLFLL | ||||||
Region | 289-715 | Disordered | ||||
Sequence: GELRRTKSKGSLEITESQSADAEPPPPPKPDLSRYTGLRTHLSLATNEDSSLLGKDSPPTPTMYKYRPGYSSSSTSAAMPHSSSAKLSRGDSLKEPTSIADSSRHPSYRSEPSLEPESFRSPTFGKSFHFDPLSSGSRSSSLKSAQGTGFELGQLQSIRSEGTTSTSYKSLANQTRNGSLSYDSLLTPSDSPDFESVQAGPEPDPPLGYTSPFLSARLAQQREAERHPRLLPTGPPHREPSPVRYDNLSRHIVASLQEREKLLRQSPPLAGREEEPGLGDSGIQSTPGSGHAPRTSSSSDDSKRSPLSKTPLGRPAVPRFGKPDGLRSRGLGSPEPGTTAPYLGRSISYSSQKAPSGVSETEEVALQPLLTPKDEVQLKTTYSKSNGQPKSIGSASPGPGQPPLSSPTRGGVKKVSGVGGTTYEISV | ||||||
Compositional bias | 327-345 | Polar residues | ||||
Sequence: RTHLSLATNEDSSLLGKDS | ||||||
Compositional bias | 354-405 | Polar residues | ||||
Sequence: YRPGYSSSSTSAAMPHSSSAKLSRGDSLKEPTSIADSSRHPSYRSEPSLEPE | ||||||
Compositional bias | 416-482 | Polar residues | ||||
Sequence: FHFDPLSSGSRSSSLKSAQGTGFELGQLQSIRSEGTTSTSYKSLANQTRNGSLSYDSLLTPSDSPDF | ||||||
Compositional bias | 570-594 | Polar residues | ||||
Sequence: GIQSTPGSGHAPRTSSSSDDSKRSP | ||||||
Compositional bias | 631-646 | Polar residues | ||||
Sequence: LGRSISYSSQKAPSGV | ||||||
Compositional bias | 662-687 | Polar residues | ||||
Sequence: DEVQLKTTYSKSNGQPKSIGSASPGP |
Domain
The DHHC domain is required for palmitoyltransferase activity.
Sequence similarities
Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q8VDZ4-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length715
- Mass (Da)77,501
- Last updated2002-03-01 v1
- Checksum6FD8E83FA3D3F961
Q8VDZ4-2
- Name2
Sequence caution
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 327-345 | Polar residues | ||||
Sequence: RTHLSLATNEDSSLLGKDS | ||||||
Compositional bias | 354-405 | Polar residues | ||||
Sequence: YRPGYSSSSTSAAMPHSSSAKLSRGDSLKEPTSIADSSRHPSYRSEPSLEPE | ||||||
Compositional bias | 416-482 | Polar residues | ||||
Sequence: FHFDPLSSGSRSSSLKSAQGTGFELGQLQSIRSEGTTSTSYKSLANQTRNGSLSYDSLLTPSDSPDF | ||||||
Compositional bias | 570-594 | Polar residues | ||||
Sequence: GIQSTPGSGHAPRTSSSSDDSKRSP | ||||||
Compositional bias | 631-646 | Polar residues | ||||
Sequence: LGRSISYSSQKAPSGV | ||||||
Alternative sequence | VSP_006936 | 641-652 | in isoform 2 | |||
Sequence: KAPSGVSETEEV → NPHLVSQRQRK | ||||||
Alternative sequence | VSP_006937 | 653-715 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 662-687 | Polar residues | ||||
Sequence: DEVQLKTTYSKSNGQPKSIGSASPGP |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY894891 EMBL· GenBank· DDBJ | AAX73370.1 EMBL· GenBank· DDBJ | mRNA | ||
AK082513 EMBL· GenBank· DDBJ | BAC38513.1 EMBL· GenBank· DDBJ | mRNA | ||
AK075641 EMBL· GenBank· DDBJ | BAC35875.1 EMBL· GenBank· DDBJ | mRNA | ||
AK173251 EMBL· GenBank· DDBJ | BAD32529.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC020051 EMBL· GenBank· DDBJ | AAH20051.1 EMBL· GenBank· DDBJ | mRNA | ||
BC027047 EMBL· GenBank· DDBJ | AAH27047.1 EMBL· GenBank· DDBJ | mRNA | ||
BC065155 EMBL· GenBank· DDBJ | AAH65155.1 EMBL· GenBank· DDBJ | mRNA |