ZDHHC23 is a membrane-associated DHHC-family protein S-palmitoyltransferase. Its conserved catalytic cysteine supports protein lipidation; characterized mammalian ZDHHC23 palmitoylates the potassium-channel subunit KCNMA1 and influences its plasma-membrane localization.
Summary: The multipass DHHC protein is associated with Golgi membrane in the human record, consistent with its conserved secretory-membrane architecture.
Reason: The multipass DHHC protein is associated with Golgi membrane in the human record, consistent with its conserved secretory-membrane architecture. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Summary: Secretory-pathway membrane localization is consistent with the phylogenetic assignment and multipass DHHC architecture.
Reason: Secretory-pathway membrane localization is consistent with the phylogenetic assignment and multipass DHHC architecture. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Summary: Golgi localization is supported by the characterized human membrane palmitoyltransferase and curated family inference.
Reason: Golgi localization is supported by the characterized human membrane palmitoyltransferase and curated family inference. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Summary: ZDHHC23-dependent palmitoylation regulates membrane targeting of KCNMA1; the catalytic cysteine is retained in the horse protein.
Reason: ZDHHC23-dependent palmitoylation regulates membrane targeting of KCNMA1; the catalytic cysteine is retained in the horse protein. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt
CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of CC palmitate onto various protein substrates and be involved in a variety CC of cellular processes (Probable). Palmitoyltransferase that mediates CC palmitoylation of KCNMA1, regulating localization of KCNMA1 to the CC plasma membrane. May be involved in NOS1 regulation and targeting to CC the synaptic membrane. {ECO:0000269|PubMed:22399288, CC ECO:0000305|PubMed:22399288}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Summary: The protein-cysteine S-palmitoyltransferase function is more precise than generic palmitoyltransferase.
Reason: The protein-cysteine S-palmitoyltransferase function is more precise than generic palmitoyltransferase. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of CC palmitate onto various protein substrates and be involved in a variety CC of cellular processes (Probable). Palmitoyltransferase that mediates CC palmitoylation of KCNMA1, regulating localization of KCNMA1 to the CC plasma membrane. May be involved in NOS1 regulation and targeting to CC the synaptic membrane. {ECO:0000269|PubMed:22399288, CC ECO:0000305|PubMed:22399288}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Summary: The acyl transfer is specifically S-palmitoylation of protein cysteine.
Reason: The acyl transfer is specifically S-palmitoylation of protein cysteine. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of CC palmitate onto various protein substrates and be involved in a variety CC of cellular processes (Probable). Palmitoyltransferase that mediates CC palmitoylation of KCNMA1, regulating localization of KCNMA1 to the CC plasma membrane. May be involved in NOS1 regulation and targeting to CC the synaptic membrane. {ECO:0000269|PubMed:22399288, CC ECO:0000305|PubMed:22399288}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Summary: Human substrate experiments support S-palmitoylation, and the horse DHHC catalytic cysteine and overall protein sequence are conserved.
Reason: Human substrate experiments support S-palmitoylation, and the horse DHHC catalytic cysteine and overall protein sequence are conserved. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt
CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of CC palmitate onto various protein substrates and be involved in a variety CC of cellular processes (Probable). Palmitoyltransferase that mediates CC palmitoylation of KCNMA1, regulating localization of KCNMA1 to the CC plasma membrane. May be involved in NOS1 regulation and targeting to CC the synaptic membrane. {ECO:0000269|PubMed:22399288, CC ECO:0000305|PubMed:22399288}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Summary: Human substrate experiments support S-palmitoylation, and the horse DHHC catalytic cysteine and overall protein sequence are conserved.
Reason: Human substrate experiments support S-palmitoylation, and the horse DHHC catalytic cysteine and overall protein sequence are conserved. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt
CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of CC palmitate onto various protein substrates and be involved in a variety CC of cellular processes (Probable). Palmitoyltransferase that mediates CC palmitoylation of KCNMA1, regulating localization of KCNMA1 to the CC plasma membrane. May be involved in NOS1 regulation and targeting to CC the synaptic membrane. {ECO:0000269|PubMed:22399288, CC ECO:0000305|PubMed:22399288}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
GO:0072659 protein localization to plasma membrane
IBA GO_REF:0000033
ACCEPT
Summary: KCNMA1 palmitoylation promotes plasma-membrane localization; transfer is supported by conserved ZDHHC23 catalytic architecture.
Reason: KCNMA1 palmitoylation promotes plasma-membrane localization; transfer is supported by conserved ZDHHC23 catalytic architecture. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt
CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of CC palmitate onto various protein substrates and be involved in a variety CC of cellular processes (Probable). Palmitoyltransferase that mediates CC palmitoylation of KCNMA1, regulating localization of KCNMA1 to the CC plasma membrane. May be involved in NOS1 regulation and targeting to CC the synaptic membrane. {ECO:0000269|PubMed:22399288, CC ECO:0000305|PubMed:22399288}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
Core Functions
ZDHHC23 is a membrane-associated DHHC-family protein S-palmitoyltransferase. Its conserved catalytic cysteine supports protein lipidation; characterized mammalian ZDHHC23 palmitoylates the potassium-channel subunit KCNMA1 and influences its plasma-membrane localization.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane CC {ECO:0000305|PubMed:22399288}; Multi-pass membrane protein CC {ECO:0000255}.
The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence.
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Assessment of 1 ProtNLM GO predictions for the selected horse ZDHHC23 protein, using mammalian experimental findings and an explicit comparison of the horse sequence.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human ZDHHC23-dependent KCNMA1 palmitoylation is experimentally supported (PMID:22399288). The horse sequence retains the DHHC catalytic cysteine (human289/horse283), with 91.07% identity over 98.53% of the human sequence. Transfer of protein-cysteine S-palmitoyltransferase activity is justified and agrees with the exact horse IBA/IEA term. This judgment rests on substrate experiments and sequence conservation, not ARBA agreement. Training-set membership is unknown.
Supporting Evidence:
file:human/ZDHHC23/ZDHHC23-uniprot.txt: "CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of CC palmitate onto various protein substrates and be involved in a variety CC of cellular processes (Probable). Palmitoyltransferase that mediates CC palmitoylation of KCNMA1, regulating localization of KCNMA1 to the CC plasma membrane. May be involved in NOS1 regulation and targeting to CC the synaptic membrane. {ECO:0000269|PubMed:22399288, CC ECO:0000305|PubMed:22399288}."
file:HORSE/ZDHHC23/ZDHHC23-bioinformatics/RESULTS.md: "The horse sequence A0A9L0T4E4 (448 residues) aligns to human Q8IYP9 (409 residues) with 91.07% identity across 403 paired residues. Paired coverage is 98.53% of the human sequence and 89.96% of the horse sequence."
PMID:22399288: "Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels."
📚 Additional Documentation
Notes
(ZDHHC23-notes.md)
ZDHHC23: paired evidence notes
Human reference: https://www.uniprot.org/uniprotkb/Q8IYP9/entry
Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels.
The horse sequence comparison is in ZDHHC23-bioinformatics/RESULTS.md. Transfer is assessed for this exact accession; human biochemical evidence is not equine experimental validation.