Palmitoyltransferase ZDHHC5 (ZDHHC5)

The protein contains 715 amino acids for an estimated molecular weight of 77545 Da.

 

Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes (PubMed:21820437). Palmitoylates the G-protein coupled receptor SSTR5 and for FLOT2 (PubMed:21820437). (updated: Oct. 7, 2020)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  2. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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No binding partner found

The reference OMIM entry for this protein is 614586

Zinc finger dhhc domain-containing protein 5; zdhhc5
Dhhc5
Zinc finger protein 375; znf375
Kiaa1748

DESCRIPTION

Palmitoylation of proteins on cysteine residues is a reversible modification that regulates protein trafficking, stability, and activity. Protein palmitoyl acyltransferases, such as ZDHHC5, share a common catalytic asp-his-his-cys (DHHC) motif (summary by Li et al., 2012).

CLONING

By sequencing clones obtained from a size-fractionated human hippocampus cDNA library, Nagase et al. (2000) cloned ZDHHC5, which they designated KIAA1748. The deduced protein contains 758 amino acids. RT-PCR ELISA detected high ZDHHC5 expression in all adult and fetal tissues examined. Expression was highest in kidney and spleen, followed by brain, liver, skeletal muscle, testis, ovary, pancreas, heart, lung, fetal liver, and fetal brain. High expression was also detected in all specific adult brain regions examined, with highest expression in cerebellum. Using rat somatostatin receptor-5 (SSTR5; 182455) as bait to screen a mouse brain cDNA library, Kokkola et al. (2011) cloned Zdhhc5. The deduced Zdhhc5 protein contains 4 transmembrane domains and cytosolic N and C termini. The DHHC motif is located in the intracellular loop between transmembrane domains 2 and 3. Zdhhc5 and Sstr5 colocalized at the plasma membrane of transfected HEK293 cells.

GENE FUNCTION

By immunoprecipitation analysis, Kokkola et al. (2011) confirmed interaction of rodent Zdhhc5 and Sstr5 in transfected HEK293 cells. Deletion analysis revealed that the first 2 transmembrane domains of Zdhhc5 were required to interact with the intracellular C-terminal tail of Sstr5. Overexpression of Zdhhc5 increased palmitoylation of Sstr5, and small interfering RNA-mediated knockdown of ZDHHC5 inhibited Sstr5 palmitoylation. Li et al. (2012) had previously found that mice homozygous for a hypomorphic Dhhc5 allele were impaired in context-dependent learning and memory. Using a quantitative proteomic analysis of cultured mouse forebrain neuronal stem cells, they found that palmitoylation and oligomerization of the lipid raft assembly protein flotillin-2 (FLOT2; 131560) were abolished in homozygous Dhhc5 mutant neuronal stem cells. The absolute amount of flotillin-2 was not changed in Dhhc5 mutant neurons. In contrast, overexpression of mouse Dhhc5 in COS-7 cells markedly stimulated palmitoylation of human flotillin-2. Expression of Dhhc5 in neuronal stem cells was rapidly upregulated by growth factors, such as EGF (131530), and rapidly degraded via the proteasome upon induction of neuronal differentiation.

MAPPING

Hartz (2012) mapped the ZDHHC5 gene to chromosome 11q12.1 based on an alignment of the ZDHHC5 sequence (GenBank GENBANK AL117662) with the genomic sequence (GRCh37). ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 614586 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).