PDZ domain-containing protein 8 (PDZD8)

The protein contains 1154 amino acids for an estimated molecular weight of 128563 Da.

 

Molecular tethering protein that connects endoplasmic reticulum and mitochondria membranes (PubMed:29097544). PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for endoplasmic reticulum-mitochondria Ca(2+) transfer (PubMed:29097544). In neurons, involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons (PubMed:29097544). Plays an indirect role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). May inhibit herpes simplex virus 1 infection at an early stage (PubMed:21549406). (updated: Sept. 12, 2018)

Protein identification was indicated in the following studies:

  1. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  2. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

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 predicted to be membranous by TOPCONS.


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

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VariantDescription
dbSNP:rs35664484
dbSNP:rs363294

No binding partner found

The reference OMIM entry for this protein is 614235

Pdz domain-containing protein 8; pdzd8

DESCRIPTION

PDZD8 is a cytoskeletal regulatory protein that interacts with moesin (MSN; 309845) and regulates stable microtubule abundance. Both MSN and PDZD8 suppress herpes simplex virus (HSV)-1 infection, but PDZD8 also promotes human immunodeficiency (HIV)-1 infection (see 609423) (Henning et al., 2010, 2011).

CLONING

By yeast 2-hybrid screening of a human testis cDNA library with HIV-1 Gag as bait, Henning et al. (2010) cloned PDZD8. The predicted 1,154-amino acid protein contains a PDZ domain, a zinc finger domain, and a coiled-coil motif.

GENE FUNCTION

By yeast 2-hybrid screening, Henning et al. (2010) showed that PDZD8 amino acids 932 to 1119, including the coiled-coil motif, interacted with HIV-1 Gag amino acids 59 to 250. Coimmunoprecipitation analysis confirmed the interaction. Overexpression of PDZD8 in human cells promoted initiation of retroviral transcription and HIV-1 infection, whereas knockdown of PDZD8 decreased HIV-1 infection. A PDZD8 mutant lacking the coiled-coil domain failed to bind Gag and promote HIV-1 infection. By yeast 2-hybrid screening and coimmunoprecipitation analysis, Henning et al. (2011) found that amino acids 990 to 1155 of human PDZD8 interacted with amino acids 158 to 279 of moesin. Expression of PDZD8 or moesin reduced the levels of stable microtubules in the human CHME3 microglial cell line. In addition, expression of PDZD8 or moesin reduced the cytopathic effects of HSV-1, as well as HSV-1 replication and spread, in CHME3 cells.

MAPPING

Gross (2011) mapped the PDZD8 gene to chromosome 10q25.3-q26.11 based on an alignment of the PDZD8 sequence (GenBank GENBANK BC028375) with the genomic sequence (GRCh37). ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 614235 was added.

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