Translocon-associated protein subunit delta (SSR4)

The protein contains 173 amino acids for an estimated molecular weight of 18999 Da.

 

TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. 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 predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 58%
Model score: 0

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VariantDescription
dbSNP:rs782018895

The reference OMIM entry for this protein is 300090

Signal sequence receptor, delta; ssr4
Translocon-associated protein, delta subunit; trapd

DESCRIPTION

The SSR4 gene encodes the delta subunit of TRAP, a heterotetrameric complex that also includes SSR1 (600868), SSR2 (600867), and SSR3 (606213). This protein complex localizes to a specific site on the membrane of the endoplasmic reticulum (ER), the so-called translocon, where nascent secretory proteins enter the ER lumen. TRAPD is assumed to be involved in the secretion of proteins and to play a role in posttranslational N-glycosylation of proteins (summary by Brenner et al., 1997 and Losfeld et al., 2014).

CLONING

By genomic sequencing and EST database searching, Brenner et al. (1997) assembled a full-length human cDNA encoding the delta subunit of the translocon-associated protein (TRAPD). Northern blot analysis detected a 3.8-kb transcript in all 8 tissues examined, with high expression in pancreas, where large quantities of lipases, nucleases, and proteases are synthesized and secreted, and low expression in the other tissues.

GENE STRUCTURE

Brenner et al. (1997) determined that the TRAPD gene contains 6 exons and spans approximately 0.7 kb.

MAPPING

Brenner et al. (1997) identified the TRAPD gene in the Xq28 region, approximately 70 kb telomeric to the ABCD1 gene (300371), and adjacent to the IDH-gamma gene (IDH3G; 300089), which they also cloned. The IDH3G and TRAPD genes are arranged in a compact head-to-head manner and are transcribed in opposite directions. The nontranscribed intergenic region between them comprises only 133 bp and is embedded in a CpG island. Brenner et al. (1997) concluded that the CpG island functions as a bidirectional promoter to initiate the transcription of both functionally unrelated genes with distinct expression patterns. Brenner et al. (1997) showed that in both rat and mouse, this region of the genome is similarly compact and comprises less than 249 bp in rat and not more than 164 bp in mouse. In both cases this intergenic region is embedded in a CpG island and is highly conserved, with nucleotide identity values ranging from 70.1% between human and rat to 92.6% between mouse and rat.

MOLECULAR GENETICS

In a 16-year-old boy with congenital disorder of glycosylation type Iy (CDG1Y; 300934), Losfeld et al. (2014) identified a de novo hemizygous truncating mutation in the SSR4 gene (300090.0001). The mutation was found by whole-exome sequencing. Patient cells showed complete absence of the SSR4 protein, 50% residual levels of SSR1 and SSR3, and 10% residual levels of SSR2. Overexpression of wildtype SSR4 rescued the levels of the subunits, presumably allowing formation of a functional SSR complex. Expression of an engineered fluorescence biomarker in patient fibroblasts showed that N-glycosylation was significantly decreased (48%) compared to controls. Losfeld et al. (2014) hypothesized that the SSR4 defect would induce ER stress, lead to the accumulation of misfolded proteins, and further the hypoglycosylation of proteins. The findings suggested that the TRAP complex directly functions in N-glycosylation. ... More on the omim web site

Subscribe to this protein entry history

May 13, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300090 was added.

Feb. 25, 2016: Protein entry updated
Automatic update: model status changed

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed