Ras-related protein Rab-6A (RAB6A)

The protein contains 208 amino acids for an estimated molecular weight of 23593 Da.

 

Protein transport. Regulator of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER). Has a low GTPase activity. Involved in COPI-independent retrograde transport from the Golgi to the ER (PubMed:25962623). (updated: Jan. 31, 2018)

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.
  5. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 97
MODL_MODELLER-9.18

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The reference OMIM entry for this protein is 179513

Ras-associated protein rab6a; rab6a
Ras-associated protein rab6; rab6

CLONING

The mammalian RAB proteins show striking similarities to the S. cerevisiae YPT1 and SEC4 proteins, Ras-related GTP-binding proteins involved in the regulation of secretion. Zahraoui et al. (1989) isolated cDNAs encoding RAB6 and several other human RAB proteins. The predicted human RAB6 protein contains 208 amino acids. Northern blot analysis revealed that the RAB6 gene was expressed as a 3.6-kb mRNA in a human fibroblast cell line. By screening a human kidney cDNA library with a DNA fragment of RAB6C (612909), Shan et al. (2000) isolated a RAB6A variant that they called RAB6C. The deduced 208-amino acid protein encoded by this variant differs at only 3 amino acids compared with the previously reported RAB6A isoform.

GENE FUNCTION

Using quantitative RT-PCR, Shan et al. (2000) showed that a RAB6A variant that they called RAB6C was downregulated in a multidrug-resistant clone of MCF7 breast cancer cells compared with the parental MCF7 cell line. Reexpression of the RAB6A variant in the resistant cell line restored sensitivity to several anticancer drugs. Flow cytometry experiments showed that sensitivity to doxorubicin was associated with increased drug accumulation in cells expressing the RAB6A variant. Using a large-scale small interfering RNA screen to identify host factors required by human immunodeficiency virus (HIV)-1 (see 609423), Brass et al. (2008) identified more than 250 HIV-dependency factors (HDFs), 79 of which showed significantly higher expression in immune tissues compared with other tissues. The HDFs RAB6 and VPS53 (615850), retrograde Golgi transport proteins, were involved in viral entry. Brass et al. (2008) proposed that targeting of HDFs essential for the viral cycle but not critical for the host may avoid drug resistance due to viral diversity and escape mutation. Pusapati et al. (2012) found that human RGP1 (615742) and RIC1 (610354) interacted independently with GDP-bound RAB6A, but neither functioned alone as a guanine nucleotide exchange factor (GEF) for RAB6A. In contrast, coexpression of RIC1 and RGP1 resulted in a RIC1-RGP1 complex that showed concentration-dependent GEF activity for RAB6A, but not other RAB proteins tested. Loss of RIC1 or RGP1 from human cell lines destabilized RAB6A protein and decreased its abundance at the Golgi complex, concomitant with a block in RAB6A-dependent retrograde transport of mannose 6-phosphate receptor (IGF2R; 147280) from late endosomes to the Golgi.

MAPPING

By in situ hybridization, Rousseau-Merck et al. (1991) assigned the RAB6 gene to chromosome 2q14-q21. ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for RAB6A

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 179513 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

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