Geranylgeranyl transferase type-2 subunit alpha (RABGGTA)

The protein contains 567 amino acids for an estimated molecular weight of 65072 Da.

 

Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A. (updated: Jan. 7, 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. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. 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.


Interpro domains
Total structural coverage: 100%
Model score: 91

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VariantDescription
dbSNP:rs729421

The reference OMIM entry for this protein is 601905

Rab geranylgeranyl transferase, alpha subunit; rabggta

See RABGGTB (179080) for general information about RAB geranylgeranyl transferase.

CLONING

Van Bokhoven et al. (1996) cloned the human RABGGTA gene from a fetal brain library. The gene encodes a 567-amino acid polypeptide. Homology to the transglutaminase gene, TGM1 (190195), which maps to 14q11, indicated that this subunit was located on the same chromosomal band; Southern blot analysis confirmed this locus. Van Bokhoven et al. (1996) found that the 3-prime end of the RABGGTA cDNA sequence overlaps the promoter region of TGM1. Further analysis revealed that the RABGGTA and TGM1 genes are located only 2 kb apart in head-to-tail tandem arrangement; however, these 2 genes are not likely to be functionally related.

GENE FUNCTION

Seabra et al. (1991) presented evidence that 2 prenyltransferases, farnesyltransferase and geranylgeranyltransferase (GGTase), are heterodimers that share a common alpha subunit with different beta subunits. The third identified prenyltransferase is a GGTase that recognizes proteins that terminate in the sequence cys-X-cys or cys-cys. Its substrates include a large family of related membrane-associated GTP-binding proteins termed RAB proteins. According to van Bokhoven et al. (1996), RAB proteins are the only known substrates of RAB GGTase. RAB GGTase is composed of 2 tightly associated subunits, alpha (RABGGTA) and beta (RABGGTB, 179080). The enzyme from rat brain contains 2 components, A and B. Seabra et al. (1992) reported the purification of component A, a single 95-kD polypeptide. The holoenzyme attaches (3)H-geranylgeranyl to cysteines in 2 GTP-binding proteins, RAB3A (179490) and RAB1A (179508). Six peptides from rat component A showed striking similarity to the product of a defective gene in choroideremia (303100). Seabra et al. (1992) hypothesized that component A binds conserved sequences in RAB and that component B transfers geranylgeranyl. Seabra et al. (1993) demonstrated a marked deficiency in the activity of component A in lymphoblasts from subjects with choroideremia.

ANIMAL MODEL

Mice homozygous for 'gunmetal' (gm), a spontaneous, recessive mutation, have prolonged bleeding caused by defects in platelets and megakaryocytes (Swank et al., 1993; Novak et al., 1995). These mice also have macrothrombocytopenia and reduced platelet alpha- and delta-granule contents (storage pool deficiency, SPD). Megakaryocytes, the progenitors of platelets, are more plentiful in gm mice, but have abnormal intracellular membranes, increased emperipolesis (the active movement of 1 cell through another), and decreased platelet synthesis. In addition, gm homozygotes have partial cutaneous albinism, the feature that gives the mutation its name. Detter et al. (2000) noted that the phenotype resembles human gray platelet syndrome (GPS; 139090) and platelet alpha- and delta-SPD (185050). By positional cloning, Detter et al. (2000) showed that gm results from a G-to-A substitution in a splice acceptor site within the alpha-subunit of RAB geranylgeranyl transferase (Rabggta). Most Rabggta mRNAs from gm tissues skipped exon 1 and lacked a start codon. Levels of the protein and of enzyme activity were reduced 4-fold in gm platelets. Geranylgeranylation and membrane association of Rab27 (603868), a RAB GGTase substrate, were significantly decreased in gm platelets. These findings indicated that geranylgeranylation of RAB GTPases is critical for hemostasis. Detter et al. (2000) suggested that Rab GGT ... More on the omim web site

Subscribe to this protein entry history

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

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

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601905 was added.