Ras-related protein Rab-12 (RAB12)

The protein contains 244 amino acids for an estimated molecular weight of 27248 Da.

 

The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab may play a role in protein transport from recycling endosomes to lysosomes regulating, for instance, the degradation of the transferrin receptor. Involved in autophagy (By similarity). (updated: April 1, 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. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.
  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: 95%
Model score: 100
MODL_MODELLER-9.18

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The reference OMIM entry for this protein is 616448

Ras-associated protein rab12; rab12

DESCRIPTION

RAB GTPases (see 179508), such as RAB12, constitute a large family of proteins that control membrane identity and regulate intracellular membrane traffic by recruitment of effector proteins. RAB12 functions in retrograde trafficking between the plasma membrane and trans-Golgi/trans-Golgi network membranes (Rydell et al., 2014).

CLONING

By screening a Madin-Darby canine kidney (MDCK) cell line, Olkkonen et al. (1993) isolated partial cDNA sequences encoding Rab12. Northern blot analysis of mouse tissues showed highest expression in lung and heart, followed by brain, kidney, spleen, and liver. Expression was low in intestine. Immunofluorescence microscopy of hamster kidney demonstrated colocalization of Rab12 with the Golgi apparatus and with the non-clathrin-coated protein Copb1 (600959), suggesting that Rab12 may be involved in biosynthetic/exocytic transport. By confocal microscopy of HeLa cells, Rydell et al. (2014) found that tagged RAB12 showed predominantly perinuclear staining, with some vesicular staining. In the peripheral region, RAB12 colocalized with early and recycling endosomal markers, and in the perinuclear region, it codistributed with a cisternal Golgi marker.

GENE FUNCTION

By examining proteins in Shiga toxin B subunit (STxB)-induced tubular membrane invaginations and performing stable isotope labeling of amino acids in cell culture, Rydell et al. (2014) identified RAB12. Confocal microscopy demonstrated localization of RAB12 on STxB-induced tubular membrane invaginations and STxB-positive vesicles. Depletion of RAB12 with small interfering RNA showed that RAB12 was functionally involved in retrograde STxB transport. Depletion of RAB12 changed the steady-state localization of TGN46 (TGOLN2; 603062) and cation-independent mannose 6-phosphate receptor (MPRI; 147280) without affecting other trafficking routes. Rydell et al. (2014) concluded that RAB12 functions in the retrograde transport route.

MAPPING

Gross (2015) mapped the RAB12 gene to chromosome 18p11.22 based on an alignment of the RAB12 sequence (GenBank GENBANK BC071600) with the genomic sequence (GRCh38). ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616448 was added.

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.

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

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