Ras-related protein Rab-14 (RAB14)

The protein contains 215 amino acids for an estimated molecular weight of 23897 Da.

 

Involved in membrane trafficking between the Golgi complex and endosomes during early embryonic development. Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. May act by modulating the kinesin KIF16B-cargo association to endosomes (By similarity). Regulates, together with its guanine nucleotide exchange factor DENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion. (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. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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: 52
MODL_MODELLER-9.18

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VariantDescription
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The reference OMIM entry for this protein is 612673

Ras-associated protein rab14; rab14

DESCRIPTION

RAB14 belongs to the large RAB family of low molecular mass GTPases that are involved in intracellular membrane trafficking. These proteins act as molecular switches that flip between an inactive GDP-bound state and an active GTP-bound state in which they recruit downstream effector proteins onto membranes (Junutula et al., 2004).

CLONING

By searching databases using rat Rab14, Junutula et al. (2004) identified human and mouse RAB14. The mouse and human proteins contain 215 amino acids and are identical to the rat protein except for the fourth residue, which is threonine in rat and alanine in mouse and human. RAB14 is most closely related to the Golgi membrane protein RAB2 (179509) and the endosomal protein RAB4 (179511). PCR analysis of human tissues detected ubiquitous RAB14 expression, with high levels in brain, heart, kidney, placenta, lung, pancreas, spleen, and testis, and lower levels in muscle, thymus, intestine, colon, and leukocytes. Western blot analysis detected Rab14 at an apparent molecular mass of 24 kD in most rat tissues examined and at 28 kD in heart. Immunohistochemical analysis of several cell lines, including HeLa cells, revealed endogenous RAB14 in small puncta throughout the cell and in perinuclear structures. RAB14 staining partially overlapped with markers for early and recycling endosomes, cis-Golgi, and trans-Golgi network. Immunogold labeling of normal rat kidney cells revealed membrane-bound Rab14 associated with multiple membrane and vesicular structures. Most Rab14 was associated with small tubulo-vesicular structures throughout the cytoplasm, with Golgi stack and associated vesicles, and with endoplasmic reticulum. A minor fraction was associated with endosomal vacuoles and the plasma membrane.

GENE FUNCTION

Junutula et al. (2004) found that overexpression of rat Rab14 with a mutation predicted to result in a GTP-bound conformation (gln70 to leu) shifted the distribution of Rab14 toward early endosome-associated vesicles. In contrast, overexpression of RAB14 with mutations predicted to result in nucleotide-free and GDP-bound conformations (asn124 to ile and ser25 to asn, respectively) induced a shift toward the Golgi region. Overexpression of these mutants caused a similar, but less pronounced, redistribution of transferrin receptor (TFRC; 190010), but transferrin (TF; 190000) uptake and receptor recycling were unaffected. Junutula et al. (2004) concluded that RAB14 is involved in the biosynthetic/recycling pathway between the Golgi and endosomal compartments. In muscle and fat cells, insulin (INS; 176730) stimulation activates a signaling cascade that causes intracellular vesicles containing glucose transporter-4 (GLUT4, or SLC2A4; 138190) to translocate to and fuse with the plasma membrane. Using mass spectrometry, Larance et al. (2005) identified Rab10 (612672), Rab11 (see RAB11A; 605570), and Rab14 on Glut4 vesicles from cultured mouse adipocytes. These vesicles also contained the RAB GTPase-activating protein (GAP) As160 (TBC1D4; 612465), suggesting that the RAB proteins may be AS160 substrates. Miinea et al. (2005) found that the purified recombinant GAP domain of human AS160 showed GAP activity with RAB2A, RAB8A (165040), RAB10, and RAB14, but not with 14 other RABs. Immunoblot analysis showed that these RABs associated with Glut4-positive vesicles in mouse adipocytes. Miinea et al. (2005) concluded that AK160 functions as a RAB GAP and that RABs may par ... 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

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 612673 was added.