Ras-related protein Rap-2a (RAP2A)

The protein contains 183 amino acids for an estimated molecular weight of 20615 Da.

 

Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading. (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. 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.
  6. 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.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 179540

Ras-related protein 2a; rap2a
Rap2
Krev

CLONING

By screening a Raji Burkitt lymphoma cell line cDNA library with Drosophila Dras3 cDNA, Pizon et al. (1988) cloned RAP1A (179520) and RAP2A. The deduced 183-amino acid protein has a calculated molecular mass of 20.7 kD. It contains domains required for GTP binding and a Ras (see 190020)-like C-terminal motif for posttranslational lipid binding and subsequent anchoring to the plasma membrane. Northern blot analysis of lymphocyte mRNA detected transcripts of 2.2, 2.5, and 4.6 kb.

GENE FUNCTION

Lerosey et al. (1991) demonstrated that purified recombinant RAP2A bound GTP and exhibited a low intrinsic GTPase activity in the presence of Mg(2+). By site-directed mutagenesis, they showed that gly12 and thr35 were involved in the GTPase activity, thr145 was involved in guanyl nucleotide binding, and ser17 coordinated the Mg(2+) required for GTP binding. Zhu et al. (2005) stated that Rap2a and Jnk (see MAPK8, 601158), as well as their regulators, are expressed at excitatory synapses in rodent brain, and they identified a functional Rap2a signaling pathway in cultured mouse hippocampal CA1 neurons. Synaptic activity and activation of NR2A (GRIN2A; 138253)-containing NMDA receptor complexes activated Rap2a, which stimulated Jnk activity. Activation of Rap2a and Jnk led to the removal of Glur1 (GRIA1; 138248)- and Glur2 (GRIA2; 138247)-containing AMPA receptor complexes, and was essential for depolarization. In the bidirectional control of synaptic strength, Rap2a activity appeared to complement the long-term depression due to Rap1 (see 179520) signaling and oppose the long-term potentiation due to Ras signaling. By affinity chromatography of rat brain synaptosome extracts, Kawabe et al. (2010) identified Tnik (610005) among 15 proteins that interacted with immobilized Nedd4 (602278), an E3 ubiquitin ligase. Rap2a coimmunoprecipitated with Nedd4 and Tnik, but only following protein crosslinking. In vitro ubiquitination experiments revealed that Nedd4 monoubiquitinated Rap2a, but not Tnik or any other Ras-related small GTPase examined. Tnik was required for Nedd4 ubiquitination of Rap2a, and Rap2a monoubiquitination blocked Rap2a/Tnik signaling. Nedd4 -/- mouse cortical neurons showed underdeveloped dendrite extensions and arborizations, and expression of dominant-negative Rap2a or Tnik mutants rescued dendrite morphology in Nedd4 -/- embryos. Kawabe et al. (2010) concluded that NEDD4 positively regulates dendrite extension by blocking RAP2A/TNIK signaling.

MAPPING

Rousseau-Merck et al. (1990) used cDNA probes to assign 3 RAP genes by in situ hybridization; RAP1A, RAP1B (179530), and RAP2A were assigned to 1p13-p12, 12q14, and 13q34, respectively, without cross-hybridization or any secondary signal. ... 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

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for RAP2A

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 179540 was added.

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

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