Protein XRP2 (RP2)

The protein contains 350 amino acids for an estimated molecular weight of 39641 Da.

 

Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane. Involved in localization of proteins, such as NPHP3, to the cilium membrane by inducing hydrolysis of GTP ARL3, leading to the release of UNC119 (or UNC119B). Acts as a GTPase-activating protein (GAP) for tubulin in concert with tubulin-specific chaperone C, but does not enhance tubulin heterodimerization. Acts as guanine nucleotide dissociation inhibitor towards ADP-ribosylation factor-like proteins. (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, is annotated as membranous in UniProt.


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

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VariantDescription
RP2
RP2
RP2; uncertain pathological significance
RP2
RP2
RP2
RP2
RP2
RP2; reduces affinity for ARL3 150-fold and inhibits the GTP-hydrolysis rate of ARL3
dbSNP:rs3126141
RP2
RP2
Reduces affinity for ARL3 3-fold
dbSNP:rs1805148

The reference OMIM entry for this protein is 300757

Rp2 gene; rp2

CLONING

By positional cloning in a 5-cM genomic interval linked to retinitis pigmentosa 2 (RP2; 312600), Schwahn et al. (1998) identified the RP2 gene. Using the YAC representation hybridization (YRH) technique, they detected a LINE 1 (L1) insertion in 1 X-linked recessive retinitis pigmentosa patient. Exon trapping experiments revealed a novel gene found to encode a 350-amino acid protein. The predicted gene product showed homology with human cofactor C (602971), a protein involved in the ultimate step of beta-tubulin (191130) folding. Northern blot hybridization with the cDNA revealed a 4-kb transcript in all fetal and adult tissues examined. RT-PCR showed expression in adult human retina using nested primers flanking the translation start and stop codons, respectively, which amplified a fragment of 1.2 kb.

GENE FUNCTION

Chapple et al. (2000) identified putative sites for N-terminal acyl modification by myristoylation and palmitoylation in the RP2 protein, consistent with its primary localization in the plasma membrane in cultured cells. Analysis of mutations in residues potentially required for N-terminal acylation revealed that the palmitoyl moiety is responsible for targeting of the myristoylated protein from intracellular membranes to the plasma membrane. By searching protein sequence databases, Schwahn et al. (2001) determined that RP2 and cofactor C represent members of 2 distinct orthologous groups. All previously identified missense mutations in RP2 affected amino acid residues which are conserved in all RP2 orthologs or both orthologous groups. Studies of RP2-green fluorescent protein fusion proteins in transiently transfected cells showed that a mutation in the N terminus of RP2 abolished localization to the plasma membrane, whereas C-terminal protein truncation mutations led to scattered fluorescent foci in the cytoplasm. Western blot analysis failed to detect RP2 protein in immortalized cell lines from patients with protein truncation mutations, while mRNA was still present. The authors concluded that loss of RP2 protein and/or aberrant intracellular distribution might be the basis for the photoreceptor cell degeneration in most RP2 cases. The RP2 protein, like cofactor C, stimulates the GTPase activity of tubulin in combination with cofactor D. RP2 has also been shown to interact with ADP-ribosylation factor-like-3 (ARL3; 604695) in a nucleotide- and myristoylation-dependent manner. Grayson et al. (2002) examined the relationship between RP2, cofactor C, and ARL3 in patient-derived cell lines and in the retina. Examination of lymphoblastoid cells from patients with the arg120-to-ter mutation in RP2 (R120X; 312600.0008) revealed that the expression levels of cofactor C and ARL3 were not affected by the absence of RP2. In human retina, RP2 was localized to the plasma membrane in both rod and cone photoreceptors, extending from the outer segment through the inner segment to the synaptic terminals. In contrast, cofactor C and ARL3 localized predominantly to the photoreceptor-connecting cilium in rod and cone photoreceptors. Cofactor C was cytoplasmic in distribution, whereas ARL3 localized to other microtubule structures within all cells. Grayson et al. (2002) suggested that RP2 may function in concert with ARL3 to link the cell membrane with the cytoskeleton in photoreceptors as part of the cell signaling or vesicular transport machinery. Evans et al. (2010) showed in vitro that the RP2 gene product loc ... 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 300757 was added.

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

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