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  6. Protein XRP2

Tbio Protein XRP2

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.

The RP2 locus has been implicated as one cause of X-linked retinitis pigmentosa. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of beta-tubulin folding. Progressive retinal degeneration may therefore be due to the accumulation of incorrectly-folded photoreceptor or neuron-specific tubulin isoforms followed by progressive cell death [provided by RefSeq, Jul 2008]

 Comments

Property Summary

NCBI Gene PubMed Count 51
PubMed Score 19.88
PubTator Score 168.53

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (4)

Disease Target Count Z-score Confidence
Aland Island eye disease 13 5.121 2.6
Night Blindness 39 3.114 1.6

Expression

  Differential Expression (13)

Disease log2 FC p
astrocytoma 1.800 8.4e-28
glioblastoma 2.100 2.0e-07
oligodendroglioma 1.700 1.2e-16
posterior fossa group B ependymoma 2.600 6.1e-09
atypical teratoid/rhabdoid tumor 1.500 2.7e-04
primitive neuroectodermal tumor 1.300 7.3e-05
lung cancer -1.300 1.8e-03
breast carcinoma 1.400 2.7e-03
pediatric high grade glioma 2.400 4.4e-08
pilocytic astrocytoma 2.100 8.1e-07
sonic hedgehog group medulloblastoma 1.100 2.3e-02
primary Sjogren syndrome 1.100 1.3e-03
aldosterone-producing adenoma -1.267 2.2e-04

Synonym

Accession O75695 Q86XJ7 Q9NU67
Symbols XRP2
NME10
TBCCD2
NM23-H10
DELXp11.3

Gene

RP2

PANTHER Protein Class (3)

PDB

2BX6   3BH6   3BH7  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (18)

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 GO Function (3)

 GO Component (9)

 GO Process (6)

 Compartment GO Term (39)

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 OMIM Phenotype (1)

 MGI Phenotype (2)

 HCA RNA Cell Line (56)

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Pathway (5)

Protein-protein Interaction (27)

UNC119B   CYS1   NPHP3   XPO7   TNPO2   GLMN   TSC2   XPO4   KIAA0368   DMXL2   PDS5A   MTOR   SYMPK   STAT3   TNPO3   TXNRD1   USP24   CSNK1D   CSNK1E   MARC2   SLC44A2   TKFC   PRAF2   CTU1   TRIP12   QSOX1   COG8  

Gene RIF (27)

PMID Text
25844643 ellipsometric measurements of naRP2 demonstrated that its particular affinity for saturated phospholipids can be explained by its larger extent of insertion in this phospholipid monolayer compared to that in polyunsaturated phospholipid monolayers.
25292197 The ability of the restored RP2 protein level to reverse the observed cellular phenotypes in cells lacking RP2 indicates that translational read-through could be clinically beneficial for patients.
25078280 The methylation state of CpG sites close to the RP2 core promoter (GAAA)n repeat serves as a proxy measurement of X-chromosome inactivation in human and non-human primates.
24479636 A novel frameshift mutation in RP2 was detected. This mutation was located in exon 2 of the RP2 gene: a nucleotide C was inserted at 111 (c.111insC, Fig. 1A), which caused a protein translation frameshift
23372056 Direct sequencing of RPGR and RP2 allowed for identification of a disease-causing mutation in 21 families. Of these "adRP" families 19 had RPGR mutations, and two had RP2 mutations.
23150612 Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration.
22183373 The localization of RP2 to basal bodies and cilia in photoreceptors and kidney cells has linked RP2 dysfunction with ciliopathies.
22072390 data support a role for RP2 in facilitating the membrane association and traffic of Gbeta1, potentially prior to the formation of the obligate Gbeta:Ggamma heterodimer; combined with other recent evidence, this suggests that RP2 may co-operate with Arl3 and its effectors in the cilia-associated traffic of G proteins
21285245 Data demonstrate that Importin beta2 is necessary for localization of retinitis pigmentosa 2 (RP2) to the primary cilium, and identify two distinct binding sites of RP2, which interact independently with Importin beta2.
20801516 Observational study of genetic testing. (HuGE Navigator)
20625056 An identifiable phenotype for RP2-X-linked retinitis pigmentosa aids in clinical diagnosis and targeted genetic screening.
20106869 We propose that RP2 regulation of Arl3 is important for maintaining Golgi cohesion, facilitating the transport and docking of vesicles and thereby carrying proteins to the base of the photoreceptor connecting cilium for transport to the outer segment.
20021257 Our results expand the frequency and spectrum of mutations at RPGR and RP2 as well as their associated clinical phenotypes in Chinese patients.
19516003 A transversion (T>A) at position -9 in intron 3 of RP2 causes X-linked retinitis pigmentosa (XLRP) by altering the splicing pattern and highlights the pathogenicity of intronic variants.
18376416 RP2 is an efficient GAP for Arl3, with structural features similar to other GAPs
17724181 The proportion of RP2-mediated XLRP in the Danish population is higher and the proportion of RPGR-ORF15 is lower than reported in other studies.
17093403 Three ORF15 mutations and one RP2 mutation in five Japanese retinitis pigmentosa families.
16969763 Observational study of genotype prevalence. (HuGE Navigator)
16936086 In this cohort of XLRP families, as has happened in previous studies, RP3 also seems to be the most prevalent form of XLRP, and, based on the results, the authors propose a four-step protocol for molecular diagnosis of XLRP families.
16472755 The N-terminal 34 residues and beta helix domain of RP2 are required for interaction with Arl3.
16457815 The data suggest that RP2 may have previously unrecognized roles as a DNA damage response factor and 3' to 5' exonuclease.
14566651 Mutations in the RP2 gene is associated with X-linked retinitis pigmentosa
14564670 Observational study of genotype prevalence and gene-disease association. (HuGE Navigator)
14564670 Patients with RP2 mutations had, on average, lower visual acuity but similar visual field area, final dark-adapted threshold, and 30-Hz ERG amplitude compared with those with RPGR mutations
11992260 A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa.
11847227 functional overlap with tubulin-specific chaperone cofactor C
11798852 The mutation 358C-->T is useful in analyzing the function of RP2 protein and gene diagnosis of X-linked retinitis pigmentosa (XLRP).

AA Sequence 

MGCFFSKRRKADKESRPENEEERPKQYSWDQREKVDPKDYMFSGLKDETVGRLPGTVAGQQFLIQDCENC      1 - 70
NIYIFDHSATVTIDDCTNCIIFLGPVKGSVFFRNCRDCKCTLACQQFRVRDCRKLEVFLCCATQPIIESS     71 - 140
SNIKFGCFQWYYPELAFQFKDAGLSIFNNTWSNIHDFTPVSGELNWSLLPEDAVVQDYVPIPTTEELKAV    141 - 210
RVSTEANRSIVPISRGQRQKSSDESCLVVLFAGDYTIANARKLIDEMVGKGFFLVQTKEVSMKAEDAQRV    211 - 280
FREKAPDFLPLLNKGPVIALEFNGDGAVEVCQLIVNEIFNGTKMFVSESKETASGDVDSFYNFADIQMGI    281 - 350
//

Text Mined References (57)

PMID Year Title
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25844643 2015 Lipid Selectivity, Orientation, and Extent of Membrane Binding of Nonacylated RP2.
25292197 2015 Translational read-through of the RP2 Arg120stop mutation in patient iPSC-derived retinal pigment epithelium cells.
25255805 2014 Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.
25078280 2014 5meCpG epigenetic marks neighboring a primate-conserved core promoter short tandem repeat indicate X-chromosome inactivation.
24479636 2014 A novel one-base insertion mutation in the retinitis pigmentosa 2 gene in a large X-linked Taiwanese family.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23372056 2013 Mutations in the X-linked retinitis pigmentosa genes RPGR and RP2 found in 8.5% of families with a provisional diagnosis of autosomal dominant retinitis pigmentosa.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23150612 2012 Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease.
22334370 2012 Next-generation genetic testing for retinitis pigmentosa.
22183373 2012 The role of the X-linked retinitis pigmentosa protein RP2 in vesicle traffic and cilia function.
22085962 2011 An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium.
22072390 2012 The X-linked retinitis pigmentosa protein RP2 facilitates G protein traffic.
21285245 2011 Localization of retinitis pigmentosa 2 to cilia is regulated by Importin beta2.
21269460 2011 Initial characterization of the human central proteome.
20801516 2011 Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip.
20625056 2010 RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa.
20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
20106869 2010 The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium.
20021257 2010 Mutations in RPGR and RP2 of Chinese patients with X-linked retinitis pigmentosa.
19852809 2009 Nme protein family evolutionary history, a vertebrate perspective.
19516003 2009 Identification of an intronic single-point mutation in RP2 as the cause of semidominant X-linked retinitis pigmentosa.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18588884 2008 Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP complex.
18376416 2008 The retinitis pigmentosa 2 gene product is a GTPase-activating protein for Arf-like 3.
17724181 2007 A population-based epidemiological and genetic study of X-linked retinitis pigmentosa.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
17093403 2006 Mutational analysis of RPGR and RP2 genes in Japanese patients with retinitis pigmentosa: identification of four mutations.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16969763 2007 Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype-phenotype correlations and impact on genetic counseling.
16936086 2006 Mutational screening of the RP2 and RPGR genes in Spanish families with X-linked retinitis pigmentosa.
16472755 2006 Crystal structure of the human retinitis pigmentosa 2 protein and its interaction with Arl3.
16457815 2006 The retinitis pigmentosa-mutated RP2 protein exhibits exonuclease activity and translocates to the nucleus in response to DNA damage.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15772651 2005 The DNA sequence of the human X chromosome.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14566651 2003 Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes.
14564670 2003 RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa.
12657579 2003 X-linked retinitis pigmentosa: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of exon ORF15.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12417528 2002 Localization in the human retina of the X-linked retinitis pigmentosa protein RP2, its homologue cofactor C and the RP2 interacting protein Arl3.
11992260 2002 A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa.
11847227 2002 Functional overlap between retinitis pigmentosa 2 protein and the tubulin-specific chaperone cofactor C.
11462235 2001 Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.
10942419 2000 Mutations in the N-terminus of the X-linked retinitis pigmentosa protein RP2 interfere with the normal targeting of the protein to the plasma membrane.
10937588 2000 X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and correlation with visual function.
10862093 2000 Novel frameshift mutations in the RP2 gene and polymorphic variants.
10634633 2000 A new Leu253Arg mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa.
10520237 1999 Genotype-phenotype correlation in X-linked retinitis pigmentosa 2 (RP2).
10090907 1999 Mutations in the RP2 gene cause disease in 10% of families with familial X-linked retinitis pigmentosa assessed in this study.
10053026 1999 Protein-truncation mutations in the RP2 gene in a North American cohort of families with X-linked retinitis pigmentosa.
9697692 1998 Positional cloning of the gene for X-linked retinitis pigmentosa 2.
8938433 1996 Mapping the RP2 locus for X-linked retinitis pigmentosa on proximal Xp: a genetically defined 5-cM critical region and exclusion of candidate genes by physical mapping.
6325945 1984 Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28.
2876947 1986 Genetic linkage between X-linked retinitis pigmentosa and DNA probe DXS7 (L1.28): further linkage data, heterogeneity testing, and risk estimation.