SpermatogenesisOnline 1.0

Tag Content
SG ID
SG00018767 
UniProt Accession
Theoretical PI
4.88  
Molecular Weight
151996 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Rpgrip1 
Gene Synonyms/Alias
 
Protein Name
X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 
Protein Synonyms/Alias
RPGR-interacting protein 1 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:14;52730578-52780982;1
View in Ensembl genome browser  
Function in Stage
Uncertain 
Function in Cell Type
Uncertain 
Probability (GAS) of Function in Spermatogenesis
0.624588048 
The probability was calculated by GAS algorithm, ranging from 0 to 1. The closer it is to 1, the more possibly it functions in spermatogenesis.
Description
Temporarily unavailable 
Abstract of related literatures
1. Retinitis pigmentosa (RP) is a blinding retinal disease in which the photoreceptor cells degenerate. Mutations in the gene for retinitis pigmentosa GTPase regulator (RPGR) are a frequent cause of RP. The function of RPGR is not well understood, but it is thought to be a putative guanine nucleotide exchange factor for an unknown G protein. Ablation of the RPGR gene in mice suggested a role in maintaining the polarized distribution of opsin across the cilia. To investigate its function, we used a protein interaction screen to identify candidate proteins that may interact physiologically with RPGR. One such protein, designated RPGR-interacting protein (RPGRIP), is expressed specifically in rod and cone photoreceptors. It consists of an N-terminal region predicted to form coiled coil structures linked to a C-terminal tail that binds RPGR. In vivo, both proteins co-localize in the photoreceptor connecting cilia. RPGRIP is stably associated with the ciliary axoneme independent of RPGR and is resistant to extraction under conditions that partially solubilized other cytoskeletal components. When over-expressed in heterologous cell lines, RPGRIP appears in insoluble punctate and filamentous structures. These data suggest that RPGRIP is a structural component of the ciliary axoneme, and one of its functions is to anchor RPGR within the cilium. RPGRIP is the only protein known to localize specifically in the photoreceptor connecting cilium. As such, it is a candidate gene for human photoreceptor disease. The tissue-specific expression of RPGRIP explains why mutations in the ubiquitously expressed RPGR confer a photoreceptor-specific phenotype. PMID: [11104772] 

2. This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development. PMID: [16141072] 

3. The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline. PMID: [15489334] 

4. The retinitis pigmentosa GTPase regulator (RPGR) is encoded by the X-linked RP3 locus, which upon genetic lesions leads to neurodegeneration of photoreceptors and blindness. The findings that RPGR specifically and directly interacts in vivo and in vitro with retina-specific RPGR-interacting protein 1 (RPGRIP) and that human mutations in RPGR uncouple its interaction with RPGRIP provided the first clue for the retina-specific pathogenesis of X-linked RP3. Recently, mutations in RPGRIP were found to lead to the retinal dystrophy, Leber congenital amaurosis. However, mouse models null for RPGR had, surprisingly, a very mild phenotype compared with those observed in XlRP3-affected humans and dogs. Moreover, recent reports are seemingly in disagreement on the localization of RPGR and RPGRIP in photoreceptors. These discrepancies were compounded with the finding of RPGR mutations leading exclusively to X-linked cone dystrophy. To resolve these discrepancies and to gain further insight into the pathology associated with RPGR- and RPGRIP-allied retinopathies, we now show, using several isoform-specific antibodies, that RPGR and RPGRIP isoforms are distributed and co-localized at restricted foci throughout the outer segments of human and bovine, but not mice rod photoreceptors. In humans, they also localize in cone outer segments. RPGRIP is also expressed in other neurons such as amacrine cells. Thus, the data lend support to the existence of species-specific subcellular processes governing the function and/or organization of the photoreceptor outer segment as reflected by the species-specific localization of RPGR and RPGRIP protein isoforms in this compartment, and provide a rationale for the disparity of phenotypes among species and in the human. PMID: [12140192] 

5. Retinitis pigmentosa is a photoreceptor degenerative disease leading to blindness in adulthood. Leber congenital amaurosis (LCA) describes a more severe condition with visual deficit in early childhood. Defects in the retinitis pigmentosa GTPase regulator (RPGR) and an RPGR-interacting protein (RPGRIP) are known causes of retinitis pigmentosa and LCA, respectively. Both proteins localize in the photoreceptor connecting cilium (CC), a thin bridge linking the cell body and the light-sensing outer segment. We show that RPGR is absent in the CC of photoreceptors lacking RPGRIP, but not vice versa. Mice lacking RPGRIP elaborate grossly oversized outer segment disks resembling a cytochalasin D-induced defect and have a more severe disease than mice lacking RPGR. Mice lacking both proteins are phenotypically indistinguishable from mice lacking RPGRIP alone. In vitro, RPGRIP forms homodimer and elongated filaments via interactions involving its coiled-coil and C-terminal domains. We conclude that RPGRIP is a stable polymer in the CC where it tethers RPGR and that RPGR depends on RPGRIP for subcellular localization and normal function. Our data suggest that RPGRIP is also required for disk morphogenesis, putatively by regulating actin cytoskeleton dynamics. The latter hypothesis may be consistent with a distant homology between the C-terminal domain of RPGRIP and an actin-fragmin kinase, predicted by fold recognition algorithms. A defect in RPGRIP encompasses loss of both functions, hence the more severe clinical manifestation as LCA. PMID: [12651948] 

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Function
Essential for RPGR function and is also required fornormal disk morphogenesis. 
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Subcellular Location
Cell projection, cilium. Note=Situatedbetween the axonemal microtubules and the plasma membrane. 
Tissue Specificity
Colocalizes with RGPR in the photoreceptorconnecting cilium, a thin bridge linking the cell body and thelight-sensing outer segment. 
Gene Ontology
GO IDGO termEvidence
GO:0005930 C:axoneme IDA:MGI.
GO:0005929 C:cilium IDA:MGI.
GO:0042462 P:eye photoreceptor cell development IMP:MGI.
GO:0050896 P:response to stimulus IEA:UniProtKB-KW.
GO:0060041 P:retina development in camera-type eye IMP:MGI.
GO:0007601 P:visual perception IMP:MGI.
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Interpro
IPR000008;    C2_Ca-dep.
IPR008973;    C2_Ca/lipid-bd_dom_CaLB.
IPR018029;    C2_membr_targeting.
IPR021656;    DUF3250.
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Pfam
PF00168;    C2;    1.
PF11618;    DUF3250;    1.
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SMART
SM00239;    C2;    1.
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PROSITE
PS50004;    C2;    1.
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PRINTS
Created Date
18-Oct-2012 
Record Type
GAS predicted 
Sequence Annotation
CHAIN         1   1331       X-linked retinitis pigmentosa GTPase
                             regulator-interacting protein 1.
                             /FTId=PRO_0000097433.
DOMAIN      750    854       C2.
REGION      997   1326       Interaction with RPGR.
COILED      236    352       Potential.
COILED      498    546       Potential.
COILED      908    999       Potential.
VAR_SEQ       1   1074       Missing (in isoform 5).
                             /FTId=VSP_009529.
VAR_SEQ       1    319       Missing (in isoform 3 and isoform 4).
                             /FTId=VSP_009528.
VAR_SEQ     320    345       EFQVRVEDLEKERKLLSDSYDRLLEN -> MLKLCNKDAGS
                             YSFEDPSDTEPGVFS (in isoform 3 and isoform
                             4).
                             /FTId=VSP_009530.
VAR_SEQ     399    399       Missing (in isoform 2 and isoform 3).
                             /FTId=VSP_009531.
VAR_SEQ     541    867       Missing (in isoform 4).
                             /FTId=VSP_009533.
VAR_SEQ     552    867       Missing (in isoform 3).
                             /FTId=VSP_009534.
VAR_SEQ     552    554       EQL -> GKS (in isoform 2).
                             /FTId=VSP_009532.
VAR_SEQ     555   1331       Missing (in isoform 2).
                             /FTId=VSP_009535.
CONFLICT    921    921       V -> A (in Ref. 2; BAB29938).
CONFLICT   1096   1096       Q -> H (in Ref. 2; BAB29685).
CONFLICT   1156   1156       P -> L (in Ref. 2; BAB29685).
CONFLICT   1197   1197       P -> S (in Ref. 2; BAB29685).
CONFLICT   1204   1204       P -> S (in Ref. 2; BAB29685).
CONFLICT   1210   1211       PR -> LM (in Ref. 2; BAB29685).
CONFLICT   1219   1219       H -> Y (in Ref. 2; BAB29685).
CONFLICT   1222   1222       K -> N (in Ref. 2; BAB29685).
CONFLICT   1252   1252       F -> V (in Ref. 2; BAB29685).
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Nucleotide Sequence
Length: 4788 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 1331 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
Other Protein-Protein interaction resources
String database  
View Microarray data
Comments