Tag Content
SG ID
SG00009823 
UniProt Accession
Theoretical PI
7.2  
Molecular Weight
24423 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Ran 
Gene Synonyms/Alias
Rasl2-8 
Protein Name
GTP-binding nuclear protein Ran 
Protein Synonyms/Alias
GTPase Ran; Ras-like protein TC4; Ras-related nuclear protein; 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:5;129525944-129530198;1
View in Ensembl genome browser  
Function in Stage
Uncertain 
Function in Cell Type
Uncertain 
Probability (GAS) of Function in Spermatogenesis
0.983327397 
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. Ran genes encode a family of well-conserve small nuclear GTPases (Ras-related nuclear proteins), whose function is implicated in both normal cell cycle progression and the transport of RNA and proteins between the nucleus and the cytoplasm. Previous studies of Ran proteins have utilized cell-free systems, yeasts, and cultured mammalian cells. We have now characterized patterns of Ran gene expression in the mouse. Serum starvation suppressed Ran gene transcription in mouse 3T3 cells. Ran mRNA reappeared in cells within 3 h after refeeding. A single Ran mRNA species was detected at low levels in most somatic tissues of the adult mouse. In testis, this Ran mRNA was abundant, as were other larger transcripts. Analysis of testis-derived Ran cDNA clones revealed the presence of two transcripts, one specifying an amino acid sequence identical to that of human Ran/TC4 and one specifying an amino acid sequence 94% identical. Northern blotting and reverse transcriptase-PCR assays with oligonucleotide probes and primers specific for each transcript demonstrated that the isoform identical to Ran/TC4 was expressed in both somatic tissues and testis, while the variant form was transcribed only in testis. The existence of tissue-specific Ran isoforms may help to rationalize the diverse roles suggested for Ran by previous biochemical studies. PMID: [7849398] 

2. Previous analysis of hybrid progeny derived from lipopolysaccharide (LPS) responder and nonresponder inbred mouse strains demonstrated that a single genetic locus controlled responsiveness to LPS. Using a differential functional screening approach, we report the isolation of a cDNA that has sequence homology to a GTP-binding protein. Expression of the cDNA in splenic B cells of C3H/HeJ nonresponder, endotoxin-resistant mice resulted in polyclonal B-cell activation in response to LPS stimulation. Thus a GTP-binding protein may be involved in LPS stimulation in B cells and perhaps other cell types. PMID: [8890215] 

3. C3H/HeJ inbred mice are defective in that they are highly resistant to endotoxic shock as compared with normal responder mice. Their B cells and macrophages do not respond significantly when exposed to lipopolysaccharide (LPS), whereas cells from the responder mice do. Using a functional assay, we previously isolated a cDNA, which encodes for Ran/TC4 GTPase. We now show that this gene is mutated in C3H/HeJ mice, which accounts for their resistance to endotoxin stimulation. Sequence analysis of independent mutant Lps(d)/Ran cDNAs isolated from splenic B cells of C3H/HeJ mice reveals a consistent single base substitution at position 870, where a thymidine is replaced with a cytidine. In situ hybridization maps the Lps(d)/Ran cDNA to mouse chromosome 4. By retroviral gene transfer, the wild-type Lps(n)/Ran cDNA but not the mutant Lps(d)/Ran cDNA can restore LPS responsiveness of C3H/HeJ cells. Adenoviral gene transfer in vivo with the mutant Lps(d)/Ran cDNA but not the wild-type Lps(n)/Ran cDNA rescues endotoxin-sensitive mice from septic shock. Thus Lps/Ran is an important target for LPS-mediated signal transduction, and the Lps(d)/Ran gene may be useful as a therapeutic sequence in gene therapy for endotoxemia and septic shock. PMID: [10500213] 

4. 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] 

5. 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] 

6. Partial sequences corresponding to eleven novel Rab proteins and one new Rho protein have been isolated using a PCR-based cloning approach. These results confirm that the overall diversity of the Rab and Rho protein subfamilies account for more than thirty different members in mammalian cells. PMID: [1555775] 

7. Microtubule spindle assembly in mitosis is stimulated by Ran.GTP, which is generated along condensed chromosomes by the guanine nucleotide exchange factor (GEF) RCC1. This relationship suggests that similar activities might modulate other microtubule structures. Interphase microtubules usually extend from the centrosome, although noncentrosomal microtubules function in some differentiated cells, including megakaryocytes. In these cells, platelet biogenesis requires massive mobilization of microtubules in the cell periphery, where they form proplatelets, the immediate precursors of platelets, in the apparent absence of centrioles. Here we identify a cytoplasmic Ran-binding protein, RanBP10, as a factor that binds beta-tubulin and associates with megakaryocyte microtubules. Unexpectedly, RanBP10 harbors GEF activity toward Ran. A point mutation in the candidate GEF domain abolishes exchange activity, and our results implicate RanBP10 as a localized cytoplasmic Ran-GEF. RNA interference-mediated loss of RanBP10 in cultured megakaryocytes disrupts microtubule organization. These results lead us to propose that spatiotemporally restricted generation of cytoplasmic Ran.GTP may influence organization of the specialized microtubules required in thrombopoiesis and that RanBP10 might serve as a molecular link between Ran and noncentrosomal microtubules. PMID: [18347012] 

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Function
GTP-binding protein involved in nucleocytoplasmictransport. Required for the import of protein into the nucleus andalso for RNA export. Involved in chromatin condensation andcontrol of cell cycle. The complex with BIRC5/survivin plays arole in mitotic spindle formation by serving as a physicalscaffold to help deliver the RAN effector molecule TPX2 tomicrotubules. Acts as a negative regulator of the kinase activityof VRK1 and VRK2 (By similarity). 
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Subcellular Location
Nucleus. Cytoplasm. Melanosome (Bysimilarity). Note=Predominantly nuclear during interphase. Becomesdispersed throughout the cytoplasm during mitosis. 
Tissue Specificity
Expressed in a variety of tissues, includingtestis. 
Gene Ontology
GO IDGO termEvidence
GO:0005737 C:cytoplasm IDA:MGI.
GO:0042470 C:melanosome IEA:UniProtKB-SubCell.
GO:0005634 C:nucleus IDA:MGI.
GO:0005525 F:GTP binding IEA:UniProtKB-KW.
GO:0003924 F:GTPase activity IEA:InterPro.
GO:0030036 P:actin cytoskeleton organization IMP:MGI.
GO:0051301 P:cell division IEA:UniProtKB-KW.
GO:0034629 P:cellular protein complex localization IMP:MGI.
GO:0007067 P:mitosis IEA:UniProtKB-KW.
GO:0006606 P:protein import into nucleus IDA:MGI.
GO:0007264 P:small GTPase mediated signal transduction IEA:InterPro.
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Interpro
IPR002041;    Ran_GTPase.
IPR005225;    Small_GTP-bd_dom.
IPR001806;    Small_GTPase.
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Pfam
PF00071;    Ras;    1.
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SMART
SM00176;    RAN;    1.
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PROSITE
PS51418;    RAN;    1.
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PRINTS
PR00627;    GTPRANTC4.;   
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Created Date
18-Oct-2012 
Record Type
GAS predicted 
Sequence Annotation
INIT_MET      1      1       Removed.
CHAIN         2    216       GTP-binding nuclear protein Ran.
                             /FTId=PRO_0000208697.
NP_BIND      17     24       GTP (By similarity).
NP_BIND      65     69       GTP (By similarity).
NP_BIND     122    125       GTP (By similarity).
MOD_RES       2      2       N-acetylalanine.
MOD_RES      60     60       N6-acetyllysine (By similarity).
MOD_RES      71     71       N6-acetyllysine (By similarity).
MOD_RES      99     99       N6-acetyllysine (By similarity).
MOD_RES     147    147       Phosphotyrosine (By similarity).
MOD_RES     155    155       Phosphotyrosine (By similarity).
MOD_RES     159    159       N6-acetyllysine (By similarity).
CROSSLNK     71     71       Glycyl lysine isopeptide (Lys-Gly)
                             (interchain with G-Cter in ubiquitin) (By
                             similarity).
MUTAGEN      24     24       T->N: No effect on RANBP10-binding.
MUTAGEN      69     69       Q->L: Partial decrease in RANBP10-
                             binding.
CONFLICT      9      9       V -> G (in Ref. 4; BAB27105).
CONFLICT     43     43       L -> P (in Ref. 4; BAB27105).
CONFLICT     49     49       P -> T (in Ref. 6; AAK14838).
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Nucleotide Sequence
Length: 994 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 216 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
Gene Symbol Ref Databases
Irs1IntAct 
Grin2bIntAct 
Grin1IntAct 
Other Protein-Protein interaction resources
String database  
View Microarray data
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