RAN RAN, member RAS oncogene family [Homo sapiens (human)] - Gene

Summary

Official Symbol: RANprovided by HGNC
Official Full Name: RAN, member RAS oncogene familyprovided by HGNC
Primary source: HGNC:HGNC:9846
See related: Ensembl:ENSG00000132341 MIM:601179; AllianceGenome:HGNC:9846
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TC4; Gsp1; ARA24
Summary: RAN (ras-related nuclear protein) is a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The RAN protein is also involved in control of DNA synthesis and cell cycle progression. Nuclear localization of RAN requires the presence of regulator of chromosome condensation 1 (RCC1). Mutations in RAN disrupt DNA synthesis. Because of its many functions, it is likely that RAN interacts with several other proteins. RAN regulates formation and organization of the microtubule network independently of its role in the nucleus-cytosol exchange of macromolecules. RAN could be a key signaling molecule regulating microtubule polymerization during mitosis. RCC1 generates a high local concentration of RAN-GTP around chromatin which, in turn, induces the local nucleation of microtubules. RAN is an androgen receptor (AR) coactivator that binds differentially with different lengths of polyglutamine within the androgen receptor. Polyglutamine repeat expansion in the AR is linked to Kennedy's disease (X-linked spinal and bulbar muscular atrophy). RAN coactivation of the AR diminishes with polyglutamine expansion within the AR, and this weak coactivation may lead to partial androgen insensitivity during the development of Kennedy's disease. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in lymph node (RPKM 71.4), testis (RPKM 70.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.33

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (130872066..130877678)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (130911164..130916776)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (131356611..131362223)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Up-regulation of RAN by MYBL2 maintains osteosarcoma cancer stem-like cells population during heterogeneous tumor generation.
Title: Up-regulation of RAN by MYBL2 maintains osteosarcoma cancer stem-like cells population during heterogeneous tumor generation.
B-type Plexins promote the GTPase activity of Ran to affect androgen receptor nuclear translocation in prostate cancer.
Title: B-type Plexins promote the GTPase activity of Ran to affect androgen receptor nuclear translocation in prostate cancer.
Development and validation of Ran as a prognostic marker in stage I and stage II primary breast cancer.
Title: Development and validation of Ran as a prognostic marker in stage I and stage II primary breast cancer.
Investigation of the association of the RAN (rs14035) and XPO5 (rs11077) polymorphisms with venous thromboembolism.
Title: Investigation of the association of the RAN (rs14035) and XPO5 (rs11077) polymorphisms with venous thromboembolism.
Matrix metalloproteinase 2 is a target of the RAN-GTP pathway and mediates migration, invasion and metastasis in human breast cancer.
Title: Matrix metalloproteinase 2 is a target of the RAN-GTP pathway and mediates migration, invasion and metastasis in human breast cancer.
Mechanistic convergence across initiation sites for RAN translation in fragile X associated tremor ataxia syndrome.
Title: Mechanistic convergence across initiation sites for RAN translation in fragile X associated tremor ataxia syndrome.
RSL1D1 promotes the progression of colorectal cancer through RAN-mediated autophagy suppression.
Title: RSL1D1 promotes the progression of colorectal cancer through RAN-mediated autophagy suppression.
NEAT1 Boosts the Development of Thoracic Aortic Aneurysm Through Targeting miR-324-5p/RAN.
Title: NEAT1 Boosts the Development of Thoracic Aortic Aneurysm Through Targeting miR-324-5p/RAN.
Ran GTPase is an independent prognostic marker in malignant melanoma which promotes tumour cell migration and invasion.
Title: Ran GTPase is an independent prognostic marker in malignant melanoma which promotes tumour cell migration and invasion.
RAN and YBX1 are required for cell proliferation and IL-4 expression and linked to poor prognosis in oral squamous cell carcinoma.
Title: RAN and YBX1 are required for cell proliferation and IL-4 expression and linked to poor prognosis in oral squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (144)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify GTP binding protein RAN (RanGTP), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify GTP binding protein RAN (RanGTP), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify GTP binding protein RAN (RanGTP), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify GTP binding protein RAN (RanGTP), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	gag	Ran terminates the nuclear import of the Matrix protein of HIV-1 Gag by directly binding to karyopherin beta and disassembling the import complex	PubMed
Rev	rev	the GTP bound form of Ran (RanGTP) binds to a preformed Rev-CRM1 (exportin 1) complex to mediate nuclear export of HIV-1 mRNA	PubMed
	rev	A dimeric CRM1-RanGTP complex binds a Rev-RRE complex to export the Rev-RRE complex from the nuclear to the cytoplasm in cells	PubMed
	rev	HIV-1 Rev interacting protein, RAN, is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells	PubMed
	rev	Rev-Rev interactions (multimerization) are enhanced by RanGTP	PubMed
	rev	binding of the GTP bound form of Ran (RanGTP) to a preformed Rev-CRM1 complex is linked to an interaction of RanGTP with the nuclear export signal (NES) of Rev (amino acids 75-83)	PubMed
Tat	tat	Interaction of HIV-1 Tat with RAN in T-cells is identified by a proteomic strategy based on affinity chromatography	PubMed
capsid	gag	RanGTP inhibits the ability of TNPO3 to stimulate the uncoating of HIV-1 CA cores	PubMed
integrase	gag-pol	The binding between HIV-1 IN and TNPO3 is inhibited by RanGTP in a dose-dependent manner, leading to a TNPO3-RanGTP complex formation	PubMed
matrix	gag	Ran terminates the nuclear import of HIV-1 Matrix by directly binding to karyopherin beta and disassembling the import complex	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-M31469 (e-PCR)
- UniSTS:4649

WI-16177 (e-PCR)
- UniSTS:69938

GDB:451538 (e-PCR)
- UniSTS:157307

RH44340 (e-PCR)
- UniSTS:60593

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein activity	IDA Inferred from Direct Assay more info	PubMed
enables GDP binding	IDA Inferred from Direct Assay more info	PubMed
enables GDP binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activity	TAS Traceable Author Statement more info	PubMed
enables RNA binding	HDA more info	PubMed
enables cadherin binding	HDA more info	PubMed
enables chromatin binding	TAS Traceable Author Statement more info	PubMed
enables dynein intermediate chain binding	IEA Inferred from Electronic Annotation more info
enables importin-alpha family protein binding	IEA Inferred from Electronic Annotation more info
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to nuclear export signal receptor activity	IC Inferred by Curator more info	PubMed
contributes_to pre-miRNA binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in GTP metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mineralocorticoid stimulus	IEA Inferred from Electronic Annotation more info
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in mitotic cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in mitotic sister chromatid segregation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic spindle organization	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of protein binding	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein import into nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pre-miRNA export from nucleus	IC Inferred by Curator more info	PubMed
involved_in protein export from nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in protein import into nucleus	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in protein import into nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to nucleolus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ribosomal large subunit export from nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ribosomal small subunit export from nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ribosomal subunit export from nucleus	IBA Inferred from Biological aspect of Ancestor more info
involved_in snRNA import into nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spermatid development	IEA Inferred from Electronic Annotation more info
involved_in viral process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
NOT located_in Flemming body	IDA Inferred from Direct Assay more info	PubMed
part_of RNA nuclear export complex	IDA Inferred from Direct Assay more info	PubMed
located_in centriole	IDA Inferred from Direct Assay more info	PubMed
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in male germ cell nucleus	IEA Inferred from Electronic Annotation more info
located_in manchette	IEA Inferred from Electronic Annotation more info
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
part_of nuclear pore	NAS Non-traceable Author Statement more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed
located_in recycling endosome	IDA Inferred from Direct Assay more info	PubMed
located_in sperm flagellum	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: GTP-binding nuclear protein Ran

Names: GTPase Ran; RanGTPase; androgen receptor-associated protein 24; guanosine triphosphatase Ran; member RAS oncogene family; ras-like protein TC4; ras-related nuclear protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001300796.2 → NP_001287725.1 GTP-binding nuclear protein Ran isoform 2

See identical proteins and their annotated locations for NP_001287725.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2 and 3 encode the same protein.

Source sequence(s)

AC073912, AF054183, AK316193

Consensus CDS

CCDS73546.1

UniProtKB/TrEMBL

B4DV51

Related

ENSP00000441210.1, ENST00000541630.5

Conserved Domains (1) summary

smart00176
Location:1 → 127

RAN; Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases
NM_001300797.2 → NP_001287726.1 GTP-binding nuclear protein Ran isoform 2

See identical proteins and their annotated locations for NP_001287726.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2 and 3 encode the same protein.

Source sequence(s)

AC073912, AK300934, HY139187

Consensus CDS

CCDS73546.1

UniProtKB/TrEMBL

B4DV51

Conserved Domains (1) summary

smart00176
Location:1 → 127

RAN; Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases
NM_006325.5 → NP_006316.1 GTP-binding nuclear protein Ran isoform 1

See identical proteins and their annotated locations for NP_006316.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AC073912, AF054183, BC000852

Consensus CDS

CCDS9271.1

UniProtKB/Swiss-Prot

A8K3Z8, P17080, P28746, P28747, P62826, Q6IPB2, Q86V08, Q8NI90, Q9CSP3, Q9CWI7, Q9CZA2, Q9UDJ5, Q9UEU9

UniProtKB/TrEMBL

B5MDF5

Related

ENSP00000446215.1, ENST00000543796.6

Conserved Domains (1) summary

smart00176
Location:16 → 215

RAN; Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases