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Protein

GTP-binding nuclear protein Ran

Gene

Ran

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs. Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis. Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport. Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation. Required for normal progress through mitosis. The complex with BIRC5/survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2. Enhances AR-mediated transactivation.By similarity

Cofactori

Mg2+By similarityNote: Mg2+ interacts primarily with the phosphate groups of the bound guanine nucleotide.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei68GTP; via amide nitrogenBy similarity1
Sitei69Essential for GTP hydrolysisBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi18 – 25GTPBy similarity8
Nucleotide bindingi36 – 42GTPBy similarity7
Nucleotide bindingi122 – 125GTPBy similarity4
Nucleotide bindingi150 – 152GTPBy similarity3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Mitosis, Protein transport, Transport
LigandGTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-MMU-5578749. Transcriptional regulation by small RNAs.

Names & Taxonomyi

Protein namesi
Recommended name:
GTP-binding nuclear protein Ran
Alternative name(s):
GTPase Ran
Ras-like protein TC4
Ras-related nuclear protein
Gene namesi
Name:Ran
Synonyms:Rasl2-8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1333112. Ran.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24T → N: No effect on RANBP10-binding. Loss of interaction with NEMP1. 2 Publications1
Mutagenesisi42T → A: Loss of interaction with NEMP1. 1 Publication1
Mutagenesisi69Q → L: Strongly decreases interaction with RANGRF. Partial decrease in RANBP10-binding. No effect on interaction with NEMP1 and KPNB1. 3 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002086972 – 216GTP-binding nuclear protein RanAdd BLAST215

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei24PhosphothreonineBy similarity1
Modified residuei60N6-acetyllysineBy similarity1
Modified residuei71N6-acetyllysine; alternateBy similarity1
Cross-linki71Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki71Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei99N6-acetyllysineBy similarity1
Modified residuei134N6-acetyllysineBy similarity1
Cross-linki152Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei159N6-acetyllysine; alternateCombined sources1
Modified residuei159N6-succinyllysine; alternateCombined sources1

Post-translational modificationi

Acetylation by KAT5 at Lys-134 is increased during mitosis, impairs RANGRF binding and enhances RCC1 binding.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP62827.
MaxQBiP62827.
PaxDbiP62827.
PeptideAtlasiP62827.
PRIDEiP62827.

2D gel databases

REPRODUCTION-2DPAGEiP62827.

PTM databases

iPTMnetiP62827.
PhosphoSitePlusiP62827.
SwissPalmiP62827.

Expressioni

Tissue specificityi

Expressed in a variety of tissues, including testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000029430.
CleanExiMM_RAN.
GenevisibleiP62827. MM.

Interactioni

Subunit structurei

Monomer. Interacts with RANGAP1, which promotes RAN-mediated GTP hydrolysis. Interacts with KPNB1. Interaction with KPNB1 inhibits RANGAP1-mediated stimulation of GTPase activity. Interacts with RCC1 which promotes the exchange of RAN-bound GDP by GTP. Interaction with KPNB1 inhibits RCC1-mediated exchange of RAN-bound GDP by GTP. Interacts (GTP-bound form) with TNPO1; the interaction is direct. Interacts with KPNB1 and with TNPO1; both inhibit RAN GTPase activity (By similarity). Interacts (via C-terminus) with RANBP1, which alleviates the inhibition of RAN GTPase activity (PubMed:7891706, PubMed:9428644). Interacts with RANGRF, which promotes the release of bound guanine nucleotide (PubMed:10811801). RANGRF and RCC1 compete for an overlapping binding site on RAN. Identified in a complex with KPNA2 and CSE1L; interaction with RANBP1 mediates dissociation of RAN from this complex. Interaction with both RANBP1 and KPNA2 promotes dissociation of the complex between RAN and KPNB1. Identified in a complex composed of RAN, RANGAP1 and RANBP1. Identified in a complex that contains TNPO1, RAN and RANBP1. Identified in a nuclear export complex with XPO1. Found in a nuclear export complex with RANBP3 and XPO1. Interacts with RANBP2/NUP358. Interaction with RANBP1 or RANBP2 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1 (By similarity). Found in a nuclear export complex with RAN, XPO5 and pre-miRNA (By similarity). Interacts (GTP-bound form) with XPO5 (By similarity). Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5 (By similarity). Interacts with RANBP9 and RANBP10 (PubMed:18347012). Interacts in its GTP-bound form with BIRC5/survivin at S and M phases of the cell cycle. Interacts with TERT; the interaction requires hydrogen peroxide-mediated phosphorylation of TERT and transports TERT to the nucleus. Interacts with MAD2L2. Interacts with VRK1 and VRK3. Interacts with VRK2 (By similarity). Interacts with NEMP1 and KPNB1 (PubMed:25946333). Interacts (GDP-bound form) with NUTF2; regulates RAN nuclear import. Interacts with CAPG; mediates CAPG nuclear import. Interacts with NUP153. Interacts with the AR N-terminal poly-Gln region; the interaction with AR is inversely correlated with the poly-Gln length (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Nemp1Q6ZQE47EBI-286564,EBI-12595939

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202580. 10 interactors.
IntActiP62827. 8 interactors.
MINTiP62827.
STRINGi10090.ENSMUSP00000031383.

Structurei

3D structure databases

ProteinModelPortaliP62827.
SMRiP62827.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni211 – 216Interaction with RANBP1By similarity6

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ran family.Curated

Phylogenomic databases

eggNOGiKOG0096. Eukaryota.
ENOG410XNRS. LUCA.
GeneTreeiENSGT00840000129836.
HOVERGENiHBG107376.
InParanoidiP62827.
KOiK07936.
OMAiYNVWDTA.
OrthoDBiEOG091G0L3X.
PhylomeDBiP62827.
TreeFamiTF106302.

Family and domain databases

InterProiView protein in InterPro
IPR027417. P-loop_NTPase.
IPR002041. Ran_GTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
PANTHERiPTHR24071. PTHR24071. 1 hit.
PfamiView protein in Pfam
PF00071. Ras. 1 hit.
PRINTSiPR00627. GTPRANTC4.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiView protein in PROSITE
PS51418. RAN. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P62827-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAQGEPQVQ FKLVLVGDGG TGKTTFVKRH LTGEFEKKYV ATLGVEVHPL
60 70 80 90 100
VFHTNRGPIK FNVWDTAGQE KFGGLRDGYY IQAQCAIIMF DVTSRVTYKN
110 120 130 140 150
VPNWHRDLVR VCENIPIVLC GNKVDIKDRK VKAKSIVFHR KKNLQYYDIS
160 170 180 190 200
AKSNYNFEKP FLWLARKLIG DPNLEFVAMP ALAPPEVVMD PALAAQYEHD
210
LEVAQTTALP DEDDDL
Length:216
Mass (Da):24,423
Last modified:January 23, 2007 - v3
Checksum:iD5C9B7275C34BCE0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9V → G in BAB27105 (PubMed:16141072).Curated1
Sequence conflicti43L → P in BAB27105 (PubMed:16141072).Curated1
Sequence conflicti49P → T in AAK14838 (PubMed:1555775).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L32751 mRNA. Translation: AAA64247.1.
S83456 mRNA. Translation: AAB50841.1.
AF159256 mRNA. Translation: AAD45343.1.
AK010569 mRNA. Translation: BAB27034.1.
AK010672 mRNA. Translation: BAB27105.1.
AK012268 mRNA. No translation available.
AK012844 mRNA. No translation available.
AK075900 mRNA. Translation: BAC36040.1.
AK087974 mRNA. Translation: BAC40068.1.
AK151341 mRNA. Translation: BAE30319.1.
AK151937 mRNA. Translation: BAE30813.1.
AK153197 mRNA. Translation: BAE31797.1.
AK153411 mRNA. Translation: BAE31971.1.
AK160647 mRNA. Translation: BAE35939.1.
AK167040 mRNA. Translation: BAE39208.1.
AK168183 mRNA. Translation: BAE40143.1.
BC014829 mRNA. Translation: AAH14829.3.
BC083356 mRNA. Translation: AAH83356.1.
M79316 mRNA. Translation: AAK14838.1.
CCDSiCCDS19693.1.
PIRiI57020.
JH0654.
RefSeqiNP_033417.1. NM_009391.3.
XP_006504343.1. XM_006504280.3.
UniGeneiMm.297440.
Mm.386831.

Genome annotation databases

EnsembliENSMUST00000031383; ENSMUSP00000031383; ENSMUSG00000029430.
ENSMUST00000111343; ENSMUSP00000106975; ENSMUSG00000029430.
GeneIDi19384.
KEGGimmu:19384.
UCSCiuc008zsr.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiRAN_MOUSE
AccessioniPrimary (citable) accession number: P62827
Secondary accession number(s): P17080
, P28746, P28747, Q3U954, Q811M2, Q86V08, Q9CSP3, Q9CWI7, Q9CZA2, Q9UDJ5, Q9UEU9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 152 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome