RAN_XENLA
ID RAN_XENLA Reviewed; 216 AA.
AC P52301; Q7ZYT6; Q9IBE8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=GTP-binding nuclear protein Ran;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:P62826};
DE AltName: Full=GTPase Ran;
DE AltName: Full=Ras-like protein TC4 {ECO:0000303|PubMed:8413630};
DE AltName: Full=Ras-related nuclear protein;
GN Name=ran;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=11180838; DOI=10.1007/s004270050320;
RA Onuma Y., Nishihara R., Takahashi S., Tanegashima K., Fukui A.,
RA Asashima M.;
RT "Expression of the Xenopus GTP-binding protein gene Ran during
RT embryogenesis.";
RL Dev. Genes Evol. 210:325-327(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 40-52 AND 62-71, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Ovary;
RX PubMed=8413630; DOI=10.1038/365661a0;
RA Moore M.S., Blobel G.;
RT "The GTP-binding protein Ran/TC4 is required for protein import into the
RT nucleus.";
RL Nature 365:661-663(1993).
RN [4]
RP FUNCTION.
RX PubMed=10408446; DOI=10.1038/22133;
RA Carazo-Salas R.E., Guarguaglini G., Gruss O.J., Segref A., Karsenti E.,
RA Mattaj I.W.;
RT "Generation of GTP-bound Ran by RCC1 is required for chromatin-induced
RT mitotic spindle formation.";
RL Nature 400:178-181(1999).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND INTERACTION WITH
RP NEMP1A AND NEMP1B.
RX PubMed=25946333; DOI=10.1371/journal.pone.0127271;
RA Shibano T., Mamada H., Hakuno F., Takahashi S., Taira M.;
RT "The inner nuclear membrane protein Nemp1 is a new type of RanGTP-binding
RT protein in eukaryotes.";
RL PLoS ONE 10:E0127271-E0127271(2015).
CC -!- FUNCTION: GTPase involved in nucleocytoplasmic transport, participating
CC both to the import and the export from the nucleus of proteins and RNAs
CC (PubMed:8413630). Switches between a cytoplasmic GDP- and a nuclear
CC GTP-bound state by nucleotide exchange and GTP hydrolysis. Nuclear
CC import receptors such as importin beta bind their substrates only in
CC the absence of GTP-bound RAN and release them upon direct interaction
CC with GTP-bound RAN, while export receptors behave in the opposite way.
CC Thereby, RAN controls cargo loading and release by transport receptors
CC in the proper compartment and ensures the directionality of the
CC transport. Interaction with RANBP1 induces a conformation change in the
CC complex formed by XPO1 and RAN that triggers the release of the nuclear
CC export signal of cargo proteins (By similarity). RAN (GTP-bound form)
CC triggers microtubule assembly at mitotic chromosomes and is required
CC for normal mitotic spindle assembly and chromosome segregation
CC (PubMed:10408446). Required for normal progress through mitosis (By
CC similarity). In concert with nemp1a/b, required for proper eye
CC development (PubMed:25946333). {ECO:0000250|UniProtKB:P62826,
CC ECO:0000269|PubMed:10408446, ECO:0000269|PubMed:25946333,
CC ECO:0000305|PubMed:8413630}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:P62826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P62826};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P62826};
CC Note=Mg(2+) interacts primarily with the phosphate groups of the bound
CC guanine nucleotide. {ECO:0000250|UniProtKB:P62826};
CC -!- SUBUNIT: Monomer. Interacts with rangap1, which promotes ran-mediated
CC GTP hydrolysis. Interacts with kpnb1. Interaction with kpnb1 inhibits
CC rangap1-mediated stimulation of GTPase activity. Interacts with rcc1
CC which promotes the exchange of ran-bound GDP by GTP. Interaction with
CC kpnb1 inhibits rcc1-mediated exchange of ran-bound GDP by GTP.
CC Interacts (GTP-bound form) with tnpo1; the interaction is direct.
CC Interacts (GTP-bound form) with tnpo3; the interaction is direct.
CC Interacts with kpnb1 and with tnpo1; both inhibit ran GTPase activity.
CC Interacts (via C-terminus) with ranbp1, which alleviates the inhibition
CC of ran GTPase activity. Interacts with rangrf, which promotes the
CC release of bound guanine nucleotide. Rangrf and rcc1 compete for an
CC overlapping binding site on ran. Identified in a complex with kpna2 and
CC cse1l; interaction with ranbp1 mediates dissociation of ran from this
CC complex. Interaction with both ranbp1 and kpna2 promotes dissociation
CC of the complex between ran and kpnb1. Identified in a complex composed
CC of ran, rangap1 and ranbp1. Identified in a complex that contains
CC tnpo1, ran and ranbp1. Identified in a nuclear export complex with
CC xpo1. Interaction with ranbp1 or ranbp2 induces a conformation change
CC in the complex formed by xpo1 and ran that triggers the release of the
CC nuclear export signal of cargo proteins. Component of a nuclear export
CC receptor complex composed of kpnb1, ran, snupn and xpo1 (By
CC similarity). Interacts with nemp1a and nemp1b (PubMed:25946333).
CC {ECO:0000250|UniProtKB:P62825, ECO:0000250|UniProtKB:P62826,
CC ECO:0000250|UniProtKB:P62827, ECO:0000269|PubMed:25946333}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P62826}. Nucleus
CC envelope {ECO:0000250|UniProtKB:P62826}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:8413630}. Cytoplasm {ECO:0000250|UniProtKB:P62826}.
CC Note=Predominantly nuclear during interphase. Becomes dispersed
CC throughout the cytoplasm during mitosis (By similarity).
CC {ECO:0000250|UniProtKB:P62826}.
CC -!- DEVELOPMENTAL STAGE: Detected throughout embryonic development
CC (PubMed:11180838). Detected within the animal pole region at the four-
CC cell stage, then in the anterior neural plate at the neurula stage, and
CC within the head region including the otic vesicles, branchial arches,
CC and the tail region at the tailbud stage (PubMed:11180838,
CC PubMed:25946333). {ECO:0000269|PubMed:11180838,
CC ECO:0000269|PubMed:25946333}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in defects in eye
CC development and reduction of cell density at the neurula stage. Co-
CC knockdown of nemp1a/b and ran elicits reduction of cell density and eye
CC defects more significantly than the individual knockdown of either one.
CC {ECO:0000269|PubMed:25946333}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ran family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB030945; BAA89696.1; -; mRNA.
DR EMBL; BC041293; AAH41293.1; -; mRNA.
DR RefSeq; NP_001080182.1; NM_001086713.1.
DR RefSeq; NP_001128547.1; NM_001135075.1.
DR RefSeq; XP_018089010.1; XM_018233521.1.
DR RefSeq; XP_018089018.1; XM_018233529.1.
DR RefSeq; XP_018117934.1; XM_018262445.1.
DR RefSeq; XP_018117939.1; XM_018262450.1.
DR AlphaFoldDB; P52301; -.
DR BMRB; P52301; -.
DR SMR; P52301; -.
DR BioGRID; 98116; 3.
DR IntAct; P52301; 1.
DR PRIDE; P52301; -.
DR DNASU; 379874; -.
DR GeneID; 108716335; -.
DR GeneID; 379874; -.
DR KEGG; xla:108716335; -.
DR KEGG; xla:379874; -.
DR CTD; 108716335; -.
DR CTD; 379874; -.
DR Xenbase; XB-GENE-17336523; ran.L.
DR Xenbase; XB-GENE-865870; ran.S.
DR OMA; TIVFHRK; -.
DR OrthoDB; 1083175at2759; -.
DR Proteomes; UP000186698; Chromosome 1L.
DR Proteomes; UP000186698; Chromosome 1S.
DR Bgee; 108716335; Expressed in gastrula and 19 other tissues.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0046039; P:GTP metabolic process; ISS:UniProtKB.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; ISS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0000055; P:ribosomal large subunit export from nucleus; IGI:ParkinsonsUK-UCL.
DR GO; GO:0000056; P:ribosomal small subunit export from nucleus; IGI:ParkinsonsUK-UCL.
DR GO; GO:0061015; P:snRNA import into nucleus; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR002041; Ran_GTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR PANTHER; PTHR24071; PTHR24071; 1.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00627; GTPRANTC4.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51418; RAN; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Developmental protein; Direct protein sequencing; GTP-binding;
KW Hydrolase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..216
FT /note="GTP-binding nuclear protein Ran"
FT /id="PRO_0000208702"
FT REGION 211..216
FT /note="Interaction with RANBP1"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT BINDING 18..25
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 36..42
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 68
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 122..125
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 150..152
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT SITE 69
FT /note="Essential for GTP hydrolysis"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT CONFLICT 199
FT /note="Q -> A (in Ref. 2; AAH41293)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 216 AA; 24398 MW; D5DB10D65C2AD5A4 CRC64;
MAAQGEPQVQ FKLVLVGDGG TGKTTFVKRH LTGEFEKKYV ATLGVEVHPL VFHTNRGPIK
FNVWDTAGQE KFGGLRDGYY IQAQCAIIMF DVTSRVTYKN VPNWHRDLVR VCENIPIVLC
GNKVDIKDRK VKAKSIVFHR KKNLQYYDIS AKSNYNFEKP FLWLARKLIG DPNLEFVAMP
ALAPPEVVMD PALAAQYEQD LQNAQATALP DEDDDL
