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Protein

Exportin-5

Gene

XPO5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos). XPO5 in the nucleus binds cooperatively to the RNA and to the GTPase Ran in its active GTP-bound form. Proteins containing dsRBDs can associate with this trimeric complex through the RNA. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause disassembly of the complex and release of the cargo from the export receptor. XPO5 then returns to the nuclear compartment by diffusion through the nuclear pore complex, to mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi). Mediates nuclear export of isoform 5 of ADAR/ADAR1 in a RanGTP-dependent manner.
Mediates the nuclear export of micro-RNA precursors, which form short hairpins. Also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference, and adenovirus VA1 dsRNA. In some circumstances can also mediate the nuclear export of deacylated and aminoacylated tRNAs. Specifically recognizes dsRNAs that lack a 5'-overhang in a sequence-independent manner, have only a short 3'-overhang, and that have a double-stranded length of at least 15 base-pairs. Binding is dependent on Ran-GTP.

GO - Molecular functioni

  • mRNA binding Source: BHF-UCL
  • nuclear export signal receptor activity Source: GO_Central
  • poly(A) RNA binding Source: UniProtKB
  • pre-miRNA binding Source: BHF-UCL
  • pre-miRNA transporter activity Source: BHF-UCL
  • Ran GTPase binding Source: BHF-UCL
  • RNA binding Source: Reactome
  • tRNA binding Source: UniProtKB-KW

GO - Biological processi

  • gene silencing by RNA Source: Reactome
  • positive regulation of RNA interference Source: BHF-UCL
  • pre-miRNA export from nucleus Source: BHF-UCL
  • protein export from nucleus Source: UniProtKB
  • regulation of protein export from nucleus Source: GO_Central
Complete GO annotation...

Keywords - Biological processi

Protein transport, RNA-mediated gene silencing, Transport

Keywords - Ligandi

RNA-binding, tRNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124571-MONOMER.
ReactomeiR-HSA-203927. MicroRNA (miRNA) biogenesis.

Protein family/group databases

TCDBi1.I.1.1.3. the nuclear pore complex (npc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Exportin-5
Short name:
Exp5
Alternative name(s):
Ran-binding protein 21
Gene namesi
Name:XPO5
Synonyms:KIAA1291, RANBP21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:17675. XPO5.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasm 1 Publication

  • Note: Shuttles between the nucleus and the cytoplasm.

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
  • nucleus Source: BHF-UCL
  • RNA nuclear export complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi57510.
OpenTargetsiENSG00000124571.
PharmGKBiPA134979214.

Polymorphism and mutation databases

BioMutaiXPO5.
DMDMi74734245.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002352992 – 1204Exportin-5Add BLAST1203

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei396N6-acetyllysineCombined sources1
Modified residuei826PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9HAV4.
MaxQBiQ9HAV4.
PaxDbiQ9HAV4.
PeptideAtlasiQ9HAV4.
PRIDEiQ9HAV4.

PTM databases

iPTMnetiQ9HAV4.
PhosphoSitePlusiQ9HAV4.

Miscellaneous databases

PMAP-CutDBQ9HAV4.

Expressioni

Tissue specificityi

Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000124571.
ExpressionAtlasiQ9HAV4. baseline and differential.
GenevisibleiQ9HAV4. HS.

Organism-specific databases

HPAiCAB012357.
HPA018402.
HPA023959.
HPA029909.
HPA029910.

Interactioni

Subunit structurei

Component of a nuclear export receptor complex composed of XPO5, Ran, dsRNA-binding proteins and dsRNA. Found in a nuclear export complex with XPO5, Ran, EEF1A1, and aminoacylated tRNA. Found in a nuclear export complex with XPO5, Ran, ILF3 and dsRNA. Found in a nuclear export complex with XPO5, Ran and pre-miRNA. Found in a nuclear export complex with XPO5, Ran, ILF3 and minihelix VA1 dsRNA. Found in a nuclear export complex with XPO5, RAN, ILF3, ZNF346 and dsRNA. Interacts with EEF1A1, ILF3, NUP153, NUP214 and ZNF346. Interacts with Ran and cargo proteins in a GTP-dependent manner. Interacts with isoform 5 of ADAR/ADAR1 (via DRBM domains). Interacts with SMAD4; mediates nuclear export of SMAD4 (PubMed:26878725).9 Publications

GO - Molecular functioni

  • Ran GTPase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi121574. 71 interactors.
DIPiDIP-34547N.
IntActiQ9HAV4. 23 interactors.
MINTiMINT-264827.
STRINGi9606.ENSP00000265351.

Structurei

Secondary structure

11204
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 21Combined sources16
Helixi27 – 43Combined sources17
Helixi47 – 54Combined sources8
Helixi61 – 77Combined sources17
Helixi79 – 81Combined sources3
Helixi84 – 100Combined sources17
Helixi110 – 127Combined sources18
Turni129 – 131Combined sources3
Helixi135 – 144Combined sources10
Helixi147 – 165Combined sources19
Helixi172 – 184Combined sources13
Helixi186 – 207Combined sources22
Helixi214 – 232Combined sources19
Turni233 – 237Combined sources5
Helixi240 – 244Combined sources5
Turni245 – 247Combined sources3
Helixi249 – 256Combined sources8
Helixi257 – 259Combined sources3
Turni261 – 263Combined sources3
Helixi264 – 275Combined sources12
Helixi281 – 284Combined sources4
Helixi285 – 291Combined sources7
Helixi293 – 304Combined sources12
Helixi313 – 338Combined sources26
Helixi349 – 360Combined sources12
Helixi365 – 379Combined sources15
Turni382 – 386Combined sources5
Helixi388 – 405Combined sources18
Helixi418 – 425Combined sources8
Helixi429 – 453Combined sources25
Helixi455 – 470Combined sources16
Beta strandi495 – 497Combined sources3
Helixi498 – 520Combined sources23
Helixi528 – 540Combined sources13
Helixi546 – 559Combined sources14
Helixi560 – 564Combined sources5
Helixi567 – 569Combined sources3
Helixi570 – 582Combined sources13
Helixi595 – 614Combined sources20
Helixi616 – 619Combined sources4
Helixi620 – 622Combined sources3
Helixi623 – 635Combined sources13
Helixi642 – 656Combined sources15
Helixi657 – 659Combined sources3
Helixi662 – 680Combined sources19
Helixi683 – 690Combined sources8
Helixi692 – 699Combined sources8
Helixi713 – 734Combined sources22
Helixi741 – 746Combined sources6
Beta strandi750 – 753Combined sources4
Beta strandi759 – 761Combined sources3
Helixi766 – 770Combined sources5
Helixi773 – 785Combined sources13
Helixi789 – 792Combined sources4
Helixi797 – 799Combined sources3
Turni800 – 803Combined sources4
Helixi807 – 813Combined sources7
Helixi832 – 858Combined sources27
Turni860 – 864Combined sources5
Helixi868 – 875Combined sources8
Turni880 – 882Combined sources3
Helixi885 – 894Combined sources10
Helixi896 – 901Combined sources6
Helixi905 – 907Combined sources3
Turni908 – 911Combined sources4
Helixi912 – 935Combined sources24
Helixi953 – 977Combined sources25
Helixi1013 – 1019Combined sources7
Helixi1022 – 1035Combined sources14
Helixi1041 – 1050Combined sources10
Helixi1052 – 1056Combined sources5
Helixi1066 – 1082Combined sources17
Helixi1087 – 1103Combined sources17
Turni1105 – 1107Combined sources3
Helixi1111 – 1115Combined sources5
Beta strandi1118 – 1120Combined sources3
Helixi1123 – 1132Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A6PX-ray2.92A/F1-1204[»]
ProteinModelPortaliQ9HAV4.
SMRiQ9HAV4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HAV4.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 108Necessary for interaction with RanAdd BLAST107
Regioni533 – 640Necessary for interaction with ILF3Add BLAST108

Sequence similaritiesi

Belongs to the exportin family.Curated

Phylogenomic databases

eggNOGiKOG2020. Eukaryota.
COG5101. LUCA.
GeneTreeiENSGT00390000013979.
HOVERGENiHBG056281.
InParanoidiQ9HAV4.
KOiK14289.
OMAiVLKPPNE.
OrthoDBiEOG091G0154.
PhylomeDBiQ9HAV4.
TreeFamiTF323382.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR013598. Exportin-1/Importin-b-like.
IPR001494. Importin-beta_N.
[Graphical view]
PfamiPF08389. Xpo1. 1 hit.
[Graphical view]
SMARTiSM00913. IBN_N. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 4 hits.

Sequencei

Sequence statusi: Complete.

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

Q9HAV4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAMDQVNALC EQLVKAVTVM MDPNSTQRYR LEALKFCEEF KEKCPICVPC
60 70 80 90 100
GLRLAEKTQV AIVRHFGLQI LEHVVKFRWN GMSRLEKVYL KNSVMELIAN
110 120 130 140 150
GTLNILEEEN HIKDALSRIV VEMIKREWPQ HWPDMLIELD TLSKQGETQT
160 170 180 190 200
ELVMFILLRL AEDVVTFQTL PPQRRRDIQQ TLTQNMERIF SFLLNTLQEN
210 220 230 240 250
VNKYQQVKTD TSQESKAQAN CRVGVAALNT LAGYIDWVSM SHITAENCKL
260 270 280 290 300
LEILCLLLNE QELQLGAAEC LLIAVSRKGK LEDRKPLMVL FGDVAMHYIL
310 320 330 340 350
SAAQTADGGG LVEKHYVFLK RLCQVLCALG NQLCALLGAD SDVETPSNFG
360 370 380 390 400
KYLESFLAFT THPSQFLRSS TQMTWGALFR HEILSRDPLL LAIIPKYLRA
410 420 430 440 450
SMTNLVKMGF PSKTDSPSCE YSRFDFDSDE DFNAFFNSSR AQQGEVMRLA
460 470 480 490 500
CRLDPKTSFQ MAGEWLKYQL STFLDAGSVN SCSAVGTGEG SLCSVFSPSF
510 520 530 540 550
VQWEAMTLFL ESVITQMFRT LNREEIPVND GIELLQMVLN FDTKDPLILS
560 570 580 590 600
CVLTNVSALF PFVTYRPEFL PQVFSKLFSS VTFETVEESK APRTRAVRNV
610 620 630 640 650
RRHACSSIIK MCRDYPQLVL PNFDMLYNHV KQLLSNELLL TQMEKCALME
660 670 680 690 700
ALVLISNQFK NYERQKVFLE ELMAPVASIW LSQDMHRVLS DVDAFIAYVG
710 720 730 740 750
TDQKSCDPGL EDPCGLNRAR MSFCVYSILG VVKRTCWPTD LEEAKAGGFV
760 770 780 790 800
VGYTSSGNPI FRNPCTEQIL KLLDNLLALI RTHNTLYAPE MLAKMAEPFT
810 820 830 840 850
KALDMLDAEK SAILGLPQPL LELNDSPVFK TVLERMQRFF STLYENCFHI
860 870 880 890 900
LGKAGPSMQQ DFYTVEDLAT QLLSSAFVNL NNIPDYRLRP MLRVFVKPLV
910 920 930 940 950
LFCPPEHYEA LVSPILGPLF TYLHMRLSQK WQVINQRSLL CGEDEAADEN
960 970 980 990 1000
PESQEMLEEQ LVRMLTREVM DLITVCCVSK KGADHSSAPP ADGDDEEMMA
1010 1020 1030 1040 1050
TEVTPSAMAE LTDLGKCLMK HEDVCTALLI TAFNSLAWKD TLSCQRTTSQ
1060 1070 1080 1090 1100
LCWPLLKQVL SGTLLADAVT WLFTSVLKGL QMHGQHDGCM ASLVHLAFQI
1110 1120 1130 1140 1150
YEALRPRYLE IRAVMEQIPE IQKDSLDQFD CKLLNPSLQK VADKRRKDQF
1160 1170 1180 1190 1200
KRLIAGCIGK PLGEQFRKEV HIKNLPSLFK KTKPMLETEV LDNDGGGLAT

IFEP
Length:1,204
Mass (Da):136,311
Last modified:March 1, 2001 - v1
Checksum:i3295A17DF7C37602
GO

Sequence cautioni

The sequence AAH00129 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA86605 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA91547 differs from that shown. Reason: Frameshift at position 920.Curated
The sequence CAI42640 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti81G → S in AAG53603 (PubMed:12426392).Curated1
Sequence conflicti697A → V in BAA86605 (PubMed:10574462).Curated1
Sequence conflicti988A → T in BAB14200 (PubMed:14574404).Curated1
Sequence conflicti1151K → E in BAA91547 (PubMed:14574404).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048960241S → N.Corresponds to variant rs34324334dbSNPEnsembl.1
Natural variantiVAR_076472552V → I Found in a patient with nephrotic syndrome; unknown pathological significance. 1 Publication1
Natural variantiVAR_028032610K → N.Corresponds to variant rs12173786dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF271159 mRNA. Translation: AAG53603.1.
AF298880 mRNA. Translation: AAG17907.1.
AB033117 mRNA. Translation: BAA86605.2. Different initiation.
AL355802 Genomic DNA. Translation: CAI42640.1. Sequence problems.
BC000129 mRNA. Translation: AAH00129.1. Different initiation.
BC008347 mRNA. Translation: AAH08347.1.
BC009969 mRNA. Translation: AAH09969.2.
BC062635 mRNA. Translation: AAH62635.1.
AL137467 mRNA. Translation: CAB70753.1.
AK001195 mRNA. Translation: BAA91547.1. Frameshift.
AK022718 mRNA. Translation: BAB14200.1.
CCDSiCCDS47430.1.
PIRiT46411.
RefSeqiNP_065801.1. NM_020750.2.
UniGeneiHs.203206.

Genome annotation databases

EnsembliENST00000265351; ENSP00000265351; ENSG00000124571.
GeneIDi57510.
KEGGihsa:57510.
UCSCiuc003ovp.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF271159 mRNA. Translation: AAG53603.1.
AF298880 mRNA. Translation: AAG17907.1.
AB033117 mRNA. Translation: BAA86605.2. Different initiation.
AL355802 Genomic DNA. Translation: CAI42640.1. Sequence problems.
BC000129 mRNA. Translation: AAH00129.1. Different initiation.
BC008347 mRNA. Translation: AAH08347.1.
BC009969 mRNA. Translation: AAH09969.2.
BC062635 mRNA. Translation: AAH62635.1.
AL137467 mRNA. Translation: CAB70753.1.
AK001195 mRNA. Translation: BAA91547.1. Frameshift.
AK022718 mRNA. Translation: BAB14200.1.
CCDSiCCDS47430.1.
PIRiT46411.
RefSeqiNP_065801.1. NM_020750.2.
UniGeneiHs.203206.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A6PX-ray2.92A/F1-1204[»]
ProteinModelPortaliQ9HAV4.
SMRiQ9HAV4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121574. 71 interactors.
DIPiDIP-34547N.
IntActiQ9HAV4. 23 interactors.
MINTiMINT-264827.
STRINGi9606.ENSP00000265351.

Protein family/group databases

TCDBi1.I.1.1.3. the nuclear pore complex (npc) family.

PTM databases

iPTMnetiQ9HAV4.
PhosphoSitePlusiQ9HAV4.

Polymorphism and mutation databases

BioMutaiXPO5.
DMDMi74734245.

Proteomic databases

EPDiQ9HAV4.
MaxQBiQ9HAV4.
PaxDbiQ9HAV4.
PeptideAtlasiQ9HAV4.
PRIDEiQ9HAV4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265351; ENSP00000265351; ENSG00000124571.
GeneIDi57510.
KEGGihsa:57510.
UCSCiuc003ovp.3. human.

Organism-specific databases

CTDi57510.
DisGeNETi57510.
GeneCardsiXPO5.
H-InvDBHIX0005908.
HGNCiHGNC:17675. XPO5.
HPAiCAB012357.
HPA018402.
HPA023959.
HPA029909.
HPA029910.
MIMi607845. gene.
neXtProtiNX_Q9HAV4.
OpenTargetsiENSG00000124571.
PharmGKBiPA134979214.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2020. Eukaryota.
COG5101. LUCA.
GeneTreeiENSGT00390000013979.
HOVERGENiHBG056281.
InParanoidiQ9HAV4.
KOiK14289.
OMAiVLKPPNE.
OrthoDBiEOG091G0154.
PhylomeDBiQ9HAV4.
TreeFamiTF323382.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124571-MONOMER.
ReactomeiR-HSA-203927. MicroRNA (miRNA) biogenesis.

Miscellaneous databases

ChiTaRSiXPO5. human.
EvolutionaryTraceiQ9HAV4.
GeneWikiiXPO5.
GenomeRNAii57510.
PMAP-CutDBQ9HAV4.
PROiQ9HAV4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124571.
ExpressionAtlasiQ9HAV4. baseline and differential.
GenevisibleiQ9HAV4. HS.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR013598. Exportin-1/Importin-b-like.
IPR001494. Importin-beta_N.
[Graphical view]
PfamiPF08389. Xpo1. 1 hit.
[Graphical view]
SMARTiSM00913. IBN_N. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 4 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiXPO5_HUMAN
AccessioniPrimary (citable) accession number: Q9HAV4
Secondary accession number(s): Q5JTE6
, Q96G48, Q96HN3, Q9BWM6, Q9BZV5, Q9H9M4, Q9NT89, Q9NW39, Q9ULC9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.