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UniProtKB - Q9HAV4 (XPO5_HUMAN)

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Protein

Exportin-5

Gene

XPO5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:14681208, PubMed:14631048, PubMed:15613540). Also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference. 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 (PubMed:19965479). Binding is dependent on Ran-GTP (PubMed:19965479).4 Publications
(Microbial infection) Mediates the nuclear export of adenovirus VA1 dsRNA.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei441Pre-miRNA binding1 Publication1
Sitei448Pre-miRNA binding1 Publication1
Sitei718Pre-miRNA binding1 Publication1
Sitei1045Pre-miRNA binding1 Publication1

GO - Molecular functioni

  • mRNA binding Source: BHF-UCL
  • nuclear export signal receptor activity Source: BHF-UCL
  • pre-miRNA binding Source: BHF-UCL
  • protein transporter activity Source: Ensembl
  • Ran GTPase binding Source: BHF-UCL
  • RNA binding Source: UniProtKB
  • tRNA binding Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • miRNA metabolic process 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
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionRNA-binding, tRNA-binding
Biological processProtein transport, RNA-mediated gene silencing, Transport

Enzyme and pathway databases

ReactomeiR-HSA-203927 MicroRNA (miRNA) biogenesis

Protein family/group databases

TCDBi1.I.1.1.3 the eukaryotic nuclear pore complex (e-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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000124571.17
HGNCiHGNC:17675 XPO5
MIMi607845 gene
neXtProtiNX_Q9HAV4

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

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
ProteomicsDBi81445

PTM databases

iPTMnetiQ9HAV4
PhosphoSitePlusiQ9HAV4

Miscellaneous databases

PMAP-CutDBiQ9HAV4

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

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 (PubMed:19965479). 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). Interacts with RAN (GTP-bound form) (PubMed:19965479).10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MYCP011062EBI-517949,EBI-447544

GO - Molecular functioni

  • Ran GTPase binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi121574, 80 interactors
CORUMiQ9HAV4
DIPiDIP-34547N
IntActiQ9HAV4, 38 interactors
MINTiQ9HAV4
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

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
Regioni641 – 642Pre-miRNA binding1 Publication2

Sequence similaritiesi

Belongs to the exportin family.Curated

Phylogenomic databases

eggNOGiKOG2020 Eukaryota
COG5101 LUCA
GeneTreeiENSGT00390000013979
HOVERGENiHBG056281
InParanoidiQ9HAV4
KOiK14289
OMAiPERHAFL
OrthoDBiEOG091G0154
PhylomeDBiQ9HAV4
TreeFamiTF323382

Family and domain databases

Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR013598 Exportin-1/Importin-b-like
IPR001494 Importin-beta_N
PfamiView protein in Pfam
PF08389 Xpo1, 1 hit
SMARTiView protein in SMART
SM00913 IBN_N, 1 hit
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 dbSNP:rs34324334Ensembl.1
Natural variantiVAR_076472552V → I Found in a patient with nephrotic syndrome; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs11544379EnsemblClinVar.1
Natural variantiVAR_028032610K → N. Corresponds to variant dbSNP:rs12173786Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiXPO5_HUMAN
AccessioniPrimary (citable) accession number: Q9HAV4
Secondary accession number(s): Q5JTE6
, Q96G48, Q96HN3, Q9BWM6, Q9BZV5, Q9H9M4, Q9NT89, Q9NW39, Q9ULC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: March 1, 2001
Last modified: July 18, 2018
This is version 147 of the entry and version 1 of the sequence. See 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

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