UniProt Accession

 XPO5_HUMAN; Q9HAV4; Q5JTE6; Q96G48; Q96HN3; Q9BWM6; Q9BZV5; Q9H9M4; Q9NT89; Q9NW39; Q9ULC9 

Genbank Protein ID

 AF271159; AF298880; AB033117; AL355802; BC000129; BC008347; BC009969; BC062635; AL137467; AK001195; AK022718 

Genbank Nucleotide ID

 AAG53603.1; AAG17907.1; BAA86605.2; CAI42640.1; AAH00129.1; AAH08347.1; AAH09969.2; AAH62635.1; CAB70753.1; BAA91547.1; BAB14200.1 

Protein Name

 Exportin-5 

Protein Synonyms/Alias

 Exp5; Ran-binding protein 21 

Gene Name

 XPO5 

Gene Synonyms/Alias

 KIAA1291; RANBP21 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
41	LKFCEEFKEKCPICV	ubiquitination	[1]
43	FCEEFKEKCPICVPC	ubiquitination	[1]
125	RIVVEMIKREWPQHW	ubiquitination	[2]
208	VNKYQQVKTDTSQES	ubiquitination	[1, 2]
216	TDTSQESKAQANCRV	ubiquitination	[1]
396	LLLAIIPKYLRASMT	acetylation	[3]
396	LLLAIIPKYLRASMT	ubiquitination	[1, 4, 5]
413	VKMGFPSKTDSPSCE	ubiquitination	[1, 6, 7]
590	FETVEESKAPRTRAV	ubiquitination	[1, 7]
610	HACSSIIKMCRDYPQ	ubiquitination	[1]
704	AYVGTDQKSCDPGLE	ubiquitination	[6]
801	KMAEPFTKALDMLDA	ubiquitination	[1, 2, 6]
930	LHMRLSQKWQVINQR	ubiquitination	[1, 2, 4, 5]
981	TVCCVSKKGADHSSA	ubiquitination	[1]
1132	SLDQFDCKLLNPSLQ	acetylation	[8]
1132	SLDQFDCKLLNPSLQ	ubiquitination	[1]
1140	LLNPSLQKVADKRRK	ubiquitination	[1, 4, 5]
1160	LIAGCIGKPLGEQFR	ubiquitination	[4, 5]
1173	FRKEVHIKNLPSLFK	ubiquitination	[4, 5]
1180	KNLPSLFKKTKPMLE	ubiquitination	[4, 5]
1181	NLPSLFKKTKPMLET	ubiquitination	[2]
1183	PSLFKKTKPMLETEV	ubiquitination	[2]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [8] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 

Functional Description

 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. 

Sequence Annotation

 REGION 2 108 Necessary for interaction with Ran.
 REGION 533 640 Necessary for interaction with ILF3.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 396 396 N6-acetyllysine.
 MOD_RES 826 826 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing; Nucleus; Phosphoprotein; Polymorphism; Protein transport; Reference proteome; RNA-binding; RNA-mediated gene silencing; Transport; tRNA-binding. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1204 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005643; C:nuclear pore; IEA:InterPro.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0008565; F:protein transporter activity; IEA:Compara.
 GO:0003723; F:RNA binding; TAS:Reactome.
 GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
 GO:0006611; P:protein export from nucleus; IEA:Compara. 

Interpro

 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR013598; Exportin-1/Importin-b-like.
 IPR001494; Importin-beta_N. 

Pfam

 PF08389; Xpo1 

SMART

 SM00913; IBN_N 

PROSITE

  

PRINTS