UniProt Accession

 XPO1_HUMAN; O14980; A6NL14; A8K1K5; D6W5E2; Q63HP8; Q68CP3; Q99433 

Genbank Protein ID

 Y08614; D89729; AK289920; BX647758; CR749840; AC016727; CH471053; CH471053; BC032847 

Genbank Nucleotide ID

 CAA69905.2; BAA23415.1; BAF82609.1; CAH56174.1; CAH18695.1; AAY14949.1; EAW99993.1; EAW99994.1; AAH32847.1 

Protein Name

 Exportin-1 

Protein Synonyms/Alias

 Exp1; Chromosome region maintenance 1 protein homolog 

Gene Name

 XPO1 

Gene Synonyms/Alias

 CRM1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
54	QEVLTHLKEHPDAWT	ubiquitination	[1, 2, 3, 4, 5]
88	QILENVIKTRWKILP	ubiquitination	[4]
92	NVIKTRWKILPRNQC	ubiquitination	[4]
144	ILKQEWPKHWPTFIS	ubiquitination	[1, 5]
190	SGQITQVKSKHLKDS	ubiquitination	[2, 4, 6, 7, 8]
192	QITQVKSKHLKDSMC	ubiquitination	[4]
339	EHDQLIEKRLNLRET	ubiquitination	[2]
415	LYLPMLFKVRLLMVS	ubiquitination	[1, 4, 5, 6, 9]
426	LMVSRMAKPEEVLVV	ubiquitination	[2, 4]
446	EVVREFMKDTDSINL	acetylation	[8, 10, 11, 12]
446	EVVREFMKDTDSINL	ubiquitination	[1, 2, 3, 5, 8]
455	TDSINLYKNMRETLV	acetylation	[10]
455	TDSINLYKNMRETLV	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 13]
479	TERIMTEKLHNQVNG	ubiquitination	[1, 2, 4, 5, 6, 8]
531	LLGLCEQKRGKDNKA	acetylation	[8]
531	LLGLCEQKRGKDNKA	ubiquitination	[3, 8, 14]
537	QKRGKDNKAIIASNI	acetylation	[12]
568	FLKTVVNKLFEFMHE	acetylation	[12]
680	TKNVDILKDPETVKQ	ubiquitination	[4]
686	LKDPETVKQLGSILK	acetylation	[10, 11, 12]
686	LKDPETVKQLGSILK	ubiquitination	[1, 2, 5]
693	KQLGSILKTNVRACK	acetylation	[10, 11]
693	KQLGSILKTNVRACK	ubiquitination	[1, 3, 4, 5, 8, 14]
700	KTNVRACKAVGHPFV	ubiquitination	[3, 4, 8, 14]
757	TVKRETLKLISGWVS	ubiquitination	[1, 4, 5, 8]

Reference

 [1] 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]
 [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] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [4] 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]
 [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] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [8] 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]
 [9] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [10] 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]
 [11] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [12] 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]
 [13] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [14] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional Description

 Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). 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, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. 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. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap. Several viruses, among them HIV-1, HTLV-1 and influenza A use it to export their unspliced or incompletely spliced RNAs out of the nucleus. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization. 

Sequence Annotation

 DOMAIN 46 112 Importin N-terminal.
 REPEAT 217 240 HEAT 1.
 REPEAT 241 277 HEAT 2.
 REPEAT 354 472 HEAT 3.
 REPEAT 515 553 HEAT 4.
 REPEAT 560 597 HEAT 5.
 REPEAT 602 639 HEAT 6.
 REPEAT 775 813 HEAT 7.
 REPEAT 885 916 HEAT 8.
 REPEAT 917 954 HEAT 9.
 REPEAT 1002 1039 HEAT 10.
 REGION 1 679 Necessary for HTLV-1 Rex-mediated mRNA
 REGION 327 450 Interaction with Ran and nuclear export
 REGION 411 481 Interaction with RANBP3.
 REGION 411 414 Necessary for HTLV-1 Rex multimerization.
 REGION 800 820 Interaction with HIV-1 Rev.
 MOD_RES 391 391 Phosphoserine.
 MOD_RES 446 446 N6-acetyllysine.
 MOD_RES 448 448 Phosphothreonine (By similarity).
 MOD_RES 450 450 Phosphoserine (By similarity).
 MOD_RES 454 454 Phosphotyrosine (By similarity).
 MOD_RES 693 693 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing; Host-virus interaction; mRNA transport; Nucleus; Phosphoprotein; Protein transport; Reference proteome; Repeat; RNA-binding; Transport. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1071 AA 

Protein Sequence

Gene Ontology

 GO:0005642; C:annulate lamellae; IDA:UniProtKB.
 GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0000776; C:kinetochore; IDA:UniProtKB.
 GO:0005635; C:nuclear envelope; TAS:ProtInc.
 GO:0005643; C:nuclear pore; IEA:InterPro.
 GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0030529; C:ribonucleoprotein complex; IDA:MGI.
 GO:0008565; F:protein transporter activity; IEA:Compara.
 GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
 GO:0005215; F:transporter activity; TAS:Reactome.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0075733; P:intracellular transport of viral material; TAS:Reactome.
 GO:0000278; P:mitotic cell cycle; TAS:Reactome.
 GO:0016071; P:mRNA metabolic process; TAS:Reactome.
 GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0006611; P:protein export from nucleus; IEA:Compara.
 GO:0034504; P:protein localization to nucleus; IEA:Compara.
 GO:0010824; P:regulation of centrosome duplication; IEA:Compara.
 GO:0042176; P:regulation of protein catabolic process; IEA:Compara.
 GO:0046825; P:regulation of protein export from nucleus; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0019058; P:viral infectious cycle; TAS:Reactome. 

Interpro

 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR014877; CRM1_C_dom.
 IPR013598; Exportin-1/Importin-b-like.
 IPR001494; Importin-beta_N. 

Pfam

 PF08767; CRM1_C
 PF03810; IBN_N
 PF08389; Xpo1 

SMART

 SM01102; CRM1_C
 SM00913; IBN_N 

PROSITE

 PS50077; HEAT_REPEAT
 PS50166; IMPORTIN_B_NT 

PRINTS