exportin-1; exp1; chromosome region maintenance 1 protein homolog (XPO1, CRM1)

Function: - component of nuclear export complex - mediates nuclear export of cellular proteins bearing a leucine-rich nuclear export signal (NED - mediates nuclear export of RNAs - U3 snoRNA transport from Cajal bodies to nucleoli - binds to late precursor U3 snoRNA bearing a TMG cap - in the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein & 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 an nuclear export complex into the cytoplasm, disassembling of the complex & hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 & RANGAP1, respectively) cause release of cargo from the export receptor - directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- & GDP-bound forms of Ran between the cytoplasm & nucleus - phosphorylated upon DNA damage, probably by ATM or ATR - found in a U snRNA export complex with RNUXA/PHAX, NCBP1, NCBP2, RAN, XPO1 & m7G-capped RNA (putative) - found in a 60S ribosomal subunit export complex with NMD3, RAN, XPO1 - interacts with DDX3X, NMD3, NUPL2, NUP88, NUP214, RANBP3 & TERT - interacts with NEMF (via its N-terminus) - interacts with the monomeric form of BIRC5/survivin deacetylated at Lys-129 Structure: - belongs to the exportin family - contains 10 HEAT repeats - contains 1 importin N-terminal domain Compartment: - nuclear & cytoplasmic, nucleoplasm, Cajal bodies, nucleoli - shuttles between nucleus/nucleolus & cytoplasm. Expression: - heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocytes - not expressed in the kidney. Pathology: 1) several viruses, among them HIV-1, HTLV-1 & influenza A highjack XPO1 to export their unspliced or incompletely spliced RNAs out of the nucleus 2) mediates nuclear export of HIV-1 Rev & HTLV-1 Rex proteins 3) role in HTLV-1 Rex multimerization 4) found in a complex with HIV-1 Rev, HIV-1 Rev response element RNA, Ran 5) found in a complex with HTLV-1 Rex, RANBP3, Ran 6) interacts with Epstein- Barr virus BMLF1 Pharmacology: - cellular target of leptomycin B

General

exportin HEAT repeat-containing protein (HEATR) nuclear protein phosphoprotein

Properties

SIZE: entity length = 1071 aa MW = 123 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Necessary for HTLV-1 Rex-mediated mRNA export {1-679} MOTIF: Importin N-terminal {46-112} HEAT repeat {217-240} HEAT repeat {241-277} domain {327-450} HEAT repeat {354-472} Ser phosphorylation site {S391} Ser phosphorylation site {S397} RANBP3 interaction {411-481} domain {411-414} HEAT repeat {515-553} HEAT repeat {560-597} HEAT repeat {602-639} HEAT repeat {775-813} HIV-1 Rev interaction {800-820} HEAT repeat {885-916} HEAT repeat {917-954} HEAT repeat {1002-1039} MOTIF: Ser phosphorylation site {S1031}

Database Correlations

OMIM 602559 UniProt O14980 PFAM correlations Entrez Gene 7514 Kegg hsa:7514

References

UniProt :accession O14980