ID   NXF1_HUMAN              Reviewed;         619 AA.
AC   Q9UBU9; Q99799; Q9UQL2;
DT   27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   14-APR-2009, entry version 102.
DE   RecName: Full=Nuclear RNA export factor 1;
DE   AltName: Full=Tip-associating protein;
DE   AltName: Full=Tip-associated protein;
DE   AltName: Full=mRNA export factor TAP;
GN   Name=NXF1; Synonyms=TAP;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS.
RC   TISSUE=Cervix carcinoma;
RX   MEDLINE=99219873; PubMed=10202158; DOI=10.1093/emboj/18.7.1953;
RA   Braun I.C., Rohrbach E., Schmitt C., Izaurralde E.;
RT   "TAP binds to the constitutive transport element (CTE) through a novel
RT   RNA-binding motif that is sufficient to promote CTE-dependent RNA
RT   export from the nucleus.";
RL   EMBO J. 18:1953-1965(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=99257272; PubMed=10323864;
RA   Kang Y., Cullen B.R.;
RT   "The human Tap protein is a nuclear mRNA export factor that contains
RT   novel RNA-binding and nucleocytoplasmic transport sequences.";
RL   Genes Dev. 13:1126-1139(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=99384298; PubMed=10454577;
RA   Bear J., Tan W., Zolotukhin A.S., Tabernero C., Hudson E.A.,
RA   Felber B.K.;
RT   "Identification of novel import and export signals of human TAP, the
RT   protein that binds to the constitutive transport element of the type D
RT   retrovirus mRNAs.";
RL   Mol. Cell. Biol. 19:6306-6317(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 61-619, AND INTERACTION WITH SAIMIRINE
RP   HERPESVIRUS 2 TIP.
RC   TISSUE=Lymphocyte;
RX   MEDLINE=97318898; PubMed=9175835; DOI=10.1016/S1074-7613(00)80345-3;
RA   Yoon D.-W., Lee H., Seol W., DeMaria M., Rosenzweig M., Jung J.U.;
RT   "Tap: a novel cellular protein that interacts with tip of herpesvirus
RT   saimiri and induces lymphocyte aggregation.";
RL   Immunity 6:571-582(1997).
RN   [7]
RP   FUNCTION.
RX   MEDLINE=98325379; PubMed=9660949; DOI=10.1016/S1097-2765(00)80065-9;
RA   Grueter P., Tabernero C., von Kobbe C., Schmitt C., Saavedra C.,
RA   Bachi A., Wilm M., Felber B.K., Izaurralde E.;
RT   "TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export
RT   from the nucleus.";
RL   Mol. Cell 1:649-659(1998).
RN   [8]
RP   INTERACTION WITH NUPL2.
RX   PubMed=10228171; DOI=10.1093/emboj/18.9.2593;
RA   Katahira J., Straesser K., Podtelejnikov A., Mann M., Jung J.U.,
RA   Hurt E.;
RT   "The Mex67p-mediated nuclear mRNA export pathway is conserved from
RT   yeast to human.";
RL   EMBO J. 18:2593-2609(1999).
RN   [9]
RP   CHARACTERIZATION.
RX   MEDLINE=21282872; PubMed=11259411; DOI=10.1074/jbc.M100400200;
RA   Braun I.C., Herold A., Rode M., Conti E., Izaurralde E.;
RT   "Overexpression of TAP/p15 heterodimers bypasses nuclear retention and
RT   stimulates nuclear mRNA export.";
RL   J. Biol. Chem. 276:20536-20543(2001).
RN   [10]
RP   CHARACTERIZATION.
RX   MEDLINE=20132240; PubMed=10668806; DOI=10.1017/S1355838200991994;
RA   Bachi A., Braun I.C., Rodrigues J.P., Pante N., Ribbeck K.,
RA   von Kobbe C., Kutay U., Wilm M., Goerlich D., Carmo-Fonseca M.,
RA   Izaurralde E.;
RT   "The C-terminal domain of TAP interacts with the nuclear pore complex
RT   and promotes export of specific CTE-bearing RNA substrates.";
RL   RNA 6:136-158(2000).
RN   [11]
RP   MUTAGENESIS.
RX   MEDLINE=21151125; PubMed=11256625; DOI=10.1093/embo-reports/kvd009;
RA   Suyama M., Doerks T., Braun I.C., Sattler M., Izaurralde E., Bork P.;
RT   "Prediction of structural domains of TAP reveals details of its
RT   interaction with p15 and nucleoporins.";
RL   EMBO Rep. 1:53-58(2000).
RN   [12]
RP   INTERACTION WITH THOC4 AND THE EXON JUNCTION COMPLEX.
RX   MEDLINE=21564074; PubMed=11707413; DOI=10.1093/emboj/20.22.6424;
RA   Kataoka N., Diem M.D., Kim V.N., Yong J., Dreyfuss G.;
RT   "Magoh, a human homolog of Drosophila mago nashi protein, is a
RT   component of the splicing-dependent exon-exon junction complex.";
RL   EMBO J. 20:6424-6433(2001).
RN   [13]
RP   IDENTIFICATION IN A MRNP COMPLEX WITH RENT3A AND RENT3B.
RX   PubMed=11546873; DOI=10.1126/science.1062829;
RA   Kim V.N., Kataoka N., Dreyfuss G.;
RT   "Role of the nonsense-mediated decay factor hUpf3 in the splicing-
RT   dependent exon-exon junction complex.";
RL   Science 293:1832-1836(2001).
RN   [14]
RP   IDENTIFICATION IN A POST-SPLICING COMPLEX WITH RBM8A; RENT1; RENT2;
RP   RENT3A; RENT3B AND RNPS1.
RX   PubMed=11546874; DOI=10.1126/science.1062786;
RA   Lykke-Andersen J., Shu M.-D., Steitz J.A.;
RT   "Communication of the position of exon-exon junctions to the mRNA
RT   surveillance machinery by the protein RNPS1.";
RL   Science 293:1836-1839(2001).
RN   [15]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 102-372.
RX   MEDLINE=20514125; PubMed=11060011; DOI=10.1093/emboj/19.21.5587;
RA   Liker E., Fernandez E., Izaurralde E., Conti E.;
RT   "The structure of the mRNA export factor TAP reveals a cis arrangement
RT   of a non-canonical RNP domain and an LRR domain.";
RL   EMBO J. 19:5587-5598(2000).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF COMPLEX WITH NXT1, AND X-RAY
RP   CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH NXT1-FG-REPEAT.
RX   MEDLINE=21468398; PubMed=11583626; DOI=10.1016/S1097-2765(01)00348-3;
RA   Fribourg S., Braun I.C., Izaurralde E., Conti E.;
RT   "Structural basis for the recognition of a nucleoporin FG repeat by
RT   the NTF2-like domain of the TAP/p15 mRNA nuclear export factor.";
RL   Mol. Cell 8:645-656(2001).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 561-619 IN COMPLEX WITH
RP   RANBP3.
RX   MEDLINE=22469929; PubMed=12581645; DOI=10.1016/S0022-2836(02)01474-2;
RA   Grant R.P., Neuhaus D., Stewart M.;
RT   "Structural basis for the interaction between the Tap/NXF1 UBA domain
RT   and FG nucleoporins at 1A resolution.";
RL   J. Mol. Biol. 326:849-858(2003).
RN   [19]
RP   STRUCTURE BY NMR OF 551-619, AND MUTAGENESIS OF PHE-617.
RX   MEDLINE=21912422; PubMed=11875519; DOI=10.1038/nsb773;
RA   Grant R.P., Hurt E., Neuhaus D., Stewart M.;
RT   "Structure of the C-terminal FG-nucleoporin binding domain of
RT   Tap/NXF1.";
RL   Nat. Struct. Biol. 9:247-251(2002).
CC   -!- FUNCTION: Involved in the nuclear export of mRNA species bearing
CC       retroviral constitutive transport elements (CTE) and in the export
CC       of mRNA from the nucleus to the cytoplasm.
CC   -!- SUBUNIT: Interacts with NXT1, NXT2, E1B-AP5, RAE1, THOC4 and with
CC       several nucleoporins. Is part of the exon junction complex (EJC)
CC       containing NCBP1, NCBP2, RNPS1, RBM8A, SRRM1, NXF1, RENT1, RENT2,
CC       RENT3A, RENT3B and THOC4. Found in a mRNA complex with RENT3A and
CC       RENT3B. Interacts with Saimiriine herpesvirus 2 TIP protein.
CC       Interacts with NUPL2.
CC   -!- INTERACTION:
CC       P22575:- (xeno); NbExp=3; IntAct=EBI-398874, EBI-866709;
CC       Q08211:DHX9; NbExp=4; IntAct=EBI-398874, EBI-352022;
CC       Q9UKK6:NXT1; NbExp=1; IntAct=EBI-398874, EBI-301889;
CC       Q07955:SFRS1; NbExp=3; IntAct=EBI-398874, EBI-398920;
CC       Q16629:SFRS7; NbExp=1; IntAct=EBI-398874, EBI-398885;
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm.
CC       Note=Localized predominantly in the nucleoplasm and at both the
CC       nucleoplasmic and cytoplasmic faces of the nuclear pore complex.
CC       Shuttles between the nucleus and the cytoplasm.
CC   -!- TISSUE SPECIFICITY: Expressed ubiquitously.
CC   -!- DOMAIN: The minimal CTE binding domain consists of an RNP-type RNA
CC       binding domain (RBD) and leucine-rich repeats.
CC   -!- DOMAIN: The nucleoporin binding domain consists of a NTF2-like
CC       domain and a TAP domain (also called UBA-like domain). The NTF2
CC       domain heterodimerizes with NXT1 and NXT2. The formation of
CC       NXF1/NXT1 heterodimers is required for NXF1-mediated nuclear mRNA
CC       export. The TAP domain mediates direct interactions with
CC       nucleoporin-FG-repeats and is necessary and sufficient for
CC       localization of NXF1 to the nuclear rim. The conserved loop 594-
CC       NWD-596 of the UBA domain has a critical role in the interaction
CC       with nucleoporins.
CC   -!- DOMAIN: The leucine-rich repeats and the NTF2-domain are essential
CC       for the export of mRNA from the nucleus.
CC   -!- MISCELLANEOUS: The RNA-binding domain is a non-canonical RNP-type
CC       domain.
CC   -!- SIMILARITY: Belongs to the NXF family.
CC   -!- SIMILARITY: Contains 4 LRR (leucine-rich) repeats.
CC   -!- SIMILARITY: Contains 1 NTF2 domain.
CC   -!- SIMILARITY: Contains 1 RRM (RNA recognition motif) domain.
CC   -!- SIMILARITY: Contains 1 TAP-C domain.
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DR   EMBL; AJ132712; CAA10753.1; -; mRNA.
DR   EMBL; AF112880; AAD39102.1; -; mRNA.
DR   EMBL; AF126246; AAD20016.1; -; mRNA.
DR   EMBL; AK027192; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BC004904; AAH04904.1; -; mRNA.
DR   EMBL; BC028041; AAH28041.1; -; mRNA.
DR   EMBL; U80073; AAB81111.1; -; mRNA.
DR   IPI; IPI00033153; -.
DR   RefSeq; NP_006353.2; -.
DR   UniGene; Hs.523739; -.
DR   UniGene; Hs.601546; -.
DR   PDB; 1FO1; X-ray; 2.90 A; A/B=102-372.
DR   PDB; 1FT8; X-ray; 3.15 A; A/B/C/D/E=102-372.
DR   PDB; 1GO5; NMR; -; A=551-619.
DR   PDB; 1JKG; X-ray; 1.90 A; B=371-619.
DR   PDB; 1JN5; X-ray; 2.80 A; B=371-619.
DR   PDB; 1KOH; X-ray; 3.80 A; A/B/C/D=96-372.
DR   PDB; 1KOO; X-ray; 3.80 A; A/B/C/D=96-372.
DR   PDB; 1OAI; X-ray; 1.00 A; A=561-619.
DR   PDB; 2Z5K; X-ray; 2.60 A; B=53-82.
DR   PDB; 2Z5M; X-ray; 3.00 A; B=53-82.
DR   PDBsum; 1FO1; -.
DR   PDBsum; 1FT8; -.
DR   PDBsum; 1GO5; -.
DR   PDBsum; 1JKG; -.
DR   PDBsum; 1JN5; -.
DR   PDBsum; 1KOH; -.
DR   PDBsum; 1KOO; -.
DR   PDBsum; 1OAI; -.
DR   PDBsum; 2Z5K; -.
DR   PDBsum; 2Z5M; -.
DR   IntAct; Q9UBU9; 8.
DR   TCDB; 3.A.18.1.1; nuclear mRNA exporter (mRNA-E) family.
DR   PhosphoSite; Q9UBU9; -.
DR   PeptideAtlas; Q9UBU9; -.
DR   PRIDE; Q9UBU9; -.
DR   Ensembl; ENSG00000162231; Homo sapiens.
DR   GeneID; 10482; -.
DR   GeneCards; GC11M062316; -.
DR   H-InvDB; HIX0009727; -.
DR   HGNC; HGNC:8071; NXF1.
DR   HPA; CAB016327; -.
DR   MIM; 602647; gene.
DR   PharmGKB; PA31858; -.
DR   HOGENOM; Q9UBU9; -.
DR   HOVERGEN; Q9UBU9; -.
DR   Reactome; REACT_1675; mRNA Processing.
DR   Reactome; REACT_71; Gene Expression.
DR   LinkHub; Q9UBU9; -.
DR   NextBio; 39766; -.
DR   ArrayExpress; Q9UBU9; -.
DR   Bgee; Q9UBU9; -.
DR   CleanEx; HS_NXF1; -.
DR   GermOnline; ENSG00000162231; Homo sapiens.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW.
DR   InterPro; IPR012677; a_b_plait_nuc_bd.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR002075; NTF2.
DR   InterPro; IPR005637; TAP_C.
DR   InterPro; IPR015245; Tap_RNA_bd.
DR   InterPro; IPR003603; U2A'_phosphoprotein32A_C.
DR   Gene3D; G3DSA:3.30.70.330; a_b_plait_nuc_bd; 1.
DR   Pfam; PF00560; LRR_1; 1.
DR   Pfam; PF02136; NTF2; 1.
DR   Pfam; PF09162; Tap-RNA_bind; 1.
DR   Pfam; PF03943; TAP_C; 1.
DR   SMART; SM00446; LRRcap; 1.
DR   SMART; SM00804; TAP_C; 1.
DR   PROSITE; PS50177; NTF2_DOMAIN; 1.
DR   PROSITE; PS50102; RRM; FALSE_NEG.
DR   PROSITE; PS51281; TAP_C; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Host-virus interaction; Leucine-rich repeat;
KW   mRNA transport; Nucleus; Repeat; RNA-binding; Transport.
FT   CHAIN         1    619       Nuclear RNA export factor 1.
FT                                /FTId=PRO_0000220529.
FT   DOMAIN      119    198       RRM.
FT   REPEAT      266    291       LRR 1.
FT   REPEAT      292    315       LRR 2.
FT   REPEAT      316    343       LRR 3.
FT   REPEAT      344    371       LRR 4.
FT   DOMAIN      386    536       NTF2.
FT   DOMAIN      565    619       TAP-C.
FT   MOTIF        67    100       Nuclear localization signal.
FT   MOTIF        83    110       Nuclear export signal.
FT   COMPBIAS    551    561       Pro-rich.
FT   MUTAGEN     306    308       ERE->AAA: Decreases the export of mRNAs
FT                                from the nucleus.
FT   MUTAGEN     594    594       W->A: Suppresses FG-nucleoporin binding.
FT   MUTAGEN     595    595       D->R: Suppresses FG-nucleoporin binding.
FT   MUTAGEN     617    617       F->A: Suppresses FG-nucleoporin binding.
FT   CONFLICT    119    119       W -> C (in Ref. 6; AAB81111).
FT   CONFLICT    256    256       T -> N (in Ref. 3; AAD20016).
FT   HELIX       132    142
FT   HELIX       173    175
FT   TURN        176    178
FT   HELIX       206    218
FT   TURN        222    224
FT   STRAND      226    228
FT   HELIX       232    234
FT   HELIX       236    240
FT   HELIX       250    263
FT   STRAND      269    271
FT   HELIX       280    285
FT   HELIX       286    289
FT   STRAND      295    297
FT   HELIX       306    312
FT   STRAND      318    321
FT   HELIX       326    330
FT   HELIX       334    344
FT   HELIX       381    398
FT   HELIX       403    408
FT   STRAND      410    419
FT   HELIX       433    436
FT   TURN        442    444
FT   HELIX       448    454
FT   STRAND      455    458
FT   HELIX       459    466
FT   STRAND      472    474
FT   HELIX       476    478
FT   STRAND      480    486
FT   STRAND      491    501
FT   TURN        505    508
FT   STRAND      510    521
FT   STRAND      525    538
FT   HELIX       541    548
FT   HELIX       565    578
FT   HELIX       582    591
FT   TURN        592    594
FT   HELIX       596    608
FT   HELIX       614    617
SQ   SEQUENCE   619 AA;  70182 MW;  338872AADA789FBF CRC64;
     MADEGKSYSE HDDERVNFPQ RKKKGRGPFR WKYGEGNRRS GRGGSGIRSS RLEEDDGDVA
     MSDAQDGPRV RYNPYTTRPN RRGDTWHDRD RIHVTVRRDR APPERGGAGT SQDGTSKNWF
     KITIPYGRKY DKAWLLSMIQ SKCSVPFTPI EFHYENTRAQ FFVEDASTAS ALKAVNYKIL
     DRENRRISII INSSAPPHTI LNELKPEQVE QLKLIMSKRY DGSQQALDLK GLRSDPDLVA
     QNIDVVLNRR SCMAATLRII EENIPELLSL NLSNNRLYRL DDMSSIVQKA PNLKILNLSG
     NELKSERELD KIKGLKLEEL WLDGNSLCDT FRDQSTYISA IRERFPKLLR LDGHELPPPI
     AFDVEAPTTL PPCKGSYFGT ENLKSLVLHF LQQYYAIYDS GDRQGLLDAY HDGACCSLSI
     PFIPQNPARS SLAEYFKDSR NVKKLKDPTL RFRLLKHTRL NVVAFLNELP KTQHDVNSFV
     VDISAQTSTL LCFSVNGVFK EVDGKSRDSL RAFTRTFIAV PASNSGLCIV NDELFVRNAS
     SEEIQRAFAM PAPTPSSSPV PTLSPEQQEM LQAFSTQSGM NLEWSQKCLQ DNNWDYTRSA
     QAFTHLKAKG EIPEVAFMK
//