Full text data of CSE1L
CSE1L
(CAS, XPO2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Exportin-2; Exp2 (Cellular apoptosis susceptibility protein; Chromosome segregation 1-like protein; Importin-alpha re-exporter)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Exportin-2; Exp2 (Cellular apoptosis susceptibility protein; Chromosome segregation 1-like protein; Importin-alpha re-exporter)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00022744
IPI00022744 Splice Isoform 1 Of Importin-alpha re-exporter Export receptor for importin alpha. Mediates importin-alpha reexport from the nucleus to the cytoplasm after import substrates have been released into the nucleoplasm. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic and nuclear isoform 1 or 3 expected molecular weight found in band found in band >188 kDa
IPI00022744 Splice Isoform 1 Of Importin-alpha re-exporter Export receptor for importin alpha. Mediates importin-alpha reexport from the nucleus to the cytoplasm after import substrates have been released into the nucleoplasm. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic and nuclear isoform 1 or 3 expected molecular weight found in band found in band >188 kDa
UniProt
P55060
ID XPO2_HUMAN Reviewed; 971 AA.
AC P55060; A3RLL6; B2R5T4; E1P5Y0; F8W904; O75432; Q32M40; Q9H5B7;
read moreAC Q9NTS0; Q9UP98; Q9UP99; Q9UPA0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 3.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Exportin-2;
DE Short=Exp2;
DE AltName: Full=Cellular apoptosis susceptibility protein;
DE AltName: Full=Chromosome segregation 1-like protein;
DE AltName: Full=Importin-alpha re-exporter;
GN Name=CSE1L; Synonyms=CAS, XPO2;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=7479798; DOI=10.1073/pnas.92.22.10427;
RA Brinkmann U., Brinkmann E., Gallo M., Pastan I.;
RT "Cloning and characterization of a cellular apoptosis susceptibility
RT gene, the human homologue to the yeast chromosome segregation gene
RT CSE1.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10427-10431(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain;
RX PubMed=10331944; DOI=10.1006/geno.1998.5700;
RA Brinkmann U., Brinkmann E., Bera T.K., Wellmann A., Pastan I.;
RT "Tissue-specific alternative splicing of the CSE1L/CAS (cellular
RT apoptosis susceptibility) gene.";
RL Genomics 58:41-49(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RX PubMed=11703094; DOI=10.1006/mcbr.2001.0303;
RA Jiang M.C., Lin T.L., Lee T.L., Huang H.T., Lin C.L., Liao C.F.;
RT "IRF-1-mediated CAS expression enhances interferon-gamma-induced
RT apoptosis of HT-29 colon adenocarcinoma cells.";
RL Mol. Cell Biol. Res. Commun. 4:353-358(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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 GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [8]
RP PROTEIN SEQUENCE OF 1-16; 18-26; 32-67; 76-83; 94-109; 138-151;
RP 166-217; 252-268; 282-288; 293-309; 332-371; 373-382; 396-418;
RP 428-440; 446-481; 560-574; 698-736; 769-777; 789-816; 825-832 AND
RP 913-934, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 356-370, FUNCTION IN PROTEIN NUCLEAR EXPORT, AND
RP IDENTIFICATION IN A COMPLEX WITH RAN AND KPNA2.
RX PubMed=9323134; DOI=10.1016/S0092-8674(00)80372-4;
RA Kutay U., Bischoff F.R., Kostka S., Kraft R., Goerlich D.;
RT "Export of importin-alpha from the nucleus is mediated by a specific
RT nuclear transport factor.";
RL Cell 90:1061-1071(1997).
RN [10]
RP INTERACTION WITH KPNA2.
RX PubMed=9786944; DOI=10.1083/jcb.143.2.309;
RA Herold A., Truant R., Wiegand H., Cullen B.R.;
RT "Determination of the functional domain organization of the importin
RT alpha nuclear import factor.";
RL J. Cell Biol. 143:309-318(1998).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-574 AND LYS-824, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP VARIANT [LARGE SCALE ANALYSIS] PHE-842.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Export receptor for importin-alpha. Mediates importin-
CC alpha re-export from the nucleus to the cytoplasm after import
CC substrates (cargos) have been released into the nucleoplasm. In
CC the nucleus binds cooperatively to importin-alpha and to the
CC GTPase Ran in its active GTP-bound form. Docking of this trimeric
CC complex to the nuclear pore complex (NPC) is mediated through
CC binding to nucleoporins. Upon transit of a nuclear export complex
CC into the cytoplasm, disassembling of the complex and hydrolysis of
CC Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively)
CC cause release of the importin-alpha from the export receptor.
CC CSE1L/XPO2 then return to the nuclear compartment and mediate
CC another round of transport. The directionality of nuclear export
CC is thought to be conferred by an asymmetric distribution of the
CC GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
CC -!- SUBUNIT: Found in a complex with CSE1L/XPO2, Ran and KPNA2. Binds
CC with high affinity to importin-alpha only in the presence of
CC RanGTP. The complex is dissociated by the combined action of
CC RanBP1 and RanGAP1.
CC -!- INTERACTION:
CC P04637:TP53; NbExp=5; IntAct=EBI-286709, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between
CC the nucleus and the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=A;
CC IsoId=P55060-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55060-2; Sequence=VSP_001222, VSP_001223;
CC Name=3;
CC IsoId=P55060-3; Sequence=VSP_001224, VSP_001225;
CC Name=4;
CC IsoId=P55060-4; Sequence=VSP_047203;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Highly expressed in proliferating cells.
CC -!- SIMILARITY: Belongs to the XPO2/CSE1 family.
CC -!- SIMILARITY: Contains 1 importin N-terminal domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSE1LID40159ch20q13.html";
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DR EMBL; U33286; AAC50367.1; -; mRNA.
DR EMBL; AF053640; AAC35007.1; -; mRNA.
DR EMBL; AF053641; AAC35008.1; -; mRNA.
DR EMBL; AF053642; AAC35009.1; -; mRNA.
DR EMBL; AF053651; AAC35297.1; -; Genomic_DNA.
DR EMBL; AF053644; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053645; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053646; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053647; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053648; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053649; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053650; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; EF426455; ABO15009.1; -; mRNA.
DR EMBL; AK312306; BAG35231.1; -; mRNA.
DR EMBL; AL121903; CAI19615.1; -; Genomic_DNA.
DR EMBL; AL133174; CAI19615.1; JOINED; Genomic_DNA.
DR EMBL; AL133174; CAI42818.1; -; Genomic_DNA.
DR EMBL; AL121903; CAI42818.1; JOINED; Genomic_DNA.
DR EMBL; CH471077; EAW75676.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75677.1; -; Genomic_DNA.
DR EMBL; BC108309; AAI08310.1; -; mRNA.
DR EMBL; BC109313; AAI09314.1; -; mRNA.
DR EMBL; BC109314; AAI09315.1; -; mRNA.
DR PIR; I39166; I39166.
DR RefSeq; NP_001243064.1; NM_001256135.1.
DR RefSeq; NP_001307.2; NM_001316.3.
DR UniGene; Hs.90073; -.
DR ProteinModelPortal; P55060; -.
DR SMR; P55060; 6-934.
DR DIP; DIP-32573N; -.
DR IntAct; P55060; 25.
DR MINT; MINT-5001090; -.
DR PhosphoSite; P55060; -.
DR DMDM; 62297557; -.
DR PaxDb; P55060; -.
DR PRIDE; P55060; -.
DR DNASU; 1434; -.
DR Ensembl; ENST00000262982; ENSP00000262982; ENSG00000124207.
DR Ensembl; ENST00000396192; ENSP00000379495; ENSG00000124207.
DR GeneID; 1434; -.
DR KEGG; hsa:1434; -.
DR UCSC; uc010ghx.4; human.
DR CTD; 1434; -.
DR GeneCards; GC20P047662; -.
DR HGNC; HGNC:2431; CSE1L.
DR HPA; CAB002140; -.
DR MIM; 601342; gene.
DR neXtProt; NX_P55060; -.
DR PharmGKB; PA26933; -.
DR eggNOG; COG5657; -.
DR HOVERGEN; HBG080050; -.
DR InParanoid; P55060; -.
DR OMA; QFVTAVW; -.
DR OrthoDB; EOG76MK7M; -.
DR PhylomeDB; P55060; -.
DR ChiTaRS; CSE1L; human.
DR GenomeRNAi; 1434; -.
DR NextBio; 5853; -.
DR PRO; PR:P55060; -.
DR ArrayExpress; P55060; -.
DR Bgee; P55060; -.
DR CleanEx; HS_CSE1L; -.
DR Genevestigator; P55060; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0008262; F:importin-alpha export receptor activity; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR005043; CAS_CSE1_C.
DR InterPro; IPR013713; Cse1.
DR InterPro; IPR001494; Importin-beta_N.
DR Pfam; PF03378; CAS_CSE1; 1.
DR Pfam; PF08506; Cse1; 1.
DR Pfam; PF03810; IBN_N; 1.
DR SMART; SM00913; IBN_N; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Polymorphism; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 971 Exportin-2.
FT /FTId=PRO_0000117287.
FT DOMAIN 29 102 Importin N-terminal.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 574 574 N6-acetyllysine.
FT MOD_RES 824 824 N6-acetyllysine.
FT VAR_SEQ 190 195 ATIELC -> VWNASW (in isoform 2).
FT /FTId=VSP_001222.
FT VAR_SEQ 196 971 Missing (in isoform 2).
FT /FTId=VSP_001223.
FT VAR_SEQ 257 312 Missing (in isoform 4).
FT /FTId=VSP_047203.
FT VAR_SEQ 943 945 VPS -> TYF (in isoform 3).
FT /FTId=VSP_001224.
FT VAR_SEQ 946 971 Missing (in isoform 3).
FT /FTId=VSP_001225.
FT VARIANT 754 754 I -> V (in dbSNP:rs2229042).
FT /FTId=VAR_029327.
FT VARIANT 842 842 C -> F (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036558.
FT VARIANT 968 968 V -> L (in dbSNP:rs3505).
FT /FTId=VAR_048836.
FT CONFLICT 231 233 FED -> WEG (in Ref. 1; AAC50367 and 2;
FT AAC35008).
FT CONFLICT 514 514 E -> G (in Ref. 1; AAC50367 and 2;
FT AAC35008).
FT CONFLICT 538 538 A -> T (in Ref. 3; ABO15009).
FT CONFLICT 848 848 K -> N (in Ref. 1; AAC50367).
FT CONFLICT 934 934 K -> M (in Ref. 1; AAC50367).
SQ SEQUENCE 971 AA; 110417 MW; 08E837AB5008EBFD CRC64;
MELSDANLQT LTEYLKKTLD PDPAIRRPAE KFLESVEGNQ NYPLLLLTLL EKSQDNVIKV
CASVTFKNYI KRNWRIVEDE PNKICEADRV AIKANIVHLM LSSPEQIQKQ LSDAISIIGR
EDFPQKWPDL LTEMVNRFQS GDFHVINGVL RTAHSLFKRY RHEFKSNELW TEIKLVLDAF
ALPLTNLFKA TIELCSTHAN DASALRILFS SLILISKLFY SLNFQDLPEF FEDNMETWMN
NFHTLLTLDN KLLQTDDEEE AGLLELLKSQ ICDNAALYAQ KYDEEFQRYL PRFVTAIWNL
LVTTGQEVKY DLLVSNAIQF LASVCERPHY KNLFEDQNTL TSICEKVIVP NMEFRAADEE
AFEDNSEEYI RRDLEGSDID TRRRAACDLV RGLCKFFEGP VTGIFSGYVN SMLQEYAKNP
SVNWKHKDAA IYLVTSLASK AQTQKHGITQ ANELVNLTEF FVNHILPDLK SANVNEFPVL
KADGIKYIMI FRNQVPKEHL LVSIPLLINH LQAESIVVHT YAAHALERLF TMRGPNNATL
FTAAEIAPFV EILLTNLFKA LTLPGSSENE YIMKAIMRSF SLLQEAIIPY IPTLITQLTQ
KLLAVSKNPS KPHFNHYMFE AICLSIRITC KANPAAVVNF EEALFLVFTE ILQNDVQEFI
PYVFQVMSLL LETHKNDIPS SYMALFPHLL QPVLWERTGN IPALVRLLQA FLERGSNTIA
SAAADKIPGL LGVFQKLIAS KANDHQGFYL LNSIIEHMPP ESVDQYRKQI FILLFQRLQN
SKTTKFIKSF LVFINLYCIK YGALALQEIF DGIQPKMFGM VLEKIIIPEI QKVSGNVEKK
ICAVGITKLL TECPPMMDTE YTKLWTPLLQ SLIGLFELPE DDTIPDEEHF IDIEDTPGYQ
TAFSQLAFAG KKEHDPVGQM VNNPKIHLAQ SLHKLSTACP GRVPSMVSTS LNAEALQYLQ
GYLQAASVTL L
//
ID XPO2_HUMAN Reviewed; 971 AA.
AC P55060; A3RLL6; B2R5T4; E1P5Y0; F8W904; O75432; Q32M40; Q9H5B7;
read moreAC Q9NTS0; Q9UP98; Q9UP99; Q9UPA0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 3.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Exportin-2;
DE Short=Exp2;
DE AltName: Full=Cellular apoptosis susceptibility protein;
DE AltName: Full=Chromosome segregation 1-like protein;
DE AltName: Full=Importin-alpha re-exporter;
GN Name=CSE1L; Synonyms=CAS, XPO2;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=7479798; DOI=10.1073/pnas.92.22.10427;
RA Brinkmann U., Brinkmann E., Gallo M., Pastan I.;
RT "Cloning and characterization of a cellular apoptosis susceptibility
RT gene, the human homologue to the yeast chromosome segregation gene
RT CSE1.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10427-10431(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain;
RX PubMed=10331944; DOI=10.1006/geno.1998.5700;
RA Brinkmann U., Brinkmann E., Bera T.K., Wellmann A., Pastan I.;
RT "Tissue-specific alternative splicing of the CSE1L/CAS (cellular
RT apoptosis susceptibility) gene.";
RL Genomics 58:41-49(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RX PubMed=11703094; DOI=10.1006/mcbr.2001.0303;
RA Jiang M.C., Lin T.L., Lee T.L., Huang H.T., Lin C.L., Liao C.F.;
RT "IRF-1-mediated CAS expression enhances interferon-gamma-induced
RT apoptosis of HT-29 colon adenocarcinoma cells.";
RL Mol. Cell Biol. Res. Commun. 4:353-358(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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 GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [8]
RP PROTEIN SEQUENCE OF 1-16; 18-26; 32-67; 76-83; 94-109; 138-151;
RP 166-217; 252-268; 282-288; 293-309; 332-371; 373-382; 396-418;
RP 428-440; 446-481; 560-574; 698-736; 769-777; 789-816; 825-832 AND
RP 913-934, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 356-370, FUNCTION IN PROTEIN NUCLEAR EXPORT, AND
RP IDENTIFICATION IN A COMPLEX WITH RAN AND KPNA2.
RX PubMed=9323134; DOI=10.1016/S0092-8674(00)80372-4;
RA Kutay U., Bischoff F.R., Kostka S., Kraft R., Goerlich D.;
RT "Export of importin-alpha from the nucleus is mediated by a specific
RT nuclear transport factor.";
RL Cell 90:1061-1071(1997).
RN [10]
RP INTERACTION WITH KPNA2.
RX PubMed=9786944; DOI=10.1083/jcb.143.2.309;
RA Herold A., Truant R., Wiegand H., Cullen B.R.;
RT "Determination of the functional domain organization of the importin
RT alpha nuclear import factor.";
RL J. Cell Biol. 143:309-318(1998).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-574 AND LYS-824, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP VARIANT [LARGE SCALE ANALYSIS] PHE-842.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Export receptor for importin-alpha. Mediates importin-
CC alpha re-export from the nucleus to the cytoplasm after import
CC substrates (cargos) have been released into the nucleoplasm. In
CC the nucleus binds cooperatively to importin-alpha and to the
CC GTPase Ran in its active GTP-bound form. Docking of this trimeric
CC complex to the nuclear pore complex (NPC) is mediated through
CC binding to nucleoporins. Upon transit of a nuclear export complex
CC into the cytoplasm, disassembling of the complex and hydrolysis of
CC Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively)
CC cause release of the importin-alpha from the export receptor.
CC CSE1L/XPO2 then return to the nuclear compartment and mediate
CC another round of transport. The directionality of nuclear export
CC is thought to be conferred by an asymmetric distribution of the
CC GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
CC -!- SUBUNIT: Found in a complex with CSE1L/XPO2, Ran and KPNA2. Binds
CC with high affinity to importin-alpha only in the presence of
CC RanGTP. The complex is dissociated by the combined action of
CC RanBP1 and RanGAP1.
CC -!- INTERACTION:
CC P04637:TP53; NbExp=5; IntAct=EBI-286709, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between
CC the nucleus and the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=A;
CC IsoId=P55060-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55060-2; Sequence=VSP_001222, VSP_001223;
CC Name=3;
CC IsoId=P55060-3; Sequence=VSP_001224, VSP_001225;
CC Name=4;
CC IsoId=P55060-4; Sequence=VSP_047203;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Highly expressed in proliferating cells.
CC -!- SIMILARITY: Belongs to the XPO2/CSE1 family.
CC -!- SIMILARITY: Contains 1 importin N-terminal domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSE1LID40159ch20q13.html";
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DR EMBL; U33286; AAC50367.1; -; mRNA.
DR EMBL; AF053640; AAC35007.1; -; mRNA.
DR EMBL; AF053641; AAC35008.1; -; mRNA.
DR EMBL; AF053642; AAC35009.1; -; mRNA.
DR EMBL; AF053651; AAC35297.1; -; Genomic_DNA.
DR EMBL; AF053644; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053645; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053646; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053647; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053648; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053649; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; AF053650; AAC35297.1; JOINED; Genomic_DNA.
DR EMBL; EF426455; ABO15009.1; -; mRNA.
DR EMBL; AK312306; BAG35231.1; -; mRNA.
DR EMBL; AL121903; CAI19615.1; -; Genomic_DNA.
DR EMBL; AL133174; CAI19615.1; JOINED; Genomic_DNA.
DR EMBL; AL133174; CAI42818.1; -; Genomic_DNA.
DR EMBL; AL121903; CAI42818.1; JOINED; Genomic_DNA.
DR EMBL; CH471077; EAW75676.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75677.1; -; Genomic_DNA.
DR EMBL; BC108309; AAI08310.1; -; mRNA.
DR EMBL; BC109313; AAI09314.1; -; mRNA.
DR EMBL; BC109314; AAI09315.1; -; mRNA.
DR PIR; I39166; I39166.
DR RefSeq; NP_001243064.1; NM_001256135.1.
DR RefSeq; NP_001307.2; NM_001316.3.
DR UniGene; Hs.90073; -.
DR ProteinModelPortal; P55060; -.
DR SMR; P55060; 6-934.
DR DIP; DIP-32573N; -.
DR IntAct; P55060; 25.
DR MINT; MINT-5001090; -.
DR PhosphoSite; P55060; -.
DR DMDM; 62297557; -.
DR PaxDb; P55060; -.
DR PRIDE; P55060; -.
DR DNASU; 1434; -.
DR Ensembl; ENST00000262982; ENSP00000262982; ENSG00000124207.
DR Ensembl; ENST00000396192; ENSP00000379495; ENSG00000124207.
DR GeneID; 1434; -.
DR KEGG; hsa:1434; -.
DR UCSC; uc010ghx.4; human.
DR CTD; 1434; -.
DR GeneCards; GC20P047662; -.
DR HGNC; HGNC:2431; CSE1L.
DR HPA; CAB002140; -.
DR MIM; 601342; gene.
DR neXtProt; NX_P55060; -.
DR PharmGKB; PA26933; -.
DR eggNOG; COG5657; -.
DR HOVERGEN; HBG080050; -.
DR InParanoid; P55060; -.
DR OMA; QFVTAVW; -.
DR OrthoDB; EOG76MK7M; -.
DR PhylomeDB; P55060; -.
DR ChiTaRS; CSE1L; human.
DR GenomeRNAi; 1434; -.
DR NextBio; 5853; -.
DR PRO; PR:P55060; -.
DR ArrayExpress; P55060; -.
DR Bgee; P55060; -.
DR CleanEx; HS_CSE1L; -.
DR Genevestigator; P55060; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0008262; F:importin-alpha export receptor activity; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR005043; CAS_CSE1_C.
DR InterPro; IPR013713; Cse1.
DR InterPro; IPR001494; Importin-beta_N.
DR Pfam; PF03378; CAS_CSE1; 1.
DR Pfam; PF08506; Cse1; 1.
DR Pfam; PF03810; IBN_N; 1.
DR SMART; SM00913; IBN_N; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Polymorphism; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 971 Exportin-2.
FT /FTId=PRO_0000117287.
FT DOMAIN 29 102 Importin N-terminal.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 574 574 N6-acetyllysine.
FT MOD_RES 824 824 N6-acetyllysine.
FT VAR_SEQ 190 195 ATIELC -> VWNASW (in isoform 2).
FT /FTId=VSP_001222.
FT VAR_SEQ 196 971 Missing (in isoform 2).
FT /FTId=VSP_001223.
FT VAR_SEQ 257 312 Missing (in isoform 4).
FT /FTId=VSP_047203.
FT VAR_SEQ 943 945 VPS -> TYF (in isoform 3).
FT /FTId=VSP_001224.
FT VAR_SEQ 946 971 Missing (in isoform 3).
FT /FTId=VSP_001225.
FT VARIANT 754 754 I -> V (in dbSNP:rs2229042).
FT /FTId=VAR_029327.
FT VARIANT 842 842 C -> F (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036558.
FT VARIANT 968 968 V -> L (in dbSNP:rs3505).
FT /FTId=VAR_048836.
FT CONFLICT 231 233 FED -> WEG (in Ref. 1; AAC50367 and 2;
FT AAC35008).
FT CONFLICT 514 514 E -> G (in Ref. 1; AAC50367 and 2;
FT AAC35008).
FT CONFLICT 538 538 A -> T (in Ref. 3; ABO15009).
FT CONFLICT 848 848 K -> N (in Ref. 1; AAC50367).
FT CONFLICT 934 934 K -> M (in Ref. 1; AAC50367).
SQ SEQUENCE 971 AA; 110417 MW; 08E837AB5008EBFD CRC64;
MELSDANLQT LTEYLKKTLD PDPAIRRPAE KFLESVEGNQ NYPLLLLTLL EKSQDNVIKV
CASVTFKNYI KRNWRIVEDE PNKICEADRV AIKANIVHLM LSSPEQIQKQ LSDAISIIGR
EDFPQKWPDL LTEMVNRFQS GDFHVINGVL RTAHSLFKRY RHEFKSNELW TEIKLVLDAF
ALPLTNLFKA TIELCSTHAN DASALRILFS SLILISKLFY SLNFQDLPEF FEDNMETWMN
NFHTLLTLDN KLLQTDDEEE AGLLELLKSQ ICDNAALYAQ KYDEEFQRYL PRFVTAIWNL
LVTTGQEVKY DLLVSNAIQF LASVCERPHY KNLFEDQNTL TSICEKVIVP NMEFRAADEE
AFEDNSEEYI RRDLEGSDID TRRRAACDLV RGLCKFFEGP VTGIFSGYVN SMLQEYAKNP
SVNWKHKDAA IYLVTSLASK AQTQKHGITQ ANELVNLTEF FVNHILPDLK SANVNEFPVL
KADGIKYIMI FRNQVPKEHL LVSIPLLINH LQAESIVVHT YAAHALERLF TMRGPNNATL
FTAAEIAPFV EILLTNLFKA LTLPGSSENE YIMKAIMRSF SLLQEAIIPY IPTLITQLTQ
KLLAVSKNPS KPHFNHYMFE AICLSIRITC KANPAAVVNF EEALFLVFTE ILQNDVQEFI
PYVFQVMSLL LETHKNDIPS SYMALFPHLL QPVLWERTGN IPALVRLLQA FLERGSNTIA
SAAADKIPGL LGVFQKLIAS KANDHQGFYL LNSIIEHMPP ESVDQYRKQI FILLFQRLQN
SKTTKFIKSF LVFINLYCIK YGALALQEIF DGIQPKMFGM VLEKIIIPEI QKVSGNVEKK
ICAVGITKLL TECPPMMDTE YTKLWTPLLQ SLIGLFELPE DDTIPDEEHF IDIEDTPGYQ
TAFSQLAFAG KKEHDPVGQM VNNPKIHLAQ SLHKLSTACP GRVPSMVSTS LNAEALQYLQ
GYLQAASVTL L
//
MIM
601342
*RECORD*
*FIELD* NO
601342
*FIELD* TI
*601342 CHROMOSOME SEGREGATION 1-LIKE; CSE1L
;;CELLULAR APOPTOSIS SUSCEPTIBILITY; CAS;;
read moreCHROMOSOME SEGREGATION GENE CSE1, YEAST, HOMOLOG OF;;
CSE1, YEAST, HOMOLOG OF
*FIELD* TX
CLONING
Brinkmann et al. (1995) cloned several HeLa cell cDNAs that render MCF-7
breast cancer cells resistant to immunotoxins. Brinkmann et al. (1995)
found that one of these cDNAs contains a portion of the human homolog of
the yeast chromosome segregation gene CSE1. They noted that an antisense
fragment of the human homolog had conferred immunotoxin resistance. They
cloned the full-length cDNA for the human homolog and designated it the
'cellular apoptosis susceptibility' (CAS) gene. Northern blot analysis
showed that the 3.1-kb CAS mRNA was expressed preferentially in
proliferating cells. On Western blots, the predicted 971-amino acid
protein migrated as an approximately 100-kD protein; its expression
correlated with cell proliferation.
MAPPING
By fluorescence in situ hybridization, Brinkmann et al. (1996) mapped
the CAS gene to 20q13. This region had been known to harbor
amplifications that correlate with aggressive breast cancer. Brinkmann
et al. (1996) used Southern hybridization with a CAS cDNA fragment and
fluorescence in situ hybridization with a P1 clone containing the CAS
gene and found elevated copy numbers of CAS in a leukemia cell line, 3
of 4 colon cell lines, and 3 of 7 breast cancer cell lines. In 2 of
these cell lines (the leukemia and a colon cancer), they attributed
elevated CAS copy number to additional copies of chromosome 20.
GENE FUNCTION
Brinkmann et al. (1996) noted that CAS may have a dual function in
mammalian cells, 1 in apoptosis and another in cell proliferation.
Brinkmann et al. (1996) observed that CAS antisense RNA can interfere
with apoptosis mediated by tumor necrosis factor-alpha (191160) and beta
(153440) and by ADP-ribosylating toxins, suggesting that CAS may play a
role in selected pathways of apoptosis.
Proteins that carry a nuclear localization signal (NLS) are transported
into the nucleus by the importin-alpha/-beta heterodimer. Importin-alpha
(see 600685 and 600686) binds the NLS, while importin-beta (see 602008)
mediates translocation through the nuclear pore complex. After
translocation, RanGTP (see RANGAP1; 602362), which has a high predicted
concentration in the nucleus and a low predicted concentration in the
cytoplasm, binds importin-beta and displaces importin-alpha.
Importin-alpha must then be returned to the cytoplasm, leaving the NLS
protein behind. Kutay et al. (1997) reported that the CAS protein
mediates importin-alpha reexport. CAS binds strongly to importin-alpha
only in the presence of RanGTP, forming an importin-alpha/CAS/RanGTP
complex. Importin-alpha is released from this complex in the cytoplasm
by the combined action of RANBP1 (601180) and RANGAP1. CAS binds
preferentially to NLS-free importin-alpha, explaining why import
substrates stay in the nucleus. In a 'Minireview,' Ullman et al. (1997)
summarized existing research relating to nuclear export receptors.
Brinkmann (1998) provided a review of the role of CAS in proliferation,
apoptosis, and cancer.
BIOCHEMICAL FEATURES
- Crystal Structure
Matsuura and Stewart (2004) presented the 2.0-angstrom crystal structure
of the nuclear export complex formed by exportin Cse1p complexed with
its cargo Kap60p (importin-alpha; see 600685) and RanGTP (see 602362),
thereby providing a structural framework for understanding nuclear
protein export and the different functions of RanGTP in export and
import. In the complex, Cse1p coils around both RanGTP and Kap60p,
stabilizing the RanGTP-state and clamping the Kap60p importin-beta (see
602738)-binding domain, ensuring that only cargo-free Kap60p is
exported. By mutagenesis, Matsuura and Stewart (2004) showed that
conformational changes in exportins couple cargo binding to high
affinity for RanGTP, generating a spring-loaded molecule to facilitate
disassembly of the export complex following GTP hydrolysis in the
cytoplasm.
Cook et al. (2005) reported the 3.1-angstrom crystal structure of
cargo-free eukaryotic Cse1, representing its cytosolic state. Cse1 is
compact, consisting of N- and C-terminal arches that interact to form a
ring. Comparison with the structure of cargo-bound Cse1 showed a major
conformational change leading to opening of the structure upon cargo
binding. The largest structural changes occurred within a hinge region
centered at HEAT repeat 8. This repeat contains a conserved insertion
that connects the RanGTP and importin-alpha contact sites and is
essential for cargo binding. In the cargo-free state, the RanGTP-binding
sites are occluded and the importin-alpha sites are distorted. Mutations
that destabilized the N- and C-terminal interactions uncoupled
importin-alpha and Ran binding, suggesting that the closed conformation
prevents association of CSE1 with importin-alpha.
*FIELD* RF
1. Brinkmann, U.: CAS, the human homologue of the yeast chromosome-segregation
gene CSE1, in proliferation, apoptosis, and cancer. Am. J. Hum. Genet. 62:
509-513, 1998.
2. Brinkmann, U.; Brinkmann, E.; Gallo, M.; Pastan, I.: Cloning and
characterization of a cellular apoptosis susceptibility gene, the
human homologue to the yeast chromosome segregation gene CSE1. Proc.
Nat. Acad. Sci. 92: 10427-10431, 1995.
3. Brinkmann, U.; Brinkmann, E.; Gallo, M.; Scherf, U.; Pastan, I.
: Role of CAS, a human homologue to the yeast chromosome segregation
gene CSE1, in toxin and tumor necrosis factor mediated apoptosis. Biochemistry 35:
6891-6899, 1996.
4. Brinkmann, U.; Brinkmann, E.; Pastan, I.: Expression cloning of
cDNAs that render cancer cells resistant to Pseudomonas and diphtheria
toxin and immunotoxins. Molec. Med. 1: 206-216, 1995.
5. Brinkmann, U.; Gallo, M.; Polymeropoulos, M. H.; Pastan, I.: The
human CAS (cellular apoptosis susceptibility) gene mapping on chromosome
20q13 is amplified in BT474 breast cancer cells and part of aberrant
chromosomes in breast and colon cancer cell lines. Genome Res. 6:
187-194, 1996.
6. Cook, A.; Fernandez, E.; Lindner, D.; Ebert, J.; Schlenstedt, G.;
Conti, E.: The structure of the nuclear export receptor Cse1 in its
cytosolic state reveals a closed conformation incompatible with cargo
binding. Molec. Cell 18: 355-367, 2005.
7. Kutay, U.; Bischoff, F. R.; Kostka, S.; Kraft, R.; Gorlich, D.
: Export of importin-alpha from the nucleus is mediated by a specific
nuclear transport factor. Cell 90: 1061-1071, 1997.
8. Matsuura, Y.; Stewart, M.: Structural basis for the assembly of
a nuclear export complex. Nature 432: 872-877, 2004.
9. Ullman, K. S.; Powers, M. A.; Forbes, D. J.: Nuclear export receptors:
from importin to exportin. Cell 90: 967-970, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 5/26/2005
Ada Hamosh - updated: 12/29/2004
Victor A. McKusick - updated: 5/8/1998
Ada Hamosh - updated: 5/5/1998
Rebekah S. Rasooly - updated: 4/24/1998
*FIELD* CD
Victor A. McKusick: 7/11/1996
*FIELD* ED
alopez: 11/16/2007
mgross: 6/6/2005
terry: 5/26/2005
alopez: 12/30/2004
terry: 12/29/2004
alopez: 9/9/1998
psherman: 5/20/1998
terry: 5/8/1998
alopez: 5/5/1998
psherman: 4/24/1998
mark: 9/20/1996
terry: 9/11/1996
mark: 7/11/1996
*RECORD*
*FIELD* NO
601342
*FIELD* TI
*601342 CHROMOSOME SEGREGATION 1-LIKE; CSE1L
;;CELLULAR APOPTOSIS SUSCEPTIBILITY; CAS;;
read moreCHROMOSOME SEGREGATION GENE CSE1, YEAST, HOMOLOG OF;;
CSE1, YEAST, HOMOLOG OF
*FIELD* TX
CLONING
Brinkmann et al. (1995) cloned several HeLa cell cDNAs that render MCF-7
breast cancer cells resistant to immunotoxins. Brinkmann et al. (1995)
found that one of these cDNAs contains a portion of the human homolog of
the yeast chromosome segregation gene CSE1. They noted that an antisense
fragment of the human homolog had conferred immunotoxin resistance. They
cloned the full-length cDNA for the human homolog and designated it the
'cellular apoptosis susceptibility' (CAS) gene. Northern blot analysis
showed that the 3.1-kb CAS mRNA was expressed preferentially in
proliferating cells. On Western blots, the predicted 971-amino acid
protein migrated as an approximately 100-kD protein; its expression
correlated with cell proliferation.
MAPPING
By fluorescence in situ hybridization, Brinkmann et al. (1996) mapped
the CAS gene to 20q13. This region had been known to harbor
amplifications that correlate with aggressive breast cancer. Brinkmann
et al. (1996) used Southern hybridization with a CAS cDNA fragment and
fluorescence in situ hybridization with a P1 clone containing the CAS
gene and found elevated copy numbers of CAS in a leukemia cell line, 3
of 4 colon cell lines, and 3 of 7 breast cancer cell lines. In 2 of
these cell lines (the leukemia and a colon cancer), they attributed
elevated CAS copy number to additional copies of chromosome 20.
GENE FUNCTION
Brinkmann et al. (1996) noted that CAS may have a dual function in
mammalian cells, 1 in apoptosis and another in cell proliferation.
Brinkmann et al. (1996) observed that CAS antisense RNA can interfere
with apoptosis mediated by tumor necrosis factor-alpha (191160) and beta
(153440) and by ADP-ribosylating toxins, suggesting that CAS may play a
role in selected pathways of apoptosis.
Proteins that carry a nuclear localization signal (NLS) are transported
into the nucleus by the importin-alpha/-beta heterodimer. Importin-alpha
(see 600685 and 600686) binds the NLS, while importin-beta (see 602008)
mediates translocation through the nuclear pore complex. After
translocation, RanGTP (see RANGAP1; 602362), which has a high predicted
concentration in the nucleus and a low predicted concentration in the
cytoplasm, binds importin-beta and displaces importin-alpha.
Importin-alpha must then be returned to the cytoplasm, leaving the NLS
protein behind. Kutay et al. (1997) reported that the CAS protein
mediates importin-alpha reexport. CAS binds strongly to importin-alpha
only in the presence of RanGTP, forming an importin-alpha/CAS/RanGTP
complex. Importin-alpha is released from this complex in the cytoplasm
by the combined action of RANBP1 (601180) and RANGAP1. CAS binds
preferentially to NLS-free importin-alpha, explaining why import
substrates stay in the nucleus. In a 'Minireview,' Ullman et al. (1997)
summarized existing research relating to nuclear export receptors.
Brinkmann (1998) provided a review of the role of CAS in proliferation,
apoptosis, and cancer.
BIOCHEMICAL FEATURES
- Crystal Structure
Matsuura and Stewart (2004) presented the 2.0-angstrom crystal structure
of the nuclear export complex formed by exportin Cse1p complexed with
its cargo Kap60p (importin-alpha; see 600685) and RanGTP (see 602362),
thereby providing a structural framework for understanding nuclear
protein export and the different functions of RanGTP in export and
import. In the complex, Cse1p coils around both RanGTP and Kap60p,
stabilizing the RanGTP-state and clamping the Kap60p importin-beta (see
602738)-binding domain, ensuring that only cargo-free Kap60p is
exported. By mutagenesis, Matsuura and Stewart (2004) showed that
conformational changes in exportins couple cargo binding to high
affinity for RanGTP, generating a spring-loaded molecule to facilitate
disassembly of the export complex following GTP hydrolysis in the
cytoplasm.
Cook et al. (2005) reported the 3.1-angstrom crystal structure of
cargo-free eukaryotic Cse1, representing its cytosolic state. Cse1 is
compact, consisting of N- and C-terminal arches that interact to form a
ring. Comparison with the structure of cargo-bound Cse1 showed a major
conformational change leading to opening of the structure upon cargo
binding. The largest structural changes occurred within a hinge region
centered at HEAT repeat 8. This repeat contains a conserved insertion
that connects the RanGTP and importin-alpha contact sites and is
essential for cargo binding. In the cargo-free state, the RanGTP-binding
sites are occluded and the importin-alpha sites are distorted. Mutations
that destabilized the N- and C-terminal interactions uncoupled
importin-alpha and Ran binding, suggesting that the closed conformation
prevents association of CSE1 with importin-alpha.
*FIELD* RF
1. Brinkmann, U.: CAS, the human homologue of the yeast chromosome-segregation
gene CSE1, in proliferation, apoptosis, and cancer. Am. J. Hum. Genet. 62:
509-513, 1998.
2. Brinkmann, U.; Brinkmann, E.; Gallo, M.; Pastan, I.: Cloning and
characterization of a cellular apoptosis susceptibility gene, the
human homologue to the yeast chromosome segregation gene CSE1. Proc.
Nat. Acad. Sci. 92: 10427-10431, 1995.
3. Brinkmann, U.; Brinkmann, E.; Gallo, M.; Scherf, U.; Pastan, I.
: Role of CAS, a human homologue to the yeast chromosome segregation
gene CSE1, in toxin and tumor necrosis factor mediated apoptosis. Biochemistry 35:
6891-6899, 1996.
4. Brinkmann, U.; Brinkmann, E.; Pastan, I.: Expression cloning of
cDNAs that render cancer cells resistant to Pseudomonas and diphtheria
toxin and immunotoxins. Molec. Med. 1: 206-216, 1995.
5. Brinkmann, U.; Gallo, M.; Polymeropoulos, M. H.; Pastan, I.: The
human CAS (cellular apoptosis susceptibility) gene mapping on chromosome
20q13 is amplified in BT474 breast cancer cells and part of aberrant
chromosomes in breast and colon cancer cell lines. Genome Res. 6:
187-194, 1996.
6. Cook, A.; Fernandez, E.; Lindner, D.; Ebert, J.; Schlenstedt, G.;
Conti, E.: The structure of the nuclear export receptor Cse1 in its
cytosolic state reveals a closed conformation incompatible with cargo
binding. Molec. Cell 18: 355-367, 2005.
7. Kutay, U.; Bischoff, F. R.; Kostka, S.; Kraft, R.; Gorlich, D.
: Export of importin-alpha from the nucleus is mediated by a specific
nuclear transport factor. Cell 90: 1061-1071, 1997.
8. Matsuura, Y.; Stewart, M.: Structural basis for the assembly of
a nuclear export complex. Nature 432: 872-877, 2004.
9. Ullman, K. S.; Powers, M. A.; Forbes, D. J.: Nuclear export receptors:
from importin to exportin. Cell 90: 967-970, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 5/26/2005
Ada Hamosh - updated: 12/29/2004
Victor A. McKusick - updated: 5/8/1998
Ada Hamosh - updated: 5/5/1998
Rebekah S. Rasooly - updated: 4/24/1998
*FIELD* CD
Victor A. McKusick: 7/11/1996
*FIELD* ED
alopez: 11/16/2007
mgross: 6/6/2005
terry: 5/26/2005
alopez: 12/30/2004
terry: 12/29/2004
alopez: 9/9/1998
psherman: 5/20/1998
terry: 5/8/1998
alopez: 5/5/1998
psherman: 4/24/1998
mark: 9/20/1996
terry: 9/11/1996
mark: 7/11/1996