ID   EXOS9_HUMAN             Reviewed;         439 AA.
AC   Q06265; Q12883; Q4W5P5; Q86Y41; Q86Y48;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   15-MAY-2007, sequence version 3.
DT   07-JUL-2009, entry version 88.
DE   RecName: Full=Exosome complex exonuclease RRP45;
DE            EC=3.1.13.-;
DE   AltName: Full=Exosome component 9;
DE   AltName: Full=Polymyositis/scleroderma autoantigen 1;
DE   AltName: Full=Autoantigen PM/Scl 1;
DE   AltName: Full=Polymyositis/scleroderma autoantigen 75 kDa;
DE            Short=PM/Scl-75;
DE   AltName: Full=P75 polymyositis-scleroderma overlap syndrome-associated autoantigen;
GN   Name=EXOSC9; Synonyms=PMSCL1;
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 3).
RC   TISSUE=Lymphoblastoma;
RX   MEDLINE=91178455; PubMed=2007859; DOI=10.1084/jem.173.4.941;
RA   Alderuccio F., Chan E.K.L., Tan E.M.;
RT   "Molecular characterization of an autoantigen of PM-Scl in the
RT   polymyositis/scleroderma overlap syndrome: a unique and complete human
RT   cDNA encoding an apparent 75-kD acidic protein of the nucleolar
RT   complex.";
RL   J. Exp. Med. 173:941-952(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA   Stahnke G., Haubruck H.;
RT   "Nucleotide sequence of an alternatively spliced cDNA coding for PM-
RT   Scl-75, an autoantigen of the Polymyositis/Scleroderma overlap
RT   syndrome.";
RL   Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX   MEDLINE=22791713; PubMed=12788944; DOI=10.1074/jbc.M302488200;
RA   Raijmakers R., Egberts W.V., van Venrooij W.J., Pruijn G.J.;
RT   "The association of the human PM/Scl-75 autoantigen with the exosome
RT   is dependent on a newly identified N terminus.";
RL   J. Biol. Chem. 278:30698-30704(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   CHARACTERIZATION.
RX   MEDLINE=99396719; PubMed=10465791;
RA   Allmang C., Petfalski E., Podtelejnikov A., Mann M., Tollervey D.,
RA   Mitchell P.;
RT   "The yeast exosome and human PM-Scl are related complexes of 3'-->5'
RT   exonucleases.";
RL   Genes Dev. 13:2148-2158(1999).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-392 AND SER-394, AND
RP   MASS SPECTROMETRY.
RC   TISSUE=Epithelium;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-392 AND
RP   SER-394, AND MASS SPECTROMETRY.
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [8]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
CC   -!- FUNCTION: Component of the exosome 3'->5' exoribonuclease complex,
CC       a complex that degrades inherently unstable mRNAs containing AU-
CC       rich elements (AREs) within their 3'-untranslated regions.
CC       Required for the 3'-processing of the 7S pre-RNA to the mature
CC       5.8S rRNA. Has a 3'-5' exonuclease activity (By similarity).
CC   -!- SUBUNIT: Component of the exosome multienzyme ribonuclease complex
CC       composed of at least 11 proteins: EXOSC1/CSL4, EXOSC2/RRP4,
CC       EXOSC3/RRP40, EXOSC4/RRP41, EXOSC5/RRP46, EXOSC6/MTR3,
CC       EXOSC7/RRP42, EXOSC8/RRP43, EXOSC9/Scl-75, DIS3/RRP44, and
CC       EXOSC10/Scl-100 (only in the nuclear complex). Also associated
CC       with the GTPase Ran (By similarity).
CC   -!- INTERACTION:
CC       Q13838:BAT1; NbExp=1; IntAct=EBI-347966, EBI-348622;
CC       Q9NPD3:EXOSC4; NbExp=1; IntAct=EBI-347966, EBI-371823;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q06265-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q06265-2; Sequence=VSP_025556;
CC       Name=3;
CC         IsoId=Q06265-3; Sequence=VSP_025555;
CC       Name=4;
CC         IsoId=Q06265-4; Sequence=VSP_025555, VSP_025556;
CC   -!- DISEASE: Recognized by patients with polymyositis and scleroderma
CC       or with overlap of these two conditions.
CC   -!- SIMILARITY: Belongs to the RNase PH family.
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DR   EMBL; M58460; AAA58384.1; -; mRNA.
DR   EMBL; U09215; AAA18832.1; -; mRNA.
DR   EMBL; AJ505989; CAD44530.1; -; mRNA.
DR   EMBL; AJ517294; CAD56889.1; -; mRNA.
DR   EMBL; AC079341; AAY40968.1; -; Genomic_DNA.
DR   IPI; IPI00029697; -.
DR   IPI; IPI00607722; -.
DR   IPI; IPI00654592; -.
DR   IPI; IPI00845426; -.
DR   PIR; G01425; G01425.
DR   RefSeq; NP_001029366.1; -.
DR   RefSeq; NP_005024.2; -.
DR   UniGene; Hs.91728; -.
DR   PDB; 2NN6; X-ray; 3.35 A; A=1-302.
DR   PDBsum; 2NN6; -.
DR   IntAct; Q06265; 2.
DR   PhosphoSite; Q06265; -.
DR   PRIDE; Q06265; -.
DR   Ensembl; ENSG00000123737; Homo sapiens.
DR   GeneID; 5393; -.
DR   KEGG; hsa:5393; -.
DR   UCSC; uc003idz.1; human.
DR   UCSC; uc003iea.1; human.
DR   GeneCards; GC04P122941; -.
DR   HGNC; HGNC:9137; EXOSC9.
DR   MIM; 606180; gene.
DR   PharmGKB; PA33463; -.
DR   HOVERGEN; Q06265; -.
DR   OMA; Q06265; MEKAPID.
DR   NextBio; 20906; -.
DR   ArrayExpress; Q06265; -.
DR   Bgee; Q06265; -.
DR   CleanEx; HS_EXOSC9; -.
DR   GermOnline; ENSG00000123737; Homo sapiens.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0000176; C:nuclear exosome (RNase complex); NAS:UniProtKB.
DR   GO; GO:0005730; C:nucleolus; TAS:ProtInc.
DR   GO; GO:0000175; F:3'-5'-exoribonuclease activity; NAS:UniProtKB.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0003723; F:RNA binding; NAS:UniProtKB.
DR   GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR   GO; GO:0006364; P:rRNA processing; NAS:UniProtKB.
DR   InterPro; IPR001247; ExoRNase_PH_dom1.
DR   InterPro; IPR015847; ExoRNase_PH_dom2.
DR   Pfam; PF01138; RNase_PH; 1.
DR   Pfam; PF03725; RNase_PH_C; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW   Exonuclease; Exosome; Hydrolase; Nuclease; Nucleus; Phosphoprotein;
KW   Polymorphism; RNA-binding; rRNA processing.
FT   CHAIN         1    439       Exosome complex exonuclease RRP45.
FT                                /FTId=PRO_0000139971.
FT   MOD_RES     306    306       Phosphoserine.
FT   MOD_RES     392    392       Phosphoserine.
FT   MOD_RES     394    394       Phosphoserine.
FT   VAR_SEQ       1     84       Missing (in isoform 3 and isoform 4).
FT                                /FTId=VSP_025555.
FT   VAR_SEQ     385    385       Q -> QELGFHHVGQTGLEFLTS (in isoform 2 and
FT                                isoform 4).
FT                                /FTId=VSP_025556.
FT   VARIANT     366    366       I -> V (in dbSNP:rs1803183).
FT                                /FTId=VAR_051867.
FT   VARIANT     425    425       S -> T (in dbSNP:rs1051881).
FT                                /FTId=VAR_014924.
SQ   SEQUENCE   439 AA;  48949 MW;  7E27322F094ED3F3 CRC64;
     MKETPLSNCE RRFLLRAIEE KKRLDGRQTY DYRNIRISFG TDYGCCIVEL GKTRVLGQVS
     CELVSPKLNR ATEGILFFNL ELSQMAAPAF EPGRQSDLLV KLNRLMERCL RNSKCIDTES
     LCVVAGEKVW QIRVDLHLLN HDGNIIDAAS IAAIVALCHF RRPDVSVQGD EVTLYTPEER
     DPVPLSIHHM PICVSFAFFQ QGTYLLVDPN EREERVMDGL LVIAMNKHRE ICTIQSSGGI
     MLLKDQVLRC SKIAGVKVAE ITELILKALE NDQKVRKEGG KFGFAESIAN QRITAFKMEK
     APIDTSDVEE KAEEIIAEAE PPSEVVSTPV LWTPGTAQIG EGVENSWGDL EDSEKEDDEG
     GGDQAIILDG IKMDTGVEVS DIGSQDAPII LSDSEEEEMI ILEPDKNPKK IRTQTTSAKQ
     EKAPSKKPVK RRKKKRAAN
//