Entry euk:CPSF2_HUMAN

ID   CPSF2_HUMAN             Reviewed;         782 AA.
AC   Q9P2I0; B3KME1; Q6NSJ1; Q9H3W7;
DT   18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 2.
DT   12-APR-2017, entry version 134.
DE   RecName: Full=Cleavage and polyadenylation specificity factor subunit 2;
DE   AltName: Full=Cleavage and polyadenylation specificity factor 100 kDa subunit;
DE            Short=CPSF 100 kDa subunit;
GN   Name=CPSF2; Synonyms=CPSF100, KIAA1367;
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 [LARGE SCALE MRNA].
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   [2]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-782.
RC   TISSUE=Brain;
RX   PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA   Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVI.
RT   The complete sequences of 150 new cDNA clones from brain which code
RT   for large proteins in vitro.";
RL   DNA Res. 7:65-73(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 279-782.
RC   TISSUE=Lymph node;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6]
RP   FUNCTION IN PRE-MRNA 3'-END PROCESSING, AND IDENTIFICATION IN THE CPSF
RP   COMPLEX.
RX   PubMed=14749727; DOI=10.1038/sj.emboj.7600070;
RA   Kaufmann I., Martin G., Friedlein A., Langen H., Keller W.;
RT   "Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and
RT   stimulates poly(A) polymerase.";
RL   EMBO J. 23:616-626(2004).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-423, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
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   [8]
RP   FUNCTION, INTERACTION WITH CPSF3; CSTF2 AND SYMPK, AND MUTAGENESIS OF
RP   HIS-67; ASP-289 AND ARG-543.
RX   PubMed=18688255; DOI=10.1038/embor.2008.146;
RA   Kolev N.G., Yario T.A., Benson E., Steitz J.A.;
RT   "Conserved motifs in both CPSF73 and CPSF100 are required to assemble
RT   the active endonuclease for histone mRNA 3'-end maturation.";
RL   EMBO Rep. 9:1013-1018(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420; SER-423
RP   AND SER-660, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma;
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   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420 AND
RP   SER-423, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [12]
RP   IDENTIFICATION IN THE CPSF COMPLEX.
RX   PubMed=21102410; DOI=10.1038/emboj.2010.287;
RA   Laishram R.S., Anderson R.A.;
RT   "The poly A polymerase Star-PAP controls 3'-end cleavage by promoting
RT   CPSF interaction and specificity toward the pre-mRNA.";
RL   EMBO J. 29:4132-4145(2010).
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420 AND
RP   SER-423, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-420 AND
RP   SER-423, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Component of the cleavage and polyadenylation
CC       specificity factor (CPSF) complex that play a key role in pre-mRNA
CC       3'-end formation, recognizing the AAUAAA signal sequence and
CC       interacting with poly(A) polymerase and other factors to bring
CC       about cleavage and poly(A) addition. Involved in the histone 3'
CC       end pre-mRNA processing. {ECO:0000269|PubMed:14749727,
CC       ECO:0000269|PubMed:18688255}.
CC   -!- SUBUNIT: Component of the cleavage and polyadenylation specificity
CC       factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and
CC       FIP1L1. Interacts with CPSF3, CSTF2 and SYMPK. Interacts with
CC       ZC3H3 (By similarity). {ECO:0000250|UniProtKB:O35218,
CC       ECO:0000269|PubMed:14749727, ECO:0000269|PubMed:18688255,
CC       ECO:0000269|PubMed:21102410}.
CC   -!- INTERACTION:
CC       P33240:CSTF2; NbExp=2; IntAct=EBI-1043224, EBI-711360;
CC       Q92797:SYMPK; NbExp=3; IntAct=EBI-1043224, EBI-1051992;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC       RNA-metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AK001627; BAG50953.1; -; mRNA.
DR   EMBL; CH471061; EAW81480.1; -; Genomic_DNA.
DR   EMBL; BC070095; AAH70095.1; -; mRNA.
DR   EMBL; AB037788; BAA92605.1; -; mRNA.
DR   EMBL; AL442079; CAC09445.1; -; mRNA.
DR   CCDS; CCDS9902.1; -.
DR   RefSeq; NP_001309201.1; NM_001322272.1.
DR   RefSeq; NP_059133.1; NM_017437.2.
DR   UniGene; Hs.657632; -.
DR   UniGene; Hs.736541; -.
DR   ProteinModelPortal; Q9P2I0; -.
DR   BioGrid; 119826; 50.
DR   DIP; DIP-42500N; -.
DR   IntAct; Q9P2I0; 19.
DR   MINT; MINT-1697677; -.
DR   STRING; 9606.ENSP00000298875; -.
DR   iPTMnet; Q9P2I0; -.
DR   PhosphoSitePlus; Q9P2I0; -.
DR   BioMuta; CPSF2; -.
DR   DMDM; 51338827; -.
DR   EPD; Q9P2I0; -.
DR   MaxQB; Q9P2I0; -.
DR   PaxDb; Q9P2I0; -.
DR   PeptideAtlas; Q9P2I0; -.
DR   PRIDE; Q9P2I0; -.
DR   Ensembl; ENST00000298875; ENSP00000298875; ENSG00000165934.
DR   GeneID; 53981; -.
DR   KEGG; hsa:53981; -.
DR   UCSC; uc001yah.3; human.
DR   CTD; 53981; -.
DR   DisGeNET; 53981; -.
DR   GeneCards; CPSF2; -.
DR   HGNC; HGNC:2325; CPSF2.
DR   HPA; HPA024238; -.
DR   MIM; 606028; gene.
DR   neXtProt; NX_Q9P2I0; -.
DR   OpenTargets; ENSG00000165934; -.
DR   PharmGKB; PA26842; -.
DR   eggNOG; KOG1135; Eukaryota.
DR   eggNOG; COG1236; LUCA.
DR   GeneTree; ENSGT00870000136523; -.
DR   HOGENOM; HOG000264343; -.
DR   HOVERGEN; HBG051106; -.
DR   InParanoid; Q9P2I0; -.
DR   KO; K14402; -.
DR   OMA; LMRNNIN; -.
DR   OrthoDB; EOG091G03GG; -.
DR   PhylomeDB; Q9P2I0; -.
DR   TreeFam; TF106131; -.
DR   Reactome; R-HSA-109688; Cleavage of Growing Transcript in the Termination Region.
DR   Reactome; R-HSA-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR   Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR   Reactome; R-HSA-72187; mRNA 3'-end processing.
DR   Reactome; R-HSA-77595; Processing of Intronless Pre-mRNAs.
DR   ChiTaRS; CPSF2; human.
DR   GeneWiki; CPSF2; -.
DR   GenomeRNAi; 53981; -.
DR   PRO; PR:Q9P2I0; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   Bgee; ENSG00000165934; -.
DR   CleanEx; HS_CPSF2; -.
DR   ExpressionAtlas; Q9P2I0; baseline and differential.
DR   Genevisible; Q9P2I0; HS.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0031124; P:mRNA 3'-end processing; TAS:Reactome.
DR   GO; GO:0006398; P:mRNA 3'-end processing by stem-loop binding and cleavage; IDA:UniProtKB.
DR   GO; GO:0006379; P:mRNA cleavage; IEA:InterPro.
DR   GO; GO:0006406; P:mRNA export from nucleus; TAS:Reactome.
DR   GO; GO:0006378; P:mRNA polyadenylation; IEA:InterPro.
DR   GO; GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome.
DR   GO; GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome.
DR   Gene3D; 3.60.15.10; -; 2.
DR   InterPro; IPR022712; Beta_Casp.
DR   InterPro; IPR027075; CPSF2.
DR   InterPro; IPR025069; Cpsf2_C.
DR   InterPro; IPR001279; Metallo-B-lactamas.
DR   InterPro; IPR011108; RMMBL.
DR   PANTHER; PTHR11203:SF41; PTHR11203:SF41; 1.
DR   Pfam; PF10996; Beta-Casp; 1.
DR   Pfam; PF13299; CPSF100_C; 1.
DR   Pfam; PF16661; Lactamase_B_6; 1.
DR   Pfam; PF07521; RMMBL; 1.
DR   SMART; SM01027; Beta-Casp; 1.
DR   SMART; SM00849; Lactamase_B; 1.
DR   SUPFAM; SSF56281; SSF56281; 2.
PE   1: Evidence at protein level;
KW   Complete proteome; mRNA processing; Nucleus; Phosphoprotein;
KW   Reference proteome; RNA-binding.
FT   CHAIN         1    782       Cleavage and polyadenylation specificity
FT                                factor subunit 2.
FT                                /FTId=PRO_0000074393.
FT   MOD_RES     419    419       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     420    420       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     423    423       Phosphoserine.
FT                                {ECO:0000244|PubMed:17081983,
FT                                ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     660    660       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MUTAGEN      67     67       H->A: Inhibits histone 3'-end processing.
FT                                {ECO:0000269|PubMed:18688255}.
FT   MUTAGEN     289    289       D->A: Does not inhibit histone 3'-end
FT                                processing.
FT                                {ECO:0000269|PubMed:18688255}.
FT   MUTAGEN     543    543       R->A: Inhibits histone 3'-end processing.
FT                                {ECO:0000269|PubMed:18688255}.
FT   CONFLICT    289    289       D -> G (in Ref. 3; AAH70095).
FT                                {ECO:0000305}.
FT   CONFLICT    654    654       K -> R (in Ref. 3; AAH70095).
FT                                {ECO:0000305}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       243    368       ismart:Beta-Casp [T]
FT   MYHIT        17    223       ismart:Lactamase_B [T]
FT   MYHIT       529    591       ipfam:RMMBL [T]
FT   MYHIT       608    779       ipfam:CPSF100_C [T]
FT   MYHIT       243    367       ipfam:Beta-Casp [T]
FT   MYHIT        22    197       ipfam:Lactamase_B_6 [T]
SQ   SEQUENCE   782 AA;  88487 MW;  F67B4813B9883CE8 CRC64;
     MTSIIKLTTL SGVQEESALC YLLQVDEFRF LLDCGWDEHF SMDIIDSLRK HVHQIDAVLL
     SHPDPLHLGA LPYAVGKLGL NCAIYATIPV YKMGQMFMYD LYQSRHNTED FTLFTLDDVD
     AAFDKIQQLK FSQIVNLKGK GHGLSITPLP AGHMIGGTIW KIVKDGEEEI VYAVDFNHKR
     EIHLNGCSLE MLSRPSLLIT DSFNATYVQP RRKQRDEQLL TNVLETLRGD GNVLIAVDTA
     GRVLELAQLL DQIWRTKDAG LGVYSLALLN NVSYNVVEFS KSQVEWMSDK LMRCFEDKRN
     NPFQFRHLSL CHGLSDLARV PSPKVVLASQ PDLECGFSRD LFIQWCQDPK NSIILTYRTT
     PGTLARFLID NPSEKITEIE LRKRVKLEGK ELEEYLEKEK LKKEAAKKLE QSKEADIDSS
     DESDIEEDID QPSAHKTKHD LMMKGEGSRK GSFFKQAKKS YPMFPAPEER IKWDEYGEII
     KPEDFLVPEL QATEEEKSKL ESGLTNGDEP MDQDLSDVPT KCISTTESIE IKARVTYIDY
     EGRSDGDSIK KIINQMKPRQ LIIVHGPPEA SQDLAECCRA FGGKDIKVYM PKLHETVDAT
     SETHIYQVRL KDSLVSSLQF CKAKDAELAW IDGVLDMRVS KVDTGVILEE GELKDDGEDS
     EMQVEAPSDS SVIAQQKAMK SLFGDDEKET GEESEIIPTL EPLPPHEVPG HQSVFMNEPR
     LSDFKQVLLR EGIQAEFVGG VLVCNNQVAV RRTETGRIGL EGCLCQDFYR IRDLLYEQYA
     IV
//