CPSF6_HUMAN
ID CPSF6_HUMAN Reviewed; 551 AA.
AC Q16630; A8K7K9; Q53ES1; Q9BSJ7; Q9BW18;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Cleavage and polyadenylation specificity factor subunit 6 {ECO:0000305};
DE AltName: Full=Cleavage and polyadenylation specificity factor 68 kDa subunit;
DE Short=CPSF 68 kDa subunit;
DE AltName: Full=Cleavage factor Im complex 68 kDa subunit {ECO:0000303|PubMed:9659921};
DE Short=CFIm68 {ECO:0000303|PubMed:9659921};
DE AltName: Full=Pre-mRNA cleavage factor Im 68 kDa subunit;
DE AltName: Full=Protein HPBRII-4/7;
GN Name=CPSF6 {ECO:0000312|HGNC:HGNC:13871};
GN Synonyms=CFIM68 {ECO:0000303|PubMed:9659921};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 125-138 AND
RP 162-168, FUNCTION, IDENTIFICATION IN THE CLEAVAGE FACTOR IM COMPLEX, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Leukemia;
RX PubMed=9659921; DOI=10.1016/s1097-2765(00)80025-8;
RA Rueegsegger U., Blank D., Keller W.;
RT "Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins
RT and can be reconstituted in vitro from recombinant subunits.";
RL Mol. Cell 1:243-253(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Leukemia;
RA Fleischhauer K.L.;
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Kidney;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX.
RX PubMed=8626397; DOI=10.1074/jbc.271.11.6107;
RA Rueegsegger U., Beyer K., Keller W.;
RT "Purification and characterization of human cleavage factor Im involved in
RT the 3' end processing of messenger RNA precursors.";
RL J. Biol. Chem. 271:6107-6113(1996).
RN [8]
RP FUNCTION.
RX PubMed=14690600; DOI=10.1016/s1097-2765(03)00453-2;
RA Brown K.M., Gilmartin G.M.;
RT "A mechanism for the regulation of pre-mRNA 3' processing by human cleavage
RT factor Im.";
RL Mol. Cell 12:1467-1476(2003).
RN [9]
RP IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, AND INTERACTION WITH
RP NUDT21/CPSF5 AND SNRNP70.
RX PubMed=14561889; DOI=10.1261/rna.5104603;
RA Awasthi S., Alwine J.C.;
RT "Association of polyadenylation cleavage factor I with U1 snRNP.";
RL RNA 9:1400-1409(2003).
RN [10]
RP FUNCTION, IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, INTERACTION WITH
RP NUDT21/CPSF5; SRSF3; SRSF7 AND TRA2B, RNA-BINDING, MUTAGENESIS OF GLY-86
RP AND ASN-87, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=15169763; DOI=10.1074/jbc.m403927200;
RA Dettwiler S., Aringhieri C., Cardinale S., Keller W., Barabino S.M.;
RT "Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im
RT mediate RNA binding, protein-protein interactions, and subcellular
RT localization.";
RL J. Biol. Chem. 279:35788-35797(2004).
RN [11]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=17267687; DOI=10.1091/mbc.e06-09-0846;
RA Cardinale S., Cisterna B., Bonetti P., Aringhieri C., Biggiogera M.,
RA Barabino S.M.;
RT "Subnuclear localization and dynamics of the pre-mRNA 3' end processing
RT factor mammalian cleavage factor I 68-kDa subunit.";
RL Mol. Biol. Cell 18:1282-1292(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-404, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NXF1; NUDT21/CPSF5; UPF1
RP AND UPF3B, ASSOCIATION WITH THE EXON JUNCTION COMPLEX AND 80S RIBOSOME
RP PARTICLE, AND DOMAIN.
RX PubMed=19864460; DOI=10.1091/mbc.e09-05-0389;
RA Ruepp M.D., Aringhieri C., Vivarelli S., Cardinale S., Paro S.,
RA Schuemperli D., Barabino S.M.;
RT "Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA
RT export.";
RL Mol. Biol. Cell 20:5211-5223(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-407, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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 [16]
RP FUNCTION, IDENTIFICATION IN THE CLEAVAGE FACTOR IM COMPLEX, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20695905; DOI=10.1111/j.1365-2443.2010.01436.x;
RA Kim S., Yamamoto J., Chen Y., Aida M., Wada T., Handa H., Yamaguchi Y.;
RT "Evidence that cleavage factor Im is a heterotetrameric protein complex
RT controlling alternative polyadenylation.";
RL Genes Cells 15:1003-1013(2010).
RN [17]
RP METHYLATION, AND MUTAGENESIS OF ARG-202; ARG-204 AND ARG-206.
RX PubMed=20562214; DOI=10.1261/rna.2164210;
RA Martin G., Ostareck-Lederer A., Chari A., Neuenkirchen N., Dettwiler S.,
RA Blank D., Rueegsegger U., Fischer U., Keller W.;
RT "Arginine methylation in subunits of mammalian pre-mRNA cleavage factor
RT I.";
RL RNA 16:1646-1659(2010).
RN [18]
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., Buerckstuemmer T.,
RA 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 [19]
RP FUNCTION, AND SUBUNIT.
RX PubMed=23187700; DOI=10.4161/rna.22570;
RA Gruber A.R., Martin G., Keller W., Zavolan M.;
RT "Cleavage factor Im is a key regulator of 3' UTR length.";
RL RNA Biol. 9:1405-1412(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-404 AND THR-407, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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 [21]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 CAPSID PROTEIN
RP P24.
RX PubMed=24130490; DOI=10.1371/journal.ppat.1003693;
RA Matreyek K.A., Yucel S.S., Li X., Engelman A.;
RT "Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding
RT pocket within the HIV-1 capsid protein to mediate lentiviral infectivity.";
RL PLoS Pathog. 9:E1003693-E1003693(2013).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [24]
RP INTERACTION WITH VIRMA.
RX PubMed=29507755; DOI=10.1038/s41421-018-0019-0;
RA Yue Y., Liu J., Cui X., Cao J., Luo G., Zhang Z., Cheng T., Gao M., Shu X.,
RA Ma H., Wang F., Wang X., Shen B., Wang Y., Feng X., He C., Liu J.;
RT "VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop
RT codon and associates with alternative polyadenylation.";
RL Cell Discov. 4:10-10(2018).
RN [25]
RP INTERACTION WITH HIV-1 CAPSID PROTEIN P24.
RX PubMed=29997211; DOI=10.1128/jvi.00648-18;
RA Buffone C., Martinez-Lopez A., Fricke T., Opp S., Severgnini M., Cifola I.,
RA Petiti L., Frabetti S., Skorupka K., Zadrozny K.K., Ganser-Pornillos B.K.,
RA Pornillos O., Di Nunzio F., Diaz-Griffero F.;
RT "Nup153 Unlocks the Nuclear Pore Complex for HIV-1 Nuclear Translocation in
RT Nondividing Cells.";
RL J. Virol. 92:0-0(2018).
RN [26]
RP FUNCTION, INTERACTION WITH NUDT21/CPSF5 AND FIP1L1, IDENTIFICATION IN THE
RP MRNA 3'-PROCESSING COMPLEX, PHOSPHORYLATION, AND DOMAIN.
RX PubMed=29276085; DOI=10.1016/j.molcel.2017.11.031;
RA Zhu Y., Wang X., Forouzmand E., Jeong J., Qiao F., Sowd G.A.,
RA Engelman A.N., Xie X., Hertel K.J., Shi Y.;
RT "Molecular mechanisms for CFIm-mediated regulation of mRNA alternative
RT polyadenylation.";
RL Mol. Cell 69:62-74(2018).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 13-235 IN COMPLEX WITH
RP NUDT21/CPSF5 AND RNA, FUNCTION, SUBUNIT, AND MUTAGENESIS OF TYR-84;
RP 90-TRP-TRP-91; ASP-94; GLU-111; PHE-126 AND LEU-128.
RX PubMed=21295486; DOI=10.1016/j.str.2010.12.021;
RA Yang Q., Coseno M., Gilmartin G.M., Doublie S.;
RT "Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex
RT provides an insight into poly(A) site recognition and RNA looping.";
RL Structure 19:368-377(2011).
RN [28] {ECO:0007744|PDB:6GX9}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 481-550 IN COMPLEX WITH TNPO3,
RP SUBCELLULAR LOCATION, INTERACTION WITH TNPO3, AND PHOSPHORYLATION AT
RP THR-157; THR-404; THR-407; SER-494; SER-500; SER-511; SER-513 AND SER-525.
RX PubMed=30916345; DOI=10.1093/nar/gkz206;
RA Jang S., Cook N.J., Pye V.E., Bedwell G.J., Dudek A.M., Singh P.K.,
RA Cherepanov P., Engelman A.N.;
RT "Differential role for phosphorylation in alternative polyadenylation
RT function versus nuclear import of SR-like protein CPSF6.";
RL Nucleic Acids Res. 47:4663-4683(2019).
CC -!- FUNCTION: Component of the cleavage factor Im (CFIm) complex that
CC functions as an activator of the pre-mRNA 3'-end cleavage and
CC polyadenylation processing required for the maturation of pre-mRNA into
CC functional mRNAs (PubMed:9659921, PubMed:8626397, PubMed:14690600,
CC PubMed:29276085). CFIm contributes to the recruitment of multiprotein
CC complexes on specific sequences on the pre-mRNA 3'-end, so called
CC cleavage and polyadenylation signals (pA signals) (PubMed:9659921,
CC PubMed:8626397, PubMed:14690600). Most pre-mRNAs contain multiple pA
CC signals, resulting in alternative cleavage and polyadenylation (APA)
CC producing mRNAs with variable 3'-end formation (PubMed:23187700,
CC PubMed:29276085). The CFIm complex acts as a key regulator of cleavage
CC and polyadenylation site choice during APA through its binding to 5'-
CC UGUA-3' elements localized in the 3'-untranslated region (UTR) for a
CC huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF6
CC enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream
CC of pA signals and promotes RNA looping, and hence activates directly
CC the mRNA 3'-processing machinery (PubMed:15169763, PubMed:29276085,
CC PubMed:21295486). Plays a role in mRNA export (PubMed:19864460).
CC {ECO:0000269|PubMed:14690600, ECO:0000269|PubMed:15169763,
CC ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:20695905,
CC ECO:0000269|PubMed:21295486, ECO:0000269|PubMed:23187700,
CC ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397,
CC ECO:0000269|PubMed:9659921}.
CC -!- FUNCTION: (Microbial infection) Binds HIV-1 capsid-nucleocapsid (HIV-1
CC CA-NC) complexes and might thereby promote the integration of the virus
CC in the nucleus of dividing cells (in vitro).
CC {ECO:0000269|PubMed:24130490}.
CC -!- SUBUNIT: Component of the cleavage factor Im (CFIm) complex which is a
CC heterotetramer composed of two subunits of NUDT21/CPSF5 and two
CC subunits of CPSF6 or CPSF7 or a heterodimer of CPSF6 and CPSF7
CC (PubMed:9659921, PubMed:8626397, PubMed:14561889, PubMed:20695905,
CC PubMed:23187700). The cleavage factor Im (CFIm) complex associates with
CC the CPSF and CSTF complexes to promote the assembly of the core mRNA
CC 3'-processing machinery (PubMed:29276085). Associates with the exon
CC junction complex (EJC) (PubMed:19864460). Associates with the 80S
CC ribosome particle (PubMed:19864460). Interacts (via the RRM domain)
CC with NUDT21/CPSF5; this interaction is direct and enhances binding to
CC RNA (PubMed:14561889, PubMed:15169763, PubMed:19864460,
CC PubMed:29276085, PubMed:21295486). Interacts (via Arg/Ser-rich domain)
CC with FIP1L1 (preferentially via unphosphorylated form and Arg/Glu/Asp-
CC rich domain); this interaction mediates, at least in part, the
CC interaction between the CFIm and CPSF complexes and may be inhibited by
CC CPSF6 hyper-phosphorylation (PubMed:29276085). Interacts (via N-
CC terminus) with NXF1; this interaction is direct (PubMed:19864460).
CC Interacts with SRSF3 (PubMed:15169763). Interacts with SRSF7
CC (PubMed:15169763). Interacts with SNRNP70 (PubMed:14561889). Interacts
CC with TRA2B/SFRS10 (PubMed:15169763). Interacts with UPF1
CC (PubMed:19864460). Interacts with UPF3B (PubMed:19864460). Interacts
CC with VIRMA (PubMed:29507755). Interacts (via Arg/Ser-rich domain) with
CC TNPO3; promoting nuclear import of CPSF6 independently of its
CC phosphorylation status (PubMed:30916345). Interacts with YTHDC1 (By
CC similarity). {ECO:0000250|UniProtKB:Q6NVF9,
CC ECO:0000269|PubMed:14561889, ECO:0000269|PubMed:15169763,
CC ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:20695905,
CC ECO:0000269|PubMed:21295486, ECO:0000269|PubMed:23187700,
CC ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:29507755,
CC ECO:0000269|PubMed:30916345, ECO:0000269|PubMed:8626397,
CC ECO:0000269|PubMed:9659921}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via C-terminus) with HIV-1
CC capsid protein p24 (CA). {ECO:0000269|PubMed:24130490,
CC ECO:0000269|PubMed:29997211}.
CC -!- INTERACTION:
CC Q16630; Q9H6L4: ARMC7; NbExp=4; IntAct=EBI-358410, EBI-742909;
CC Q16630; O43809: NUDT21; NbExp=5; IntAct=EBI-358410, EBI-355720;
CC Q16630; Q96DC9: OTUB2; NbExp=3; IntAct=EBI-358410, EBI-746259;
CC Q16630; O15162: PLSCR1; NbExp=2; IntAct=EBI-358410, EBI-740019;
CC Q16630; Q9Y3C6: PPIL1; NbExp=3; IntAct=EBI-358410, EBI-2557649;
CC Q16630; Q6FIE9: TOLLIP; NbExp=3; IntAct=EBI-358410, EBI-10249783;
CC Q16630; Q9H0M0: WWP1; NbExp=3; IntAct=EBI-358410, EBI-742157;
CC Q16630-1; O43809: NUDT21; NbExp=4; IntAct=EBI-1019636, EBI-355720;
CC Q16630-2; Q9H6L4: ARMC7; NbExp=3; IntAct=EBI-11088043, EBI-742909;
CC Q16630-2; O95817: BAG3; NbExp=3; IntAct=EBI-11088043, EBI-747185;
CC Q16630-2; O43639: NCK2; NbExp=3; IntAct=EBI-11088043, EBI-713635;
CC Q16630-2; O43809: NUDT21; NbExp=7; IntAct=EBI-11088043, EBI-355720;
CC Q16630-2; Q9UK80: USP21; NbExp=3; IntAct=EBI-11088043, EBI-373242;
CC Q16630-2; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-11088043, EBI-12040603;
CC Q16630-2; P07947: YES1; NbExp=3; IntAct=EBI-11088043, EBI-515331;
CC Q16630-2; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-11088043, EBI-746595;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15169763,
CC ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:20695905,
CC ECO:0000269|PubMed:30916345, ECO:0000269|PubMed:9659921}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:17267687}. Nucleus speckle
CC {ECO:0000269|PubMed:17267687}. Cytoplasm {ECO:0000269|PubMed:19864460,
CC ECO:0000269|PubMed:30916345}. Note=Shuttles between the nucleus and the
CC cytoplasm in a transcription- and XPO1/CRM1-independent manner, most
CC probably in complex with the cleavage factor Im complex (CFIm)
CC (PubMed:19864460). Colocalizes with PSPC1 in punctate subnuclear
CC structures often located adjacent to nuclear speckles, called
CC paraspeckles, and corresponding to interchromatin granules-associated
CC zones (IGAZs) (PubMed:17267687). Distribution in speckles and
CC paraspeckles varies during the cell cycle (PubMed:17267687). Associates
CC at sites of active transcription on nascent perichromatin fibrils (PFs)
CC and perichromatin granules (PubMed:17267687). Nuclear import is
CC mediated via interaction with TNPO3 independently of CPSF6
CC phosphorylation status (PubMed:30916345). {ECO:0000269|PubMed:15169763,
CC ECO:0000269|PubMed:17267687, ECO:0000269|PubMed:19864460,
CC ECO:0000269|PubMed:30916345}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q16630-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16630-2; Sequence=VSP_017192;
CC Name=3;
CC IsoId=Q16630-3; Sequence=VSP_017191;
CC -!- DOMAIN: Contains an Arg/Ser-rich domain composed of arginine-serine
CC dipeptide repeats within the C-terminal region that is necessary and
CC sufficient for activating mRNA 3'-processing and alternative
CC polyadenylation (APA). {ECO:0000269|PubMed:29276085}.
CC -!- PTM: Phosphorylated (PubMed:29276085). Phosphorylated in the Arg/Ser-
CC rich domain by SRPK1, in vitro (PubMed:29276085).
CC {ECO:0000269|PubMed:29276085}.
CC -!- PTM: Symmetrically dimethylated on arginine residues in the GAR motif
CC by PRMT5 in a WDR77- and CLNS1A-dependent manner (PubMed:20562214).
CC Asymmetrically dimethylated on arginine residues in the GAR motif by
CC PRMT1 (PubMed:20562214). {ECO:0000269|PubMed:20562214}.
CC -!- SIMILARITY: Belongs to the RRM CPSF6/7 family. {ECO:0000305}.
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DR EMBL; X67336; CAA47751.1; -; Genomic_DNA.
DR EMBL; X67337; CAA47752.1; -; mRNA.
DR EMBL; AK223568; BAD97288.1; -; mRNA.
DR EMBL; AK292024; BAF84713.1; -; mRNA.
DR EMBL; CH471054; EAW97215.1; -; Genomic_DNA.
DR EMBL; BC000714; AAH00714.1; -; mRNA.
DR EMBL; BC005000; AAH05000.1; -; mRNA.
DR CCDS; CCDS73494.1; -. [Q16630-2]
DR CCDS; CCDS8988.1; -. [Q16630-1]
DR PIR; S57447; S57447.
DR RefSeq; NP_001287876.1; NM_001300947.1. [Q16630-2]
DR RefSeq; NP_008938.2; NM_007007.2. [Q16630-1]
DR PDB; 3P5T; X-ray; 2.70 A; L/M/N/O/P/Q=80-161.
DR PDB; 3P6Y; X-ray; 2.90 A; C/D/G/H/K/L/O/P=80-161.
DR PDB; 3Q2S; X-ray; 2.90 A; C/D=13-235.
DR PDB; 3Q2T; X-ray; 3.06 A; C/D=13-235.
DR PDB; 4B4N; X-ray; 1.81 A; B=276-290.
DR PDB; 4U0A; X-ray; 2.05 A; B=276-290.
DR PDB; 4U0B; X-ray; 2.80 A; M/N/O/P/Q/R/S/T/U/V/W/X=276-290.
DR PDB; 4WYM; X-ray; 2.60 A; M/N/O/P/Q/R/S/T/U/V/W=276-290.
DR PDB; 6AY9; X-ray; 2.50 A; B=276-287.
DR PDB; 6GX9; X-ray; 2.70 A; C/D=481-550.
DR PDBsum; 3P5T; -.
DR PDBsum; 3P6Y; -.
DR PDBsum; 3Q2S; -.
DR PDBsum; 3Q2T; -.
DR PDBsum; 4B4N; -.
DR PDBsum; 4U0A; -.
DR PDBsum; 4U0B; -.
DR PDBsum; 4WYM; -.
DR PDBsum; 6AY9; -.
DR PDBsum; 6GX9; -.
DR AlphaFoldDB; Q16630; -.
DR SMR; Q16630; -.
DR BioGRID; 116238; 228.
DR ComplexPortal; CPX-941; mRNA cleavage factor I(m) complex, CPSF6 variant.
DR CORUM; Q16630; -.
DR DIP; DIP-34501N; -.
DR IntAct; Q16630; 80.
DR MINT; Q16630; -.
DR GlyGen; Q16630; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q16630; -.
DR MetOSite; Q16630; -.
DR PhosphoSitePlus; Q16630; -.
DR SwissPalm; Q16630; -.
DR BioMuta; CPSF6; -.
DR DMDM; 88909266; -.
DR EPD; Q16630; -.
DR jPOST; Q16630; -.
DR MassIVE; Q16630; -.
DR MaxQB; Q16630; -.
DR PaxDb; Q16630; -.
DR PeptideAtlas; Q16630; -.
DR PRIDE; Q16630; -.
DR ProteomicsDB; 60979; -. [Q16630-1]
DR ProteomicsDB; 60980; -. [Q16630-2]
DR ProteomicsDB; 60981; -. [Q16630-3]
DR Antibodypedia; 29392; 240 antibodies from 28 providers.
DR DNASU; 11052; -.
DR Ensembl; ENST00000266679.8; ENSP00000266679.8; ENSG00000111605.18. [Q16630-2]
DR Ensembl; ENST00000435070.7; ENSP00000391774.2; ENSG00000111605.18. [Q16630-1]
DR GeneID; 11052; -.
DR KEGG; hsa:11052; -.
DR MANE-Select; ENST00000435070.7; ENSP00000391774.2; NM_007007.3; NP_008938.2.
DR UCSC; uc001sut.4; human. [Q16630-1]
DR CTD; 11052; -.
DR DisGeNET; 11052; -.
DR GeneCards; CPSF6; -.
DR HGNC; HGNC:13871; CPSF6.
DR HPA; ENSG00000111605; Low tissue specificity.
DR MIM; 604979; gene.
DR neXtProt; NX_Q16630; -.
DR OpenTargets; ENSG00000111605; -.
DR PharmGKB; PA26846; -.
DR VEuPathDB; HostDB:ENSG00000111605; -.
DR eggNOG; KOG4849; Eukaryota.
DR GeneTree; ENSGT00730000110905; -.
DR InParanoid; Q16630; -.
DR OMA; MFQGGPM; -.
DR OrthoDB; 1016696at2759; -.
DR PhylomeDB; Q16630; -.
DR TreeFam; TF316430; -.
DR PathwayCommons; Q16630; -.
DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants.
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-HSA-77595; Processing of Intronless Pre-mRNAs.
DR SignaLink; Q16630; -.
DR SIGNOR; Q16630; -.
DR BioGRID-ORCS; 11052; 657 hits in 1093 CRISPR screens.
DR ChiTaRS; CPSF6; human.
DR GeneWiki; CPSF6; -.
DR GenomeRNAi; 11052; -.
DR Pharos; Q16630; Tbio.
DR PRO; PR:Q16630; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q16630; protein.
DR Bgee; ENSG00000111605; Expressed in ganglionic eminence and 201 other tissues.
DR ExpressionAtlas; Q16630; baseline and differential.
DR Genevisible; Q16630; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0035061; C:interchromatin granule; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; IDA:UniProtKB.
DR GO; GO:0005849; C:mRNA cleavage factor complex; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042382; C:paraspeckles; IDA:UniProtKB.
DR GO; GO:0005726; C:perichromatin fibrils; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:1990448; F:exon-exon junction complex binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0043023; F:ribosomal large subunit binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:1990120; P:messenger ribonucleoprotein complex assembly; IDA:UniProtKB.
DR GO; GO:0031124; P:mRNA 3'-end processing; IDA:ComplexPortal.
DR GO; GO:0110104; P:mRNA alternative polyadenylation; IMP:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IDA:UniProtKB.
DR GO; GO:0046833; P:positive regulation of RNA export from nucleus; IMP:UniProtKB.
DR GO; GO:0098789; P:pre-mRNA cleavage required for polyadenylation; IDA:ComplexPortal.
DR GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
DR DisProt; DP02869; -.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR034769; CPSF6.
DR InterPro; IPR034772; CPSF6/7.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR PANTHER; PTHR23204; PTHR23204; 1.
DR PANTHER; PTHR23204:SF3; PTHR23204:SF3; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Methylation; mRNA processing; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding.
FT CHAIN 1..551
FT /note="Cleavage and polyadenylation specificity factor
FT subunit 6"
FT /id="PRO_0000081521"
FT DOMAIN 81..161
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 1..213
FT /note="Necessary for interaction with NXF1"
FT /evidence="ECO:0000269|PubMed:19864460"
FT REGION 81..161
FT /note="Necessary for interaction with NUDT21/CPSF5"
FT /evidence="ECO:0000269|PubMed:15169763"
FT REGION 81..161
FT /note="Necessary for nuclear paraspeckles localization"
FT /evidence="ECO:0000269|PubMed:17267687"
FT REGION 169..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 358..551
FT /note="(Microbial infection) Binds to HIV-1 capsid protein
FT p24 (CA)"
FT /evidence="ECO:0000269|PubMed:24130490"
FT REGION 404..551
FT /note="Sufficient for nuclear speckle localization"
FT /evidence="ECO:0000269|PubMed:17267687"
FT REGION 405..551
FT /note="Necessary for RNA-binding"
FT /evidence="ECO:0000269|PubMed:15169763"
FT REGION 477..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 481..551
FT /note="Necessary for interaction with SRSF3, SRSF7 and
FT TRA2B/SFRS10"
FT /evidence="ECO:0000269|PubMed:15169763"
FT REGION 490..551
FT /note="Arg/Ser-rich domain"
FT /evidence="ECO:0000269|PubMed:29276085,
FT ECO:0000269|PubMed:30916345"
FT REGION 510..551
FT /note="Sufficient for nuclear targeting"
FT /evidence="ECO:0000269|PubMed:15169763"
FT MOTIF 202..206
FT /note="GAR"
FT /evidence="ECO:0000269|PubMed:20562214"
FT COMPBIAS 219..366
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..394
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..501
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..551
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:30916345"
FT MOD_RES 404
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:30916345,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:23186163"
FT MOD_RES 407
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:30916345,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:30916345"
FT MOD_RES 500
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:30916345"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:30916345"
FT MOD_RES 513
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:30916345"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:30916345"
FT VAR_SEQ 188..260
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017191"
FT VAR_SEQ 231
FT /note="P -> PGNLIKHLVKGTRPLFLETRIPWHMGHSIEEIPIFGLK (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017192"
FT MUTAGEN 84
FT /note="Y->A: Reduces affinity for UGUA RNA by 40%; when
FT associated with A-128."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 86
FT /note="G->V: Abolishes interaction with NUDT21/CPSF5; when
FT associated with V-87."
FT /evidence="ECO:0000269|PubMed:15169763"
FT MUTAGEN 87
FT /note="N->V: Abolishes interaction with NUDT21/CPSF5; when
FT associated with V-86."
FT /evidence="ECO:0000269|PubMed:15169763"
FT MUTAGEN 90..91
FT /note="WW->AA: Reduces affinity for UGUA RNA by 70%.
FT Strongly reduced affinity for UGUA RNA; when associated
FT with A-94."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 94
FT /note="D->A: Strongly reduced affinity for UGUA RNA; when
FT associated with 90-A-A-91."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 111
FT /note="E->A: Reduces affinity for UGUA RNA by 85%."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 126
FT /note="F->A: Increases affinity for UGUA RNA by 40%."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 128
FT /note="L->A: Reduces affinity for UGUA RNA by 40%; when
FT associated with A-84."
FT /evidence="ECO:0000269|PubMed:21295486"
FT MUTAGEN 202
FT /note="R->A: Decreased methylation in presence of
FT PRMT5/WDR77. Loss of methylation in presence of PRMT5/WDR77
FT or PRMT1; when associated with A-204 and A-206."
FT /evidence="ECO:0000269|PubMed:20562214"
FT MUTAGEN 204
FT /note="R->A: Decreased methylation in presence of
FT PRMT5/WDR77. Loss of methylation in presence of PRMT5/WDR77
FT or PRMT1; when associated with A-202 and A-206."
FT /evidence="ECO:0000269|PubMed:20562214"
FT MUTAGEN 206
FT /note="R->A: Loss of methylation in presence of PRMT5/WDR77
FT or PRMT1."
FT /evidence="ECO:0000269|PubMed:20562214"
FT CONFLICT 9
FT /note="D -> N (in Ref. 2; CAA47751/CAA47752)"
FT /evidence="ECO:0000305"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:3P5T"
FT HELIX 94..102
FT /evidence="ECO:0007829|PDB:3P5T"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:3P5T"
FT STRAND 112..116
FT /evidence="ECO:0007829|PDB:3P5T"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:3P5T"
FT STRAND 123..129
FT /evidence="ECO:0007829|PDB:3P5T"
FT HELIX 134..143
FT /evidence="ECO:0007829|PDB:3P5T"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:3P5T"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:3P5T"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:3P6Y"
FT HELIX 161..170
FT /evidence="ECO:0007829|PDB:3Q2S"
SQ SEQUENCE 551 AA; 59210 MW; 721A5DA1B456AA79 CRC64;
MADGVDHIDI YADVGEEFNQ EAEYGGHDQI DLYDDVISPS ANNGDAPEDR DYMDTLPPTV
GDDVGKGAAP NVVYTYTGKR IALYIGNLTW WTTDEDLTEA VHSLGVNDIL EIKFFENRAN
GQSKGFALVG VGSEASSKKL MDLLPKRELH GQNPVVTPCN KQFLSQFEMQ SRKTTQSGQM
SGEGKAGPPG GSSRAAFPQG GRGRGRFPGA VPGGDRFPGP AGPGGPPPPF PAGQTPPRPP
LGPPGPPGPP GPPPPGQVLP PPLAGPPNRG DRPPPPVLFP GQPFGQPPLG PLPPGPPPPV
PGYGPPPGPP PPQQGPPPPP GPFPPRPPGP LGPPLTLAPP PHLPGPPPGA PPPAPHVNPA
FFPPPTNSGM PTSDSRGPPP TDPYGRPPPY DRGDYGPPGR EMDTARTPLS EAEFEEIMNR
NRAISSSAIS RAVSDASAGD YGSAIETLVT AISLIKQSKV SADDRCKVLI SSLQDCLHGI
ESKSYGSGSR RERSRERDHS RSREKSRRHK SRSRDRHDDY YRERSRERER HRDRDRDRDR
ERDREREYRH R
