CPSF6_PONAB
ID CPSF6_PONAB Reviewed; 552 AA.
AC Q5NVH8;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 25-MAY-2022, entry version 83.
DE RecName: Full=Cleavage and polyadenylation specificity factor subunit 6 {ECO:0000250|UniProtKB:Q16630};
GN Name=CPSF6 {ECO:0000250|UniProtKB:Q16630};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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. 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). Most pre-mRNAs
CC contain multiple pA signals, resulting in alternative cleavage and
CC polyadenylation (APA) producing mRNAs with variable 3'-end formation.
CC The CFIm complex acts as a key regulator of cleavage and
CC polyadenylation site choice during APA through its binding to 5'-UGUA-
CC 3' elements localized in the 3'-untranslated region (UTR) for a huge
CC number of pre-mRNAs. CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3'
CC elements localized upstream of pA signals and promotes RNA looping, and
CC hence activates directly the mRNA 3'-processing machinery. Plays a role
CC in mRNA export. {ECO:0000250|UniProtKB:Q16630}.
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. The
CC cleavage factor Im (CFIm) complex associates with the CPSF and CSTF
CC complexes to promote the assembly of the core mRNA 3'-processing
CC machinery. Associates with the exon junction complex (EJC). Associates
CC with the 80S ribosome particle. Interacts (via the RRM domain) with
CC NUDT21/CPSF5; this interaction is direct and enhances binding to RNA.
CC Interacts (via Arg/Ser-rich domain) with FIP1L1 (preferentially via
CC unphosphorylated form and Arg/Glu/Asp-rich domain); this interaction
CC mediates, at least in part, the interaction between the CFIm and CPSF
CC complexes and may be inhibited by CPSF6 hyper-phosphorylation.
CC Interacts (via N-terminus) with NXF1; this interaction is direct.
CC Interacts with SRSF3. Interacts with SRSF7. Interacts with SNRNP70.
CC Interacts with TRA2B/SFRS10. Interacts with UPF1. Interacts with UPF3B.
CC Interacts with VIRMA. Interacts (via Arg/Ser-rich domain) with TNPO3;
CC promoting nuclear import of CPSF6 independently of its phosphorylation
CC status (By similarity). Interacts with YTHDC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q16630, ECO:0000250|UniProtKB:Q6NVF9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q16630}. Nucleus,
CC nucleoplasm {ECO:0000250|UniProtKB:Q16630}. Nucleus speckle
CC {ECO:0000250|UniProtKB:Q16630}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q16630}. Note=Shuttles between the nucleus and
CC the cytoplasm in a transcription- and XPO1/CRM1-independent manner,
CC most probably in complex with the cleavage factor Im complex (CFIm).
CC Colocalizes with PSPC1 in punctate subnuclear structures often located
CC adjacent to nuclear speckles, called paraspeckles, and corresponding to
CC interchromatin granules-associated zones (IGAZs). Distribution in
CC speckles and paraspeckles varies during the cell cycle. Associates at
CC sites of active transcription on nascent perichromatin fibrils (PFs)
CC and perichromatin granules. Nuclear import is mediated via interaction
CC with TNPO3 independently of CPSF6 phosphorylation status.
CC {ECO:0000250|UniProtKB:Q16630}.
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:0000250|UniProtKB:Q16630}.
CC -!- PTM: Phosphorylated. Phosphorylated in the Arg/Ser-rich domain by
CC SRPK1, in vitro. {ECO:0000250|UniProtKB:Q16630}.
CC -!- PTM: Symmetrically dimethylated on arginine residues in the GAR motif
CC by PRMT5 in a WDR77- and CLNS1A-dependent manner. Asymmetrically
CC dimethylated on arginine residues in the GAR motif by PRMT1.
CC {ECO:0000250|UniProtKB:Q16630}.
CC -!- SIMILARITY: Belongs to the RRM CPSF6/7 family. {ECO:0000305}.
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DR EMBL; CR926054; CAI29685.1; -; mRNA.
DR RefSeq; NP_001127689.1; NM_001134217.1.
DR AlphaFoldDB; Q5NVH8; -.
DR SMR; Q5NVH8; -.
DR STRING; 9601.ENSPPYP00000005418; -.
DR GeneID; 100174771; -.
DR KEGG; pon:100174771; -.
DR CTD; 11052; -.
DR eggNOG; KOG4849; Eukaryota.
DR InParanoid; Q5NVH8; -.
DR OrthoDB; 1016696at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0035061; C:interchromatin granule; ISS:UniProtKB.
DR GO; GO:0005849; C:mRNA cleavage factor complex; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0042382; C:paraspeckles; ISS:UniProtKB.
DR GO; GO:0005726; C:perichromatin fibrils; ISS:UniProtKB.
DR GO; GO:1990448; F:exon-exon junction complex binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:0043023; F:ribosomal large subunit binding; ISS:UniProtKB.
DR GO; GO:1990120; P:messenger ribonucleoprotein complex assembly; ISS:UniProtKB.
DR GO; GO:0110104; P:mRNA alternative polyadenylation; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0046833; P:positive regulation of RNA export from nucleus; ISS:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Cytoplasm; Methylation; mRNA processing; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding.
FT CHAIN 1..552
FT /note="Cleavage and polyadenylation specificity factor
FT subunit 6"
FT /id="PRO_0000081523"
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:0000250|UniProtKB:Q16630"
FT REGION 81..161
FT /note="Necessary for interaction with NUDT21/CPSF5"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT REGION 81..161
FT /note="Necessary for nuclear paraspeckles localization"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT REGION 169..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 404..552
FT /note="Sufficient for nuclear speckle localization"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT REGION 405..552
FT /note="Necessary for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT REGION 479..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 481..552
FT /note="Necessary for interaction with SRSF3, SRSF7 and
FT TRA2B/SFRS10"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT REGION 491..552
FT /note="Arg/Ser-rich domain"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT REGION 511..552
FT /note="Sufficient for nuclear targeting"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOTIF 202..206
FT /note="GAR"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
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..502
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 514..552
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOD_RES 404
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOD_RES 407
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16630"
SQ SEQUENCE 552 AA; 59394 MW; 873611DB18AA666E CRC64;
MADGVDHIDI YADVGEEFNQ EAEYGGHDQI DLYDDVISPS ANNGDAPEDR DYMDTLPPTV
GDDVGKGAAP NVVYTYTGKR IALYIGNLTR WTTDEDLTEA VHSLGVNDIL EIKFFENRAN
GQSKGFALVG VGSEASSKKL MDLLPKRELH GQNPVVTPCN KQFLSQFEMQ SRKTTQSGQM
SGEGKAGPPG GSSRAAFPQG GRGRGRFPGA VPGGDRFPGP TGPGGPPPPF PAGQTPPRPP
LGPPGPPGPP GPPPPGQVLP PPLAGPPNRG DRPPPPVLFP GQPFGQPPLG PLPPGPPPPV
PGYGPPPGPP PPQQGPPPPP GPFPPRPPGP LGPPLTLAPP PHLPGPPPGA PPPAPHVNPA
FFPPPTNSGM PTSDSRGPPP TDPYGRPPPY DRGDYGPPGR EMDTARTPLS EAEFEEIMNR
NRAISSSAIS RAVSDASVGD YGSAIETLVT AISLIKQSKV SADDRCKVLI SSLQDCLHGI
ESKSYGSGSR RRERSRERDH SRSREKSRRH KSRSRDRHDD YYRERSRERE RHRDRDRDRD
RERDREREYR HR
