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Protein

Cleavage and polyadenylation specificity factor subunit 6

Gene

CPSF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:9659921, PubMed:8626397, PubMed:14690600, PubMed:29276085). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:9659921, PubMed:8626397, PubMed:14690600). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream of pA signals and promotes RNA looping, and hence activates directly the mRNA 3'-processing machinery (PubMed:15169763, PubMed:29276085, PubMed:21295486). Plays a role in mRNA export (PubMed:19864460).9 Publications

GO - Molecular functioni

  • exon-exon junction complex binding Source: UniProtKB
  • mRNA binding Source: UniProtKB
  • ribosomal large subunit binding Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • messenger ribonucleoprotein complex assembly Source: UniProtKB
  • mRNA alternative polyadenylation Source: UniProtKB
  • mRNA processing Source: UniProtKB
  • positive regulation of RNA export from nucleus Source: UniProtKB
  • pre-mRNA cleavage required for polyadenylation Source: UniProtKB
  • protein heterotetramerization Source: UniProtKB
  • protein tetramerization Source: UniProtKB

Keywordsi

Molecular functionRNA-binding
Biological processmRNA processing

Enzyme and pathway databases

ReactomeiR-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants
R-HSA-5655302 Signaling by FGFR1 in disease

Names & Taxonomyi

Protein namesi
Recommended name:
Cleavage and polyadenylation specificity factor subunit 6Curated
Alternative name(s):
Cleavage and polyadenylation specificity factor 68 kDa subunit
Short name:
CPSF 68 kDa subunit
Cleavage factor Im complex 68 kDa subunit1 Publication
Short name:
CFIm681 Publication
Pre-mRNA cleavage factor Im 68 kDa subunit
Protein HPBRII-4/7
Gene namesi
Name:CPSF6Imported
Synonyms:CFIM681 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111605.16
HGNCiHGNC:13871 CPSF6
MIMi604979 gene
neXtProtiNX_Q16630

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi84Y → A: Reduces affinity for UGUA RNA by 40%; when associated with A-128. 1 Publication1
Mutagenesisi86G → V: Abolishes interaction with NUDT21/CPSF5; when associated with V-87. 1 Publication1
Mutagenesisi87N → V: Abolishes interaction with NUDT21/CPSF5; when associated with V-86. 1 Publication1
Mutagenesisi90 – 91WW → AA: Reduces affinity for UGUA RNA by 70%. Strongly reduced affinity for UGUA RNA; when associated with A-94. 1 Publication2
Mutagenesisi94D → A: Strongly reduced affinity for UGUA RNA; when associated with 90-A-A-91. 1 Publication1
Mutagenesisi111E → A: Reduces affinity for UGUA RNA by 85%. 1 Publication1
Mutagenesisi126F → A: Increases affinity for UGUA RNA by 40%. 1 Publication1
Mutagenesisi128L → A: Reduces affinity for UGUA RNA by 40%; when associated with A-84. 1 Publication1
Mutagenesisi202R → A: Decreased methylation in presence of PRMT5/WDR77. Loss of methylation in presence of PRMT5/WDR77 or PRMT1; when associated with A-204 and A-206. 1 Publication1
Mutagenesisi204R → A: Decreased methylation in presence of PRMT5/WDR77. Loss of methylation in presence of PRMT5/WDR77 or PRMT1; when associated with A-202 and A-206. 1 Publication1
Mutagenesisi206R → A: Loss of methylation in presence of PRMT5/WDR77 or PRMT1. 1 Publication1

Organism-specific databases

DisGeNETi11052
OpenTargetsiENSG00000111605
PharmGKBiPA26846

Polymorphism and mutation databases

BioMutaiCPSF6
DMDMi88909266

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000815211 – 551Cleavage and polyadenylation specificity factor subunit 6Add BLAST551

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei404PhosphothreonineCombined sources1
Modified residuei407PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated (PubMed:29276085). Phosphorylated in the Arg/Ser-rich domain by SRPK1, in vitro (PubMed:29276085).1 Publication
Symmetrically dimethylated on arginine residues in the GAR motif by PRMT5 in a WDR77- and CLNS1A-dependent manner (PubMed:20562214). Asymmetrically dimethylated on arginine residues in the GAR motif by PRMT1 (PubMed:20562214).1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ16630
MaxQBiQ16630
PaxDbiQ16630
PeptideAtlasiQ16630
PRIDEiQ16630
ProteomicsDBi60979
60980 [Q16630-2]
60981 [Q16630-3]

PTM databases

iPTMnetiQ16630
PhosphoSitePlusiQ16630
SwissPalmiQ16630

Expressioni

Gene expression databases

BgeeiENSG00000111605
CleanExiHS_CPSF6
ExpressionAtlasiQ16630 baseline and differential
GenevisibleiQ16630 HS

Organism-specific databases

HPAiHPA039973

Interactioni

Subunit structurei

Component of the cleavage factor Im (CFIm) complex which is an heterotetramer composed of two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or an heterodimer of CPSF6 and CPSF7 (PubMed:9659921, PubMed:8626397, PubMed:14561889, PubMed:20695905, PubMed:23187700). The cleavage factor Im (CFIm) complex associates with the CPSF and CSTF complexes to promote the assembly of the core mRNA 3'-processing machinery (PubMed:29276085). Associates with the exon junction complex (EJC) (PubMed:19864460). Associates with the 80S ribosome particle (PubMed:19864460). Interacts (via the RRM domain) with NUDT21/CPSF5; this interaction is direct and enhances binding to RNA (PubMed:14561889, PubMed:15169763, PubMed:19864460, PubMed:29276085, PubMed:21295486). Interacts (via Arg/Ser-rich domain) with FIP1L1 (preferentially via unphosphorylated form and Arg/Glu/Asp-rich domain); this interaction mediates, at least in part, the interaction between the CFIm and CPSF complexes and may be inhibited by CPSF6 hyper-phosphorylation (PubMed:29276085). Interacts (via N-terminus) with NXF1; this interaction is direct (PubMed:19864460). Interacts with SRSF3 (PubMed:15169763). Interacts with SRSF7 (PubMed:15169763). Interacts with SNRNP70 (PubMed:14561889). Interacts with TRA2B/SFRS10 (PubMed:15169763). Interacts with UPF1 (PubMed:19864460). Interacts with UPF3B (PubMed:19864460). Interacts with VIRMA (PubMed:29507755).10 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi116238, 123 interactors
CORUMiQ16630
DIPiDIP-34501N
IntActiQ16630, 56 interactors
MINTiQ16630
STRINGi9606.ENSP00000391774

Structurei

Secondary structure

1551
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi84 – 87Combined sources4
Helixi94 – 102Combined sources9
Turni103 – 105Combined sources3
Beta strandi112 – 116Combined sources5
Turni118 – 120Combined sources3
Beta strandi123 – 129Combined sources7
Helixi134 – 143Combined sources10
Helixi144 – 146Combined sources3
Beta strandi149 – 151Combined sources3
Beta strandi155 – 158Combined sources4
Helixi161 – 170Combined sources10

3D structure databases

ProteinModelPortaliQ16630
SMRiQ16630
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 161RRMPROSITE-ProRule annotationAdd BLAST81

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 213Necessary for interaction with NXF11 PublicationAdd BLAST213
Regioni81 – 161Necessary for interaction with NUDT21/CPSF51 PublicationAdd BLAST81
Regioni81 – 161Necessary for nuclear paraspeckles localization1 PublicationAdd BLAST81
Regioni404 – 551Sufficient for nuclear speckle localization1 PublicationAdd BLAST148
Regioni405 – 551Necessary for RNA-binding1 PublicationAdd BLAST147
Regioni481 – 551Necessary for interaction with SRSF3, SRSF7 and TRA2B/SFRS101 PublicationAdd BLAST71
Regioni490 – 551Arg/Ser-rich domain1 PublicationAdd BLAST62
Regioni510 – 551Sufficient for nuclear targeting1 PublicationAdd BLAST42

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi202 – 206GAR1 Publication5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi208 – 398Pro-richAdd BLAST191
Compositional biasi490 – 551Arg-richAdd BLAST62

Domaini

Contains an Arg/Ser-rich domain composed of arginine-serine dipeptide repeats within the C-terminal region that is necessary and sufficient for activating mRNA 3'-processing and alternative polyadenylation (APA).1 Publication

Sequence similaritiesi

Belongs to the RRM CPSF6/7 family.Curated

Phylogenomic databases

eggNOGiKOG4849 Eukaryota
ENOG410Y0H0 LUCA
GeneTreeiENSGT00730000110905
HOGENOMiHOG000111137
InParanoidiQ16630
KOiK14398
OMAiMGNQQPP
OrthoDBiEOG091G0CVC
PhylomeDBiQ16630
TreeFamiTF316430

Family and domain databases

Gene3Di3.30.70.330, 1 hit
InterProiView protein in InterPro
IPR034769 CPSF6
IPR034772 CPSF6/7
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PANTHERiPTHR23204 PTHR23204, 1 hit
PTHR23204:SF3 PTHR23204:SF3, 1 hit
PfamiView protein in Pfam
PF00076 RRM_1, 1 hit
SMARTiView protein in SMART
SM00360 RRM, 1 hit
SUPFAMiSSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q16630-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MADGVDHIDI YADVGEEFNQ EAEYGGHDQI DLYDDVISPS ANNGDAPEDR
60 70 80 90 100
DYMDTLPPTV GDDVGKGAAP NVVYTYTGKR IALYIGNLTW WTTDEDLTEA
110 120 130 140 150
VHSLGVNDIL EIKFFENRAN GQSKGFALVG VGSEASSKKL MDLLPKRELH
160 170 180 190 200
GQNPVVTPCN KQFLSQFEMQ SRKTTQSGQM SGEGKAGPPG GSSRAAFPQG
210 220 230 240 250
GRGRGRFPGA VPGGDRFPGP AGPGGPPPPF PAGQTPPRPP LGPPGPPGPP
260 270 280 290 300
GPPPPGQVLP PPLAGPPNRG DRPPPPVLFP GQPFGQPPLG PLPPGPPPPV
310 320 330 340 350
PGYGPPPGPP PPQQGPPPPP GPFPPRPPGP LGPPLTLAPP PHLPGPPPGA
360 370 380 390 400
PPPAPHVNPA FFPPPTNSGM PTSDSRGPPP TDPYGRPPPY DRGDYGPPGR
410 420 430 440 450
EMDTARTPLS EAEFEEIMNR NRAISSSAIS RAVSDASAGD YGSAIETLVT
460 470 480 490 500
AISLIKQSKV SADDRCKVLI SSLQDCLHGI ESKSYGSGSR RERSRERDHS
510 520 530 540 550
RSREKSRRHK SRSRDRHDDY YRERSRERER HRDRDRDRDR ERDREREYRH

R
Length:551
Mass (Da):59,210
Last modified:February 7, 2006 - v2
Checksum:i721A5DA1B456AA79
GO
Isoform 2 (identifier: Q16630-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     231-231: P → PGNLIKHLVKGTRPLFLETRIPWHMGHSIEEIPIFGLK

Show »
Length:588
Mass (Da):63,471
Checksum:i1F2B7051251A7E52
GO
Isoform 3 (identifier: Q16630-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     188-260: Missing.

Show »
Length:478
Mass (Da):52,326
Checksum:i464F41AA4386F880
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9D → N in CAA47751 (Ref. 2) Curated1
Sequence conflicti9D → N in CAA47752 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017191188 – 260Missing in isoform 3. 1 PublicationAdd BLAST73
Alternative sequenceiVSP_017192231P → PGNLIKHLVKGTRPLFLETR IPWHMGHSIEEIPIFGLK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67336 Genomic DNA Translation: CAA47751.1
X67337 mRNA Translation: CAA47752.1
AK223568 mRNA Translation: BAD97288.1
AK292024 mRNA Translation: BAF84713.1
CH471054 Genomic DNA Translation: EAW97215.1
BC000714 mRNA Translation: AAH00714.1
BC005000 mRNA Translation: AAH05000.1
CCDSiCCDS73494.1 [Q16630-2]
CCDS8988.1 [Q16630-1]
PIRiS57447
RefSeqiNP_001287876.1, NM_001300947.1 [Q16630-2]
NP_008938.2, NM_007007.2 [Q16630-1]
UniGeneiHs.369606

Genome annotation databases

EnsembliENST00000266679; ENSP00000266679; ENSG00000111605 [Q16630-2]
ENST00000435070; ENSP00000391774; ENSG00000111605 [Q16630-1]
GeneIDi11052
KEGGihsa:11052
UCSCiuc001sut.4 human [Q16630-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCPSF6_HUMAN
AccessioniPrimary (citable) accession number: Q16630
Secondary accession number(s): A8K7K9
, Q53ES1, Q9BSJ7, Q9BW18
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: February 7, 2006
Last modified: July 18, 2018
This is version 167 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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