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Protein

Cleavage and polyadenylation specificity factor subunit 6

Gene

CPSF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping.5 Publications

GO - Molecular functioni

  • mRNA binding Source: UniProtKB
  • nucleotide binding Source: InterPro
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  • mRNA polyadenylation Source: UniProtKB
  • mRNA processing Source: UniProtKB
  • protein tetramerization Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

mRNA processing

Keywords - Ligandi

RNA-binding

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 6
Alternative name(s):
Cleavage and polyadenylation specificity factor 68 kDa subunit
Short name:
CFIm68
Short name:
CPSF 68 kDa subunit
Pre-mRNA cleavage factor Im 68 kDa subunit
Protein HPBRII-4/7
Gene namesi
Name:CPSF6
Synonyms:CFIM68
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:13871. CPSF6.

Subcellular locationi

GO - Cellular componenti

  • intracellular ribonucleoprotein complex Source: MGI
  • membrane Source: UniProtKB
  • mRNA cleavage factor complex Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • paraspeckles Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ16630.
MaxQBiQ16630.
PaxDbiQ16630.
PeptideAtlasiQ16630.
PRIDEiQ16630.

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, composed at least of NUDT21/CPSF5 and CPSF6 or CPSF7. Within the cleavage factor Im complex, the NUDT21/CPSF5 homodimer is at the core of a heterotetramer, and is clasped by two additional subunits (CPSF6 or CPSF7). Interacts with NUDT21/CPSF5, SFRS3, SFRS7, SNRNP70 and TRA2B/SFRS10.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARMC7Q9H6L44EBI-358410,EBI-742909
NUDT21O438095EBI-358410,EBI-355720
OTUB2Q96DC93EBI-358410,EBI-746259
PLSCR1O151622EBI-358410,EBI-740019
PPIL1Q9Y3C63EBI-358410,EBI-2557649
TOLLIPQ6FIE93EBI-358410,EBI-10249783
WWP1Q9H0M03EBI-358410,EBI-742157

Protein-protein interaction databases

BioGridi116238. 86 interactors.
DIPiDIP-34501N.
IntActiQ16630. 39 interactors.
MINTiMINT-1153789.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P5TX-ray2.70L/M/N/O/P/Q80-161[»]
3P6YX-ray2.90C/D/G/H/K/L/O/P80-161[»]
3Q2SX-ray2.90C/D13-235[»]
3Q2TX-ray3.06C/D13-235[»]
4B4NX-ray1.81B276-290[»]
4U0AX-ray2.05B276-290[»]
4U0BX-ray2.80M/N/O/P/Q/R/S/T/U/V/W/X276-290[»]
4WYMX-ray2.60M/N/O/P/Q/R/S/T/U/V/W276-290[»]
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
Regioni81 – 161Necessary for interaction with NUDT21/CPSF5Add BLAST81
Regioni510 – 551Sufficient for nuclear targetingAdd BLAST42

Compositional bias

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

Sequence similaritiesi

Belongs to the RRM CPSF6/7 family.Curated
Contains 1 RRM (RNA recognition motif) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4849. Eukaryota.
ENOG410Y0H0. LUCA.
GeneTreeiENSGT00730000110905.
HOGENOMiHOG000111137.
InParanoidiQ16630.
KOiK14398.
OMAiPIFGLKX.
OrthoDBiEOG091G0CVC.
PhylomeDBiQ16630.
TreeFamiTF316430.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P5TX-ray2.70L/M/N/O/P/Q80-161[»]
3P6YX-ray2.90C/D/G/H/K/L/O/P80-161[»]
3Q2SX-ray2.90C/D13-235[»]
3Q2TX-ray3.06C/D13-235[»]
4B4NX-ray1.81B276-290[»]
4U0AX-ray2.05B276-290[»]
4U0BX-ray2.80M/N/O/P/Q/R/S/T/U/V/W/X276-290[»]
4WYMX-ray2.60M/N/O/P/Q/R/S/T/U/V/W276-290[»]
ProteinModelPortaliQ16630.
SMRiQ16630.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116238. 86 interactors.
DIPiDIP-34501N.
IntActiQ16630. 39 interactors.
MINTiMINT-1153789.
STRINGi9606.ENSP00000391774.

PTM databases

iPTMnetiQ16630.
PhosphoSitePlusiQ16630.
SwissPalmiQ16630.

Polymorphism and mutation databases

BioMutaiCPSF6.
DMDMi88909266.

Proteomic databases

EPDiQ16630.
MaxQBiQ16630.
PaxDbiQ16630.
PeptideAtlasiQ16630.
PRIDEiQ16630.

Protocols and materials databases

DNASUi11052.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi11052.
DisGeNETi11052.
GeneCardsiCPSF6.
HGNCiHGNC:13871. CPSF6.
HPAiHPA039973.
MIMi604979. gene.
neXtProtiNX_Q16630.
OpenTargetsiENSG00000111605.
PharmGKBiPA26846.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4849. Eukaryota.
ENOG410Y0H0. LUCA.
GeneTreeiENSGT00730000110905.
HOGENOMiHOG000111137.
InParanoidiQ16630.
KOiK14398.
OMAiPIFGLKX.
OrthoDBiEOG091G0CVC.
PhylomeDBiQ16630.
TreeFamiTF316430.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiCPSF6. human.
GeneWikiiCPSF6.
GenomeRNAii11052.
PROiQ16630.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111605.
CleanExiHS_CPSF6.
ExpressionAtlasiQ16630. baseline and differential.
GenevisibleiQ16630. HS.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCPSF6_HUMAN
AccessioniPrimary (citable) accession number: Q16630
Secondary accession number(s): A8K7K9
, Q53ES1, Q9BSJ7, Q9BW18
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: February 7, 2006
Last modified: November 30, 2016
This is version 154 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.