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Protein

Cleavage and polyadenylation specificity factor subunit 3

Gene

CPSF3

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

Functioni

Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as mRNA 3'-end-processing endonuclease. Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner.4 Publications

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi71Zinc 1Combined sources1 Publication1
Metal bindingi73Zinc 1Combined sources1 Publication1
Metal bindingi75Zinc 2Combined sources1 Publication1
Metal bindingi76Zinc 2Combined sources1 Publication1
Metal bindingi158Zinc 1Combined sources1 Publication1
Metal bindingi179Zinc 1Combined sources1 Publication1
Metal bindingi179Zinc 2Combined sources1 Publication1
Active sitei396Proton donorSequence analysis1
Metal bindingi418Zinc 2Combined sources1 Publication1

GO - Molecular functioni

GO - Biological processi

  • mRNA 3'-end processing Source: Reactome
  • mRNA 3'-end processing by stem-loop binding and cleavage Source: UniProtKB
  • mRNA cleavage Source: ProtInc
  • mRNA export from nucleus Source: Reactome
  • mRNA polyadenylation Source: ProtInc
  • mRNA splicing, via spliceosome Source: Reactome
  • termination of RNA polymerase II transcription Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease, Ribonucleoprotein

Keywords - Biological processi

mRNA processing

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000119203-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-159231. Transport of Mature mRNA Derived from an Intronless Transcript.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
R-HSA-77595. Processing of Intronless Pre-mRNAs.

Names & Taxonomyi

Protein namesi
Recommended name:
Cleavage and polyadenylation specificity factor subunit 3 (EC:3.1.27.-2 Publications)
Alternative name(s):
Cleavage and polyadenylation specificity factor 73 kDa subunit
Short name:
CPSF 73 kDa subunit
mRNA 3'-end-processing endonuclease CPSF-73
Gene namesi
Name:CPSF3
Synonyms:CPSF73
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:2326. CPSF3.

Subcellular locationi

  • Nucleus 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73H → A: Inhibits histone 3'-end processing. 1 Publication1
Mutagenesisi75 – 76DH → KA: Loss of histone 3'-end processing. 1 Publication2
Mutagenesisi75D → A: Inhibits histone 3'-end processing. 1 Publication1
Mutagenesisi76H → A: Inhibits histone 3'-end processing. 1 Publication1
Mutagenesisi334S → A: Does not inhibit histone 3'-end processing. 1 Publication1
Mutagenesisi396H → A: Inhibits histone 3'-end processing. 1 Publication1
Mutagenesisi462K → R: Reduced sumoylation; when associated with R-465 and R-545. 1 Publication1
Mutagenesisi465K → R: Reduced sumoylation; when associated with R-462 and R-545. 1 Publication1
Mutagenesisi545K → R: Reduced sumoylation; when associated with R-462 and R-465. 1 Publication1

Organism-specific databases

DisGeNETi51692.
OpenTargetsiENSG00000119203.
PharmGKBiPA26843.

Polymorphism and mutation databases

BioMutaiCPSF3.
DMDMi18203503.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000744002 – 684Cleavage and polyadenylation specificity factor subunit 3Add BLAST683

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Cross-linki462Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linki465Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linki545Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei659PhosphoserineBy similarity1
Modified residuei681PhosphothreonineCombined sources1

Post-translational modificationi

Sumoylated on Lys-462, Lys-465 and Lys-545, preferentially by SUMO3.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UKF6.
MaxQBiQ9UKF6.
PaxDbiQ9UKF6.
PeptideAtlasiQ9UKF6.
PRIDEiQ9UKF6.

PTM databases

iPTMnetiQ9UKF6.
PhosphoSitePlusiQ9UKF6.

Expressioni

Gene expression databases

BgeeiENSG00000119203.
CleanExiHS_CPSF3.
ExpressionAtlasiQ9UKF6. baseline and differential.
GenevisibleiQ9UKF6. HS.

Organism-specific databases

HPAiHPA034657.

Interactioni

Subunit structurei

Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Interacts with CPSF2, CSTF2 and SYMPK. Interacts with TUT1; the interaction is direct and mediates the recruitment of the CPSF complex on the 3'UTR of pre-mRNAs. Interacts with WDR33. Interacts with ZC3H3 (By similarity).By similarity5 Publications

Protein-protein interaction databases

BioGridi119680. 45 interactors.
DIPiDIP-42501N.
IntActiQ9UKF6. 28 interactors.
MINTiMINT-1742891.
STRINGi9606.ENSP00000238112.

Structurei

Secondary structure

1684
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi10 – 25Combined sources16
Beta strandi27 – 32Combined sources6
Beta strandi35 – 39Combined sources5
Helixi49 – 52Combined sources4
Helixi56 – 58Combined sources3
Helixi61 – 63Combined sources3
Beta strandi66 – 68Combined sources3
Helixi74 – 77Combined sources4
Helixi80 – 86Combined sources7
Beta strandi91 – 96Combined sources6
Helixi97 – 110Combined sources14
Helixi125 – 131Combined sources7
Helixi132 – 134Combined sources3
Beta strandi135 – 138Combined sources4
Beta strandi144 – 146Combined sources3
Beta strandi149 – 155Combined sources7
Beta strandi163 – 169Combined sources7
Beta strandi172 – 176Combined sources5
Beta strandi186 – 188Combined sources3
Beta strandi199 – 204Combined sources6
Turni206 – 209Combined sources4
Helixi215 – 231Combined sources17
Beta strandi235 – 239Combined sources5
Beta strandi242 – 245Combined sources4
Helixi246 – 259Combined sources14
Helixi261 – 263Combined sources3
Beta strandi268 – 271Combined sources4
Helixi275 – 284Combined sources10
Turni285 – 287Combined sources3
Beta strandi307 – 310Combined sources4
Helixi314 – 316Combined sources3
Beta strandi321 – 328Combined sources8
Helixi335 – 344Combined sources10
Beta strandi351 – 354Combined sources4
Helixi363 – 367Combined sources5
Beta strandi372 – 375Combined sources4
Beta strandi381 – 383Combined sources3
Beta strandi386 – 390Combined sources5
Helixi399 – 409Combined sources11
Beta strandi412 – 419Combined sources8
Helixi421 – 435Combined sources15
Beta strandi444 – 446Combined sources3
Beta strandi454 – 458Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I7TX-ray2.10A1-459[»]
2I7VX-ray2.10A1-459[»]
ProteinModelPortaliQ9UKF6.
SMRiQ9UKF6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKF6.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1137. Eukaryota.
COG1236. LUCA.
GeneTreeiENSGT00860000133746.
HOGENOMiHOG000203394.
HOVERGENiHBG051107.
InParanoidiQ9UKF6.
KOiK14403.
OMAiHTMNSNI.
OrthoDBiEOG091G03UN.
PhylomeDBiQ9UKF6.
TreeFamiTF105643.

Family and domain databases

Gene3Di3.60.15.10. 1 hit.
InterProiIPR022712. Beta_Casp.
IPR021718. CPSF73-100_C.
IPR001279. Metallo-B-lactamas.
IPR011108. RMMBL.
[Graphical view]
PfamiPF10996. Beta-Casp. 1 hit.
PF11718. CPSF73-100_C. 1 hit.
PF00753. Lactamase_B. 1 hit.
PF07521. RMMBL. 1 hit.
[Graphical view]
SMARTiSM01027. Beta-Casp. 1 hit.
SM01098. CPSF73-100_C. 1 hit.
SM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMiSSF56281. SSF56281. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UKF6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAIPAEESD QLLIRPLGAG QEVGRSCIIL EFKGRKIMLD CGIHPGLEGM
60 70 80 90 100
DALPYIDLID PAEIDLLLIS HFHLDHCGAL PWFLQKTSFK GRTFMTHATK
110 120 130 140 150
AIYRWLLSDY VKVSNISADD MLYTETDLEE SMDKIETINF HEVKEVAGIK
160 170 180 190 200
FWCYHAGHVL GAAMFMIEIA GVKLLYTGDF SRQEDRHLMA AEIPNIKPDI
210 220 230 240 250
LIIESTYGTH IHEKREEREA RFCNTVHDIV NRGGRGLIPV FALGRAQELL
260 270 280 290 300
LILDEYWQNH PELHDIPIYY ASSLAKKCMA VYQTYVNAMN DKIRKQININ
310 320 330 340 350
NPFVFKHISN LKSMDHFDDI GPSVVMASPG MMQSGLSREL FESWCTDKRN
360 370 380 390 400
GVIIAGYCVE GTLAKHIMSE PEEITTMSGQ KLPLKMSVDY ISFSAHTDYQ
410 420 430 440 450
QTSEFIRALK PPHVILVHGE QNEMARLKAA LIREYEDNDE VHIEVHNPRN
460 470 480 490 500
TEAVTLNFRG EKLAKVMGFL ADKKPEQGQR VSGILVKRNF NYHILSPCDL
510 520 530 540 550
SNYTDLAMST VKQTQAIPYT GPFNLLCYQL QKLTGDVEEL EIQEKPALKV
560 570 580 590 600
FKNITVIQEP GMVVLEWLAN PSNDMYADTV TTVILEVQSN PKIRKGAVQK
610 620 630 640 650
VSKKLEMHVY SKRLEIMLQD IFGEDCVSVK DDSILSVTVD GKTANLNLET
660 670 680
RTVECEEGSE DDESLREMVE LAAQRLYEAL TPVH
Length:684
Mass (Da):77,486
Last modified:May 1, 2000 - v1
Checksum:iF8AA24EA6FB78377
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037646142E → G.1 PublicationCorresponds to variant rs17850770dbSNPEnsembl.1
Natural variantiVAR_035873578D → N in a breast cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF171877 mRNA. Translation: AAF00224.1.
AC080162 Genomic DNA. Translation: AAY14858.1.
CH471053 Genomic DNA. Translation: EAX00989.1.
BC011654 mRNA. Translation: AAH11654.1.
BC020211 mRNA. Translation: AAH20211.1.
AF017269 mRNA. Translation: AAB70268.1.
CCDSiCCDS1664.1.
RefSeqiNP_057291.1. NM_016207.3.
UniGeneiHs.515972.

Genome annotation databases

EnsembliENST00000238112; ENSP00000238112; ENSG00000119203.
GeneIDi51692.
KEGGihsa:51692.
UCSCiuc002qzo.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF171877 mRNA. Translation: AAF00224.1.
AC080162 Genomic DNA. Translation: AAY14858.1.
CH471053 Genomic DNA. Translation: EAX00989.1.
BC011654 mRNA. Translation: AAH11654.1.
BC020211 mRNA. Translation: AAH20211.1.
AF017269 mRNA. Translation: AAB70268.1.
CCDSiCCDS1664.1.
RefSeqiNP_057291.1. NM_016207.3.
UniGeneiHs.515972.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I7TX-ray2.10A1-459[»]
2I7VX-ray2.10A1-459[»]
ProteinModelPortaliQ9UKF6.
SMRiQ9UKF6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119680. 45 interactors.
DIPiDIP-42501N.
IntActiQ9UKF6. 28 interactors.
MINTiMINT-1742891.
STRINGi9606.ENSP00000238112.

PTM databases

iPTMnetiQ9UKF6.
PhosphoSitePlusiQ9UKF6.

Polymorphism and mutation databases

BioMutaiCPSF3.
DMDMi18203503.

Proteomic databases

EPDiQ9UKF6.
MaxQBiQ9UKF6.
PaxDbiQ9UKF6.
PeptideAtlasiQ9UKF6.
PRIDEiQ9UKF6.

Protocols and materials databases

DNASUi51692.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000238112; ENSP00000238112; ENSG00000119203.
GeneIDi51692.
KEGGihsa:51692.
UCSCiuc002qzo.3. human.

Organism-specific databases

CTDi51692.
DisGeNETi51692.
GeneCardsiCPSF3.
HGNCiHGNC:2326. CPSF3.
HPAiHPA034657.
MIMi606029. gene.
neXtProtiNX_Q9UKF6.
OpenTargetsiENSG00000119203.
PharmGKBiPA26843.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1137. Eukaryota.
COG1236. LUCA.
GeneTreeiENSGT00860000133746.
HOGENOMiHOG000203394.
HOVERGENiHBG051107.
InParanoidiQ9UKF6.
KOiK14403.
OMAiHTMNSNI.
OrthoDBiEOG091G03UN.
PhylomeDBiQ9UKF6.
TreeFamiTF105643.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000119203-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-159231. Transport of Mature mRNA Derived from an Intronless Transcript.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
R-HSA-77595. Processing of Intronless Pre-mRNAs.

Miscellaneous databases

ChiTaRSiCPSF3. human.
EvolutionaryTraceiQ9UKF6.
GeneWikiiCPSF3.
GenomeRNAii51692.
PROiQ9UKF6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119203.
CleanExiHS_CPSF3.
ExpressionAtlasiQ9UKF6. baseline and differential.
GenevisibleiQ9UKF6. HS.

Family and domain databases

Gene3Di3.60.15.10. 1 hit.
InterProiIPR022712. Beta_Casp.
IPR021718. CPSF73-100_C.
IPR001279. Metallo-B-lactamas.
IPR011108. RMMBL.
[Graphical view]
PfamiPF10996. Beta-Casp. 1 hit.
PF11718. CPSF73-100_C. 1 hit.
PF00753. Lactamase_B. 1 hit.
PF07521. RMMBL. 1 hit.
[Graphical view]
SMARTiSM01027. Beta-Casp. 1 hit.
SM01098. CPSF73-100_C. 1 hit.
SM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMiSSF56281. SSF56281. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCPSF3_HUMAN
AccessioniPrimary (citable) accession number: Q9UKF6
Secondary accession number(s): O14769, Q53RS2, Q96F36
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 143 of the entry and version 1 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, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.