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Protein

Cleavage and polyadenylation specificity factor subunit 3

Gene

CPSF3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionEndonuclease, Hydrolase, Nuclease, Ribonucleoprotein, RNA-binding
Biological processmRNA processing
LigandMetal-binding, Zinc

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000119203.13
HGNCiHGNC:2326 CPSF3
MIMi606029 gene
neXtProtiNX_Q9UKF6

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

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

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
ProteomicsDBi84782

PTM databases

iPTMnetiQ9UKF6
PhosphoSitePlusiQ9UKF6

Expressioni

Gene expression databases

BgeeiENSG00000119203 Expressed in 200 organ(s), highest expression level in testis
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, 54 interactors
CORUMiQ9UKF6
DIPiDIP-42501N
IntActiQ9UKF6, 36 interactors
MINTiQ9UKF6
STRINGi9606.ENSP00000238112

Structurei

Secondary structure

1684
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UKF6
SMRiQ9UKF6
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKF6

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1137 Eukaryota
COG1236 LUCA
GeneTreeiENSGT00910000144162
HOGENOMiHOG000203394
HOVERGENiHBG051107
InParanoidiQ9UKF6
KOiK14403
OMAiQMLYTEA
OrthoDBiEOG091G03UN
PhylomeDBiQ9UKF6
TreeFamiTF105643

Family and domain databases

Gene3Di3.60.15.10, 2 hits
InterProiView protein in InterPro
IPR022712 Beta_Casp
IPR021718 CPSF73-100_C
IPR001279 Metallo-B-lactamas
IPR036866 RibonucZ/Hydroxyglut_hydro
IPR011108 RMMBL
PfamiView protein in Pfam
PF10996 Beta-Casp, 1 hit
PF11718 CPSF73-100_C, 1 hit
PF00753 Lactamase_B, 1 hit
PF07521 RMMBL, 1 hit
SMARTiView protein in SMART
SM01027 Beta-Casp, 1 hit
SM01098 CPSF73-100_C, 1 hit
SM00849 Lactamase_B, 1 hit
SUPFAMiSSF56281 SSF56281, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G5E9W3G5E9W3_HUMAN
Cleavage and polyadenylation specif...
CPSF3 hCG_1784298
647Annotation score:
C9JZH6C9JZH6_HUMAN
Cleavage and polyadenylation-specif...
CPSF3
136Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037646142E → G1 PublicationCorresponds to variant dbSNP:rs17850770Ensembl.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

Similar proteinsi

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, 54 interactors
CORUMiQ9UKF6
DIPiDIP-42501N
IntActiQ9UKF6, 36 interactors
MINTiQ9UKF6
STRINGi9606.ENSP00000238112

PTM databases

iPTMnetiQ9UKF6
PhosphoSitePlusiQ9UKF6

Polymorphism and mutation databases

BioMutaiCPSF3
DMDMi18203503

Proteomic databases

EPDiQ9UKF6
MaxQBiQ9UKF6
PaxDbiQ9UKF6
PeptideAtlasiQ9UKF6
PRIDEiQ9UKF6
ProteomicsDBi84782

Protocols and materials databases

DNASUi51692
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi51692
EuPathDBiHostDB:ENSG00000119203.13
GeneCardsiCPSF3
HGNCiHGNC:2326 CPSF3
HPAiHPA034657
MIMi606029 gene
neXtProtiNX_Q9UKF6
OpenTargetsiENSG00000119203
PharmGKBiPA26843
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1137 Eukaryota
COG1236 LUCA
GeneTreeiENSGT00910000144162
HOGENOMiHOG000203394
HOVERGENiHBG051107
InParanoidiQ9UKF6
KOiK14403
OMAiQMLYTEA
OrthoDBiEOG091G03UN
PhylomeDBiQ9UKF6
TreeFamiTF105643

Enzyme and pathway databases

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
PROiPR:Q9UKF6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119203 Expressed in 200 organ(s), highest expression level in testis
CleanExiHS_CPSF3
ExpressionAtlasiQ9UKF6 baseline and differential
GenevisibleiQ9UKF6 HS

Family and domain databases

Gene3Di3.60.15.10, 2 hits
InterProiView protein in InterPro
IPR022712 Beta_Casp
IPR021718 CPSF73-100_C
IPR001279 Metallo-B-lactamas
IPR036866 RibonucZ/Hydroxyglut_hydro
IPR011108 RMMBL
PfamiView protein in Pfam
PF10996 Beta-Casp, 1 hit
PF11718 CPSF73-100_C, 1 hit
PF00753 Lactamase_B, 1 hit
PF07521 RMMBL, 1 hit
SMARTiView protein in SMART
SM01027 Beta-Casp, 1 hit
SM01098 CPSF73-100_C, 1 hit
SM00849 Lactamase_B, 1 hit
SUPFAMiSSF56281 SSF56281, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCPSF3_HUMAN
AccessioniPrimary (citable) accession number: Q9UKF6
Secondary accession number(s): O14769, Q53RS2, Q96F36
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 157 of the entry and version 1 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, 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. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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