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O43809 (CPSF5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cleavage and polyadenylation specificity factor subunit 5
Alternative name(s):
Cleavage and polyadenylation specificity factor 25 kDa subunit
Short name=CFIm25
Short name=CPSF 25 kDa subunit
Nucleoside diphosphate-linked moiety X motif 21
Short name=Nudix motif 21
Pre-mRNA cleavage factor Im 25 kDa subunit
Gene names
Name:NUDT21
Synonyms:CFIM25, CPSF25, CPSF5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length227 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the cleavage factor Im (CFIm) complex that plays a key role in pre-mRNA 3'-processing. Involved in association with CPSF6 or CPSF7 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. NUDT21/CPSF5 binds to cleavage and polyadenylation RNA substrates. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA. Binds to, but does not hydrolyze mono- and di-adenosine nucleotides. May have a role in mRNA export. Ref.1 Ref.7 Ref.8 Ref.14 Ref.18 Ref.20

Subunit structure

Homodimer. Component of the cleavage factor Im (CFIm) complex, composed of, at least, 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 CPSF6, CPSF7, PABPN1 and SNRNP70. Interacts with PAPOLA; the interaction is diminished by acetylation. Ref.1 Ref.7 Ref.9 Ref.10 Ref.12 Ref.14 Ref.16 Ref.18 Ref.19 Ref.20

Subcellular location

Nucleus. Note: In punctate subnuclear structures localized adjacent to nuclear speckles, called paraspeckles. Ref.1 Ref.10 Ref.14

Post-translational modification

Acetylated mainly by p300/CBP, recruited to the complex by CPSF6. Acetylation decreases interaction with PAPAO. Deacetylated by the class I/II HDACs, HDAC1, HDAC3 and HDAC10, and by the class III HDACs, SIRT1 AND SIRT2. Ref.6 Ref.12

Sequence similarities

Belongs to the Nudix hydrolase family. CPSF5 subfamily.

Contains 1 nudix hydrolase domain.

Caution

Lacks the conserved metal-binding residues in the NUDIX motif and does not have hydrolase activity.

Ontologies

Keywords
   Biological processmRNA processing
   Cellular componentNucleus
   LigandRNA-binding
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

mRNA 3'-end processing

Traceable author statement. Source: Reactome

mRNA polyadenylation

Inferred from mutant phenotype Ref.14. Source: UniProtKB

mRNA processing

Inferred from direct assay Ref.7. Source: UniProtKB

mRNA splicing, via spliceosome

Traceable author statement. Source: Reactome

protein tetramerization

Inferred from direct assay Ref.20. Source: UniProtKB

termination of RNA polymerase II transcription

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentcentrosome

Inferred from direct assay. Source: LIFEdb

mRNA cleavage factor complex

Inferred from direct assay Ref.14Ref.20. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.14. Source: UniProtKB

paraspeckles

Inferred from direct assay Ref.10. Source: UniProtKB

   Molecular_functionAU-rich element binding

Inferred from direct assay Ref.18Ref.20. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction Ref.12. Source: UniProtKB

hydrolase activity

Inferred from electronic annotation. Source: InterPro

mRNA binding

Inferred from direct assay Ref.20. Source: UniProtKB

poly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 11716503Ref.9Ref.10Ref.14Ref.20. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.18Ref.20. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6
Chain2 – 227226Cleavage and polyadenylation specificity factor subunit 5
PRO_0000057150

Regions

Domain76 – 201126Nudix hydrolase
Region2 – 147146Necessary for RNA-binding
Region81 – 16080Necessary for interactions with PAPOLA and PABPN1
Region102 – 1043Interaction with RNA
Motif109 – 13022Nudix box

Sites

Site551Interaction with RNA
Site631Interaction with RNA
Site2081Interaction with RNA

Amino acid modifications

Modified residue21N-acetylserine Ref.6
Modified residue231N6-acetyllysine Ref.12 Ref.13
Modified residue291N6-acetyllysine Ref.13
Modified residue401Phosphotyrosine Ref.11
Modified residue561N6-acetyllysine Ref.13

Experimental info

Mutagenesis231K → R: Abolishes acetylation. Ref.12
Mutagenesis291K → R: No effect on acetylation. Ref.12
Mutagenesis551E → A: Reduces affinity for UGUA RNA by 88%. Ref.18 Ref.20
Mutagenesis631R → S: Reduces affinity for UGUA RNA by 99%. Ref.18 Ref.20
Mutagenesis811E → A: Reduces affinity for UGUA RNA by 12%. Ref.18
Mutagenesis1031F → A: Reduces affinity for UGUA RNA by 99%. Ref.18 Ref.20
Mutagenesis1031F → W: Reduces affinity for UGUA RNA by over 90%. Ref.18 Ref.20
Mutagenesis1541E → A: Reduces affinity for UGUA RNA by 50%.
Mutagenesis1581Y → A: Abolishes interaction with CPSF6; when associated with A-160. Ref.20
Mutagenesis1601Y → A: Abolishes interaction with CPSF6; when associated with A-158. Ref.20
Sequence conflict571D → G in CAG33200. Ref.2
Sequence conflict1121N → D in CAD97606. Ref.3
Sequence conflict2181L → P in CAD97606. Ref.3

Secondary structure

......................................... 227
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43809 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: D204243E57F1CCC5

FASTA22726,227
        10         20         30         40         50         60 
MSVVPPNRSQ TGWPRGVTQF GNKYIQQTKP LTLERTINLY PLTNYTFGTK EPLYEKDSSV 

        70         80         90        100        110        120 
AARFQRMREE FDKIGMRRTV EGVLIVHEHR LPHVLLLQLG TTFFKLPGGE LNPGEDEVEG 

       130        140        150        160        170        180 
LKRLMTEILG RQDGVLQDWV IDDCIGNWWR PNFEPPQYPY IPAHITKPKE HKKLFLVQLQ 

       190        200        210        220 
EKALFAVPKN YKLVAAPLFE LYDNAPGYGP IISSLPQLLS RFNFIYN 

« Hide

References

« Hide 'large scale' references
[1]"Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits."
Rueegsegger U., Blank D., Keller W.
Mol. Cell 1:243-253(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-73 AND 183-189, FUNCTION, IDENTIFICATION IN THE CLEAVAGE FACTOR IM COMPLEX, SUBCELLULAR LOCATION.
Tissue: Brain.
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Retina.
[4]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[6]Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-15; 24-50 AND 79-131, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Ovarian carcinoma.
[7]"Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors."
Rueegsegger U., Beyer K., Keller W.
J. Biol. Chem. 271:6107-6113(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, RNA-BINDING.
[8]"A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor Im."
Brown K.M., Gilmartin G.M.
Mol. Cell 12:1467-1476(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, RNA-BINDING.
[9]"Association of polyadenylation cleavage factor I with U1 snRNP."
Awasthi S., Alwine J.C.
RNA 9:1400-1409(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, INTERACTION WITH CPSF6 AND SNRNP70, IDENTIFICATION BY MASS SPECTROMETRY.
[10]"Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization."
Dettwiler S., Aringhieri C., Cardinale S., Keller W., Barabino S.M.
J. Biol. Chem. 279:35788-35797(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, INTERACTION WITH CPSF6; PAPOLA AND PABPN1, RNA-BINDING, SUBCELLULAR LOCATION.
[11]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-40, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing."
Shimazu T., Horinouchi S., Yoshida M.
J. Biol. Chem. 282:4470-4478(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-23, INTERACTION WITH PAPOLA AND CPSF6, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF LYS-23 AND LYS-29.
[13]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-23; LYS-29 AND LYS-56, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation."
Kim S., Yamamoto J., Chen Y., Aida M., Wada T., Handa H., Yamaguchi Y.
Genes Cells 15:1003-1013(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Crystal structure of the 25 kDa subunit of human cleavage factor Im."
Coseno M., Martin G., Berger C., Gilmartin G., Keller W., Doublie S.
Nucleic Acids Res. 36:3474-3483(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF APO FORM AND IN COMPLEX WITH BETA DIADENOSINE TETRAPHOSPHATE, LACK OF METAL-BINDING, HOMODIMERIZATION.
[17]"The crystal structure of human cleavage and polyadenylation specific factor-5 reveals a dimeric Nudix protein with a conserved catalytic site."
Tresaugues L., Stenmark P., Schaeler H., Flodin S., Welin M., Nyman T., Hammarstroem M., Moche M., Graeslund S., Nordlund P.
Proteins 73:1047-1052(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF APO FORM AND IN COMPLEX WITH SULFATE.
[18]"Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing."
Yang Q., Gilmartin G.M., Doublie S.
Proc. Natl. Acad. Sci. U.S.A. 107:10062-10067(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) IN COMPLEXES WITH RNA UGUAAA AND UUGUAU, FUNCTION, SUBUNIT, MUTAGENESIS OF GLU-55; ARG-63; GLU-81 AND PHE-103.
[19]"Crystal structure of the complex between the 25 kDA subunit and the 59 kDA subunit (RRM domain) of human cleavage factor Im."
Structural genomics consortium (SGC)
Submitted (JUL-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 21-227 IN COMPLEX WITH CPSF7, SUBUNIT.
[20]"Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA looping."
Yang Q., Coseno M., Gilmartin G.M., Doublie S.
Structure 19:368-377(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 21-227 IN COMPLEX WITH CPSF6 AND RNA, FUNCTION, SUBUNIT, MUTAGENESIS OF GLU-55; ARG-63; PHE-103; TYR-158 AND TYR-160.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ001810 mRNA. Translation: CAA05026.1.
CR456919 mRNA. Translation: CAG33200.1.
BX537360 mRNA. Translation: CAD97606.1.
AC092140 Genomic DNA. No translation available.
BC001403 mRNA. Translation: AAH01403.1.
CCDSCCDS10760.1.
RefSeqNP_008937.1. NM_007006.2.
UniGeneHs.528834.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CL3X-ray1.90A21-227[»]
2J8QX-ray2.30A/B24-227[»]
3BAPX-ray1.85A1-227[»]
3BHOX-ray1.80A20-227[»]
3MDGX-ray2.22A/B1-227[»]
3MDIX-ray2.07A/B1-227[»]
3N9UX-ray1.92A/B21-227[»]
3P5TX-ray2.70A/B/C/D/E/F34-227[»]
3P6YX-ray2.90A/B/E/F/I/J/M/N34-227[»]
3Q2SX-ray2.90A/B21-227[»]
3Q2TX-ray3.06A/B21-227[»]
ProteinModelPortalO43809.
SMRO43809. Positions 22-227.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116237. 100 interactions.
DIPDIP-42502N.
IntActO43809. 55 interactions.
MINTMINT-5002263.
STRING9606.ENSP00000300291.

PTM databases

PhosphoSiteO43809.

2D gel databases

UCD-2DPAGEO43809.

Proteomic databases

MaxQBO43809.
PaxDbO43809.
PeptideAtlasO43809.
PRIDEO43809.

Protocols and materials databases

DNASU11051.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300291; ENSP00000300291; ENSG00000167005.
GeneID11051.
KEGGhsa:11051.
UCSCuc002eja.3. human.

Organism-specific databases

CTD11051.
GeneCardsGC16M056463.
HGNCHGNC:13870. NUDT21.
HPAHPA019863.
MIM604978. gene.
neXtProtNX_O43809.
PharmGKBPA26845.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG294795.
HOGENOMHOG000161320.
HOVERGENHBG052968.
InParanoidO43809.
KOK14397.
OMACLAQWWR.
OrthoDBEOG7KSX9M.
PhylomeDBO43809.
TreeFamTF106356.

Enzyme and pathway databases

ReactomeREACT_1788. Transcription.
REACT_71. Gene Expression.
REACT_78. Post-Elongation Processing of the Transcript.

Gene expression databases

ArrayExpressO43809.
BgeeO43809.
CleanExHS_NUDT21.
GenevestigatorO43809.

Family and domain databases

Gene3D3.90.79.10. 1 hit.
InterProIPR016706. Cleav_polyA_spec_factor_su5.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
[Graphical view]
PANTHERPTHR13047. PTHR13047. 1 hit.
PfamPF13869. NUDIX_2. 1 hit.
[Graphical view]
PIRSFPIRSF017888. CPSF-25. 1 hit.
SUPFAMSSF55811. SSF55811. 1 hit.
PROSITEPS51462. NUDIX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNUDT21. human.
EvolutionaryTraceO43809.
GeneWikiNUDT21.
GenomeRNAi11051.
NextBio41991.
PROO43809.
SOURCESearch...

Entry information

Entry nameCPSF5_HUMAN
AccessionPrimary (citable) accession number: O43809
Secondary accession number(s): Q6IB85, Q6NE84
Entry history
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM