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Protein

Cleavage and polyadenylation specificity factor subunit 5

Gene

NUDT21

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:15937220, PubMed:17024186, PubMed:17098938, 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, PubMed:17024186). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:17098938, 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:17098938, PubMed:20695905, PubMed:29276085). NUDT21/CPSF5 activates indirectly the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7 (PubMed:29276085). Binds to 5'-UGUA-3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing (PubMed:8626397, PubMed:14690600, PubMed:15169763, PubMed:17024186, PubMed:22813749, PubMed:20479262). The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA (PubMed:20479262, PubMed:21295486). Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function (By similarity). Binds to chromatin (By similarity). Binds to, but does not hydrolyze mono- and di-adenosine nucleotides (PubMed:18445629).By similarity14 Publications

Caution

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

GO - Molecular functioni

  • AU-rich element binding Source: UniProtKB
  • chromatin binding Source: Ensembl
  • histone deacetylase binding Source: UniProtKB
  • hydrolase activity Source: InterPro
  • identical protein binding Source: UniProtKB
  • mRNA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • messenger ribonucleoprotein complex assembly Source: UniProtKB
  • mRNA 3'-end processing Source: Reactome
  • mRNA polyadenylation Source: UniProtKB
  • mRNA processing Source: UniProtKB
  • mRNA splicing, via spliceosome Source: Reactome
  • positive regulation of mRNA 3'-end processing Source: UniProtKB
  • positive regulation of mRNA cleavage Source: UniProtKB
  • positive regulation of mRNA polyadenylation Source: UniProtKB
  • positive regulation of pro-B cell differentiation Source: UniProtKB
  • positive regulation of stem cell differentiation Source: UniProtKB
  • posttranscriptional regulation of gene expression Source: UniProtKB
  • pre-mRNA cleavage required for polyadenylation Source: UniProtKB
  • protein heterotetramerization Source: UniProtKB
  • protein tetramerization Source: UniProtKB
  • termination of RNA polymerase II transcription Source: Reactome

Keywordsi

Molecular functionRNA-binding
Biological processDifferentiation, mRNA processing

Enzyme and pathway databases

ReactomeiR-HSA-109688 Cleavage of Growing Transcript in the Termination Region
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 51 Publication
Alternative name(s):
Cleavage and polyadenylation specificity factor 25 kDa subunit
Short name:
CPSF 25 kDa subunit
Cleavage factor Im complex 25 kDa subunit1 Publication
Short name:
CFIm251 Publication
Nucleoside diphosphate-linked moiety X motif 21
Short name:
Nudix motif 21
Nudix hydrolase 21Curated
Pre-mRNA cleavage factor Im 68 kDa subunit
Gene namesi
Name:NUDT21Imported
Synonyms:CFIM251 Publication, CPSF25, CPSF51 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000167005.13
HGNCiHGNC:13870 NUDT21
MIMi604978 gene
neXtProtiNX_O43809

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
Mutagenesisi23K → R: Abolishes acetylation. 1 Publication1
Mutagenesisi29K → R: No effect on acetylation. 1 Publication1
Mutagenesisi55E → A: Reduces affinity for UGUA RNA by 88%. 2 Publications1
Mutagenesisi63R → S: Reduces affinity for UGUA RNA by 99%. 2 Publications1
Mutagenesisi81E → A: Reduces affinity for UGUA RNA by 12%. 1 Publication1
Mutagenesisi103F → A: Reduces affinity for UGUA RNA by 99%. 2 Publications1
Mutagenesisi103F → W: Reduces affinity for UGUA RNA by over 90%. 2 Publications1
Mutagenesisi154E → A: Reduces affinity for UGUA RNA by 50%. 1
Mutagenesisi158Y → A: Abolishes interaction with CPSF6; when associated with A-160. 1 Publication1
Mutagenesisi160Y → A: Abolishes interaction with CPSF6; when associated with A-158. 1 Publication1
Mutagenesisi218L → R: Reduces interactions with CPSF6 and CPSF7 and deacreases mRNA 3'-processing activity. 1 Publication1

Organism-specific databases

DisGeNETi11051
OpenTargetsiENSG00000167005
PharmGKBiPA26845

Polymorphism and mutation databases

BioMutaiNUDT21

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000571502 – 227Cleavage and polyadenylation specificity factor subunit 5Add BLAST226

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine1 Publication1
Modified residuei15Omega-N-methylarginineCombined sources1
Modified residuei23N6-acetyllysineCombined sources1 Publication1
Modified residuei29N6-acetyllysineCombined sources1
Modified residuei40PhosphotyrosineCombined sources1
Modified residuei56N6-acetyllysineCombined sources1

Post-translational modificationi

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 SIRT2.1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiO43809
MaxQBiO43809
PaxDbiO43809
PeptideAtlasiO43809
PRIDEiO43809
TopDownProteomicsiO43809

2D gel databases

UCD-2DPAGEiO43809

PTM databases

iPTMnetiO43809
PhosphoSitePlusiO43809
SwissPalmiO43809

Expressioni

Tissue specificityi

Expressed in the heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000167005
CleanExiHS_NUDT21
ExpressionAtlasiO43809 baseline and differential
GenevisibleiO43809 HS

Organism-specific databases

HPAiHPA019863
HPA074228

Interactioni

Subunit structurei

Homodimer (via N- and C-terminus); binds RNA as homodimer (PubMed:20695905, PubMed:18445629, PubMed:20479262). 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, PubMed:21295486). 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). Interacts with CPSF6 (via the RRM domain); this interaction is direct and enhances binding to RNA (PubMed:14561889, PubMed:15169763, PubMed:17172643, PubMed:19864460, PubMed:29276085). Interacts with CPSF7 (PubMed:29276085, Ref. 29). Interacts with FIP1L1; this interaction occurs in a RNA sequence-specific manner (PubMed:15937220). Interacts with PABPN1 (PubMed:15169763). Interacts (via N-terminus) with PAPOLA (via C-terminus); this interaction is direct and diminished by acetylation (PubMed:15169763, PubMed:17172643). Interacts with SNRNP70 (PubMed:14561889).14 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei55Interaction with RNA1 PublicationImported1
Sitei63Interaction with RNA1 PublicationImported1

Binary interactionsi

Show more details

GO - Molecular functioni

  • histone deacetylase binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi116237, 124 interactors
CORUMiO43809
DIPiDIP-42502N
IntActiO43809, 97 interactors
MINTiO43809
STRINGi9606.ENSP00000300291

Structurei

Secondary structure

1227
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni31 – 33Combined sources3
Beta strandi36 – 39Combined sources4
Helixi42 – 44Combined sources3
Beta strandi45 – 50Combined sources6
Helixi60 – 74Combined sources15
Beta strandi76 – 88Combined sources13
Beta strandi91 – 100Combined sources10
Beta strandi103 – 105Combined sources3
Beta strandi107 – 110Combined sources4
Helixi117 – 129Combined sources13
Beta strandi132 – 134Combined sources3
Beta strandi140 – 150Combined sources11
Beta strandi152 – 155Combined sources4
Beta strandi158 – 160Combined sources3
Beta strandi169 – 178Combined sources10
Beta strandi181 – 188Combined sources8
Beta strandi192 – 197Combined sources6
Helixi198 – 201Combined sources4
Helixi205 – 212Combined sources8
Helixi215 – 219Combined sources5
Beta strandi223 – 226Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliO43809
SMRiO43809
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43809

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini76 – 201Nudix hydrolasePROSITE-ProRule annotationAdd BLAST126

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 147Necessary for RNA-binding1 PublicationAdd BLAST146
Regioni81 – 160Necessary for interactions with PAPOLA and PABPN11 PublicationAdd BLAST80
Regioni102 – 104Interaction with RNA2 PublicationsImported3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi109 – 130Nudix boxAdd BLAST22

Sequence similaritiesi

Belongs to the Nudix hydrolase family. CPSF5 subfamily.Curated

Phylogenomic databases

eggNOGiKOG1689 Eukaryota
ENOG410XS8Z LUCA
GeneTreeiENSGT00390000015814
HOGENOMiHOG000161320
HOVERGENiHBG052968
InParanoidiO43809
KOiK14397
OMAiCLAQWWR
OrthoDBiEOG091G0HGL
PhylomeDBiO43809
TreeFamiTF106356

Family and domain databases

InterProiView protein in InterPro
IPR016706 Cleav_polyA_spec_factor_su5
IPR015797 NUDIX_hydrolase-like_dom_sf
IPR000086 NUDIX_hydrolase_dom
PANTHERiPTHR13047 PTHR13047, 1 hit
PfamiView protein in Pfam
PF13869 NUDIX_2, 1 hit
PIRSFiPIRSF017888 CPSF-25, 1 hit
SUPFAMiSSF55811 SSF55811, 1 hit
PROSITEiView protein in PROSITE
PS51462 NUDIX, 1 hit

Sequencei

Sequence statusi: Complete.

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

O43809-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVVPPNRSQ TGWPRGVTQF GNKYIQQTKP LTLERTINLY PLTNYTFGTK
60 70 80 90 100
EPLYEKDSSV AARFQRMREE FDKIGMRRTV EGVLIVHEHR LPHVLLLQLG
110 120 130 140 150
TTFFKLPGGE LNPGEDEVEG LKRLMTEILG RQDGVLQDWV IDDCIGNWWR
160 170 180 190 200
PNFEPPQYPY IPAHITKPKE HKKLFLVQLQ EKALFAVPKN YKLVAAPLFE
210 220
LYDNAPGYGP IISSLPQLLS RFNFIYN
Length:227
Mass (Da):26,227
Last modified:June 1, 1998 - v1
Checksum:iD204243E57F1CCC5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57D → G in CAG33200 (Ref. 2) Curated1
Sequence conflicti112N → D in CAD97606 (PubMed:17974005).Curated1
Sequence conflicti218L → P in CAD97606 (PubMed:17974005).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10760.1
RefSeqiNP_008937.1, NM_007006.2
UniGeneiHs.528834

Genome annotation databases

EnsembliENST00000300291; ENSP00000300291; ENSG00000167005
GeneIDi11051
KEGGihsa:11051
UCSCiuc002eja.4 human

Similar proteinsi

Entry informationi

Entry nameiCPSF5_HUMAN
AccessioniPrimary (citable) accession number: O43809
Secondary accession number(s): Q6IB85, Q6NE84
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: June 1, 1998
Last modified: April 25, 2018
This is version 165 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, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health