CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000778
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Cleavage and polyadenylation specificity factor subunit 5 
Protein Synonyms/Alias
 Cleavage and polyadenylation specificity factor 25 kDa subunit; CFIm25; CPSF 25 kDa subunit; Nucleoside diphosphate-linked moiety X motif 21; Nudix motif 21; Pre-mRNA cleavage factor Im 25 kDa subunit 
Gene Name
 NUDT21 
Gene Synonyms/Alias
 CFIM25; CPSF25; CPSF5 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
23GVTQFGNKYIQQTKPacetylation[1, 2, 3, 4, 5, 6, 7]
23GVTQFGNKYIQQTKPubiquitination[7, 8, 9, 10, 11, 12]
29NKYIQQTKPLTLERTacetylation[2, 6]
29NKYIQQTKPLTLERTubiquitination[7, 8, 9, 10, 12, 13, 14, 15]
50TNYTFGTKEPLYEKDubiquitination[10, 11, 13]
56TKEPLYEKDSSVAARacetylation[2, 6]
56TKEPLYEKDSSVAARubiquitination[7, 10, 11, 13]
73RMREEFDKIGMRRTVacetylation[2]
73RMREEFDKIGMRRTVubiquitination[10]
122EDEVEGLKRLMTEILubiquitination[10, 11, 13, 16]
182FLVQLQEKALFAVPKubiquitination[8, 10, 11, 12, 13]
189KALFAVPKNYKLVAAacetylation[2]
189KALFAVPKNYKLVAAubiquitination[8, 12]
192FAVPKNYKLVAAPLFubiquitination[10]
Reference
 [1] Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing.
 Shimazu T, Horinouchi S, Yoshida M.
 J Biol Chem. 2007 Feb 16;282(7):4470-8. [PMID: 17172643]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [4] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [5] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [6] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [8] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [9] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [10] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [11] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [12] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [13] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [14] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [15] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [16] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931
Functional Description
 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. 
Sequence Annotation
 DOMAIN 76 201 Nudix hydrolase.
 REGION 2 147 Necessary for RNA-binding.
 REGION 81 160 Necessary for interactions with PAPOLA
 REGION 102 104 Interaction with RNA.
 MOTIF 109 130 Nudix box.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 23 23 N6-acetyllysine.
 MOD_RES 29 29 N6-acetyllysine.
 MOD_RES 40 40 Phosphotyrosine.
 MOD_RES 56 56 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Complete proteome; Direct protein sequencing; mRNA processing; Nucleus; Phosphoprotein; Reference proteome; RNA-binding. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 227 AA 
Protein Sequence
MSVVPPNRSQ TGWPRGVTQF GNKYIQQTKP LTLERTINLY PLTNYTFGTK EPLYEKDSSV 60
AARFQRMREE FDKIGMRRTV EGVLIVHEHR LPHVLLLQLG TTFFKLPGGE LNPGEDEVEG 120
LKRLMTEILG RQDGVLQDWV IDDCIGNWWR PNFEPPQYPY IPAHITKPKE HKKLFLVQLQ 180
EKALFAVPKN YKLVAAPLFE LYDNAPGYGP IISSLPQLLS RFNFIYN 227 
Gene Ontology
 GO:0005813; C:centrosome; IDA:LIFEdb.
 GO:0005849; C:mRNA cleavage factor complex; IDA:UniProtKB.
 GO:0042382; C:paraspeckles; IDA:UniProtKB.
 GO:0017091; F:AU-rich element binding; IDA:UniProtKB.
 GO:0016787; F:hydrolase activity; IEA:InterPro.
 GO:0003729; F:mRNA binding; IDA:UniProtKB.
 GO:0006378; P:mRNA polyadenylation; IMP:UniProtKB.
 GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome.
 GO:0051262; P:protein tetramerization; IDA:UniProtKB.
 GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome. 
Interpro
 IPR016706; Cleav_polyA_spec_factor_su5.
 IPR000086; NUDIX_hydrolase_dom.
 IPR015797; NUDIX_hydrolase_dom-like. 
Pfam
 PF13869; NUDIX_2 
SMART
  
PROSITE
 PS51462; NUDIX
 PS00893; NUDIX_BOX 
PRINTS