CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023090
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Cleavage and polyadenylation specificity factor subunit 3 
Protein Synonyms/Alias
 Cleavage and polyadenylation specificity factor 73 kDa subunit; CPSF 73 kDa subunit; mRNA 3'-end-processing endonuclease CPSF-73 
Gene Name
 CPSF3 
Gene Synonyms/Alias
 CPSF73 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
277YASSLAKKCMAVYQTubiquitination[1]
292YVNAMNDKIRKQINIubiquitination[1]
295AMNDKIRKQININNPubiquitination[1, 2, 3, 4]
306INNPFVFKHISNLKSubiquitination[1, 2, 4]
312FKHISNLKSMDHFDDubiquitination[1, 3]
348FESWCTDKRNGVIIAubiquitination[1]
381ITTMSGQKLPLKMSVubiquitination[1, 3, 5]
410SEFIRALKPPHVILVubiquitination[1]
428QNEMARLKAALIREYubiquitination[1, 3, 5]
462TLNFRGEKLAKVMGFsumoylation[6]
462TLNFRGEKLAKVMGFubiquitination[1]
465FRGEKLAKVMGFLADsumoylation[6]
465FRGEKLAKVMGFLADubiquitination[1]
473VMGFLADKKPEQGQRubiquitination[2, 4, 7]
474MGFLADKKPEQGQRVubiquitination[1, 2, 3, 4, 7]
487RVSGILVKRNFNYHIubiquitination[1, 2, 3, 4, 7]
545EELEIQEKPALKVFKsumoylation[6]
545EELEIQEKPALKVFKubiquitination[1, 3, 5]
549IQEKPALKVFKNITVubiquitination[1]
552KPALKVFKNITVIQEubiquitination[1]
604AVQKVSKKLEMHVYSubiquitination[1]
612LEMHVYSKRLEIMLQubiquitination[1]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] Sumoylation modulates the assembly and activity of the pre-mRNA 3' processing complex.
 Vethantham V, Rao N, Manley JL.
 Mol Cell Biol. 2007 Dec;27(24):8848-58. [PMID: 17923699]
 [7] 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] 
Functional Description
 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. 
Sequence Annotation
 ACT_SITE 396 396 Proton donor (Potential).
 METAL 71 71 Zinc 1.
 METAL 73 73 Zinc 1.
 METAL 75 75 Zinc 2.
 METAL 76 76 Zinc 2.
 METAL 158 158 Zinc 1.
 METAL 179 179 Zinc 1.
 METAL 179 179 Zinc 2.
 METAL 418 418 Zinc 2.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 681 681 Phosphothreonine.
 CROSSLNK 462 462 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 465 465 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 545 545 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Complete proteome; Endonuclease; Hydrolase; Isopeptide bond; Metal-binding; mRNA processing; Nuclease; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Ribonucleoprotein; RNA-binding; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 684 AA 
Protein Sequence
MSAIPAEESD QLLIRPLGAG QEVGRSCIIL EFKGRKIMLD CGIHPGLEGM DALPYIDLID 60
PAEIDLLLIS HFHLDHCGAL PWFLQKTSFK GRTFMTHATK AIYRWLLSDY VKVSNISADD 120
MLYTETDLEE SMDKIETINF HEVKEVAGIK FWCYHAGHVL GAAMFMIEIA GVKLLYTGDF 180
SRQEDRHLMA AEIPNIKPDI LIIESTYGTH IHEKREEREA RFCNTVHDIV NRGGRGLIPV 240
FALGRAQELL LILDEYWQNH PELHDIPIYY ASSLAKKCMA VYQTYVNAMN DKIRKQININ 300
NPFVFKHISN LKSMDHFDDI GPSVVMASPG MMQSGLSREL FESWCTDKRN GVIIAGYCVE 360
GTLAKHIMSE PEEITTMSGQ KLPLKMSVDY ISFSAHTDYQ QTSEFIRALK PPHVILVHGE 420
QNEMARLKAA LIREYEDNDE VHIEVHNPRN TEAVTLNFRG EKLAKVMGFL ADKKPEQGQR 480
VSGILVKRNF NYHILSPCDL SNYTDLAMST VKQTQAIPYT GPFNLLCYQL QKLTGDVEEL 540
EIQEKPALKV FKNITVIQEP GMVVLEWLAN PSNDMYADTV TTVILEVQSN PKIRKGAVQK 600
VSKKLEMHVY SKRLEIMLQD IFGEDCVSVK DDSILSVTVD GKTANLNLET RTVECEEGSE 660
DDESLREMVE LAAQRLYEAL TPVH 684 
Gene Ontology
 GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; IDA:UniProtKB.
 GO:0030529; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
 GO:0008409; F:5'-3' exonuclease activity; ISS:UniProtKB.
 GO:0004521; F:endoribonuclease activity; ISS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0003723; F:RNA binding; ISS:UniProtKB.
 GO:0006398; P:histone mRNA 3'-end processing; IDA:UniProtKB.
 GO:0006379; P:mRNA cleavage; TAS:ProtInc.
 GO:0006406; P:mRNA export from nucleus; TAS:Reactome.
 GO:0006378; P:mRNA polyadenylation; TAS:ProtInc.
 GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome.
 GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome. 
Interpro
 IPR001279; Beta-lactamas-like.
 IPR022712; Beta_Casp.
 IPR021718; CPSF73-100_C.
 IPR011108; RMMBL. 
Pfam
 PF10996; Beta-Casp
 PF11718; CPSF73-100_C
 PF00753; Lactamase_B
 PF07521; RMMBL 
SMART
 SM01027; Beta-Casp
 SM01098; CPSF73-100_C
 SM00849; Lactamase_B 
PROSITE
  
PRINTS