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Cleavage and polyadenylation specificity factor subunit 3

 
Known also as: Cleavage and polyadenylation specificity factor 73 kDa subunit, CPSF 73 kDa subunit, mRNA 3'-end-processing endonuclease CPSF-73

Known abbreviations: CPSF3, CPSF73

 

FUNCTION:
 
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. 
 
COFACTOR:
 
Binds 2 zinc ions per subunit.
 
SUBUNIT STRUCTURE:
 
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.
 
CELLULAR LOCALIZATION:
 
Nucleus 
 
POST-TRANSLATIONAL MODIFICATION:
 
Sumoylated on Lys-462, Lys-465 and Lys-545, preferentially by SUMO3



This protein can be a part of a given complexes: Activities in which Cleavage and polyadenylation specificity factor subunit 3 is involved: Pathways in which Cleavage and polyadenylation specificity factor subunit 3 is involved:

NCBI GI number(s): 7706427
21314666
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q9UKF6 Q9UKF6
BRENDA - -
KEGG hsa:51692 hsa:51692
PFAM: PF10996
PF11718
PF00753
PF07521
PF10996
PF11718
PF00753
PF07521
InterPro: IPR001279
IPR022712
IPR021718
IPR011108
IPR001279
IPR022712
IPR021718
IPR011108
CATH: - -
SCOP: - -
Solved crystal structures: 2I7T
2I7V
[PDB] [details]
[PDB] [details]


Protein sequence:
MSAIPAEESDQLLIRPLGAGQEVGRSCIILEFKGRKIMLDCGIHPGLEGM
DALPYIDLIDPAEIDLLLISHFHLDHCGALPWFLQKTSFKGRTFMTHATK
AIYRWLLSDYVKVSNISADDMLYTETDLEESMDKIETINFHEVKEVAGIK
FWCYHAGHVLGAAMFMIEIAGVKLLYTGDFSRQEDRHLMAAEIPNIKPDI
LIIESTYGTHIHEKREEREARFCNTVHDIVNRGGRGLIPVFALGRAQELL
LILDEYWQNHPELHDIPIYYASSLAKKCMAVYQTYVNAMNDKIRKQININ
NPFVFKHISNLKSMDHFDDIGPSVVMASPGMMQSGLSRELFESWCTDKRN
GVIIAGYCVEGTLAKHIMSEPEEITTMSGQKLPLKMSVDYISFSAHTDYQ
QTSEFIRALKPPHVILVHGEQNEMARLKAALIREYEDNDEVHIEVHNPRN
TEAVTLNFRGEKLAKVMGFLADKKPEQGQRVSGILVKRNFNYHILSPCDL
SNYTDLAMSTVKQTQAIPYTGPFNLLCYQLQKLTGDVEELEIQEKPALKV
FKNITVIQEPGMVVLEWLANPSNDMYADTVTTVILEVQSNPKIRKGAVQK
VSKKLEMHVYSKRLEIMLQDIFGEDCVSVKDDSILSVTVDGKTANLNLET
RTVECEEGSEDDESLREMVELAAQRLYEALTPVH

Cleavage and polyadenylation specificity factor subunit 3 (Homo sapiens) is product of expression of CPSF3 gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, K Genome Res 2004-10-01 (14) 15489334
Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M Nature 2005-04-07 (434) 15815621
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal 2009-01-01 (2) 19690332
The consensus coding sequences of human breast and colorectal cancers. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE Science 2006-10-13 (314) 16959974
Evidence that polyadenylation factor CPSF-73 is the mRNA 3' processing endonuclease. Ryan K, Calvo O, Manley JL RNA 2004-04-01 (10) 15037765
Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. Kaufmann I, Martin G, Friedlein A, Langen H, Keller W EMBO J 2004-01-11 (23) 14749727
Sumoylation modulates the assembly and activity of the pre-mRNA 3' processing complex. Vethantham V, Rao N, Manley JL Mol Cell Biol 2007-12-01 (27) 17923699
Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3'-end maturation. Kolev NG, Yario TA, Benson E, Steitz JA EMBO Rep 2008-10-01 (9) 18688255
Molecular architecture of the human pre-mRNA 3' processing complex. Shi Y, Di Giammartino DC, Taylor D, Sarkeshik A, Rice WJ, Yates JR 3rd, Frank J, Manley JL Mol Cell 2009-01-13 (33) 19217410
The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA. Laishram RS, Anderson RA EMBO J 2010-12-15 (29) 21102410
Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease. Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L Nature 2006-12-14 (444) 17128255



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Last modification of this entry: Sept. 25, 2012.

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