Cleavage and polyadenylation specificity factor subunit 6

Known also as: Pre-mRNA cleavage factor Im 68 kDa subunit, Protein HPBRII-4/7
Known abbreviations: CPSF6, CFIM, CFIm68, HPBRII-4, HPBRII-7

Yeast homolog: not known

Protein

551

RRM_6

Structures

Models
Domains

Secondary structure

Disorder

This protein is highly disordered (82 % of residues are predicted to be disordered)

Top 3 models:


Template: 3q2s, chain C Method: hhsearch Fragment: 14-273	Template: 3pgw, chain S Method: hhsearch Fragment: 1-551,many gaps	Template: 3dxj, chain N Method: compass Fragment: 4-304

This protein has alternative isoforms:
Isoform 1:

Sequence length:	551 aa
Molecular weight:	59.21 kDa
Isoelectric point:	6.9

Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MADGVDHIDIYADVGEEFNQEAEYGGHDQIDLYDDVISPSANNGDAPEDRDYMDTLPPTVGDDVGKGAAPNVVYTYTGKRIALYIGNLTWWTTDEDLTEAVHSLGVNDILEIKFFENRANGQSKGFALVG
VGSEASSKKLMDLLPKRELHGQNPVVTPCNKQFLSQFEMQSRKTTQSGQMSGEGKAGPPGGSSRAAFPQGGRGRGRFPGAVPGGDRFPGPAGPGGPPPPFPAGQTPPRPPLGPPGPPGPPGPPPPGQVLP
PPLAGPPNRGDRPPPPVLFPGQPFGQPPLGPLPPGPPPPVPGYGPPPGPPPPQQGPPPPPGPFPPRPPGPLGPPLTLAPPPHLPGPPPGAPPPAPHVNPAFFPPPTNSGMPTSDSRGPPPTDPYGRPPPY
DRGDYGPPGREMDTARTPLSEAEFEEIMNRNRAISSSAISRAVSDASAGDYGSAIETLVTAISLIKQSKVSADDRCKVLISSLQDCLHGIESKSYGSGSRRERSRERDHSRSREKSRRHKSRSRDRHDDY
YRERSRERERHRDRDRDRDRERDREREYRHR

Isoform 2:

Sequence length:	588 aa
Molecular weight:	63.471 kDa
Isoelectric point:	7.56

Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MADGVDHIDIYADVGEEFNQEAEYGGHDQIDLYDDVISPSANNGDAPEDRDYMDTLPPTVGDDVGKGAAPNVVYTYTGKRIALYIGNLTWWTTDEDLTEAVHSLGVNDILEIKFFENRANGQSKGFALVG
VGSEASSKKLMDLLPKRELHGQNPVVTPCNKQFLSQFEMQSRKTTQSGQMSGEGKAGPPGGSSRAAFPQGGRGRGRFPGAVPGGDRFPGPAGPGGPPPPFPGNLIKHLVKGTRPLFLETRIPWHMGHSIE
EIPIFGLKAGQTPPRPPLGPPGPPGPPGPPPPGQVLPPPLAGPPNRGDRPPPPVLFPGQPFGQPPLGPLPPGPPPPVPGYGPPPGPPPPQQGPPPPPGPFPPRPPGPLGPPLTLAPPPHLPGPPPGAPPP
APHVNPAFFPPPTNSGMPTSDSRGPPPTDPYGRPPPYDRGDYGPPGREMDTARTPLSEAEFEEIMNRNRAISSSAISRAVSDASAGDYGSAIETLVTAISLIKQSKVSADDRCKVLISSLQDCLHGIESK
SYGSGSRRERSRERDHSRSREKSRRHKSRSRDRHDDYYRERSRERERHRDRDRDRDRERDREREYRHR

Isoform 3:

Sequence length:	478 aa
Molecular weight:	52.326 kDa
Isoelectric point:	6.18

Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MADGVDHIDIYADVGEEFNQEAEYGGHDQIDLYDDVISPSANNGDAPEDRDYMDTLPPTVGDDVGKGAAPNVVYTYTGKRIALYIGNLTWWTTDEDLTEAVHSLGVNDILEIKFFENRANGQSKGFALVG
VGSEASSKKLMDLLPKRELHGQNPVVTPCNKQFLSQFEMQSRKTTQSGQMSGEGKAGPPLAGPPNRGDRPPPPVLFPGQPFGQPPLGPLPPGPPPPVPGYGPPPGPPPPQQGPPPPPGPFPPRPPGPLGP
PLTLAPPPHLPGPPPGAPPPAPHVNPAFFPPPTNSGMPTSDSRGPPPTDPYGRPPPYDRGDYGPPGREMDTARTPLSEAEFEEIMNRNRAISSSAISRAVSDASAGDYGSAIETLVTAISLIKQSKVSAD
DRCKVLISSLQDCLHGIESKSYGSGSRRERSRERDHSRSREKSRRHKSRSRDRHDDYYRERSRERERHRDRDRDRDRERDREREYRHR

Gene location: 12q15

Summary
CPSF6 is a component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. It has a domain organization reminiscent of spliceosomal proteins. 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).

Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition.

The N-terminal region of the 68 kD subunit contains an RNP-type RNA binding domain (RBD), which is necessary for binding to the 25 kD subunit. The C-terminal region of the 68 kD subunit is rich in RS, RD and RE repeats that are similar to pre-mRNA splicing SR proteins. In fact, this region interacts with the spliceosomal SR proteins, and CF Im has been identified as a component of purified spliceosomes.

CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping. Component of the cleavage factor Im (CFIm) complex, composed at least of NUDT21/CPSF5 and CPSF6 or CPSF7.

Interacts with NUDT21/CPSF5, SFRS3, SFRS7, SNRNP70 and TRA2B/SFRS10.

Phosphorylated upon DNA damage, probably by ATM or ATR.

See this protein in other databases:

Literature:

Brown KM, Gilmartin GM. A mechanism for the regulation of pre-mRNA 3" processing by human cleavage factor Im. Mol Cell 2003 12(6):1467-76, doi: , PMID: 14690600.
Dettwiler S, Aringhieri C, Cardinale S et al. Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization. J Biol Chem 2004 279(34):35788-97, doi: 10.1074/jbc.M403927200, PMID: 15169763.
Sartini BL, Wang H, Wang W et al. Pre-messenger RNA cleavage factor I (CFIm): potential role in alternative polyadenylation during spermatogenesis. Biol Reprod 2008 78(3):472-82, doi: 10.1095/biolreprod.107.064774, PMID: 18032416.
Kim S, Yamamoto J, Chen Y et al. Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells 2010 15(9):1003-13, doi: 10.1111/j.1365-2443.2010.01436.x, PMID: 20695905.
Yang Q, Coseno M, Gilmartin GM et al. 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. Structure 2011 19(3):368-77, doi: 10.1016/j.str.2010.12.021, PMID: 21295486.
Ruegsegger U, Beyer K, Keller W et al. Purification and characterization of human cleavage factor Im involved in the 3" end processing of messenger RNA precursors. J Biol Chem 1996 271(11):6107-13, doi: , PMID: 8626397.
Ruegsegger U, Blank D, Keller W et al. Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits. Mol Cell 1998 1(2):243-53, doi: , PMID: 9659921.

Additional computationally mapped references ...

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