Cleavage stimulation factor subunit 2

Known also as: CF-1 64 kDa subunit, Cleavage stimulation factor 64 kDa subunit
Known abbreviations: CSTF2, CstF-64

Yeast homolog: RNA15

Protein

577

RRM_1

CSTF2_hinge

CSTF_C

Structures
Models
Domains

Secondary structure

Disorder

This protein is highly disordered (79 % of residues are predicted to be disordered)

Top 3 models:


Template: 1cvj, chain A Method: hhsearch Fragment: 1-208	Template: 3dxj, chain N Method: compass Fragment: 1-476	Template: 2qfj, chain A Method: phyre Fragment: 2-176

This protein has alternative isoforms:
Isoform 1:

Sequence length:	577 aa
Molecular weight:	60.959 kDa
Isoelectric point:	6.56

Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MAGLTVRDPAVDRSLRSVFVGNIPYEATEEQLKDIFSEVGPVVSFRLVYDRETGKPKGYGFCEYQDQETALSAMRNLNGREFSGRALRVDNAASEKNKEELKSLGTGAPVIESPYGETISPEDAPESISK
AVASLPPEQMFELMKQMKLCVQNSPQEARNMLLQNPQLAYALLQAQVVMRIVDPEIALKILHRQTNIPTLIAGNPQPVHGAGPGSGSNVSMNQQNPQAPQAQSLGGMHVNGAPPLMQASMQGGVPAPGQM
PAAVTGPGPGSLAPGGGMQAQVGMPGSGPVSMERGQVPMQDPRAAMQRGSLPANVPTPRGLLGDAPNDPRGGTLLSVTGEVEPRGYLGPPHQGPPMHHVPGHESRGPPPHELRGGPLPEPRPLMAEPRGP
MLDQRGPPLDGRGGRDPRGIDARGMEARAMEARGLDARGLEARAMEARAMEARAMEARAMEARAMEVRGMEARGMDTRGPVPGPRGPIPSGMQGPSPINMGAVVPQGSRQVPVMQGTGMQGASIQGGSQP
GGFSPGQNQVTPQDHEKAALIMQVLQLTADQIAMLPPEQRQSILILKEQIQKSTGAP

Isoform 2:

Sequence length:	560 aa
Molecular weight:	59.252 kDa
Isoelectric point:	6.5

Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MAGLTVRDPAVDRSLRSVFVGNIPYEATEEQLKDIFSEVGPVVSFRLVYDRETGKPKGYGFCEYQDQETALSAMRNLNGREFSGRALRVDNAASEKNKEELKSLGTGAPVIESPYGETISPEDAPESISK
AVASLPPEQMFELMKQMKLCVQNSPQEARNMLLQNPQLAYALLQAQVVMRIVDPEIALKILHRQTNIPTLIAGNPQPVHGAGPGSGSNVSMNQQNPQAPQAQSLGGVPAPGQMPAAVTGPGPGSLAPGGG
MQAQVGMPGSGPVSMERGQVPMQDPRAAMQRGSLPANVPTPRGLLGDAPNDPRGGTLLSVTGEVEPRGYLGPPHQGPPMHHVPGHESRGPPPHELRGGPLPEPRPLMAEPRGPMLDQRGPPLDGRGGRDP
RGIDARGMEARAMEARGLDARGLEARAMEARAMEARAMEARAMEARAMEVRGMEARGMDTRGPVPGPRGPIPSGMQGPSPINMGAVVPQGSRQVPVMQGTGMQGASIQGGSQPGGFSPGQNQVTPQDHEK
AALIMQVLQLTADQIAMLPPEQRQSILILKEQIQKSTGAP

Gene location: Xq22.1

Summary
CSTF2 is a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs.

CstF-64 contains a conserved RNA recognition motif (RRM) RNA binding domain (43% identity between CstF-64 and Rna15p) at its N-terminus. The RRM alone is sufficient for RNA binding and shows preference for the G/U- rich DSE. The structure of the RRM of CstF-64 has been determined by NMR, which showed the presence of a UU dinucleotide-specific binding site and that the protein:RNA interface is highly mobile. This flexibility may allow CstF-64 to form stable complexes with a wide range of GU-rich sequences.

Metazoan CstF-64 homologs contain additional sequences between the hinge region and the CTD, including a proline/glycine-rich segment followed by 12 repeats of the MEAR(A/G) pentapeptide motif. The length and composition of this region is variable among metazoans and its function is unknown. The MEAR(A/G) repeats may form a helical structure in solution.

CstF-64 has a second isoform in humans, known as tau CstF-64. It is expressed in male germ cells and may have important roles in germ-cell-specific polyadenylation and spermatogenesis.

CSTF2 directly interacts with CSTF3, SYMPK and RPO2TC1.

Interacts with HSF1 in heat-stressed cells.

Interacts with CPSF2, CPSF3 and FIP1L1. Interacts with DDX1.

Up-regulated during the G0 to S phase transition. Phosphorylated upon DNA damage, probably by ATM or ATR.

See this protein in other databases:

Literature:

Perez Canadillas JM, Varani G. Recognition of GU-rich polyadenylation regulatory elements by human CstF-64 protein. EMBO J 2003 22(11):2821-30, doi: 10.1093/emboj/cdg259, PMID: 12773396.
Deka P, Rajan PK, Perez-Canadillas JM et al. Protein and RNA dynamics play key roles in determining the specific recognition of GU-rich polyadenylation regulatory elements by human Cstf-64 protein. J Mol Biol 2005 347(4):719-33, doi: 10.1016/j.jmb.2005.01.046, PMID: 15769465.
Salisbury J, Hutchison KW, Graber JH et al. A multispecies comparison of the metazoan 3"-processing downstream elements and the CstF-64 RNA recognition motif. BMC Genomics 2006 7:55, doi: 10.1186/1471-2164-7- 55, PMID: 16542450.
Qu X, Perez-Canadillas JM, Agrawal S et al. The C-terminal domains of vertebrate CstF-64 and its yeast orthologue Rna15 form a new structure critical for mRNA 3"-end processing. J Biol Chem 2007 282(3):2101-15, doi: 10.1074/jbc.M609981200, PMID: 17116658.
Takagaki Y, MacDonald CC, Shenk T et al. The human 64-kDa polyadenylylation factor contains a ribonucleoprotein-type RNA binding domain and unusual auxiliary motifs. Proc Natl Acad Sci U S A 1992 89(4):1403-7, doi: , PMID: 1741396.
Shankarling GS, Coates PW, Dass B et al. A family of splice variants of CstF-64 expressed in vertebrate nervous systems. BMC Mol Biol 2009 10:22, doi: 10.1186/1471-2199-10-22, PMID: 19284619.
Hockert JA, Yeh HJ, MacDonald CC et al. The hinge domain of the cleavage stimulation factor protein CstF-64 is essential for CstF-77 interaction, nuclear localization, and polyadenylation. J Biol Chem 2010 285(1):695-704, doi: 10.1074/jbc.M109.061705, PMID: 19887456.
Ruepp MD, Schweingruber C, Kleinschmidt N et al. Interactions of CstF-64, CstF-77, and symplekin: implications on localisation and function. Mol Biol Cell 2011 22(1):91-104, doi: 10.1091/mbc.E10-06-0543, PMID: 21119002.
Martincic K, Campbell R, Edwalds-Gilbert G et al. Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition. Proc Natl Acad Sci U S A 1998 95(19):11095-100, doi: , PMID: 9736695.

Additional computationally mapped references ...

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