PROSITE documentation PDOC00361
CTF/NF-I DNA-binding domain signature and profile


Nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF) [1,2] (also known as TGGCA-binding proteins) are a family of vertebrate nuclear proteins which recognize and bind, as dimers, the palindromic DNA sequence 5'-TTGGCNNNNNGCCAA-3'. CTF/NF-I binding sites are present in viral and cellular promoters and in the origin of DNA replication of Adenovirus type 2.

The CTF/NF-I proteins were first identified as nuclear factor I, a collection of proteins that activate the replication of several Adenovirus serotypes (together with NF-II and NF-III) [3]. The family of proteins was also identified as the CTF transcription factors, before the NFI and CTF families were found to be identical [4]. The CTF/NF-I proteins are individually capable of activating transcription and DNA replication. The CTF/NF-I family name has also been dubbed as NFI, NF-I or NF1.

In a given species, there are a large number of different CTF/NF-I proteins. The multiplicity of CTF/NF-I is known to be generated both by alternative splicing and by the occurrence of four different genes. The known forms of NF-I genes have been classified as:

  • The CTF-like factors subfamily (prototype form: CTF-1) [4]
  • The NFI-X proteins.
  • The NFI-A proteins.
  • The NFI-B proteins.

So far, all CTF/NF-I family members appear to have similar transcription and replication activities.

CTF/NF-I proteins contains 400 to 600 amino acids. The N-terminal 200 amino-acid sequence, almost perfectly conserved in all species and genes sequenced, mediates site-specific DNA recognition, protein dimerization and Adenovirus DNA replication. The C-terminal 100 amino acids contain the transcriptional activation domain. This activation domain is the target of gene expression regulatory pathways ellicited by growth factors and it interacts with basal transcription factors and with histone H3 [6].

The CTF/NF-I DNA-binding domain contains four conserved Cys residues, which are required for its DNA-binding activity [7].

As a specific signature for this family of proteins, we selected a perfectly conserved, highly charged 12 residue peptide located in the DNA-binding domain of CTF/NF-I. We also developed a profile that covers the entire CTF/NF-I DNA-binding domain.


It has been said that the CTF/NF-I DNA-binding domain might be related to the MH1 domain (see <PDOC51075>) [8,9].

Expert(s) to contact by email:

Mermod N.
Gronostajski R.M.

Last update:

February 2005 / Text revised; profile added.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

CTF_NFI_2, PS51080; CTF/NF-I DNA-binding domain profile  (MATRIX)

CTF_NFI_1, PS00349; CTF/NF-I DNA-binding domain signature  (PATTERN)


1AuthorsMermod N. O'Neill E.A. Kelly T.J. Tjian R.
TitleThe proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain.
SourceCell 58:741-753(1989).
PubMed ID2504497

2AuthorsRupp R.A.W. Kruse U. Multhaup G. Goebel U. Beyreuther K. Sippel A.E.
TitleChicken NFI/TGGCA proteins are encoded by at least three independent genes: NFI-A, NFI-B and NFI-C with homologues in mammalian genomes.
SourceNucleic Acids Res. 18:2607-2616(1990).
PubMed ID2339052

3AuthorsNagata K. Guggenheimer R.A. Enomoto T. Lichy J.H. Hurwitz J.
TitleAdenovirus DNA replication in vitro: identification of a host factor that stimulates synthesis of the preterminal protein-dCMP complex.
SourceProc. Natl. Acad. Sci. U.S.A. 79:6438-6442(1982).
PubMed ID6216480

4AuthorsSantoro C. Mermod N. Andrews P.C. Tjian R.
SourceNature 334:2118-2224(1988).

5AuthorsGil G. Smith J.R. Goldstein J.L. Slaughter C.A. Orth K. Brown M.S. Osborne T.F.
TitleMultiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
SourceProc. Natl. Acad. Sci. U.S.A. 85:8963-8967(1988).
PubMed ID3194401

6AuthorsAlevizopoulos A. Dusserre Y. Tsai-Pflugfelder M. von der Weid T. Wahli W. Mermod N.
TitleA proline-rich TGF-beta-responsive transcriptional activator interacts with histone H3.
SourceGenes Dev. 9:3051-3066(1995).
PubMed ID8543151

7AuthorsNovak A. Goyal N. Gronostajski R.M.
TitleFour conserved cysteine residues are required for the DNA binding activity of nuclear factor I.
SourceJ. Biol. Chem. 267:12986-12990(1992).
PubMed ID1618796

8AuthorsStefancsik R. Sarkar S.
TitleRelationship between the DNA binding domains of SMAD and NFI/CTF transcription factors defines a new superfamily of genes.
SourceDNA Seq. 14:233-239(2003).
PubMed ID14631647

9AuthorsSadreyev R. Grishin N.
TitleCOMPASS: a tool for comparison of multiple protein alignments with assessment of statistical significance.
SourceJ. Mol. Biol. 326:317-336(2003).
PubMed ID12547212

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