Krüppel-like factor 3 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''KLF3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Structure

KLF3, originally termed Basic Krüppel-like Factor (BKLF), was the third member of the Krüppel-like factor family of

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s to be discovered. Transcription factors in this family bind DNA by virtue of 3 characteristic three C₂H₂

s at their C-termini. Since their DNA-binding domains are highly conserved within the family, all KLF proteins recognize CACCC or CGCCC boxes of the general form NCR CRC CCN, (where N is any base and R is a

purine Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...

Function

While the C-termini are similar in different KLFs, the

N-termini The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

vary and accordingly different KLFs can either activate or repress transcription or both. KLF3 appears to function predominantly as a

repressor In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...

of transcription. It turns genes off. It does this by recruiting the C-terminal Binding Protein co-repressors

CTBP1 C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the ''CTBP1'' gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2. Function The CtBP1 protein was originally identified as a human prote ...

and

CTBP2 C-terminal-binding protein 2 also known as CtBP2 is a protein that in humans is encoded by the ''CTBP2'' gene. Function The CtBPs - CTBP1, CtBP1 and CtBP2 in mammals - are among the best characterized transcriptional corepressors. They typicall ...

. CtBP docks onto a short motif (residues 61-65) in the N-terminus of KLF3, of the general form Proline – Isoleucine – Aspartate – Leucine – Serine (the PIDLS motif). CtBP in turn recruits

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...

modifying enzymes to alter

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

and repress gene expression. KLF3 is expressed highly in the red blood cell or erythroid lineage. Here it is driven by another KLF, Erythroid KLF or

KLF1 Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 is a transcription factor that is necessary for the proper maturatio ...

, and its expression increases as erythroid cells mature. Studies in

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

reveal a mild anemia in the absence of functional KLF3 and the de-repression of several target genes that contain CACCC boxes in their regulatory regions. Many of these genes are activated by KLF1, hence it appears that KLF3 operates in a negative feedback loop to balance the activating potential of KLF1. KLF3 also regulates another repressive KLF,

KLF8 Krueppel-like factor 8 is a protein that in humans is encoded by the ''KLF8'' gene. KLF8 belongs to the family of KLF protein. KLF8 is activated by KLF1 along with KLF3 while KLF3 represses KLF8. Interactions KLF8 has been shown to interact wi ...

. Thus KLF1, KLF3 and KLF8 operate in a tight regulatory network. KLF3 and KLF8 may have redundant functions, as mice lacking both KLF3 and KLF8 show defects that are more severe than in either single knockout. They die in utero around day 14 of gestation. As well as being expressed in erythroid cells, KLF3 is present in other cell types and analysis of the

has revealed defects affecting

adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...

and

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s. KLF3 deficient mice have less adipose tissue and indications of metabolic health that may be attributable to de-repression of the

adipokine The adipokines, or adipocytokines (Greek ', fat; ', cell; and ', movement) are cytokines (cell signaling proteins) secreted by adipose tissue. Some contribute to an obesity-related low-grade state of inflammation or to the development of metabolic ...

hormone gene adipolin. The role of KLF3 in B lymphocytes is complex but it appears to operate in a network with KLF2 and KLF4 to influence the switch between

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

marginal zone The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen. (Some sources consider it to be the part of red pulp which borders on the white pulp, while other sources consider it to ...

and

follicular B cell Within the immune system, Follicular B cells (FO B cells) are a type of B cell that reside in primary and secondary lymphoid follicles (containing germinal centers) of secondary and tertiary lymphoid organs, including spleen and lymph nodes. Antibod ...

Interactions

KLF3 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

and *

FHL3 Four and a half LIM domains protein 3 is a protein that in humans is encoded by the ''FHL3'' gene. LIM proteins are defined by the possession of a highly conserved double zinc finger motif called the LIM domain. upplied by OMIMref name="entrez"/ ...

References

External links

* {{Transcription factors, g2 Transcription factors

Structure

Function

Interactions

References

Further reading

External links