KLF3

KLF3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1P7A, 1U85, 1U86
Identifiers
Aliases	KLF3, BKLF, Kruppel-like factor 3 (basic), Kruppel like factor 3
External IDs	OMIM: 609392 MGI: 1342773 HomoloGene: 7396 GeneCards: KLF3
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4p14 Start 38,664,197 bp[1] End 38,701,517 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 C3.1 Start 64,960,731 bp[2] End 64,990,244 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in human penis jejunal mucosa trabecular bone oral cavity gums vulva parietal pleura germinal epithelium rectum urethra Top expressed in left colon epithelium of stomach conjunctival fornix Paneth cell left lung lobe blood seminal vesicula belly cord calvaria lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription factor activity DNA binding protein binding metal ion binding nucleic acid binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus nucleoplasm Biological process multicellular organism development cellular response to peptide regulation of transcription, DNA-templated transcription, DNA-templated negative regulation of transcription by RNA polymerase II regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51274 16599 Ensembl ENSG00000109787 ENSMUSG00000029178 UniProt P57682 Q60980 RefSeq (mRNA) NM_016531 NM_008453 RefSeq (protein) NP_057615 NP_032479 Location (UCSC) Chr 4: 38.66 – 38.7 Mb Chr 5: 64.96 – 64.99 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Krüppel-like factor 3 is a protein that in humans is encoded by the KLF3 gene.

Structure

KLF3, originally termed Basic Krüppel-like Factor (BKLF), was the third member of the Krüppel-like factor family of zinc finger transcription factors to be discovered.^[5] Transcription factors in this family bind DNA by virtue of 3 characteristic three C₂H₂ zinc fingers 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).

Function

While the C-termini are similar in different KLFs, the N-termini vary and accordingly different KLFs can either activate or repress transcription or both. KLF3 appears to function predominantly as a repressor of transcription. It turns genes off. It does this by recruiting the C-terminal Binding Protein co-repressors CTBP1 and CTBP2.^[6][7] 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).^[6][7] CtBP in turn recruits histone modifying enzymes to alter chromatin 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, and its expression increases as erythroid cells mature. Studies in knockout mice 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.^[8] 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.^[9] 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.^[10]

As well as being expressed in erythroid cells, KLF3 is present in other cell types and analysis of the knockout mice has revealed defects affecting adipose tissue^[11] and B cells.^[12] KLF3 deficient mice have less adipose tissue and indications of metabolic health that may be attributable to de-repression of the adipokine hormone gene adipolin.^[13] 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 marginal zone and follicular B cells.^[14]

Interactions

KLF3 has been shown to interact with:

• CTBP2^[6][7] and
• FHL3.^[6]

References

Further reading

External links

• KLF3 protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)