KLF6 (Krüppel like factor 6)
2007-03-01 Scott L. Friedman  , Goutham Narla  , John A. Martignetti   AffiliationDivision of Liver Diseases, Box 1123, Mount Sinai School of Medicine, 1425 Madison Ave., Room 11-70C, New York, NY 10029-6574, USA
Identity
HGNC
LOCATION
10p15.1
LOCUSID
ALIAS
BCD1,CBA1,COPEB,CPBP,GBF,PAC1,ST12,ZF9
FUSION GENES
DNA/RNA
Description
Spans 11 kb; five exons; 4 CDS exons.
Transcription
Full length transcript of 4.1 kb, open reading frame 849 bp. There are at least three alternative splice transcripts.
Proteins
Description
Full length transcript encodes a 283 amino acids protein, 42 kDa, with a 201 amino acids transactivation domain and an 82 amino acids DNA binding domain with 3 C2H2 zinc fingers. There is at least one putative nuclear localization signal immediately 5 to the DNA binding domain.
There are at least three alternative splice transcripts encoding proteins of 195 (KLF6-SV1), 237 (KLF6-SV3), and 241 amino acids (KLF6-SV2).
Several post-translational modifications including phosphorylation, ubiquitinylation, acetylation are suggested based on encoded protein sequence motifs.
There are at least three alternative splice transcripts encoding proteins of 195 (KLF6-SV1), 237 (KLF6-SV3), and 241 amino acids (KLF6-SV2).
Several post-translational modifications including phosphorylation, ubiquitinylation, acetylation are suggested based on encoded protein sequence motifs.
Expression
Ubiquitously expressed in adult tissues, restricted during embryogenesis but includes placenta, neural and non-neural tissues, and cornea. Full-length KLF6 downregulated in many human cancers (see below). Expression pattern of KLF6 splice variants may be upregulated.
Localisation
Found in both nucleus and cytoplasm, but predominantly nuclear. Splice variants SV1 and SV2 primarily cytoplasmic and believed to be the result of loss of nuclear localization signal (NLS). Splice variant 3 retains the NLS.
Function
Tumor suppressor gene, immediate early gene in tissue injury and fibrosis, during adenoviral and pseudomonas infections and during ischemic reperfusion in kidney.
Transactivator of multiple target genes including p21, TGFbeta1, TGFbeta receptors type II and TGFbeta receptors type III, human keratin 4 and 12 genes: inducible nitric oxide synthase, endoglin, insulin-like growth factor receptor 1, multi-drug resistance transporters, E-cadherin, leukotriene C(4)(LTC4S), laminin 111, acid ceramidase, alpha 1 proteinase inhibitor.
Suppresses growth by inducing p21, sequestering cyclin D1 and/or inhibiting c-jun oncogene.
Promotes differentiation of preadipocytes to adipocytes in culture and hepatocytes in vivo.
Contributes to fetal development of mouse cornea and lens; and immune and hematopoietic systems by contributing to hemangioblast phenotype.
Interacts with the core promoter element of a TATA box-less gene.
Induces apoptosis of lung cancer cells.
Transactivator of multiple target genes including p21, TGFbeta1, TGFbeta receptors type II and TGFbeta receptors type III, human keratin 4 and 12 genes: inducible nitric oxide synthase, endoglin, insulin-like growth factor receptor 1, multi-drug resistance transporters, E-cadherin, leukotriene C(4)(LTC4S), laminin 111, acid ceramidase, alpha 1 proteinase inhibitor.
Suppresses growth by inducing p21, sequestering cyclin D1 and/or inhibiting c-jun oncogene.
Promotes differentiation of preadipocytes to adipocytes in culture and hepatocytes in vivo.
Contributes to fetal development of mouse cornea and lens; and immune and hematopoietic systems by contributing to hemangioblast phenotype.
Interacts with the core promoter element of a TATA box-less gene.
Induces apoptosis of lung cancer cells.
Homology
The 47 N-terminal amino acids are identical to KLF7, and the 82 amino acids DNA binding domain highly homologous to other members of the KLF family. Also homologous to the Drosophila Luna gene.
Mutations
Germinal
None identified to date. However, a germline single nucleotide intronic polymorphism (IVS1-27 G > A) has been identified that creates a novel SRp40 DNA binding site, therby increasing the generation of three alternatively spliced mRNAs, and which is associated with an increased risk of prostate cancer. Other low frequency coding and non-coding SNPs have been identified.
Somatic
A number of somatic mutations were originally identified in prostate cancer and shown to result in loss of function. These include Trp64Arg, Ser116Pro, Ala123Asp and Ser137X.
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15172998 | 2004 | Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1. | Benzeno S et al |
| 11429296 | 2001 | Co-localization of KLF6 and KLF4 with pregnancy-specific glycoproteins during human placenta development. | Blanchon L et al |
| 12433697 | 2002 | Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury. | Botella LM et al |
| 12651626 | 2003 | Deletion, mutation, and loss of expression of KLF6 in human prostate cancer. | Chen C et al |
| 12407152 | 2002 | Regulation of corneal keratin-12 gene expression by the human Krüppel-like transcription factor 6. | Chiambaretta F et al |
| 15824733 | 2005 | Genetic alterations of the KLF6 gene in gastric cancer. | Cho YG et al |
| 14527717 | 2003 | Identification of the Drosophila progenitor of mammalian Krüppel-like factors 6 and 7 and a determinant of fly development. | De Graeve F et al |
| 16778100 | 2006 | Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. | DiFeo A et al |
| 11274234 | 2001 | Klf6 is a zinc finger protein expressed in a cell-specific manner during kidney development. | Fischer EA et al |
| 16054710 | 2005 | Genomic organization and functional analysis of the gene encoding the Krüppel-like transcription factor KLF6. | Gehrau RC et al |
| 15172991 | 2004 | Krüppel-like factor 6 is frequently down-regulated and induces apoptosis in non-small cell lung cancer cells. | Ito G et al |
| 12740910 | 2003 | KLF6, a putative tumor suppressor gene, is mutated in astrocytic gliomas. | Jeng YM et al |
| 9837963 | 1998 | Transcriptional activation of transforming growth factor beta1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1. Potential mechanisms for autocrine fibrogenesis in response to injury. | Kim Y et al |
| 15064720 | 2004 | Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6. | Kimmelman AC et al |
| 10666204 | 2000 | Transcriptional activation of urokinase by the Krüppel-like factor Zf9/COPEB activates latent TGF-beta1 in vascular endothelial cells. | Kojima S et al |
| 15486921 | 2004 | Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in hepatocellular carcinoma. | Kremer-Tal S et al |
| 11472850 | 2001 | Embryonic expression of Krüppel-like factor 6 in neural and non-neural tissues. | Laub F et al |
| 15917248 | 2005 | Krüppel-like factor-6 promotes preadipocyte differentiation through histone deacetylase 3-dependent repression of DLK1. | Li D et al |
| 16234353 | 2006 | Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6. | Matsumoto N et al |
| 15557439 | 2004 | Developmentally regulated expression of KLF6 in the mouse cornea and lens. | Nakamura H et al |
| 15994951 | 2005 | Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread. | Narla G et al |
| 15735005 | 2005 | A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. | Narla G et al |
| 11752579 | 2001 | KLF6, a candidate tumor suppressor gene mutated in prostate cancer. | Narla G et al |
| 10802067 | 2000 | The Krüppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact. | Okano J et al |
| 9689109 | 1998 | Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis. | Ratziu V et al |
| 15057748 | 2004 | Kruppel-like factor 6 (KLF6) is a tumor-suppressor gene frequently inactivated in colorectal cancer. | Reeves HL et al |
| 15131018 | 2004 | Transcriptional activation of the insulin-like growth factor I receptor gene by the Kruppel-like factor 6 (KLF6) tumor suppressor protein: potential interactions between KLF6 and p53. | Rubinstein M et al |
| 15378003 | 2004 | A new role for the Kruppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function. | Slavin DA et al |
| 17223258 | 2007 | Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene. | Spinola M et al |
| 12590140 | 2003 | Transcriptional activation of the human inducible nitric-oxide synthase promoter by Kruppel-like factor 6. | Warke VG et al |
| 12235161 | 2002 | The Kruppel-like factor Zf9 and proteins in the Sp1 family regulate the expression of HSP47, a collagen-specific molecular chaperone. | Yasuda K et al |
| 17143513 | 2007 | KLF6: mutational analysis and effect on cancer cell proliferation. | Yin D et al |
| 10722737 | 2000 | Cell-specific transcription of leukotriene C(4) synthase involves a Kruppel-like transcription factor and Sp1. | Zhao JL et al |
Other Information
Locus ID:
NCBI: 1316
MIM: 602053
HGNC: 2235
Ensembl: ENSG00000067082
Variants:
dbSNP: 1316
ClinVar: 1316
TCGA: ENSG00000067082
COSMIC: KLF6
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000067082 | ENST00000469435 | Q99612 |
| ENSG00000067082 | ENST00000497571 | Q99612 |
| ENSG00000067082 | ENST00000542957 | Q99612 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38064851 | 2024 | Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer. | 1 |
| 38159857 | 2024 | KLF6 activates Sp1-mediated prolidase transcription during TGF-β(1) signaling. | 1 |
| 38516774 | 2024 | miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway. | 0 |
| 38761988 | 2024 | Decreased expression of KLF6 in ectopic endometrial stromal cells contributes to endometriosis progression by targeting CTNNB1. | 0 |
| 38064851 | 2024 | Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer. | 1 |
| 38159857 | 2024 | KLF6 activates Sp1-mediated prolidase transcription during TGF-β(1) signaling. | 1 |
| 38516774 | 2024 | miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway. | 0 |
| 38761988 | 2024 | Decreased expression of KLF6 in ectopic endometrial stromal cells contributes to endometriosis progression by targeting CTNNB1. | 0 |
| 35761154 | 2023 | MiRNA-21-5p Accelerates EMT and Inhibits Apoptosis of Laryngeal Carcinoma via Inhibiting KLF6 Expression. | 4 |
| 37159192 | 2023 | MicroRNA-22-3p Regulates the Apoptosis of Lens Epithelial Cells Through Targeting KLF6 in Diabetic Cataracts. | 1 |
| 37263229 | 2023 | Roles of Krüppel-Like Transcription Factors KLF6 and KLF15 in Proximal Tubular Metabolism. | 0 |
| 37545272 | 2023 | MiR-191-5p inhibits KLF6 to promote epithelial-mesenchymal transition in breast cancer. | 0 |
| 37955538 | 2023 | The Krüppel-like factor 6 represses proliferation and invasion of cutaneous malignant melanoma. | 0 |
| 37975481 | 2023 | TNF-α stimulated exosome derived from fibroblast-like synoviocytes isolated from rheumatoid arthritis patients promotes HUVEC migration, invasion and angiogenesis by targeting the miR-200a-3p/KLF6/VEGFA axis. | 3 |
| 35761154 | 2023 | MiRNA-21-5p Accelerates EMT and Inhibits Apoptosis of Laryngeal Carcinoma via Inhibiting KLF6 Expression. | 4 |
Citation
Scott L. Friedman ; Goutham Narla ; John A. Martignetti
KLF6 (Krüppel like factor 6)
Atlas Genet Cytogenet Oncol Haematol. 2007-03-01
Online version: http://atlasgeneticsoncology.org/gene/44002/klf6
