KLF6 (Krüppel like factor 6)

2007-03-01   Scott L. Friedman  , Goutham Narla  , John A. Martignetti  

Division 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.

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.

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 IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 1316
MIM: 602053
HGNC: 2235
Ensembl: ENSG00000067082

Variants:

dbSNP: 1316
ClinVar: 1316
TCGA: ENSG00000067082
COSMIC: KLF6

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000067082ENST00000469435Q99612
ENSG00000067082ENST00000497571Q99612
ENSG00000067082ENST00000542957Q99612

Expression (GTEx)

0
50
100
150
200
250
300

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
380648512024Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer.1
381598572024KLF6 activates Sp1-mediated prolidase transcription during TGF-β(1) signaling.1
385167742024miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway.0
387619882024Decreased expression of KLF6 in ectopic endometrial stromal cells contributes to endometriosis progression by targeting CTNNB1.0
380648512024Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer.1
381598572024KLF6 activates Sp1-mediated prolidase transcription during TGF-β(1) signaling.1
385167742024miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway.0
387619882024Decreased expression of KLF6 in ectopic endometrial stromal cells contributes to endometriosis progression by targeting CTNNB1.0
357611542023MiRNA-21-5p Accelerates EMT and Inhibits Apoptosis of Laryngeal Carcinoma via Inhibiting KLF6 Expression.4
371591922023MicroRNA-22-3p Regulates the Apoptosis of Lens Epithelial Cells Through Targeting KLF6 in Diabetic Cataracts.1
372632292023Roles of Krüppel-Like Transcription Factors KLF6 and KLF15 in Proximal Tubular Metabolism.0
375452722023MiR-191-5p inhibits KLF6 to promote epithelial-mesenchymal transition in breast cancer.0
379555382023The Krüppel-like factor 6 represses proliferation and invasion of cutaneous malignant melanoma.0
379754812023TNF-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
357611542023MiRNA-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/cancer-prone-explorer/favicon/js/lib/jquery-3.5.1.min.js