KLF4
Krueppel-like factor 4
Also known as: EZF, GKLF, KLF4_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O43474
- Gene
- KLF4
- Ensembl
- ENSG00000136826
- Chromosome
- 9
- Canonical length
- 513 aa
- Protein class
- Cancer-related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Cytosol
OverviewNCBI Gene
This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is required for normal development of the barrier function of skin. The encoded protein is thought to control the G1-to-S transition of the cell cycle following DNA damage by mediating the tumor suppressor gene p53. Mice lacking this gene have a normal appearance but lose weight rapidly, and die shortly after birth due to fluid evaporation resulting from compromised epidermal barrier function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]
Canonical amino-acid sequenceUniProt
513 residues, UniProt reviewed canonical sequence.
>O43474|KLF4
1 MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRQAGAP NNRWREELSH MKRLPPVLPG
61 RPYDLAAATV ATDLESGGAG AACGGSNLAP LPRRETEEFN DLLDLDFILS NSLTHPPESV
121 AATVSSSASA SSSSSPSSSG PASAPSTCSF TYPIRAGNDP GVAPGGTGGG LLYGRESAPP
181 PTAPFNLADI NDVSPSGGFV AELLRPELDP VYIPPQQPQP PGGGLMGKFV LKASLSAPGS
241 EYGSPSVISV SKGSPDGSHP VVVAPYNGGP PRTCPKIKQE AVSSCTHLGA GPPLSNGHRP
301 AAHDFPLGRQ LPSRTTPTLG LEEVLSSRDC HPALPLPPGF HPHPGPNYPS FLPDQMQPQV
361 PPLHYQGQSR GFVARAGEPC VCWPHFGTHG MMLTPPSSPL ELMPPGSCMP EEPKPKRGRR
421 SWPRKRTATH TCDYAGCGKT YTKSSHLKAH LRTHTGEKPY HCDWDGCGWK FARSDELTRH
481 YRKHTGHRPF QCQKCDRAFS RSDHLALHMK RHFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against KLF4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.65
- Highest tissue expression
- 186 nTPM
Expression across tissuesHPA
Tissue
- skin: 186 nTPM
- esophagus: 96 nTPM
- rectum: 90 nTPM
- colon: 82 nTPM
- adipose tissue: 69 nTPM
- breast: 60 nTPM
Single-cell type
- goblet cells: 917 nCPM
- colonocytes: 645 nCPM
- esophageal apical cells: 600 nCPM
- suprabasal keratinocytes: 583 nCPM
- ocular epithelial cells: 495 nCPM
- breast secretory cells: 466 nCPM
Immune cell
- intermediate monocyte: 1 nTPM
- non-classical monocyte: 1 nTPM
- classical monocyte: 0.9 nTPM
- myeloid DC: 0.5 nTPM
- neutrophil: 0.2 nTPM
- plasmacytoid DC: 0.2 nTPM
Brain region
- thalamus: 10 nTPM
- hypothalamus: 8.1 nTPM
- amygdala: 8 nTPM
- medulla oblongata: 8 nTPM
- pons: 8 nTPM
- basal ganglia: 7.3 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.17
- gnomAD pLI
- 1
- gnomAD missense Z
- 0.1
- DepMap mean gene effect
- 0
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- canonical Wnt signaling pathway
- cellular response to endothelin
- cellular response to growth factor stimulus
- cellular response to hydrogen peroxide
- cellular response to laminar fluid shear stress
- cellular response to leukemia inhibitory factor
- cellular response to retinoic acid
- defense response to tumor cell
- epidermal cell differentiation
- epidermis morphogenesis
- establishment of skin barrier
- fat cell differentiation
- mesodermal cell fate determination
- negative regulation of angiogenesis
- negative regulation of canonical NF-kappaB signal transduction
- negative regulation of cell migration involved in sprouting angiogenesis
- negative regulation of cell population proliferation
- negative regulation of chemokine (C-X-C motif) ligand 2 production
- negative regulation of DNA-templated transcription
- negative regulation of ERK1 and ERK2 cascade
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- negative regulation of G1/S transition of mitotic cell cycle
- negative regulation of gene expression
- negative regulation of heterotypic cell-cell adhesion
- negative regulation of inflammatory response
- negative regulation of interleukin-8 production
- negative regulation of muscle hyperplasia
- negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- negative regulation of response to cytokine stimulus
- negative regulation of smooth muscle cell proliferation
- negative regulation of transcription by RNA polymerase II
- positive regulation of DNA-templated transcription
- positive regulation of gene expression
- positive regulation of hemoglobin biosynthetic process
- positive regulation of miRNA transcription
- positive regulation of nitric oxide biosynthetic process
- positive regulation of protein metabolic process
- positive regulation of sprouting angiogenesis
- positive regulation of telomere maintenance
- positive regulation of transcription by RNA polymerase II
- post-embryonic camera-type eye development
- post-embryonic hemopoiesis
- regulation of axon regeneration
- regulation of blastocyst development
- regulation of cell differentiation
- regulation of transcription by RNA polymerase II
- somatic stem cell population maintenance
- stem cell population maintenance
- transcription by RNA polymerase II
- negative regulation of leukocyte adhesion to arterial endothelial cell
Molecular functions
- beta-catenin binding
- chromatin DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- histone deacetylase binding
- lncRNA binding
- phosphatidylinositol 3-kinase regulator activity
- promoter-specific chromatin binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- sequence-specific double-stranded DNA binding
- transcription cis-regulatory region binding
- transcription coregulator binding
- zinc ion binding
- RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of KLF4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads KLF4 as an antibody target. Whether an autoantibody or antibody against KLF4 could matter depends on whether native KLF4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
KLF4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label KLF4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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