O43474 (KLF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 124.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Krueppel-like factor 4 Alternative name(s): Epithelial zinc finger protein EZF Gut-enriched krueppel-like factor | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 513 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription. Ref.9 Ref.14 |
| Subunit structure | Interacts with POU5F1/OCT4 and SOX2 By similarity. Interacts with MUC1 (via the C-terminal domain). Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a. Ref.9 Ref.16 |
| Subcellular location | |
| Domain | the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. Ref.11 |
| Biotechnological use | POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Ref.10 |
| Sequence similarities | Belongs to the krueppel C2H2-type zinc-finger protein family. Contains 3 C2H2-type zinc fingers. |
| Sequence caution | The sequence AAB48399.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAC03462.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAD42165.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH29923.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH30811.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence ABG25917.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAG36271.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence EAW59020.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence EAW59021.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O43474-3) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: O43474-1) The sequence of this isoform differs from the canonical sequence as follows: 367-400: Missing. | ||||||
| Isoform 3 (identifier: O43474-4) The sequence of this isoform differs from the canonical sequence as follows: 1-50: Missing. 367-400: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 513 | 513 | Krueppel-like factor 4 | PRO_0000047167 | |||||
Regions | |||||||||
| Zinc finger | 430 – 454 | 25 | C2H2-type 1 | ||||||
| Zinc finger | 460 – 484 | 25 | C2H2-type 2 | ||||||
| Zinc finger | 490 – 512 | 23 | C2H2-type 3 | ||||||
| Region | 473 – 504 | 32 | Interaction with target DNA By similarity | ||||||
| Motif | 101 – 109 | 9 | 9aaTAD | ||||||
| Compositional bias | 125 – 149 | 25 | Ser-rich | ||||||
| Compositional bias | 179 – 415 | 237 | Pro-rich | ||||||
Amino acid modifications | |||||||||
| Modified residue | 254 | 1 | Phosphoserine Ref.15 | ||||||
| Cross-link | 32 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.13 | |||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 50 | 50 | Missing in isoform 3. | VSP_040569 | |||||
| Alternative sequence | 367 – 400 | 34 | Missing in isoform 2 and isoform 3. | VSP_036399 | |||||
| Natural variant | 315 | 1 | T → S. Ref.3 Corresponds to variant rs1059913 [ dbSNP | Ensembl ]. | VAR_059888 | |||||
| Natural variant | 321 | 1 | L → F. Ref.3 Corresponds to variant rs1059914 [ dbSNP | Ensembl ]. | VAR_059889 | |||||
Experimental info | |||||||||
| Sequence conflict | 60 – 61 | 2 | GR → AG in AAC03462. Ref.1 | ||||||
| Sequence conflict | 77 | 1 | G → A in AAC03462. Ref.1 | ||||||
| Sequence conflict | 251 | 1 | S → T in AAC03462. Ref.1 | ||||||
| Sequence conflict | 304 | 1 | D → N in AAB48399. Ref.3 | ||||||
| Sequence conflict | 329 | 1 | D → E in AAB48399. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human EZF, a Kruppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains." Yet S.-F., McA'Nulty M.M., Folta S.C., Yen H.-W., Yoshizumi M., Hsieh C.-M., Layne M.D., Chin M.T., Wang H., Perrella M.A., Jain M.K., Lee M.-E. J. Biol. Chem. 273:1026-1031(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). |
| [2] | "Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells: transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF." Foster K.W., Ren S., Louro I.D., Lobo-Ruppert S.M., McKie-Bell P., Grizzle W., Hayes M.R., Broker T.R., Chow L.T., Ruppert J.M. Cell Growth Differ. 10:423-434(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). |
| [3] | Garrett-Sinha L.A., de Crombrugghe B. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS SER-315 AND PHE-321. Tissue: Placenta. |
| [4] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Substantia nigra and Tongue. |
| [5] | SeattleSNPs variation discovery resource Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [6] | "DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I.Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Cervix and Lung. |
| [9] | "Human mucin 1 oncoprotein represses transcription of the p53 tumor suppressor gene." Wei X., Xu H., Kufe D. Cancer Res. 67:1853-1858(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MUC1, FUNCTION. |
| [10] | "Induction of pluripotent stem cells from adult human fibroblasts by defined factors." Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., Yamanaka S. Cell 131:861-872(2007) [PubMed] [Europe PMC] [Abstract] Cited for: BIOTECHNOLOGY. |
| [11] | "Nine-amino-acid transactivation domain: establishment and prediction utilities." Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M. Genomics 89:756-768(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN. |
| [12] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| [13] | "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells." Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X. Proteomics 8:2885-2896(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-32, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [14] | "Kruppel-like factor 4 (Klf4) prevents embryonic stem (ES) cell differentiation by regulating Nanog gene expression." Zhang P., Andrianakos R., Yang Y., Liu C., Lu W. J. Biol. Chem. 285:9180-9189(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [15] | "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [16] | "Cooperative transcriptional activation by Klf4, Meis2, and Pbx1." Bjerke G.A., Hyman-Walsh C., Wotton D. Mol. Cell. Biol. 31:3723-3733(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PBX1 AND MEIS2. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF022184 mRNA. Translation: AAC03462.1. Different initiation. AF105036 mRNA. Translation: AAD42165.1. Different initiation. U70663 mRNA. Translation: AAB48399.1. Different initiation. AK095134 mRNA. Translation: BAG52991.1. AK313489 mRNA. Translation: BAG36271.1. Different initiation. DQ658241 Genomic DNA. Translation: ABG25917.1. Sequence problems. AL360218 Genomic DNA. Translation: CAI12254.2. CH471105 Genomic DNA. Translation: EAW59020.1. Sequence problems. CH471105 Genomic DNA. Translation: EAW59021.1. Sequence problems. BC029923 mRNA. Translation: AAH29923.1. Different initiation. BC030811 mRNA. Translation: AAH30811.1. Different initiation. |
| IPI | IPI00012531. IPI00167069. IPI00643479. |
| RefSeq | NP_004226.3. NM_004235.4. |
| UniGene | Hs.376206. |
3D structure databases | |
| ProteinModelPortal | O43474. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-57667N. |
| MINT | MINT-7261942. |
| STRING | 9606.ENSP00000363804. |
PTM databases | |
| PhosphoSite | O43474. |
Proteomic databases | |
| PaxDb | O43474. |
| PRIDE | O43474. |
Protocols and materials databases | |
| DNASU | 9314. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000374672; ENSP00000363804; ENSG00000136826. |
| GeneID | 9314. |
| KEGG | hsa:9314. |
| UCSC | uc004bdf.2. human. uc004bdg.3. human. uc004bdh.3. human. |
Organism-specific databases | |
| CTD | 9314. |
| GeneCards | GC09M110247. |
| HGNC | HGNC:6348. KLF4. |
| HPA | HPA002926. |
| MIM | 602253. gene. |
| neXtProt | NX_O43474. |
| PharmGKB | PA30138. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG5048. |
| HOVERGEN | HBG006220. |
| KO | K09204. |
| OMA | CTVGRPL. |
Gene expression databases | |
| ArrayExpress | O43474. |
| Bgee | O43474. |
| CleanEx | HS_KLF4. |
| Genevestigator | O43474. |
| GermOnline | ENSG00000136826. Homo sapiens. |
Family and domain databases | |
| Gene3D | 3.30.160.60. 3 hits. |
| InterPro | IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view] |
| SMART | SM00355. ZnF_C2H2. 3 hits. [Graphical view] |
| PROSITE | PS00028. ZINC_FINGER_C2H2_1. 3 hits. PS50157. ZINC_FINGER_C2H2_2. 3 hits. [Graphical view] |
| ProtoNet | Search... |
Other | |
| GenomeRNAi | 9314. |
| NextBio | 34891. |
| SOURCE | Search... |
Entry information
| Entry name | KLF4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O43474 Secondary accession number(s): B2R8S4 Q9UNP3 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
