Reviewed, UniProtKB/Swiss-Prot O43474 (KLF4_HUMAN)

Names 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

Name:	KLF4
Synonyms:	EZF, GKLF

Organism

Homo sapiens (Human)

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.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transcription factor which acts as both an activator and repressor. Binds the CACCC core sequence. Binds to multiple sites in the 5'-flanking region of its own gene and can activate its own transcription. 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. Ref.9
Subunit structure	Interaction with the C-terminal domain of MUC1 enhances suppression of TP53/p53 transcription.
Subcellular location	Nucleus.
Sequence similarities	Belongs to the krueppel C2H2-type zinc-finger protein family. Contains 3 C2H2-type zinc fingers.
Sequence caution	The sequence ABG25917.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI12253.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI12254.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI12255.1 differs from that shown. Reason: Erroneous gene model prediction. 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

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
Gene Ontology (GO)
Biological process	mesodermal cell fate determination Traceable author statement. Source: ProtInc negative regulation of cell proliferation Traceable author statement. Source: ProtInc negative regulation of transcription, DNA-dependent Ref.1 Inferred from expression pattern. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	transcription activator activity Ref.1 Non-traceable author statement. Source: UniProtKB transcription factor activity Ref.1 Non-traceable author statement. Source: UniProtKB transcription repressor activity Ref.1 Inferred from direct assay. Source: UniProtKB zinc ion binding Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 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.

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
	Compositional bias	125 – 149	25	Ser-rich
	Compositional bias	179 – 415	237	Pro-rich
Natural variations
	Alternative sequence	367 – 400	34	Missing in isoform 2.		VSP_036399
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	315	1	T → S in AAB48399. Ref.3
	Sequence conflict	321	1	L → F in AAB48399. Ref.3
	Sequence conflict	329	1	D → E in AAB48399. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 10, 2009. Version 3. Checksum: 3B6113A3EF333935	FASTA	513	54,671
	10 20 30 40 50 60 MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRQAGAP NNRWREELSH MKRLPPVLPG 70 80 90 100 110 120 RPYDLAAATV ATDLESGGAG AACGGSNLAP LPRRETEEFN DLLDLDFILS NSLTHPPESV 130 140 150 160 170 180 AATVSSSASA SSSSSPSSSG PASAPSTCSF TYPIRAGNDP GVAPGGTGGG LLYGRESAPP 190 200 210 220 230 240 PTAPFNLADI NDVSPSGGFV AELLRPELDP VYIPPQQPQP PGGGLMGKFV LKASLSAPGS 250 260 270 280 290 300 EYGSPSVISV SKGSPDGSHP VVVAPYNGGP PRTCPKIKQE AVSSCTHLGA GPPLSNGHRP 310 320 330 340 350 360 AAHDFPLGRQ LPSRTTPTLG LEEVLSSRDC HPALPLPPGF HPHPGPNYPS FLPDQMQPQV 370 380 390 400 410 420 PPLHYQGQSR GFVARAGEPC VCWPHFGTHG MMLTPPSSPL ELMPPGSCMP EEPKPKRGRR 430 440 450 460 470 480 SWPRKRTATH TCDYAGCGKT YTKSSHLKAH LRTHTGEKPY HCDWDGCGWK FARSDELTRH 490 500 510 YRKHTGHRPF QCQKCDRAFS RSDHLALHMK RHF
	Isoform 2. Checksum: 039095BBF3E3F78D	FASTA	479	51,076
	10 20 30 40 50 60 MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRQAGAP NNRWREELSH MKRLPPVLPG 70 80 90 100 110 120 RPYDLAAATV ATDLESGGAG AACGGSNLAP LPRRETEEFN DLLDLDFILS NSLTHPPESV 130 140 150 160 170 180 AATVSSSASA SSSSSPSSSG PASAPSTCSF TYPIRAGNDP GVAPGGTGGG LLYGRESAPP 190 200 210 220 230 240 PTAPFNLADI NDVSPSGGFV AELLRPELDP VYIPPQQPQP PGGGLMGKFV LKASLSAPGS 250 260 270 280 290 300 EYGSPSVISV SKGSPDGSHP VVVAPYNGGP PRTCPKIKQE AVSSCTHLGA GPPLSNGHRP 310 320 330 340 350 360 AAHDFPLGRQ LPSRTTPTLG LEEVLSSRDC HPALPLPPGF HPHPGPNYPS FLPDQMQPQV 370 380 390 400 410 420 PPLHYQELMP PGSCMPEEPK PKRGRRSWPR KRTATHTCDY AGCGKTYTKS SHLKAHLRTH 430 440 450 460 470 TGEKPYHCDW DGCGWKFARS DELTRHYRKH TGHRPFQCQK CDRAFSRSDH LALHMKRHF

References

	« Hide 'large scale' referencesShow '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: 9422764] [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: 10392904] [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). 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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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: 15489334] [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: 17308127] [Abstract] Cited for: INTERACTION WITH MUC1, FUNCTION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. Different initiation. AK313489 mRNA. Translation: BAG36271.1. Different initiation. DQ658241 Genomic DNA. Translation: ABG25917.1. Sequence problems. AL360218 Genomic DNA. Translation: CAI12253.1. Sequence problems. AL360218 Genomic DNA. Translation: CAI12254.1. Sequence problems. AL360218 Genomic DNA. Translation: CAI12255.1. Sequence problems. 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.
RefSeq	NP_004226.3.
UniGene	Hs.376206
3D structure databases
HSSP	HSSP built from PDB template 1SP2 based on UniProtKB P08047.
ModBase	Search...
PTM databases
PhosphoSite	O43474.
Proteomic databases
PRIDE	O43474.
Genome annotation databases
Ensembl	ENSG00000136826. Homo sapiens. [Contig view]
GeneID	9314.
KEGG	hsa:9314.
Organism-specific databases
GeneCards	GC09M109286.
H-InvDB	HIX0008262.
HGNC	HGNC:6348. KLF4.
MIM	602253. gene.
PharmGKB	PA30138.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O43474.
Gene expression databases
ArrayExpress	O43474.
Bgee	O43474.
CleanEx	HS_KLF4.
GermOnline	ENSG00000136826. Homo sapiens.
Family and domain databases
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 1 hit.
Pfam	PF00096. zf-C2H2. 3 hits. [Graphical view]
ProDom	PD000003. Znf_C2H2. 3 hits. [Graphical view] [Entries sharing at least one domain]
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 Resources
NextBio	34891.
SOURCE	Search...

Entry information

Entry name

KLF4_HUMAN

Accession

Primary (citable) accession number: O43474
Secondary accession number(s): B2R8S4 , B3KT79, P78338, Q5T3J8, Q5T3J9, Q8N717, Q9UNP3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	February 10, 2009
Last modified:	June 16, 2009
This is version 84 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)