Q99612 (KLF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Krueppel-like factor 6

Alternative name(s):
B-cell-derived protein 1
Core promoter element-binding protein
GC-rich sites-binding factor GBF
Proto-oncogene BCD1
Suppressor of tumorigenicity 12 protein
Transcription factor Zf9

Gene names

Name:	KLF6
Synonyms:	BCD1, COPEB, CPBP, ST12

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	283 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator By similarity. Binds a GC box motif. Could play a role in B-cell growth and development.
Subcellular location	Nucleus.
Tissue specificity	Highly expressed in placenta followed by spleen, thymus, prostate, testis, small intestine and colon. Weakly expressed in pancreas, lung, liver, heart and skeletal muscle. Also expressed in fetal brain, spleen and thymus.
Domain	The acidic N-terminal part may favor interaction with the basic domain of transcription factors.
Involvement in disease	Defects in KLF6 are a cause of gastric cancer (GASC) [MIM:613659]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Ref.12 Defects in KLF6 are a cause of prostate cancer (PC) [MIM:176807]. Prostate cancer is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Ref.11
Sequence similarities	Belongs to the krueppel C2H2-type zinc-finger protein family. Contains 3 C2H2-type zinc fingers.
Sequence caution	The sequence AAC23699.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAA33050.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	B cell differentiation Non-traceable author statement Ref.1. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Traceable author statement Ref.3. Source: UniProtKB
Molecular function	zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99612-1)

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: Q99612-2)

The sequence of this isoform differs from the canonical sequence as follows:
     227-283: EKPYRCSWEG...HLALHMKRHL → QCPRGPRRAA...QSIRSFWSSE

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 283	283	Krueppel-like factor 6		PRO_0000047171
Regions
	Zinc finger	200 – 224	25	C2H2-type 1
	Zinc finger	230 – 254	25	C2H2-type 2
	Zinc finger	260 – 282	23	C2H2-type 3
Natural variations
	Alternative sequence	227 – 283	57	EKPYR…MKRHL → QCPRGPRRAAAGGRHCIAPA LEGAGPGCTGCGQGRQILTS SDVFHQSIRSFWSSE in isoform 2.		VSP_015715
	Natural variant	64	1	W → R Found in prostate cancer samples; somatic mutation; does not up-regulates CDKN1A in a p53-independent manner and significantly reduces cell proliferation. Ref.11		VAR_065136
	Natural variant	116	1	S → P Found in prostate cancer samples; somatic mutation; does not up-regulates CDKN1A in a p53-independent manner and significantly reduces cell proliferation. Ref.11		VAR_065137
	Natural variant	123	1	A → D Found in prostate cancer samples; somatic mutation; does not up-regulates CDKN1A in a p53-independent manner and significantly reduces cell proliferation. Ref.11		VAR_065138
	Natural variant	155	1	S → R Found in gastric cancer samples; somatic mutation. Ref.12		VAR_065139
	Natural variant	169	1	L → P Found in prostate cancer samples; somatic mutation; does not up-regulates CDKN1A in a p53-independent manner and significantly reduces cell proliferation. Ref.11		VAR_065140
	Natural variant	172	1	P → T Found in gastric cancer samples; somatic mutation. Ref.12		VAR_065141
	Natural variant	180	1	S → L Found in gastric cancer samples; somatic mutation. Ref.12		VAR_065142
	Natural variant	198	1	R → K Found in gastric cancer samples; somatic mutation. Ref.12		VAR_065143
Experimental info
	Sequence conflict	276	1	A → G in AAC39929. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2000. Version 3. Checksum: 84294A7E6D0A0231	FASTA	283	31,865
	10 20 30 40 50 60 MDVLPMCSIF QELQIVHETG YFSALPSLEE YWQQTCLELE RYLQSEPCYV SASEIKFDSQ 70 80 90 100 110 120 EDLWTKIILA REKKEESELK ISSSPPEDTL ISPSFCYNLE TNSLNSDVSS ESSDSSEELS 130 140 150 160 170 180 PTAKFTSDPI GEVLVSSGKL SSSVTSTPPS SPELSREPSQ LWGCVPGELP SPGKVRSGTS 190 200 210 220 230 240 GKPGDKGNGD ASPDGRRRVH RCHFNGCRKV YTKSSHLKAH QRTHTGEKPY RCSWEGCEWR 250 260 270 280 FARSDELTRH FRKHTGAKPF KCSHCDRCFS RSDHLALHMK RHL
	Isoform 2 [UniParc]. Checksum: 99ECF169C9933D03	FASTA	281	30,615
	10 20 30 40 50 60 MDVLPMCSIF QELQIVHETG YFSALPSLEE YWQQTCLELE RYLQSEPCYV SASEIKFDSQ 70 80 90 100 110 120 EDLWTKIILA REKKEESELK ISSSPPEDTL ISPSFCYNLE TNSLNSDVSS ESSDSSEELS 130 140 150 160 170 180 PTAKFTSDPI GEVLVSSGKL SSSVTSTPPS SPELSREPSQ LWGCVPGELP SPGKVRSGTS 190 200 210 220 230 240 GKPGDKGNGD ASPDGRRRVH RCHFNGCRKV YTKSSHLKAH QRTHTGQCPR GPRRAAAGGR 250 260 270 280 HCIAPALEGA GPGCTGCGQG RQILTSSDVF HQSIRSFWSS E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of Bcd, a novel proto-oncogene expressed in B-cells." El Rouby S., Newcomb E.W. Oncogene 13:2623-2630(1996) [PubMed: 9000136] [Abstract] Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE (ISOFORM 1).
[2]	"A novel human zinc finger protein that interacts with the core promoter element of a TATA box-less gene." Koritschoner N.P., Bocco J.L., Panzetta-Dutari G.M., Dumur C.I., Flury A., Patrito L.C. J. Biol. Chem. 272:9573-9580(1997) [PubMed: 9083102] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[3]	"Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis." Ratziu V., Lalazar A., Wong L., Dang Q., Collins C., Shaulian E., Jensen S., Friedman S.L. Proc. Natl. Acad. Sci. U.S.A. 95:9500-9505(1998) [PubMed: 9689109] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Hepatic stellate cell.
[4]	"Isolation and initial characterization of GBF, a novel DNA-binding zinc finger protein that binds to the GC-rich binding sites of the HIV-1 promoter." Suzuki T., Yamamoto T., Kurabayashi M., Nagai R., Yazaki Y., Horikoshi M. J. Biochem. 124:389-395(1998) [PubMed: 9685731] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. Tissue: Leukocyte.
[5]	"Genomic organization of the human COPEB/CPBP locus." Koritschoner N.P. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"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] (ISOFORMS 1 AND 2). Tissue: Brain.
[8]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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] (ISOFORM 1). Tissue: Lung.
[11]	"KLF6, a candidate tumor suppressor gene mutated in prostate cancer." Narla G., Heath K.E., Reeves H.L., Li D., Giono L.E., Kimmelman A.C., Glucksman M.J., Narla J., Eng F.J., Chan A.M., Ferrari A.C., Martignetti J.A., Friedman S.L. Science 294:2563-2566(2001) [PubMed: 11752579] [Abstract] Cited for: INVOLVEMENT IN PC, VARIANTS ARG-64; PRO-116; ASP-123 AND PRO-169, CHARACTERIZATION OF VARIANTS ARG-64; PRO-116; ASP-123 AND PRO-169.
[12]	"Genetic alterations of the KLF6 gene in gastric cancer." Cho Y.G., Kim C.J., Park C.H., Yang Y.M., Kim S.Y., Nam S.W., Lee S.H., Yoo N.J., Lee J.Y., Park W.S. Oncogene 24:4588-4590(2005) [PubMed: 15824733] [Abstract] Cited for: INVOLVEMENT IN GASC, VARIANTS ARG-155; THR-172; LEU-180 AND LYS-198.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U44975 mRNA. Translation: AAC23699.1. Different initiation. AF001461 mRNA. Translation: AAC39929.1. AB017493 mRNA. Translation: BAA33050.1. Different initiation. AF284036 Genomic DNA. Translation: AAM73548.1. BT006778 mRNA. Translation: AAP35424.1. AL513303, AL450322 Genomic DNA. Translation: CAH74049.1. AK293259 mRNA. Translation: BAG56791.1. AK316596 mRNA. Translation: BAG38183.1. AL513303, AL450322 Genomic DNA. Translation: CAH74050.1. AL450322, AL513303 Genomic DNA. Translation: CAH71010.1. AL450322, AL513303 Genomic DNA. Translation: CAH71011.1. CH471072 Genomic DNA. Translation: EAW86477.1. CH471072 Genomic DNA. Translation: EAW86479.1. BC000311 mRNA. Translation: AAH00311.1.
IPI	IPI00293523. IPI00478435.
PIR	JE0235.
RefSeq	NP_001153596.1. NM_001160124.1. NP_001153597.1. NM_001160125.1. NP_001291.3. NM_001300.5.
UniGene	Hs.4055. Hs.709396.
3D structure databases
ProteinModelPortal	Q99612.
SMR	Q99612. Positions 200-283.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99612. 8 interactions.
MINT	MINT-250061.
STRING	Q99612.
PTM databases
PhosphoSite	Q99612.
Polymorphism databases
DMDM	7387592.
Proteomic databases
PRIDE	Q99612.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000497571; ENSP00000419923; ENSG00000067082.
GeneID	1316.
KEGG	hsa:1316.
UCSC	uc001iha.1. human. uc001ihb.1. human.
Organism-specific databases
CTD	1316.
GeneCards	GC10M003812.
H-InvDB	HIX0008600.
HGNC	HGNC:2235. KLF6.
HPA	CAB013529.
MIM	176807. phenotype. 602053. gene. 613659. phenotype.
neXtProt	NX_Q99612.
PharmGKB	PA26751.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15274.
GeneTree	ENSGT00590000082798.
HOGENOM	HBG403112.
HOVERGEN	HBG000836.
InParanoid	Q99612.
OMA	SHLWGCV.
OrthoDB	EOG49079R.
PhylomeDB	Q99612.
Gene expression databases
ArrayExpress	Q99612.
Bgee	Q99612.
CleanEx	HS_KLF6.
Genevestigator	Q99612.
GermOnline	ENSG00000067082. 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. 3 hits.
KO	K09207.
Pfam	PF00096. zf-C2H2. 3 hits. [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
NextBio	5383.
SOURCE	Search...

Entry information

Entry name

KLF6_HUMAN

Accession

Primary (citable) accession number: Q99612
Secondary accession number(s): B2RE86 , B4DDN0, D3DRR1, Q5VUT7, Q5VUT8, Q9BT79

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 30, 2000
Last modified:	December 14, 2011
This is version 122 of the entry and version 3 of the sequence. [Complete history]

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.