ID KLF11_HUMAN Reviewed; 512 AA. AC O14901; B4DZE7; Q9EPF4; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 2. DT 11-NOV-2015, entry version 152. DE RecName: Full=Krueppel-like factor 11; DE AltName: Full=Transforming growth factor-beta-inducible early growth response protein 2; DE Short=TGFB-inducible early growth response protein 2; DE Short=TIEG-2; GN Name=KLF11; Synonyms=FKLF, TIEG2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR RP LOCATION, AND INDUCTION. RC TISSUE=Pancreas; RX PubMed=9748269; DOI=10.1074/jbc.273.40.25929; RA Cook T., Gebelein B., Mesa K., Mladek A., Urrutia R.; RT "Molecular cloning and characterization of TIEG2 reveals a new RT subfamily of transforming growth factor-beta-inducible Sp1-like zinc RT finger-encoding genes involved in the regulation of cell growth."; RL J. Biol. Chem. 273:25929-25936(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Erythroid cell; RX PubMed=10207080; RA Asano H., Li X.S., Stamatoyannopoulos G.; RT "FKLF, a novel Kruppel-like factor that activates human embryonic and RT fetal beta-like globin genes."; RL Mol. Cell. Biol. 19:3571-3579(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hepatoma; RX PubMed=11087666; DOI=10.1006/geno.2000.6362; RA Scohy S., Gabant P., Van Reeth T., Hertveldt V., Dreze P.-L., RA Van Vooren P., Riviere M., Szpirer J., Szpirer C.; RT "Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF RT transcription factor family."; RL Genomics 70:93-101(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION. RX PubMed=16131492; DOI=10.1074/jbc.M504402200; RA Blau C.A., Barbas C.F., Bomhoff A.L., Neades R., Yan J., Navas P.A., RA Peterson K.R.; RT "{gamma}-Globin gene expression in chemical inducer of dimerization RT (CID)-dependent multipotential cells established from human {beta}- RT globin locus yeast artificial chromosome ({beta}-YAC) transgenic RT mice."; RL J. Biol. Chem. 280:36642-36647(2005). RN [9] RP VARIANTS MODY7 MET-220 AND SER-347, VARIANT ARG-62, CHARACTERIZATION RP OF VARIANTS MODY7 MET-220 AND SER-347, CHARACTERIZATION OF VARIANT RP ARG-62, AND INTERACTION WITH SIN3A. RX PubMed=15774581; DOI=10.1073/pnas.0409177102; RA Neve B., Fernandez-Zapico M.E., Ashkenazi-Katalan V., Dina C., RA Hamid Y.H., Joly E., Vaillant E., Benmezroua Y., Durand E., RA Bakaher N., Delannoy V., Vaxillaire M., Cook T., Dallinga-Thie G.M., RA Jansen H., Charles M.-A., Clement K., Galan P., Hercberg S., RA Helbecque N., Charpentier G., Prentki M., Hansen T., Pedersen O., RA Urrutia R., Melloul D., Froguel P.; RT "Role of transcription factor KLF11 and its diabetes-associated gene RT variants in pancreatic beta cell function."; RL Proc. Natl. Acad. Sci. U.S.A. 102:4807-4812(2005). CC -!- FUNCTION: Transcription factor (PubMed:9748269, PubMed:10207080). CC Activates the epsilon- and gamma-globin gene promoters and, to a CC much lower degree, the beta-globin gene and represses promoters CC containing SP1-like binding inhibiting cell growth CC (PubMed:9748269, PubMed:10207080, PubMed:16131492). Represses CC transcription of SMAD7 which enhances TGF-beta signaling (By CC similarity). Induces apoptosis (By similarity). CC {ECO:0000250|UniProtKB:Q8K1S5, ECO:0000269|PubMed:10207080, CC ECO:0000269|PubMed:16131492}. CC -!- SUBUNIT: Interacts with SIN3A. {ECO:0000269|PubMed:15774581}. CC -!- INTERACTION: CC Q92624:APPBP2; NbExp=3; IntAct=EBI-948266, EBI-743771; CC O14530:TXNDC9; NbExp=3; IntAct=EBI-948266, EBI-707554; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9748269}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O14901-1; Sequence=Displayed; CC Name=2; CC IsoId=O14901-2; Sequence=VSP_042695; CC -!- TISSUE SPECIFICITY: Ubiquitous. Higher expression in erythroid CC cells. {ECO:0000269|PubMed:10207080}. CC -!- INDUCTION: By TGFB1. {ECO:0000269|PubMed:9748269}. CC -!- DISEASE: Maturity-onset diabetes of the young 7 (MODY7) CC [MIM:610508]: A form of diabetes that is characterized by an CC autosomal dominant mode of inheritance, onset in childhood or CC early adulthood (usually before 25 years of age), a primary defect CC in insulin secretion and frequent insulin-independence at the CC beginning of the disease. {ECO:0000269|PubMed:15774581}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 3 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- CAUTION: PubMed:11087666 sequence was originally thought to CC originate from mouse. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF028008; AAC61880.1; -; mRNA. DR EMBL; AF272830; AAF75793.1; -; mRNA. DR EMBL; AK302880; BAG64059.1; -; mRNA. DR EMBL; AC104794; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471053; EAX00972.1; -; Genomic_DNA. DR EMBL; BC063286; AAH63286.1; -; mRNA. DR EMBL; BC069383; AAH69383.1; -; mRNA. DR EMBL; BC074922; AAH74922.1; -; mRNA. DR CCDS; CCDS1668.1; -. [O14901-1] DR CCDS; CCDS54333.1; -. [O14901-2] DR RefSeq; NP_001171187.1; NM_001177716.1. [O14901-2] DR RefSeq; NP_001171189.1; NM_001177718.1. [O14901-2] DR RefSeq; NP_003588.1; NM_003597.4. [O14901-1] DR RefSeq; XP_005246236.1; XM_005246179.3. [O14901-2] DR UniGene; Hs.12229; -. DR PDB; 1PO4; Model; -; A=40-52. DR PDBsum; 1PO4; -. DR ProteinModelPortal; O14901; -. DR SMR; O14901; 378-476. DR BioGrid; 114040; 16. DR IntAct; O14901; 10. DR MINT; MINT-2795353; -. DR STRING; 9606.ENSP00000307023; -. DR PhosphoSite; O14901; -. DR BioMuta; KLF11; -. DR MaxQB; O14901; -. DR PaxDb; O14901; -. DR PRIDE; O14901; -. DR Ensembl; ENST00000305883; ENSP00000307023; ENSG00000172059. [O14901-1] DR Ensembl; ENST00000535335; ENSP00000442722; ENSG00000172059. [O14901-2] DR Ensembl; ENST00000540845; ENSP00000444690; ENSG00000172059. [O14901-2] DR GeneID; 8462; -. DR KEGG; hsa:8462; -. DR UCSC; uc002raf.1; human. [O14901-1] DR CTD; 8462; -. DR GeneCards; KLF11; -. DR HGNC; HGNC:11811; KLF11. DR MIM; 603301; gene. DR MIM; 606391; phenotype. DR MIM; 610508; phenotype. DR neXtProt; NX_O14901; -. DR Orphanet; 552; MODY. DR PharmGKB; PA36518; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00760000118984; -. DR HOGENOM; HOG000059558; -. DR HOVERGEN; HBG052264; -. DR InParanoid; O14901; -. DR KO; K09209; -. DR OMA; SCQPCLH; -. DR PhylomeDB; O14901; -. DR TreeFam; TF315506; -. DR SignaLink; O14901; -. DR ChiTaRS; KLF11; human. DR GeneWiki; KLF11; -. DR GenomeRNAi; 8462; -. DR NextBio; 31670; -. DR PRO; PR:O14901; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; O14901; -. DR CleanEx; HS_KLF11; -. DR ExpressionAtlas; O14901; baseline and differential. DR Genevisible; O14901; HS. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:BHF-UCL. DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc. DR Gene3D; 3.30.160.60; -; 3. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00096; zf-C2H2; 1. DR SMART; SM00355; ZnF_C2H2; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Apoptosis; KW Complete proteome; Diabetes mellitus; Disease mutation; DNA-binding; KW Metal-binding; Nucleus; Polymorphism; Reference proteome; Repeat; KW Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 512 Krueppel-like factor 11. FT /FTId=PRO_0000047180. FT ZN_FING 394 418 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 424 448 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 454 476 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT VAR_SEQ 1 17 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_042695. FT VARIANT 62 62 Q -> R (high frequency in individuals FT with diabetes mellitus type 2; increased FT repression activity; increased binding to FT SIN3A; impairs activation of insulin FT promoter; dbSNP:rs35927125). FT {ECO:0000269|PubMed:15774581}. FT /FTId=VAR_031522. FT VARIANT 220 220 T -> M (in MODY7; absent in one family FT member with diabetes; increased FT repression activity; no alteration in FT binding affinity to SIN3A; FT dbSNP:rs34336420). FT {ECO:0000269|PubMed:15774581}. FT /FTId=VAR_031523. FT VARIANT 347 347 A -> S (in MODY7; increased repression FT activity; no alteration in binding FT affinity to SIN3A). FT {ECO:0000269|PubMed:15774581}. FT /FTId=VAR_031524. FT VARIANT 378 378 S -> F (in dbSNP:rs35476458). FT /FTId=VAR_052717. FT CONFLICT 125 125 P -> S (in Ref. 3). {ECO:0000305}. FT CONFLICT 144 150 VVARALS -> QWPDSD (in Ref. 3). FT {ECO:0000305}. FT CONFLICT 371 371 P -> L (in Ref. 3). {ECO:0000305}. FT CONFLICT 415 415 L -> V (in Ref. 3). {ECO:0000305}. SQ SEQUENCE 512 AA; 55139 MW; A69863B5467FB068 CRC64; MHTPDFAGPD DARAVDIMDI CESILERKRH DSERSTCSIL EQTDMEAVEA LVCMSSWGQR SQKGDLLRIR PLTPVSDSGD VTTTVHMDAA TPELPKDFHS LSTLCITPPQ SPDLVEPSTR TPVSPQVTDS KACTATDVLQ SSAVVARALS GGAERGLLGL EPVPSSPCRA KGTSVIRHTG ESPAACFPTI QTPDCRLSDS REGEEQLLGH FETLQDTHLT DSLLSTNLVS CQPCLHKSGG LLLTDKGQQA GWPGAVQTCS PKNYENDLPR KTTPLISVSV PAPPVLCQMI PVTGQSSMLP AFLKPPPQLS VGTVRPILAQ AAPAPQPVFV GPAVPQGAVM LVLPQGALPP PAPCAANVMA AGNTKLLPLA PAPVFITSSQ NCVPQVDFSR RRNYVCSFPG CRKTYFKSSH LKAHLRTHTG EKPFNCSWDG CDKKFARSDE LSRHRRTHTG EKKFVCPVCD RRFMRSDHLT KHARRHMTTK KIPGWQAEVG KLNRIASAES PGSPLVSMPA SA //