ID   KLF11_HUMAN             Reviewed;         512 AA.
AC   O14901; Q9EPF4;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 2.
DT   03-NOV-2009, entry version 96.
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], AND CHARACTERIZATION.
RC   TISSUE=Pancreas;
RX   MEDLINE=98421516; 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], FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Erythroid cell;
RX   MEDLINE=99223585; 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].
RC   TISSUE=Hepatoma;
RX   MEDLINE=20541714; 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].
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   [5]
RP   VARIANTS MODY7 MET-220 AND SER-347, VARIANT ARG-62, CHARACTERIZATION
RP   OF VARIANTS MODY7 MET-220 AND SER-347, AND CHARACTERIZATION OF VARIANT
RP   ARG-62.
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. Activates the epsilon- and gamma-
CC       globin gene promoters and, to a much lower degree, the beta-globin
CC       gene and represses promoters containing SP1-like binding
CC       inhibiting cell growth. Represses transcription of SMAD7 which
CC       enhances TGF-beta signaling. Induces apoptosis.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Higher expression in erythroid
CC       cells.
CC   -!- INDUCTION: By TGF-beta.
CC   -!- DISEASE: Defects in KLF11 are the cause of maturity-onset diabetes
CC       of the young type 7 (MODY7) [MIM:610508]. MODY [MIM:606391] has an
CC       autosomal dominant inheritance, onset at age less than 25 years
CC       and a primary defect in insulin secretion. MODY pedigrees are
CC       usually multigenerational families with penetrance of 80 to 95%.
CC       Patients have a nonobese body habitus and the so-called metabolic
CC       syndrome characterized by diabetes, insulin resistance,
CC       hypertension, and hypertriglyceridemia is absent.
CC   -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein
CC       family.
CC   -!- SIMILARITY: Contains 3 C2H2-type zinc fingers.
CC   -!- CAUTION: PubMed:11087666 sequence was originally thought to
CC       originate from mouse.
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DR   EMBL; AF028008; AAC61880.1; -; mRNA.
DR   EMBL; AF272830; AAF75793.1; -; mRNA.
DR   EMBL; BC063286; AAH63286.1; -; mRNA.
DR   EMBL; BC069383; AAH69383.1; -; mRNA.
DR   EMBL; BC074922; AAH74922.1; -; mRNA.
DR   IPI; IPI00024692; -.
DR   RefSeq; NP_003588.1; -.
DR   UniGene; Hs.12229; -.
DR   UniGene; Hs.694968; -.
DR   PDB; 1PO4; Model; -; A=40-52.
DR   PDBsum; 1PO4; -.
DR   IntAct; O14901; 1.
DR   STRING; O14901; -.
DR   PhosphoSite; O14901; -.
DR   PRIDE; O14901; -.
DR   Ensembl; ENST00000305883; ENSP00000307023; ENSG00000172059; Homo sapiens.
DR   Ensembl; ENST00000401510; ENSP00000386058; ENSG00000172059; Homo sapiens.
DR   Ensembl; ENST00000440320; ENSP00000388263; ENSG00000172059; Homo sapiens.
DR   Ensembl; ENST00000448523; ENSP00000387866; ENSG00000172059; Homo sapiens.
DR   GeneID; 8462; -.
DR   KEGG; hsa:8462; -.
DR   UCSC; uc002raf.1; human.
DR   CTD; 8462; -.
DR   GeneCards; GC02P010100; -.
DR   H-InvDB; HIX0001814; -.
DR   HGNC; HGNC:11811; KLF11.
DR   MIM; 603301; gene.
DR   MIM; 606391; phenotype.
DR   MIM; 610508; phenotype.
DR   Orphanet; 552; MODY syndrome.
DR   PharmGKB; PA36518; -.
DR   HOGENOM; O14901; -.
DR   HOVERGEN; O14901; -.
DR   OMA; CSPKNYE; -.
DR   NextBio; 31670; -.
DR   ArrayExpress; O14901; -.
DR   Bgee; O14901; -.
DR   CleanEx; HS_KLF11; -.
DR   Genevestigator; O14901; -.
DR   GermOnline; ENSG00000172059; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR   GO; GO:0003700; F:transcription factor activity; TAS:ProtInc.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006915; P:apoptosis; IEA:UniProtKB-KW.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR   GO; GO:0000122; P:negative regulation of transcription from R...; TAS:ProtInc.
DR   GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR   InterPro; IPR007087; Znf_C2H2.
DR   InterPro; IPR015880; Znf_C2H2-like.
DR   InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR   Gene3D; G3DSA:3.30.160.60; Znf_C2H2/integrase_DNA-bd; 3.
DR   Pfam; PF00096; zf-C2H2; 3.
DR   ProDom; PD000003; Znf_C2H2; 2.
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; Apoptosis; Complete proteome;
KW   Diabetes mellitus; Disease mutation; DNA-binding; Metal-binding;
KW   Nucleus; Polymorphism; Repeat; Repressor; Transcription;
KW   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.
FT   ZN_FING     424    448       C2H2-type 2.
FT   ZN_FING     454    476       C2H2-type 3.
FT   VARIANT      62     62       Q -> R (high frequency in individuals
FT                                with diabetes mellitus type 2; increased
FT                                repression activity; increased binding to
FT                                mSin3A; impairs activation of insulin
FT                                promoter; dbSNP:rs35927125).
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 mSin3A;
FT                                dbSNP:rs34336420).
FT                                /FTId=VAR_031523.
FT   VARIANT     347    347       A -> S (in MODY7; increased repression
FT                                activity; no alteration in binding
FT                                affinity to mSin3A).
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).
FT   CONFLICT    144    150       VVARALS -> QWPDSD (in Ref. 3).
FT   CONFLICT    371    371       P -> L (in Ref. 3).
FT   CONFLICT    415    415       L -> V (in Ref. 3).
FT   HELIX        43     49
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
//