N-terminal domain of Kruppel-like factor 4; Kruppel-like factor 4 (KLF4; also known as Krueppel-like factor 4 or gut-enriched Kruppel-like factor/GKLF) is a protein that, in humans, is encoded by the KLF4 gene. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer, gastric cancer, esophageal squamous cell carcinoma, intestinal cancer, prostate cancer, bladder cancer and lung cancer. It may act as a tumor promoter where increased KLF4 expression has been reported, such as in oral squamous cell carcinoma and in primary breast ductal carcinoma. KLF4 is one of four key factors that are essential for inducing pluripotent stem cells. KLF4 is highly expressed in non-dividing cells and its overexpression induces cell cycle arrest. KLF proteins KLF1, KLF2, KLF4, KLF5, KLF6, and KLF7 are transcriptional activators. KLF4 belongs to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF4, which is related to the N-terminal domains of KLF1 and KLF2.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253   7 ESDMAVSDALLPSFSTFASGPAGREKTLRPaGAPTNRWREELSHMKRLPPlpgrpydlaatvatdlesgGAGAACSSNNP 86
Cdd:cd21582    1 EFDMALSGTLLPSISTFASGPAVKEKALGQ-GSANNRWREELSHLKRPCP-------------------PLGGRCYDQDP 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253  87 ALLARRETEEFNDLLDLDFILSNSLTHQESVAATVTTSASASSSSSpassgpasapsTCSFSYPIRAggdpgvaASNTGG 166
Cdd:cd21582   61 PLGMRRKEEEFNDLLDYDFILSNSLLQQQQQQQQAASTSSSTSSSS-----------SSPYSYQLPS-------PQGTAT 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 167 GLLYsresappPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppgggLMGKFVLKASLTTpgSEYSSPSVIS 246
Cdd:cd21582  123 SFLY-------PIPRANLADINDVSPSGGFVAELMRPDLDPAYLQPTS-------LHGKFVVKTTMDM--GDYSQSINVS 186

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 247 VSKGSPDGShpvvvAPYSGGPPRMCPKIKQEAVPSCTVSRSLEAHLsagpqlsngHRPNTHDFPLGRQLPTRTTPTLSPE 326
Cdd:cd21582  187 KSAPMTKSS-----VAPSSSLPFMCPRIKQENPSTCTISRPMDGHL---------GGNSQHGFSQRAPLPSRTTPSGGPG 252

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 327 EL-------LNSRDCHPG------LPLPPGFHPHPGPNYPPFLPDQMQSQvpslHYQELMPPGSCLPEEPKPKRGRRSWP 393
Cdd:cd21582  253 GGnsstaesLMSRDHHPSsqvlshPPLPLPQGYHPSPGYPPFPPPPSQPQ----QYQELMSPGSCLPEEPKPKRGRRSWP 328

                 ....*..
gi 223590253 394 RKRTATH 400
Cdd:cd21582  329 RKRTATH 335

FOG: Zn-finger [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 395 KRTATHTCDYAGCGKTYTKSSHLKAHLRTHTGEKPYHCDWDGCGWKFARSDELTRHYRKHTGHRPFQCQKCdRAFSRSDH 474
Cdd:COG5048  382 KNDKKSETLSNSCIRNFKRDSNLSLHIITHLSFRPYNCKNPPCSKSFNRHYNLIPHKKIHTNHAPLLCSIL-KSFRRDLD 460

                 ....
gi 223590253 475 LALH 478
Cdd:COG5048  461 LSNH 464

N-terminal domain of Kruppel-like factor 4; Kruppel-like factor 4 (KLF4; also known as Krueppel-like factor 4 or gut-enriched Kruppel-like factor/GKLF) is a protein that, in humans, is encoded by the KLF4 gene. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer, gastric cancer, esophageal squamous cell carcinoma, intestinal cancer, prostate cancer, bladder cancer and lung cancer. It may act as a tumor promoter where increased KLF4 expression has been reported, such as in oral squamous cell carcinoma and in primary breast ductal carcinoma. KLF4 is one of four key factors that are essential for inducing pluripotent stem cells. KLF4 is highly expressed in non-dividing cells and its overexpression induces cell cycle arrest. KLF proteins KLF1, KLF2, KLF4, KLF5, KLF6, and KLF7 are transcriptional activators. KLF4 belongs to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF4, which is related to the N-terminal domains of KLF1 and KLF2.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253   7 ESDMAVSDALLPSFSTFASGPAGREKTLRPaGAPTNRWREELSHMKRLPPlpgrpydlaatvatdlesgGAGAACSSNNP 86
Cdd:cd21582    1 EFDMALSGTLLPSISTFASGPAVKEKALGQ-GSANNRWREELSHLKRPCP-------------------PLGGRCYDQDP 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253  87 ALLARRETEEFNDLLDLDFILSNSLTHQESVAATVTTSASASSSSSpassgpasapsTCSFSYPIRAggdpgvaASNTGG 166
Cdd:cd21582   61 PLGMRRKEEEFNDLLDYDFILSNSLLQQQQQQQQAASTSSSTSSSS-----------SSPYSYQLPS-------PQGTAT 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 167 GLLYsresappPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppgggLMGKFVLKASLTTpgSEYSSPSVIS 246
Cdd:cd21582  123 SFLY-------PIPRANLADINDVSPSGGFVAELMRPDLDPAYLQPTS-------LHGKFVVKTTMDM--GDYSQSINVS 186

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 247 VSKGSPDGShpvvvAPYSGGPPRMCPKIKQEAVPSCTVSRSLEAHLsagpqlsngHRPNTHDFPLGRQLPTRTTPTLSPE 326
Cdd:cd21582  187 KSAPMTKSS-----VAPSSSLPFMCPRIKQENPSTCTISRPMDGHL---------GGNSQHGFSQRAPLPSRTTPSGGPG 252

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 327 EL-------LNSRDCHPG------LPLPPGFHPHPGPNYPPFLPDQMQSQvpslHYQELMPPGSCLPEEPKPKRGRRSWP 393
Cdd:cd21582  253 GGnsstaesLMSRDHHPSsqvlshPPLPLPQGYHPSPGYPPFPPPPSQPQ----QYQELMSPGSCLPEEPKPKRGRRSWP 328

                 ....*..
gi 223590253 394 RKRTATH 400
Cdd:cd21582  329 RKRTATH 335

FOG: Zn-finger [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 395 KRTATHTCDYAGCGKTYTKSSHLKAHLRTHTGEKPYHCDWDGCGWKFARSDELTRHYRKHTGHRPFQCQKCdRAFSRSDH 474
Cdd:COG5048  382 KNDKKSETLSNSCIRNFKRDSNLSLHIITHLSFRPYNCKNPPCSKSFNRHYNLIPHKKIHTNHAPLLCSIL-KSFRRDLD 460

                 ....
gi 223590253 475 LALH 478
Cdd:COG5048  461 LSNH 464

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 223590253   460 FQCQKCDRAFSRSDHLALHMKRH 482
Cdd:smart00355   1 YRCPECGKVFKSKSALREHMRTH 23

N-terminal domain of Kruppel-like factor 4; Kruppel-like factor 4 (KLF4; also known as Krueppel-like factor 4 or gut-enriched Kruppel-like factor/GKLF) is a protein that, in humans, is encoded by the KLF4 gene. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer, gastric cancer, esophageal squamous cell carcinoma, intestinal cancer, prostate cancer, bladder cancer and lung cancer. It may act as a tumor promoter where increased KLF4 expression has been reported, such as in oral squamous cell carcinoma and in primary breast ductal carcinoma. KLF4 is one of four key factors that are essential for inducing pluripotent stem cells. KLF4 is highly expressed in non-dividing cells and its overexpression induces cell cycle arrest. KLF proteins KLF1, KLF2, KLF4, KLF5, KLF6, and KLF7 are transcriptional activators. KLF4 belongs to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF4, which is related to the N-terminal domains of KLF1 and KLF2.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253   7 ESDMAVSDALLPSFSTFASGPAGREKTLRPaGAPTNRWREELSHMKRLPPlpgrpydlaatvatdlesgGAGAACSSNNP 86
Cdd:cd21582    1 EFDMALSGTLLPSISTFASGPAVKEKALGQ-GSANNRWREELSHLKRPCP-------------------PLGGRCYDQDP 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253  87 ALLARRETEEFNDLLDLDFILSNSLTHQESVAATVTTSASASSSSSpassgpasapsTCSFSYPIRAggdpgvaASNTGG 166
Cdd:cd21582   61 PLGMRRKEEEFNDLLDYDFILSNSLLQQQQQQQQAASTSSSTSSSS-----------SSPYSYQLPS-------PQGTAT 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 167 GLLYsresappPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppgggLMGKFVLKASLTTpgSEYSSPSVIS 246
Cdd:cd21582  123 SFLY-------PIPRANLADINDVSPSGGFVAELMRPDLDPAYLQPTS-------LHGKFVVKTTMDM--GDYSQSINVS 186

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 247 VSKGSPDGShpvvvAPYSGGPPRMCPKIKQEAVPSCTVSRSLEAHLsagpqlsngHRPNTHDFPLGRQLPTRTTPTLSPE 326
Cdd:cd21582  187 KSAPMTKSS-----VAPSSSLPFMCPRIKQENPSTCTISRPMDGHL---------GGNSQHGFSQRAPLPSRTTPSGGPG 252

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 327 EL-------LNSRDCHPG------LPLPPGFHPHPGPNYPPFLPDQMQSQvpslHYQELMPPGSCLPEEPKPKRGRRSWP 393
Cdd:cd21582  253 GGnsstaesLMSRDHHPSsqvlshPPLPLPQGYHPSPGYPPFPPPPSQPQ----QYQELMSPGSCLPEEPKPKRGRRSWP 328

                 ....*..
gi 223590253 394 RKRTATH 400
Cdd:cd21582  329 RKRTATH 335

N-terminal domain of Kruppel-like factor (KLF) 1, KLF2, KLF4, and similar proteins; Kruppel/Krueppel-like transcription factors (KLFs) belong to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specifity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the related N-terminal domains of KLF1, KLF2, KLF4, and similar proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 175 APPPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppggglmgkfvlKASLTTPGSEYSSPSVISVSKGSPDG 254
Cdd:cd21972   12 AKPEDDLSKFLDLEFILSNTVTSDNDNPPPPDPAYPPPES--------------PESCSTVYDSDGCHPTPNAYCGPNGP 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223590253 255 SHPVVVApYSGGPPRMCPKIKQEAVPSCTvsrsleaHLSAGPQLSNGHRPNTHDFPlgrqlptrttptlspeellnsrdc 334
Cdd:cd21972   78 GLPGHFL-LAGNSPNLGPKIKTENQEQAC-------MPVAGYSGHYGPREPQRVPP------------------------ 125

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 223590253 335 HPGLPlppgfhphpgPNYPPFLPDQMQSQVPSLHYQ-------------ELMPPGSCLPEEPKPKRGRRSWPRKRTATH 400
Cdd:cd21972  126 APPPP----------QYAGHFQYHGHFNMFSPPLRAnhpgmstvmltplSTPPLGFLSPEEAKPKRGRRSWARKRTATH 194

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 223590253  446 ELTRHYRKHTGHRPFQCQKCDRAFSR 471
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 26

N-terminal domain of Kruppel-like Factor 1; Kruppel-like Factor 1 (KLF1, also known as Krueppel-like factor 1 or Erythroid Kruppel-like Factor/EKLF) was the first Kruppel-like factor discovered. It was found to be vitally important for embryonic erythropoiesis in promoting the switch from fetal hemoglobin (Hemoglobin F) to adult hemoglobin (Hemoglobin A) gene expression by binding to highly conserved CACCC domains. EKLF ablation in mouse embryos produces a lethal anemic phenotype, causing death by embryonic day 14, and natural mutations lead to beta+ thalassemia in humans. However, expression of embryonic hemoglobin and fetal hemoglobin genes is normal in EKLF-deficient mice, suggesting other factors may be involved. KLF1 functions as a transcriptional activator. It belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specifity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF1, which is related to the N-terminal domains of KLF2 and KLF4.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 223590253 355 FLPDQMQSQVPS--LHYQELMPPGSCLPEE-PKPKRGRRSWPRKRTATH 400
Cdd:cd21581  230 LFPDYAHSPGPGhlPLGQQPLLPDPPLPPGgAEGKRGRRSWAKKRPAVH 278

Zinc finger, C2H2 type; The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter.

                          10        20
                  ....*....|....*....|....*
gi 223590253  400 HTCDYagCGKTYTKSSHLKAHLRTH 424
Cdd:pfam00096   1 YKCPD--CGKSFSRKSNLKRHLRTH 23

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*...
gi 223590253  416 HLKAHLRTHTGEKPYHCdwDGCGWKFAR 443
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKC--PECGKSFKS 26

Zinc finger, C2H2 type; The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter.

                          10        20
                  ....*....|....*....|....*
gi 223590253  430 YHCDwdGCGWKFARSDELTRHYRKH 454
Cdd:pfam00096   1 YKCP--DCGKSFSRKSNLKRHLRTH 23