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 16758530   7 ESDMAVSDALLPSFSTFASGPAGREKTLRPaGAPTNRWREELSHMKRLP-PLPGRPYDlaatvatdlesggagaacsSNN 85
Cdd:cd21582   1 EFDMALSGTLLPSISTFASGPAVKEKALGQ-GSANNRWREELSHLKRPCpPLGGRCYD-------------------QDP 60

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530  86 PALPRRETEEFNDLLDLDFILSNSLSHQESVAATVTTSASASSSSSpassgpasapsTCSFSYPIRAGGDpgvaagnTGG 165
Cdd:cd21582  61 PLGMRRKEEEFNDLLDYDFILSNSLLQQQQQQQQAASTSSSTSSSS-----------SSPYSYQLPSPQG-------TAT 122

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 166 GLLYsresappPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppgggLMGKFVLKASLSTPGSEYTspsvIS 245
Cdd:cd21582 123 SFLY-------PIPRANLADINDVSPSGGFVAELMRPDLDPAYLQPTS-------LHGKFVVKTTMDMGDYSQS----IN 184

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 246 VSKGSPdgsHPVVVAPYSGGPPRMCPKIKQEAVPSCTVSRSLEAHLsagpqlsngHRPNTHDFPLGRQLPTRTTPTLSPE 325
Cdd:cd21582 185 VSKSAP---MTKSSVAPSSSLPFMCPRIKQENPSTCTISRPMDGHL---------GGNSQHGFSQRAPLPSRTTPSGGPG 252

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 326 EL-------LNSRDCHPG------LPLPPGFHPHPGPSYPPFLPDQMQSQvpslHYQELMPPGSCLPEEPKPKRGRRSWP 392
Cdd:cd21582 253 GGnsstaesLMSRDHHPSsqvlshPPLPLPQGYHPSPGYPPFPPPPSQPQ----QYQELMSPGSCLPEEPKPKRGRRSWP 328

                ....*..
gi 16758530 393 RKRTATH 399
Cdd:cd21582 329 RKRTATH 335

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 394 KRTATHTCDYAGCGKTYTKSSHLKAHLRTHTGEKPYHCDWDGCGWKFARSDELTRHYRKHTGHRPFQCQKCdRAFSRSDH 473
Cdd:COG5048 382 KNDKKSETLSNSCIRNFKRDSNLSLHIITHLSFRPYNCKNPPCSKSFNRHYNLIPHKKIHTNHAPLLCSIL-KSFRRDLD 460

                ....
gi 16758530 474 LALH 477
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 16758530   7 ESDMAVSDALLPSFSTFASGPAGREKTLRPaGAPTNRWREELSHMKRLP-PLPGRPYDlaatvatdlesggagaacsSNN 85
Cdd:cd21582   1 EFDMALSGTLLPSISTFASGPAVKEKALGQ-GSANNRWREELSHLKRPCpPLGGRCYD-------------------QDP 60

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530  86 PALPRRETEEFNDLLDLDFILSNSLSHQESVAATVTTSASASSSSSpassgpasapsTCSFSYPIRAGGDpgvaagnTGG 165
Cdd:cd21582  61 PLGMRRKEEEFNDLLDYDFILSNSLLQQQQQQQQAASTSSSTSSSS-----------SSPYSYQLPSPQG-------TAT 122

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 166 GLLYsresappPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppgggLMGKFVLKASLSTPGSEYTspsvIS 245
Cdd:cd21582 123 SFLY-------PIPRANLADINDVSPSGGFVAELMRPDLDPAYLQPTS-------LHGKFVVKTTMDMGDYSQS----IN 184

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 246 VSKGSPdgsHPVVVAPYSGGPPRMCPKIKQEAVPSCTVSRSLEAHLsagpqlsngHRPNTHDFPLGRQLPTRTTPTLSPE 325
Cdd:cd21582 185 VSKSAP---MTKSSVAPSSSLPFMCPRIKQENPSTCTISRPMDGHL---------GGNSQHGFSQRAPLPSRTTPSGGPG 252

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 326 EL-------LNSRDCHPG------LPLPPGFHPHPGPSYPPFLPDQMQSQvpslHYQELMPPGSCLPEEPKPKRGRRSWP 392
Cdd:cd21582 253 GGnsstaesLMSRDHHPSsqvlshPPLPLPQGYHPSPGYPPFPPPPSQPQ----QYQELMSPGSCLPEEPKPKRGRRSWP 328

                ....*..
gi 16758530 393 RKRTATH 399
Cdd:cd21582 329 RKRTATH 335

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 394 KRTATHTCDYAGCGKTYTKSSHLKAHLRTHTGEKPYHCDWDGCGWKFARSDELTRHYRKHTGHRPFQCQKCdRAFSRSDH 473
Cdd:COG5048 382 KNDKKSETLSNSCIRNFKRDSNLSLHIITHLSFRPYNCKNPPCSKSFNRHYNLIPHKKIHTNHAPLLCSIL-KSFRRDLD 460

                ....
gi 16758530 474 LALH 477
Cdd:COG5048 461 LSNH 464

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 16758530    459 FQCQKCDRAFSRSDHLALHMKRH 481
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 16758530   7 ESDMAVSDALLPSFSTFASGPAGREKTLRPaGAPTNRWREELSHMKRLP-PLPGRPYDlaatvatdlesggagaacsSNN 85
Cdd:cd21582   1 EFDMALSGTLLPSISTFASGPAVKEKALGQ-GSANNRWREELSHLKRPCpPLGGRCYD-------------------QDP 60

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530  86 PALPRRETEEFNDLLDLDFILSNSLSHQESVAATVTTSASASSSSSpassgpasapsTCSFSYPIRAGGDpgvaagnTGG 165
Cdd:cd21582  61 PLGMRRKEEEFNDLLDYDFILSNSLLQQQQQQQQAASTSSSTSSSS-----------SSPYSYQLPSPQG-------TAT 122

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 166 GLLYsresappPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppgggLMGKFVLKASLSTPGSEYTspsvIS 245
Cdd:cd21582 123 SFLY-------PIPRANLADINDVSPSGGFVAELMRPDLDPAYLQPTS-------LHGKFVVKTTMDMGDYSQS----IN 184

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 246 VSKGSPdgsHPVVVAPYSGGPPRMCPKIKQEAVPSCTVSRSLEAHLsagpqlsngHRPNTHDFPLGRQLPTRTTPTLSPE 325
Cdd:cd21582 185 VSKSAP---MTKSSVAPSSSLPFMCPRIKQENPSTCTISRPMDGHL---------GGNSQHGFSQRAPLPSRTTPSGGPG 252

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 326 EL-------LNSRDCHPG------LPLPPGFHPHPGPSYPPFLPDQMQSQvpslHYQELMPPGSCLPEEPKPKRGRRSWP 392
Cdd:cd21582 253 GGnsstaesLMSRDHHPSsqvlshPPLPLPQGYHPSPGYPPFPPPPSQPQ----QYQELMSPGSCLPEEPKPKRGRRSWP 328

                ....*..
gi 16758530 393 RKRTATH 399
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 16758530 174 APPPTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQpqppggglmgkfvlKASLSTPGSEYTSPSVISVSKGSPDG 253
Cdd:cd21972  12 AKPEDDLSKFLDLEFILSNTVTSDNDNPPPPDPAYPPPES--------------PESCSTVYDSDGCHPTPNAYCGPNGP 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758530 254 SHPVVVApYSGGPPRMCPKIKQEAVPSCTvsrsleaHLSAGPQLSNGHRPNTHDFPlgrqlptrttptlspeellnsrdc 333
Cdd:cd21972  78 GLPGHFL-LAGNSPNLGPKIKTENQEQAC-------MPVAGYSGHYGPREPQRVPP------------------------ 125

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 16758530 334 HPGLPlppgfhphpgPSYPPFLPDQMQSQVPSLHYQ-------------ELMPPGSCLPEEPKPKRGRRSWPRKRTATH 399
Cdd:cd21972 126 APPPP----------QYAGHFQYHGHFNMFSPPLRAnhpgmstvmltplSTPPLGFLSPEEAKPKRGRRSWARKRTATH 194

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 16758530   445 ELTRHYRKHTGHRPFQCQKCDRAFSR 470
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 16758530 354 FLPDQMQSQVPS--LHYQELMPPGSCLPEE-PKPKRGRRSWPRKRTATH 399
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 16758530   399 HTCDYagCGKTYTKSSHLKAHLRTH 423
Cdd:pfam00096   1 YKCPD--CGKSFSRKSNLKRHLRTH 23

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*...
gi 16758530   415 HLKAHLRTHTGEKPYHCdwDGCGWKFAR 442
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 16758530   429 YHCDwdGCGWKFARSDELTRHYRKH 453
Cdd:pfam00096   1 YKCP--DCGKSFSRKSNLKRHLRTH 23