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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246  10 SISTLTALGPFPDTQDDFLKWWRSEEAQDMGPGPPDPTEPPLHVKSE-DQPGEEEDDERGADATWDLDLLLTNFSGP--E 86
Cdd:cd21581   1 AVLPSFSSFSFLDHQSDNMKVWKSEEGQLPLDGPPDKLSPSGSEQLQvSQPMTEELLDDDSQASWDIEFLLSNWSSPslN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246  87 PGGAPQTCALAPSEASGAQYPP----PPETLGAYAGGPGLVAGLLGSEDHSGWVRPALRARAPDAFVGPALAPAPAPEPK 162
Cdd:cd21581  81 PSLDNNTQALPQEEQPGAYYEPpkkdQPGTEGLQVGGPGLMAELLSPEESTGWAPPEPHHGYPDAFVGPALFPAPANVDQ 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246 163 ALALQPVYPGPGAGSSGG-------YFPRTGLSVPAASGAPYGLLSGYPAMYPAPQYQGHFQLFRGLQGPAPGPATSPSf 235
Cdd:cd21581 161 FGFPQGGSVDRRGNLSKSgswdfgsYYPQQHPSVVAFPDSRFGPLSGPQALTPDPQHYGYFQLFRHNAALFPDYAHSPG- 239

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 10835246 236 lsclgPGTVGTGLGGTAEDPGVIAETAPSKRGRRSWARKRQAAH 279
Cdd:cd21581 240 -----PGHLPLGQQPLLPDPPLPPGGAEGKRGRRSWAKKRPAVH 278

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246  10 SISTLTALGPFPDTQDDFLKWWRSEEAQDMGPGPPDPTEPPLHVKSE-DQPGEEEDDERGADATWDLDLLLTNFSGP--E 86
Cdd:cd21581   1 AVLPSFSSFSFLDHQSDNMKVWKSEEGQLPLDGPPDKLSPSGSEQLQvSQPMTEELLDDDSQASWDIEFLLSNWSSPslN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246  87 PGGAPQTCALAPSEASGAQYPP----PPETLGAYAGGPGLVAGLLGSEDHSGWVRPALRARAPDAFVGPALAPAPAPEPK 162
Cdd:cd21581  81 PSLDNNTQALPQEEQPGAYYEPpkkdQPGTEGLQVGGPGLMAELLSPEESTGWAPPEPHHGYPDAFVGPALFPAPANVDQ 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246 163 ALALQPVYPGPGAGSSGG-------YFPRTGLSVPAASGAPYGLLSGYPAMYPAPQYQGHFQLFRGLQGPAPGPATSPSf 235
Cdd:cd21581 161 FGFPQGGSVDRRGNLSKSgswdfgsYYPQQHPSVVAFPDSRFGPLSGPQALTPDPQHYGYFQLFRHNAALFPDYAHSPG- 239

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 10835246 236 lsclgPGTVGTGLGGTAEDPGVIAETAPSKRGRRSWARKRQAAH 279
Cdd:cd21581 240 -----PGHLPLGQQPLLPDPPLPPGGAEGKRGRRSWAKKRPAVH 278

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246 281 CAHPGCGKSYTKSSHLKAHLRT--HTGE--KPYACTWEGCGWRFARSDELTRHYRKHTGQRPFRCQLCPRafSRSDHLAL 356
Cdd:COG5048 290 IKSKQCNISFSRSSPLTRHLRSvnHSGEslKPFSCPYSLCGKLFSRNDALKRHILLHTSISPAKEKLLNS--SSKFSPLL 367

                ....*
gi 10835246 357 HMKRH 361
Cdd:COG5048 368 NNEPP 372

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 10835246    339 FRCQLCPRAFSRSDHLALHMKRH 361
Cdd:smart00355   1 YRCPECGKVFKSKSALREHMRTH 23

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246  10 SISTLTALGPFPDTQDDFLKWWRSEEAQDMGPGPPDPTEPPLHVKSE-DQPGEEEDDERGADATWDLDLLLTNFSGP--E 86
Cdd:cd21581   1 AVLPSFSSFSFLDHQSDNMKVWKSEEGQLPLDGPPDKLSPSGSEQLQvSQPMTEELLDDDSQASWDIEFLLSNWSSPslN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246  87 PGGAPQTCALAPSEASGAQYPP----PPETLGAYAGGPGLVAGLLGSEDHSGWVRPALRARAPDAFVGPALAPAPAPEPK 162
Cdd:cd21581  81 PSLDNNTQALPQEEQPGAYYEPpkkdQPGTEGLQVGGPGLMAELLSPEESTGWAPPEPHHGYPDAFVGPALFPAPANVDQ 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246 163 ALALQPVYPGPGAGSSGG-------YFPRTGLSVPAASGAPYGLLSGYPAMYPAPQYQGHFQLFRGLQGPAPGPATSPSf 235
Cdd:cd21581 161 FGFPQGGSVDRRGNLSKSgswdfgsYYPQQHPSVVAFPDSRFGPLSGPQALTPDPQHYGYFQLFRHNAALFPDYAHSPG- 239

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 10835246 236 lsclgPGTVGTGLGGTAEDPGVIAETAPSKRGRRSWARKRQAAH 279
Cdd:cd21581 240 -----PGHLPLGQQPLLPDPPLPPGGAEGKRGRRSWAKKRPAVH 278

Erythroid krueppel-like transcription factor, transactivation 2; This family is the second part of the minimal transactivation domain of erythroid-specific transcription factor EKFL in craniates. EKLF plays an important role in red blood cell development; it is post-translationally modified by ubiquitin on several lysine residues, and its turnover in the cell is regulated by ubiquitin-mediated degradation. In the first 90 residues at the N-terminus EKLF carries a minimal transactivation or TAD domain that is highly acidic. This minimal TAD of EKLF can be further subdivided into two independent domains EKLF_TAD1 (residues 1-40), pfam16832, and EKLF_TAD2 (residues 51-90) that are both capable of independently activating transcription. Both TAD1 and TAD2 are highly acidic and carry a PEST (sequence rich in proline, glutamic acid, serine, and threonine) region. Deletion of either PEST domain significantly slows down degradation of EKLF by ubiquitin. The minimal TAD has an overlapping activation/degradation function that is critical for the role of EKLF in red blood cell development.

                          10        20
                  ....*....|....*....|....*..
gi 10835246    59 PGEEEDDERGADATWDLDLLLTNFSGP 85
Cdd:pfam16833   1 PGEDEDDERDAAAAWDLDLFLTNFPGP 27

N-terminal domain of Kruppel-like factors with similarity to the N-terminal domains of Kruppel-like factor (KLF)1, KLF2, and KLF4; 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 N-terminal domains of an unknown subfamily of KLFs, predominantly found in fish, related to the N-terminal domains of KLF1, KLF2, and KLF4.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246 203 YPAMYPAPQYQGHFQLFR--------GLQGPAPGPATSPSFLSCLGpgtvgtglggtAEDPGviaETAPsKRGRRSWARK 274
Cdd:cd22056 270 HYAHQGAPQFHGQYSVFRepmrvhhqGHPGSMLTPPSSPPLLEFYA-----------QDEPE---DIKP-KRGRRSWARK 334

                ....*
gi 10835246 275 RQAAH 279
Cdd:cd22056 335 RTATH 339

Erythroid krueppel-like transcription factor, transactivation 1; This family is the first part of the minimal transactivation domain of erythroid-specific transcription factor EKFL in craniates. EKLF plays an important role in red blood cell development; it is posttranslationally modified by UBI on several lysine residues, and its turnover in the cell is regulated by ubiquitin-mediated degradation. In the first 90 residues at the N-terminus EKLF carries a minimal transactivation or TAD domain that is highly acidic. This minimal TAD of EKLF can be further subdivided into two independent domains EKLF_TAD1 (residues 1-40) and EKLF_TAD2 (residues 51-90), pfam16833, that are both capable of independently activating transcription. TAD1, is able to form a non-covalent interaction with ubiquitin. Both TAD1 and TAd2 are highly acidic and carry a PEST (sequence rich in proline, glutamic acid, serine, and threonine) region. Deletion of either PEST domain significantly slows down degradation of EKLF by ubiquitin. The minimal TAD has an overlapping activation/degradation function that is critical for the role of EKLF in red blood cell development.

                          10        20
                  ....*....|....*....|.
gi 10835246    22 DTQDDFLKWWRSEEAQDMGPG 42
Cdd:pfam16832   1 DAQEDFLKWWHSEEEQDLGPG 21

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 10835246   339 FRCQLCPRAFSRSDHLALHMKRH 361
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRTH 23

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*...
gi 10835246   295 HLKAHLRTHTGEKPYACtwEGCGWRFAR 322
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKC--PECGKSFKS 26

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 10835246    339 FRCQLCPRAFSRSDHLALHMKRH 361
Cdd:smart00355   1 YRCPECGKVFKSKSALREHMRTH 23

N-terminal domain of Kruppel-like factor 2; Kruppel-like Factor 2 (KLF2, also known as Krueppel-like factor 2 or lung Kruppel-like Factor/LKLF) is a protein that, in humans, is encoded by the KLF2 gene on chromosome 19. It has been implicated in a variety of biochemical processes in the human body, including lung development, embryonic erythropoiesis, epithelial integrity, T-cell viability, and adipogenesis. KLF proteins KLF1, KLF2, KLF4, KLF5, KLF6, and KLF7 are transcriptional activators. KLF2 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 KLF2, which is related to the N-terminal domains of KLF1 and KLF4.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246   5 ETALPSISTLTAlgpfpDTQDDFLKWWRSeeaqDMGPGPPDPTEPPLHVKSEDQPGEEEDDErgaDATWDLDLLLTNFSG 84
Cdd:cd21583   2 GTILPSISTFAN-----QKEKCWEDRWKG----EEDKSSLSSCLLDLQNGDSCLGRKDDEDL---DNYLDLDFILANTAG 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246  85 PEP-GGAPQTCALAPSEASGAQYPPPPETLGAYA--------GGPGLVAGLLGSEDHSGWVRPALRAR---APDAFVGPA 152
Cdd:cd21583  70 SDSaGAAGGGYYGSLPEPAAPYSASNPPGAYSVPeqgsppppYSSSLMAELLRDSDSDYGPSNSIQGRflvSSAFFPRQD 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246 153 LAPAPAPEPKALALQPVYPGPGAGSSG----------GYF--PRTGLSVPAA---------------------------S 193
Cdd:cd21583 150 DPDSIKVEPSMDSYGPVMGMVPQSCPKikqegnvscmMSFeqPRLANSPQAAgsmtpplspddlmasecqqqmmcspsfP 229

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10835246 194 GAPYGLLSGYPAMYPAPQYQGHFQLFR---GLQGPAP-GPATSPSflsclgpgtvgtglggtaeDPGVIAETAPsKRGRR 269
Cdd:cd21583 230 QPHHPHYPPPPQPPLQYQSPHQFGLFEdglPLQPSAQrVLLTPPS-------------------SPLELLESKP-KRGRR 289

                       330
                ....*....|
gi 10835246 270 SWARKRQAAH 279
Cdd:cd21583 290 SWPRKRTATH 299

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 10835246 208 PAPQYQGHFQLfrglqGPAPGPATSPSFLSCLGPGTVGTGLGGTAEDPGVIAETAPSKRGRRSWARKRQAAH 279
Cdd:cd21582 269 PSSQVLSHPPL-----PLPQGYHPSPGYPPFPPPPSQPQQYQELMSPGSCLPEEPKPKRGRRSWPRKRTATH 335