KRAB (Kruppel-associated box) domain -A box; The KRAB domain is a transcription repression module, found in a subgroup of the zinc finger proteins (ZFPs) of the C2H2 family, KRAB-ZFPs. KRAB-ZFPs comprise the largest group of transcriptional regulators in mammals, and are only found in tetrapods. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta , KRAB-A interacting protein , and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 32698678 202 VALGDIPFYFSREEWGTLDPAQRDLFWDIKRENSRN 237
Cdd:cd07765   1 VTFEDVAVYFSQEEWELLDPAQRDLYRDVMLENYEN 36

SCAN domain; The SCAN domain (named after SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) is found in several pfam00096 proteins. The domain has been shown to be able to mediate homo- and hetero-oligomerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32698678    41 SEACRQRFRQFCYGDVHGPHEAFSQLWELCCRWLRPELRTKEQILELLVLEQFLTVLPGEIQGWVREQHPGSGEEAVALV 120
Cdd:pfam02023   1 PEASRQRFRQFCYQEAEGPREALSQLRELCHQWLRPEKHTKEQILELLVLEQFLTILPEEIQSWVREHHPESGEEAVALA 80

                  ....*..
gi 32698678   121 EDLQKQP 127
Cdd:pfam02023  81 EDLLLER 87

KRAB (Kruppel-associated box) domain -A box; The KRAB domain is a transcription repression module, found in a subgroup of the zinc finger proteins (ZFPs) of the C2H2 family, KRAB-ZFPs. KRAB-ZFPs comprise the largest group of transcriptional regulators in mammals, and are only found in tetrapods. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta , KRAB-A interacting protein , and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 32698678 202 VALGDIPFYFSREEWGTLDPAQRDLFWDIKRENSRN 237
Cdd:cd07765   1 VTFEDVAVYFSQEEWELLDPAQRDLYRDVMLENYEN 36

krueppel associated box;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 32698678    202 VALGDIPFYFSREEWGTLDPAQRDLFWDIKRENSRN-TTLGFGLKGQSEKSLLQ 254
Cdd:smart00349   1 VTFEDVAVYFTQEEWEQLDPAQKNLYRDVMLENYSNlVSLGFQVPKPDLISQLE 54

KRAB box; The KRAB domain (or Kruppel-associated box) is present in about a third of zinc finger proteins containing C2H2 fingers. The KRAB domain is found to be involved in protein-protein interactions. The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B. The A box plays an important role in repression by binding to corepressors, while the B box is thought to enhance this repression brought about by the A box. KRAB-containing proteins are thought to have critical functions in cell proliferation and differentiation, apoptosis and neoplastic transformation.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 32698678   201 PVALGDIPFYFSREEWGTLDPAQRDLFWDIKRENSRN 237
Cdd:pfam01352   1 SVTFEDVAVDFTQEEWALLDPAQRNLYRDVMLENYRN 37

SCAN domain; The SCAN domain (named after SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) is found in several pfam00096 proteins. The domain has been shown to be able to mediate homo- and hetero-oligomerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32698678    41 SEACRQRFRQFCYGDVHGPHEAFSQLWELCCRWLRPELRTKEQILELLVLEQFLTVLPGEIQGWVREQHPGSGEEAVALV 120
Cdd:pfam02023   1 PEASRQRFRQFCYQEAEGPREALSQLRELCHQWLRPEKHTKEQILELLVLEQFLTILPEEIQSWVREHHPESGEEAVALA 80

                  ....*..
gi 32698678   121 EDLQKQP 127
Cdd:pfam02023  81 EDLLLER 87

KRAB (Kruppel-associated box) domain -A box; The KRAB domain is a transcription repression module, found in a subgroup of the zinc finger proteins (ZFPs) of the C2H2 family, KRAB-ZFPs. KRAB-ZFPs comprise the largest group of transcriptional regulators in mammals, and are only found in tetrapods. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta , KRAB-A interacting protein , and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 32698678 202 VALGDIPFYFSREEWGTLDPAQRDLFWDIKRENSRN 237
Cdd:cd07765   1 VTFEDVAVYFSQEEWELLDPAQRDLYRDVMLENYEN 36

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32698678 318 SCGQCGKRFRWGSDLARHQRTHTGEKPHKCPECDKSFRSSSDLVRHQGVHTGE-------KPFSCSECGKSFSRSAYLAD 390
Cdd:COG5048 228 PLTTNSQLSPKSLLSQSPSSLSSSDSSSSASESPRSSLPTASSQSSSPNESDSssekgfsLPIKSKQCNISFSRSSPLTR 307

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32698678 391 HQR--IHTGE--KPFGC--SDCGKSFSLRSYLLDHRRVHTGERPFGC--GECDKSFKQRAHLIAHQSLHAK 453
Cdd:COG5048 308 HLRsvNHSGEslKPFSCpySLCGKLFSRNDALKRHILLHTSISPAKEklLNSSSKFSPLLNNEPPQSLQQY 378

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 32698678   331 DLARHQRTHTGEKPHKCPECDKSFRS 356
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 26

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32698678 343 KPHKCPECDKSFRSSSDLVRHQGVHTGEKPFSCS--ECGKSFSRSAYLADHQRIHTGEKPFGCSDCGKS--FSLRSYLLD 418
Cdd:COG5048  32 RPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSysGCDKSFSRPLELSRHLRTHHNNPSDLNSKSLPLsnSKASSSSLS 111

                .
gi 32698678 419 H 419
Cdd:COG5048 112 S 112

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 32698678 371 KPFSCSECGKSFSRSAYLADHQRIHTGEKPFGCSD--CGKSFSLRSYLLDHRRVHT 424
Cdd:COG5048  32 RPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYsgCDKSFSRPLELSRHLRTHH 87

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32698678 313 AEKPHSCGQCGKRFRWGSDLARHQRTHTGEKPHKC--PECDKSFRSSSDLVRHQGVHTGEKPFSCSECGKS--FSRSAYL 388
Cdd:COG5048  30 APRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCsySGCDKSFSRPLELSRHLRTHHNNPSDLNSKSLPLsnSKASSSS 109

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 32698678 389 ADHQrIHTGEKPFGCSDCGKSFSLRSYLLDHRRVHT 424
Cdd:COG5048 110 LSSS-SSNSNDNNLLSSHSLPPSSRDPQLPDLLSIS 144

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 32698678   373 FSCSECGKSFSRSAYLADHQRIH 395
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRTH 23

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 32698678   415 YLLDHRRVHTGERPFGCGECDKSFKQ 440
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 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 32698678   403 CSDCGKSFSLRSYLLDHRRVH 423
Cdd:pfam00096   3 CPDCGKSFSRKSNLKRHLRTH 23