Zic proteins zinc finger domain; This is the ZF1 (Zinc Finger 1) domain found in Zic family proteins found in Eukaryotes. In humans, there are five members of the Zic family that are involved in human congenital anomalies. One of them, ZIC3, causes X-linked heterotaxy (HTX1), which is a left-right axis disturbance that manifests as variable combinations of heart malformation, altered lung lobation, splenic abnormality and gastrointestinal malrotation. Zic faily proteins contain multiple zinc finger domains (ZFD), which are generally composed of five tandemly repeated C2H2 zinc finger (ZF) motifs. Sequence comparison analysis reveal that this N-terminal ZF (ZF1) domain of the Zic zinc finger domains is unique in that it possesses more amino acid residues (6-38 amino acids) between the two cysteine residues of the C2H2 motif compared to Gli and Glis ZF1s or any of the other ZFs (ZF2-5) in the Gli/Glis/Zic superfamily of proteins. Mutations in cysteine 253 (C253S) or histidine 286 (H286R) in ZIC3 ZF1, which are found in heterotaxy patients, result in extranuclear localization of the mutant ZIC3 protein. Furthermore, mutations in the evolutionarily conserved amino acid residues (C253, W255, C268, H281 and H286) of ZF1 generally impair nuclear localization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1605358373 225 QCIKQELICKWIDPEQlNNPKKSCNKTFSTMHELVTHVSVEHVGGP 270
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1605358373 295 LVNHIRVHTGEKPFPCPFPGCGKVFARSENLKIHKRTHTGEKPFQCEFEGCDRRFANSSDrKKHMHVHTSDKPYLCKMCD 374
Cdd:COG5048    49 LTRHIRSHTGEKPSQCSYSGCDKSFSRPLELSRHLRTHHNNPSDLNSKSLPLSNSKASSS-SLSSSSSNSNDNNLLSSHS 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1605358373 375 KSYTHPSSLRK--HMKVYHIAVFPADILGGGRKTKTGAASSPGCKARESLLGTGGRAWVPGSAlalrgwcelcALRTGTL 452
Cdd:COG5048   128 LPPSSRDPQLPdlLSISNLRNNPLPGNNSSSVNTPQSNSLHPPLPANSLSKDPSSNLSLLISS----------NVSTSIP 197

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1605358373 453 TPPCLVAFAFQVHESSPQGSESSPAASSGYESSTPPGLVSPSAETQSTTNLSP 505
Cdd:COG5048   198 SSSENSPLSSSYSIPSSSSDQNLENSSSSLPLTTNSQLSPKSLLSQSPSSLSS 250

Zic proteins zinc finger domain; This is the ZF1 (Zinc Finger 1) domain found in Zic family proteins found in Eukaryotes. In humans, there are five members of the Zic family that are involved in human congenital anomalies. One of them, ZIC3, causes X-linked heterotaxy (HTX1), which is a left-right axis disturbance that manifests as variable combinations of heart malformation, altered lung lobation, splenic abnormality and gastrointestinal malrotation. Zic faily proteins contain multiple zinc finger domains (ZFD), which are generally composed of five tandemly repeated C2H2 zinc finger (ZF) motifs. Sequence comparison analysis reveal that this N-terminal ZF (ZF1) domain of the Zic zinc finger domains is unique in that it possesses more amino acid residues (6-38 amino acids) between the two cysteine residues of the C2H2 motif compared to Gli and Glis ZF1s or any of the other ZFs (ZF2-5) in the Gli/Glis/Zic superfamily of proteins. Mutations in cysteine 253 (C253S) or histidine 286 (H286R) in ZIC3 ZF1, which are found in heterotaxy patients, result in extranuclear localization of the mutant ZIC3 protein. Furthermore, mutations in the evolutionarily conserved amino acid residues (C253, W255, C268, H281 and H286) of ZF1 generally impair nuclear localization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1605358373 225 QCIKQELICKWIDPEQlNNPKKSCNKTFSTMHELVTHVSVEHVGGP 270
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1605358373 295 LVNHIRVHTGEKPFPCPFPGCGKVFARSENLKIHKRTHTGEKPFQCEFEGCDRRFANSSDrKKHMHVHTSDKPYLCKMCD 374
Cdd:COG5048    49 LTRHIRSHTGEKPSQCSYSGCDKSFSRPLELSRHLRTHHNNPSDLNSKSLPLSNSKASSS-SLSSSSSNSNDNNLLSSHS 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1605358373 375 KSYTHPSSLRK--HMKVYHIAVFPADILGGGRKTKTGAASSPGCKARESLLGTGGRAWVPGSAlalrgwcelcALRTGTL 452
Cdd:COG5048   128 LPPSSRDPQLPdlLSISNLRNNPLPGNNSSSVNTPQSNSLHPPLPANSLSKDPSSNLSLLISS----------NVSTSIP 197

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1605358373 453 TPPCLVAFAFQVHESSPQGSESSPAASSGYESSTPPGLVSPSAETQSTTNLSP 505
Cdd:COG5048   198 SSSENSPLSSSYSIPSSSSDQNLENSSSSLPLTTNSQLSPKSLLSQSPSSLSS 250

Zic proteins zinc finger domain; This is the ZF1 (Zinc Finger 1) domain found in Zic family proteins found in Eukaryotes. In humans, there are five members of the Zic family that are involved in human congenital anomalies. One of them, ZIC3, causes X-linked heterotaxy (HTX1), which is a left-right axis disturbance that manifests as variable combinations of heart malformation, altered lung lobation, splenic abnormality and gastrointestinal malrotation. Zic faily proteins contain multiple zinc finger domains (ZFD), which are generally composed of five tandemly repeated C2H2 zinc finger (ZF) motifs. Sequence comparison analysis reveal that this N-terminal ZF (ZF1) domain of the Zic zinc finger domains is unique in that it possesses more amino acid residues (6-38 amino acids) between the two cysteine residues of the C2H2 motif compared to Gli and Glis ZF1s or any of the other ZFs (ZF2-5) in the Gli/Glis/Zic superfamily of proteins. Mutations in cysteine 253 (C253S) or histidine 286 (H286R) in ZIC3 ZF1, which are found in heterotaxy patients, result in extranuclear localization of the mutant ZIC3 protein. Furthermore, mutations in the evolutionarily conserved amino acid residues (C253, W255, C268, H281 and H286) of ZF1 generally impair nuclear localization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1605358373 225 QCIKQELICKWIDPEQlNNPKKSCNKTFSTMHELVTHVSVEHVGGP 270
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1605358373 305 EKPFPCPFPGCGKVFARSENLKIHKRTHTGEKPFQCEFEGCDRRFANSSDRKKHMHVHTSDKPYLCKMCDKSYTHPSS 382
Cdd:COG5048    29 NAPRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELSRHLRTHHNNPSDLNSKSLPLSNSKAS 106

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1605358373 218 FFRYMRQQCIKQELICKWIDPEQLNNPKKSCNKTFSTMHELVTHVSVEHVGGPEQSNHIcYWEECPREGKPFKAKYKLVN 297
Cdd:COG5048   235 LSPKSLLSQSPSSLSSSDSSSSASESPRSSLPTASSQSSSPNESDSSSEKGFSLPIKSK-QCNISFSRSSPLTRHLRSVN 313

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1605358373 298 HIRVHTgeKPFPCPFPGCGKVFARSENLKIHKRTHTGEKPFQCEFEGCDRRFANSSDRKKHMHVHTSDKPylcKMCDKSY 377
Cdd:COG5048   314 HSGESL--KPFSCPYSLCGKLFSRNDALKRHILLHTSISPAKEKLLNSSSKFSPLLNNEPPQSLQQYKDL---KNDKKSE 388

                         170
                  ....*....|....*.
gi 1605358373 378 THPSSLRKHMKVYHIA 393
Cdd:COG5048   389 TLSNSCIRNFKRDSNL 404

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*..
gi 1605358373 295 LVNHIRVHTGEKPFPCPFpgCGKVFAR 321
Cdd:pfam13465   2 LKRHMRTHTGEKPYKCPE--CGKSFKS 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 1605358373 308 FPCPfpGCGKVFARSENLKIHKRTH 332
Cdd:pfam00096   1 YKCP--DCGKSFSRKSNLKRHLRTH 23

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 1605358373 368 YLCKMCDKSYTHPSSLRKHMKV 389
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRT 22