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 22547197   250 QCIKQELICKWIDPEQlSNPKKSCNKTFSTMHELVTHVSVEHVGGP 295
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

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 22547197   250 QCIKQELICKWIDPEQlSNPKKSCNKTFSTMHELVTHVSVEHVGGP 295
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*...
gi 22547197   349 NLKIHKRTHTGEKPFQCEFegCDRRFAN 376
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPE--CGKSFKS 26

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 22547197    393 YLCKMCDKSYTHPSSLRKHMKVH 415
Cdd:smart00355   1 YRCPECGKVFKSKSALREHMRTH 23

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 22547197   250 QCIKQELICKWIDPEQlSNPKKSCNKTFSTMHELVTHVSVEHVGGP 295
Cdd:pfam18366   1 QPIKQELSCKWIDPEQ-PAPKKPCNKTFSTMHEIVTHLTVEHVGGP 45

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547197 265 QLSNPKKSCNKTFSTMHELVTHVSVEHVGGPEQSNHVCFWEECPregKPFKAKYKLVNHIRVHTGEKPFPCPFPGCGKVF 344
Cdd:COG5048 287 SLPIKSKQCNISFSRSSPLTRHLRSVNHSGESLKPFSCPYSLCG---KLFSRNDALKRHILLHTSISPAKEKLLNSSSKF 363

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547197 345 ARSENLKIHKRTH-----TGEKPFQCEFEGCDRRFANSSDRKKHMHVHTSDKPYLCK--MCDKSYTHPSSLRKHMKVHES 417
Cdd:COG5048 364 SPLLNNEPPQSLQqykdlKNDKKSETLSNSCIRNFKRDSNLSLHIITHLSFRPYNCKnpPCSKSFNRHYNLIPHKKIHTN 443

                ..
gi 22547197 418 SP 419
Cdd:COG5048 444 HA 445

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*...
gi 22547197   349 NLKIHKRTHTGEKPFQCEFegCDRRFAN 376
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPE--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 22547197   393 YLCKMCDKSYTHPSSLRKHMKVH 415
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRTH 23

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547197 243 FFRYMRQQCIKQELICKWIDPEQLSNPKKSCNKTFSTMHELVTHVSVEHVGGPEQSNHVCfWEECPREGKPFKAKYKLVN 322
Cdd:COG5048 235 LSPKSLLSQSPSSLSSSDSSSSASESPRSSLPTASSQSSSPNESDSSSEKGFSLPIKSKQ-CNISFSRSSPLTRHLRSVN 313

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547197 323 HIRVhtGEKPFPCPFPGCGKVFARSENLKIHKRTHTGEKPFQCEFEGCDRRFANSSDRKKHmhvhtsdkpylckmcdkSY 402
Cdd:COG5048 314 HSGE--SLKPFSCPYSLCGKLFSRNDALKRHILLHTSISPAKEKLLNSSSKFSPLLNNEPP-----------------QS 374

                       170       180       190
                ....*....|....*....|....*....|....
gi 22547197 403 THPSSLRKHMKVHESSPQGSESSPAASSGYESST 436
Cdd:COG5048 375 LQQYKDLKNDKKSETLSNSCIRNFKRDSNLSLHI 408

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 22547197   333 FPCPfpGCGKVFARSENLKIHKRTH 357
Cdd:pfam00096   1 YKCP--DCGKSFSRKSNLKRHLRTH 23